Characteristics of bitter cassava films in kin to commercial PLA bio-film.
\\n\\n
Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\\n\\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\\n\\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\\n\\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\\n\\nThank you all for being part of the journey. 5,000 times thank you!
\\n\\nNow with 5,000 titles available Open Access, which one will you read next?
\\n\\nRead, share and download for free: https://www.intechopen.com/books
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Preparation of Space Experiments edited by international leading expert Dr. Vladimir Pletser, Director of Space Training Operations at Blue Abyss is the 5,000th Open Access book published by IntechOpen and our milestone publication!
\n\n"This book presents some of the current trends in space microgravity research. The eleven chapters introduce various facets of space research in physical sciences, human physiology and technology developed using the microgravity environment not only to improve our fundamental understanding in these domains but also to adapt this new knowledge for application on earth." says the editor. Listen what else Dr. Pletser has to say...
\n\n\n\nDr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\n\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\n\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\n\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\n\nThank you all for being part of the journey. 5,000 times thank you!
\n\nNow with 5,000 titles available Open Access, which one will you read next?
\n\nRead, share and download for free: https://www.intechopen.com/books
\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:"7539",leadTitle:null,fullTitle:"Connective Tissue Disease - Current State of the Art",title:"Connective Tissue Disease",subtitle:"Current State of the Art",reviewType:"peer-reviewed",abstract:"Connective tissue diseases (CTDs) comprise a number of systemic autoimmune disorders and related conditions characterized by rheumatic manifestations, production of myriad autoantibodies, and varied immune-mediated organ injury. To achieve the best outcomes for patients, accurate evaluation has become critical, and thus advanced diagnostic and assessment modalities have been developed that have had a revolutionary impact in precise characterization of the disease conditions in CTDs. This book provides an in-depth look at the current state of CTDs, while also presenting an overview that is easily understandable to newcomers to the field. Chapters cover such conditions as rheumatoid arthritis, lupus, systemic sclerosis spectrum diseases, and spondyloarthritis, as well as the importance of physical activity and exercise training in the clinical course of CTDs.",isbn:"978-1-78985-841-9",printIsbn:"978-1-78985-698-9",pdfIsbn:"978-1-78985-842-6",doi:"10.5772/intechopen.76664",price:100,priceEur:109,priceUsd:129,slug:"connective-tissue-disease-current-state-of-the-art",numberOfPages:96,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"392aff20e98be42f46dd35a6bf02e392",bookSignature:"Akira Takeda",publishedDate:"September 16th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/7539.jpg",numberOfDownloads:4619,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:4,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:4,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 26th 2018",dateEndSecondStepPublish:"June 18th 2018",dateEndThirdStepPublish:"August 17th 2018",dateEndFourthStepPublish:"November 5th 2018",dateEndFifthStepPublish:"January 4th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"202405",title:"Dr.",name:"Akira",middleName:null,surname:"Takeda",slug:"akira-takeda",fullName:"Akira Takeda",profilePictureURL:"https://mts.intechopen.com/storage/users/202405/images/system/202405.jpg",biography:"Akira Takeda, MD, PhD, is the founder and director of the Division of Clinical Immunology & Rheumatology at International University of Health and Welfare Hospital, Japan. He graduated from Akita University School of Medicine, Japan, after which he joined Jichi Medical School, where he was actively involved in clinical rheumatology practice as well as basic research in the field of Immunology. After completing his thesis studies, he worked as an assistant professor at the University of Massachusetts Medical School while pursuing extensive studies of cellular and humoral immunity against pathogens to elucidate the precise host defense mechanisms. Upon his return to Japan, Dr. Takeda joined Dokkyo University School of Medicine and the current institute where he has been exploring the immuno-pathogenesis of connective tissue disease (CTD)-associated organ injury, leading to numerous publications including novel research into how T cells trigger and promote interstitial pneumonia in CTDs.",institutionString:"International University of Health and Welfare",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"International University of Health and Welfare",institutionURL:null,country:{name:"Japan"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"184",title:"Immunology, Allergology and Rheumatology",slug:"immunology-allergology-and-rheumatology"}],chapters:[{id:"72793",title:"Growing Need for Diagnostic Precision in Rheumatoid Arthritis: Proposal of MR Imaging Criteria for Early Diagnosis",doi:"10.5772/intechopen.92989",slug:"growing-need-for-diagnostic-precision-in-rheumatoid-arthritis-proposal-of-mr-imaging-criteria-for-ea",totalDownloads:696,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The recent and revolutionary paradigm shift involving novel therapeutics for the treatment of rheumatoid arthritis (RA) has called for changes in the early diagnosis of RA. Physicians now need to diagnose RA earlier, and with greater accuracy, in order to initiate effective definitive treatment as early as possible. However, due to the complexity and diverseness of RA, we still do not have comprehensive diagnostic criteria for RA readily available. To find a solution to this challenge, we aimed to develop practically useful criteria which integrate gadolinium (Gd) contrast-enhanced magnetic resonance imaging (MRI) findings with clinical manifestations of the disease. These diagnostic criteria we propose, the “diagnostic criteria for early RA with MRI findings,” are composed of two domains. The first domain consists of clinical findings suggestive of RA, which include both entry criteria—i.e., polyarthralgia of hands (joint pain of three or more joint areas confirmed by a physician), and exclusion criteria—i.e., exclusion of other rheumatic conditions including systemic lupus erythematosus (SLE), dermatomyositis and polymyositis (PM/DM), mixed connective tissue disease (MCTD), primary Sjögren’s syndrome (SS), and Behçet’s disease (BD). The second domain constitutes MRI criteria, which represent Gd-enhanced MRI findings indicating bilateral synovial enhancement seen in any joints of the proximal interphalangeal (PIP), metacarpophalangeal (MCP), or wrist joints. RA is defined by fulfilling all conditions of both domains. Our prospective study demonstrated that these criteria for the diagnosis of early RA, incorporating MRI findings with physical manifestations, can successfully distinguish patients with RA from those with other mimicking conditions, showing a sensitivity of 96%, specificity of 86%, and accuracy of 92%. When a case does not meet the criteria, RA can be ruled out with a high negative predictive value of 95%. We believe our “diagnostic criteria for early RA with MRI findings” can greatly help to solve unmet diagnostic needs in the early treatment of RA.",signatures:"Akira Takeda and Hideharu Sugimoto",downloadPdfUrl:"/chapter/pdf-download/72793",previewPdfUrl:"/chapter/pdf-preview/72793",authors:[null],corrections:null},{id:"68660",title:"Lupus Erythematosus: Dermatologic Perspectives on the Diversity",doi:"10.5772/intechopen.88446",slug:"lupus-erythematosus-dermatologic-perspectives-on-the-diversity",totalDownloads:787,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Lupus is one of the complex autoimmune disease, which is difficult to diagnose and consists of few subtypes that are required to be classified. During our clinical work, we found out that the dermoscopy can be of great benefit to diagnose discoid lupus erythematosus (DLE). The histopathological examination is very important to confirm the diagnosis. The cases of infant LE patients, may derive the autoimmune antibodies from their mothers in order to diagnose the neonatal lupus erythematosus. Thus, it is very important to examine the antibodies of the mother, who may also be a subclinical LE patient and need continuous follow-ups or even treatment managements. Here, we present the cases of lupus with particular characteristics including linear cutaneous lupus erythematosus, DLE, and neonatal lupus erythematosus.",signatures:"Ran Xin, Wang Peng, Huang Jinghong, Pradhan Sushmita, Yang Heli and Ran Yuping",downloadPdfUrl:"/chapter/pdf-download/68660",previewPdfUrl:"/chapter/pdf-preview/68660",authors:[null],corrections:null},{id:"65046",title:"The Established and Evolving Role of Nailfold Capillaroscopy in Connective-Tissue Disease",doi:"10.5772/intechopen.82386",slug:"the-established-and-evolving-role-of-nailfold-capillaroscopy-in-connective-tissue-disease",totalDownloads:1262,totalCrossrefCites:0,totalDimensionsCites:4,hasAltmetrics:1,abstract:"Nailfold capillaroscopy (NFC) is a low-cost, non-invasive, rapid, highly specific and reproducible investigation well established in the diagnosis of systemic sclerosis and related conditions. This chapter will detail the relevant underlying scientific principles that underpin the investigation, the methods for performing NFC, the range of abnormalities that can be present and the currently available classification criteria before moving on to discuss the various established and emerging applications as relevant to the connective tissue diseases. In addition to its role in the diagnosis of SSc, highlighted by its inclusion in the most recent ACR/EULAR consensus classification criteria, NFC has been shown to predict disease activity, many organ-specific complications such as digital ulcers, pulmonary hypertension and interstitial lung disease, and even mortality. It is emerging as a useful investigation in other CTDs characterised by microvasculopathy, such as in the idiopathic inflammatory myopathies and mixed connective tissue disease, as well as being studied as a serial investigation in patients to act as a potential biomarker and measure of treatment efficacy. NFC can contribute to the earlier identification of patients with CTDs with clinically important complications and if applied accurately, therefore, can help improve outcomes in these often challenging diseases.",signatures:"Matthew J.S. Parker and Neil W. McGill",downloadPdfUrl:"/chapter/pdf-download/65046",previewPdfUrl:"/chapter/pdf-preview/65046",authors:[null],corrections:null},{id:"65424",title:"Ankylosing Spondylitis and Other Seronegative Arthritis",doi:"10.5772/intechopen.82332",slug:"ankylosing-spondylitis-and-other-seronegative-arthritis",totalDownloads:932,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Spondyloarthropathies are a group of disorders having some common features. They are characterised by inflammation of the attachment of tendons known as enthesitis. They are common in males. There is a familial occurrence. There is an association with HLA-B 27. Rheumatoid factor will be negative. Axial skeleton involvement in the form of sacroiliitis or spondylitis is common. The common conditions include ankylosing spondylitis, Reiter’s disease, psoriatic arthritis, enteropathic arthritis and reactive arthritis. In this chapter we are going to describe the clinical features, evaluation and management of common spondyloarthropathies.",signatures:"Balaji Zacharia and Antony Roy",downloadPdfUrl:"/chapter/pdf-download/65424",previewPdfUrl:"/chapter/pdf-preview/65424",authors:[null],corrections:null},{id:"65765",title:"Physical Exercise Improves Quality of Life in Patients with Connective Tissue Disease",doi:"10.5772/intechopen.83388",slug:"physical-exercise-improves-quality-of-life-in-patients-with-connective-tissue-disease",totalDownloads:942,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Connective tissue diseases (CTDs) affect the parts of the body that connect the structures of the body components together. As the conditions involve inflammatory responses in the joints, tendons, ligaments, skin, cornea, cartilage, bones, muscles and blood vessels, which cause symptoms of rheumatism, the CTDs can also be referred to as rheumatic diseases. The symptoms include pain, swelling, redness, warmth in a joint or affected area and functional loss of motion. The medical domain for these types of disorders is called rheumatology. Among various conditions fell under the broad heading of rheumatism, the common rheumatic disorders that here we take care of are rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), scleroderma (S), systemic sclerosis (SS), polymyositis/dermatomyositis (PM/DM), spondyloarthropathies (SA) (ankylosing spondylitis (AS) and psoriatic arthritis (PsA)), juvenile idiopathic arthritis (JIA), polymyalgia rheumatica (PMR), Sjogren’s syndrome, osteoarthritis, etc. When the diagnosis of CTDs is made by the rheumatologists, they oversee a treatment plan for the patients, which may include not only medications but also physical exercises. In this chapter, we will describe how the physical exercise contributes to the patients who suffered from CTDs. Furthermore, we intend to explain what type of exercise should be performed as well as its intensity, duration frequency and the benefits of those exercises to the health of those patients.",signatures:"Ricardo Munir Nahas, Vivianne Horsti Dos Santos and Silvio Lopes Alabarse",downloadPdfUrl:"/chapter/pdf-download/65765",previewPdfUrl:"/chapter/pdf-preview/65765",authors:[null],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"10426",title:"Inflammation in the 21st Century",subtitle:null,isOpenForSubmission:!1,hash:"73637d19c1b71e285a3483d6df1c2e0f",slug:"inflammation-in-the-21st-century",bookSignature:"Vijay Kumar, Alexandro Aguilera Salgado and Seyyed Shamsadin Athari",coverURL:"https://cdn.intechopen.com/books/images_new/10426.jpg",editedByType:"Edited by",editors:[{id:"63844",title:"Dr.",name:"Vijay",surname:"Kumar",slug:"vijay-kumar",fullName:"Vijay Kumar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11031",title:"Rheumatoid Arthritis",subtitle:null,isOpenForSubmission:!1,hash:"b27b90045995c761c0d2f975e895c5d4",slug:"rheumatoid-arthritis",bookSignature:"Hechmi Toumi",coverURL:"https://cdn.intechopen.com/books/images_new/11031.jpg",editedByType:"Edited by",editors:[{id:"196403",title:"Prof.",name:"Hechmi",surname:"Toumi",slug:"hechmi-toumi",fullName:"Hechmi Toumi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10585",title:"Interleukins",subtitle:"The Immune and Non-Immune Systems’ Related Cytokines",isOpenForSubmission:!1,hash:"6d4ebb087fdb199287bc765704246b60",slug:"interleukins-the-immune-and-non-immune-systems-related-cytokines",bookSignature:"Payam Behzadi",coverURL:"https://cdn.intechopen.com/books/images_new/10585.jpg",editedByType:"Edited by",editors:[{id:"45803",title:"Ph.D.",name:"Payam",surname:"Behzadi",slug:"payam-behzadi",fullName:"Payam Behzadi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8114",title:"Recent Advances in Gout",subtitle:null,isOpenForSubmission:!1,hash:"737c7c9f4b2c0fb7a9a6416dc39ab844",slug:"recent-advances-in-gout",bookSignature:"Rie Kurose",coverURL:"https://cdn.intechopen.com/books/images_new/8114.jpg",editedByType:"Edited by",editors:[{id:"176402",title:"Dr.",name:"Rie",surname:"Kurose",slug:"rie-kurose",fullName:"Rie Kurose"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8702",title:"Different Aspects of Behçet's Disease",subtitle:null,isOpenForSubmission:!1,hash:"c4ea8fc9f142d35669fb8f27635db26b",slug:"different-aspects-of-beh-et-s-disease",bookSignature:"Müzeyyen Gönül and Arzu Kılıç",coverURL:"https://cdn.intechopen.com/books/images_new/8702.jpg",editedByType:"Edited by",editors:[{id:"187044",title:"Dr.",name:"Müzeyyen",surname:"Gönül",slug:"muzeyyen-gonul",fullName:"Müzeyyen Gönül"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8329",title:"Work-related Musculoskeletal Disorders",subtitle:null,isOpenForSubmission:!1,hash:"98a4aa04591a37613848a2ed2f12c21f",slug:"work-related-musculoskeletal-disorders",bookSignature:"Orhan Korhan",coverURL:"https://cdn.intechopen.com/books/images_new/8329.jpg",editedByType:"Edited by",editors:[{id:"101698",title:"Dr.",name:"Orhan",surname:"Korhan",slug:"orhan-korhan",fullName:"Orhan Korhan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6775",title:"Newest Updates in Rheumatology",subtitle:null,isOpenForSubmission:!1,hash:"3d7e986fd74dc49e9319a558a4b4e95d",slug:"newest-updates-in-rheumatology",bookSignature:"Wahid Ali Khan",coverURL:"https://cdn.intechopen.com/books/images_new/6775.jpg",editedByType:"Edited by",editors:[{id:"64042",title:"Dr.",name:"Wahid Ali",surname:"Khan",slug:"wahid-ali-khan",fullName:"Wahid Ali Khan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5992",title:"Discussions of Unusual Topics in Fibromyalgia",subtitle:null,isOpenForSubmission:!1,hash:"7a396ba585f062de1cbd1df985fbff71",slug:"discussions-of-unusual-topics-in-fibromyalgia",bookSignature:"William S. 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Enabling Technologies and Emerging Applications",slug:"medical-internet-of-things-m-iot-enabling-technologies-and-emerging-applications",publishedDate:"February 27th 2019",bookSignature:"Hamed Farhadi",coverURL:"https://cdn.intechopen.com/books/images_new/6655.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"171143",title:"Dr.",name:"Hamed",middleName:null,surname:"Farhadi",slug:"hamed-farhadi",fullName:"Hamed Farhadi"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"7059",leadTitle:null,title:"Amyloid Diseases",subtitle:null,reviewType:"peer-reviewed",abstract:"Neurodegenerative diseases are severe, rapidly developing, and currently incurable conditions that result in progressive degeneration and the death of neurons. This causes dementia, movement problems, and essentially loss of personal identity. Amyloids attempts to answer the following questions: (1) why do we develop these severe neurodegenerative diseases? (2) what histological and physiological changes are observed upon development and progression of these diseases? and (3) how can we treat amyloid-associated diseases?",isbn:"978-1-78985-382-7",printIsbn:"978-1-78985-381-0",pdfIsbn:"978-1-83881-132-7",doi:"10.5772/intechopen.73821",price:119,priceEur:129,priceUsd:155,slug:"amyloid-diseases",numberOfPages:242,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"d9a197d34d3d6006af726d577060f928",bookSignature:"Dmitry Kurouski",publishedDate:"August 7th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/7059.jpg",keywords:null,numberOfDownloads:13380,numberOfWosCitations:5,numberOfCrossrefCitations:8,numberOfDimensionsCitations:19,numberOfTotalCitations:32,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 27th 2018",dateEndSecondStepPublish:"October 8th 2018",dateEndThirdStepPublish:"December 7th 2018",dateEndFourthStepPublish:"February 25th 2019",dateEndFifthStepPublish:"April 26th 2019",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"4 years",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:"Edited by",kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"264297",title:"Dr.",name:"Dmitry",middleName:null,surname:"Kurouski",slug:"dmitry-kurouski",fullName:"Dmitry Kurouski",profilePictureURL:"https://mts.intechopen.com/storage/users/264297/images/system/264297.JPG",biography:"Dmitry Kurouski earned an MS in Biochemistry from Belarusian State University, Belarus, and a Ph.D. (Distinguished Dissertation) in Analytical Chemistry from SUNY Albany, New York. After completing a postdoc in the laboratory of Professor Richard P. Van Duyne at Northwestern University, Illinois, Dr. Kurouski joined Boehringer Ingelheim Pharmaceuticals, where he worked as Senior Research Scientist. In 2017, Dr. Kurouski joined the Biochemistry and Biophysics Department of Texas A&M University as Assistant Professor. His research focuses on the nanoscale characterization of biological and photocatalytic systems using tip-enhanced Raman spectroscopy (TERS) and atomic force microscope infrared spectroscopy (AFM-IR).",institutionString:"Texas A&M University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Texas A&M University",institutionURL:null,country:{name:"United States of America"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"178",title:"Endocrinology",slug:"medicine-endocrinology"}],chapters:[{id:"64910",title:"The Clinical Spectrum of Amyloidosis",slug:"the-clinical-spectrum-of-amyloidosis",totalDownloads:1280,totalCrossrefCites:0,authors:[{id:"267372",title:"Prof.",name:"Jonathan",surname:"Harrison",slug:"jonathan-harrison",fullName:"Jonathan Harrison"},{id:"283311",title:"Dr.",name:"Aswanth",surname:"Reddy",slug:"aswanth-reddy",fullName:"Aswanth Reddy"},{id:"285338",title:"Dr.",name:"Enrique",surname:"Ballesteros",slug:"enrique-ballesteros",fullName:"Enrique Ballesteros"}]},{id:"66228",title:"Amyloidosis: Systems-Based Therapies",slug:"amyloidosis-systems-based-therapies",totalDownloads:855,totalCrossrefCites:0,authors:[{id:"232127",title:"Dr.",name:"Matthew",surname:"Zabel",slug:"matthew-zabel",fullName:"Matthew Zabel"},{id:"284963",title:"MSc.",name:"Kayla",surname:"Sheehan",slug:"kayla-sheehan",fullName:"Kayla Sheehan"},{id:"285159",title:"BSc.",name:"Yasmeen",surname:"Alhomsy",slug:"yasmeen-alhomsy",fullName:"Yasmeen Alhomsy"},{id:"285160",title:"MSc.",name:"Quinto",surname:"Gesiotto",slug:"quinto-gesiotto",fullName:"Quinto Gesiotto"},{id:"285162",title:"BSc.",name:"Eileen",surname:"Ly",slug:"eileen-ly",fullName:"Eileen Ly"},{id:"285164",title:"MSc.",name:"Anu",surname:"Stephen",slug:"anu-stephen",fullName:"Anu Stephen"},{id:"285165",title:"BSc.",name:"Asal",surname:"Homayouni",slug:"asal-homayouni",fullName:"Asal Homayouni"},{id:"285166",title:"MSc.",name:"Joshua",surname:"Fisher",slug:"joshua-fisher",fullName:"Joshua Fisher"},{id:"285168",title:"BSc.",name:"Prashanth",surname:"Venkataraman",slug:"prashanth-venkataraman",fullName:"Prashanth Venkataraman"},{id:"285169",title:"BSc.",name:"Matthew",surname:"Habib",slug:"matthew-habib",fullName:"Matthew Habib"}]},{id:"64236",title:"The Role of Inflammation in Amyloid Diseases",slug:"the-role-of-inflammation-in-amyloid-diseases",totalDownloads:1038,totalCrossrefCites:0,authors:[{id:"45002",title:"Dr.",name:"Debora",surname:"Foguel",slug:"debora-foguel",fullName:"Debora Foguel"},{id:"266464",title:"Dr.",name:"Estefania",surname:"Azevedo",slug:"estefania-azevedo",fullName:"Estefania Azevedo"}]},{id:"65517",title:"Pathologic Findings of Amyloidosis: Recent Advances",slug:"pathologic-findings-of-amyloidosis-recent-advances",totalDownloads:1243,totalCrossrefCites:2,authors:[{id:"265784",title:"Dr.",name:"Luan",surname:"Truong",slug:"luan-truong",fullName:"Luan Truong"},{id:"288705",title:"Prof.",name:"Jae Y.",surname:"Ro",slug:"jae-y.-ro",fullName:"Jae Y. 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Electrophoretic methods compose a family of related techniques that use narrow-bore fused-silica capillaries to perform high efficiency separations of both small and large molecules. These methods are commonly known as capillary electrophoretic methods. Capillary electrophoresis (CE) has, over the years, demonstrated its powerful separation ability in the area of chiral and achiral analysis. This is contributed to the advantages it offers when compared to chromatographic techniques: (1) low consumption of samples and solvents; (2) high separation efficiency and resolution; (3) versatility [1,2].
Two of the most important modes of CE, which will be discussed in this chapter, are capillary zone electrophoresis (CZE) and micellar electrokinetic chromatography (MEKC). CZE is the simplest and the most widely used mode of CE [1]. The separation mechanism of the analytes is based on their difference in charge-to-size ratios and their difference in electrophoretic mobilities, which, in turn, result in different velocities. However, due to the fact that neutral species do not possess an electrophoretic mobility, they cannot be separated by use of this mode.
In order to circumvent this problem, new modes of CE have been suggested as alternatives. MEKC, which combines the best features of both electrophoresis and chromatography, is considered an alternative mode because it can be used for the separation of charged as well as neutral compounds. It involves the introduction of a surfactant at a concentration above the critical micellar concentration (CMC), at which micelles are formed. MEKC was first introduced by Terabe
CE was originally considered as a powerful analytical tool for the analysis of biological macromolecules. It has though, over the years, been extensively used for the separation of other compounds, such as chiral drugs, food additives, pesticides, inorganic ions, organic acids, and others. In this chapter, the ability of CE, and particularly CZE and MEKC, to be used for the qualitative and quantitative determination of compounds in pharmaceutical, biological and natural samples is investigated. In each approach, a number of studies are reported and discussed. These studies involve establishment of optimum separation conditions, method validation, optimization of sample-preparation procedure and application for the determination of the analytes under study in real samples. The first part of this chapter involves the determination of polyphenolic compounds using CZE with UV-Vis detector in red and white wines, while the second part involves the determination of pharmaceutical compounds in biological samples, such as blood and urine, using the hyphenated technique CE-MS (mass spectrometry). The third and final part emphasizes the importance of MEKC in chiral analysis since it has been known that usually only one enantiomer is active, while the other may be less active, inactive or has adverse effects.
Polyphenolic compounds exist in a variety of natural products, such as fruits, vegetables, beverages (tea, wine and juices), honey, cacao and herbs. They attract a lot of interest due to their beneficial implication in human health. They have been widely studied due to their antioxidant capacity and their association with several pathological conditions, such as hypertension, cardiovascular disease, dementia, and even cancer [7-9]. Therefore, due to their health significance, numerous analytical methods have, over the last decades, been developed for their separation, identification and quantitation in natural products [10-13].
According to literature, the simplest CE method, CZE, proved to be the best method for the determination of polyphenolic compounds in wine samples [14-17]. In such studies, and in each case, when the optimum CZE method was applied to different red and white wines, it was established that red wines have higher levels of polyphenolic compounds than white wines and that the polyphenolic composition varies among different wines.
In this part of the chapter, a representative study performed recently in Cypriot wines is briefly described [17]. The influence of several experimental parameters is initially illustrated in order to obtain improved selectivity and resolution for the separation of seven flavonoids, which constitute the most important group of polyphenols, and trans-rasveratrol that are usually present in wine. This is accomplished by use of CZE and by examining different sample preparation procedures. Due to the low concentrations of flavonoids in wine and the high complexity of wine matrices, preconcentration methods are required, which can simplify the electropherograms. The optimized CZE and pre-treatment methods proved to be effective in characterizing flavonoids in red and white wine samples.
The effect of column temperature, and concentration and pH of background electrolyte (BGE) were investigated. These parameters, along with the applied voltage, are the most common parameters that are required to be examined in order to optimize a separation in CZE. Figure 1 illustrates the influence of the pH on the resolution and the analysis time. The last two increased with increasing the pH, possibly due to an increase in the negative charge, which resulted in a greater affinity and a higher complexation between borate and phenols. Taking into consideration the migration times, the peak efficiency and the sufficient resolution, the following parameters provided a baseline separation of all polyphenolic compounds: BGE containing 50 mM borate and 10 mM phosphate at pH 9.6 and column temperature of 25 ºC (Figure 1C). The use of alkaline borate-based BGEs, in CZE, resulted in a sufficient separation of polyphenols due to the complex-formation ability of borate. In addition, an increase in the borate concentration from 25 to 50 mM and an increase in the pH value from 9 to 10 resulted in an increase in the migration times of all analytes, while the resolution was significantly improved. At pH 10 though, the analysis time was very long (~ 50 min) and joule heating effects, such as high current generation and peak broadering, were observed. An increase in pH increased the negative charge of the analytes, which, in turn, favored a greater affinity for the buffer and a higher complexation between borate and phenols [18].
Effect of pH value on the separation of the eight polyphenols. (A) pH 9; (B) pH 9.3; (C) pH 9.6. Conditions: BGE 50 mM borate, 10 mM phosphate and 20 mM SDS; pressure injection, 30 mbar for 3 sec; applied voltage, 25 kV; temperature, 25 ºC; fused-silica capillary, 64 cm (55.5 cm effective length) x 50 μm i.d.; detection, 205 nm. Peak identification: trans-resveratrol (1), epicatechin (2), catechin (3), naringenin (4), kaempferol (5), apigenin (6), myricetin (7), quercetin (8) [
The method was then validated by the terms of linearity, precision and LOD. Linearities for the eight analytes were very good, and precision, which was based on the relative standard deviation, was below 1%, indicating an excellent reproducibility. In addition, LODs, which were calculated as three times the standard deviation via the slope of the calibration curve, were between 0.03 and 5.05 μg/mL for all eight polyphenolic compounds.
The qualitative and quantitative analysis of analytes in real samples is often difficult due to interruptions caused by different interfering substances found in the sample matrix. Therefore, a sample-preparation procedure is a necessary step prior to the electrophoretic analysis, in order to isolate the analytes under study from real samples. Different preconcentration methods have been used over the years, including solid-phase extraction (SPE) with C-18, silica, or other cartridges [14,16,19] and liquid-liquid extraction (LLE) with different organic solvents [10,20,21].
In the study performed in Cypriot wines, the sample preparation procedure was optimized in order to determine the one that was simple, fast and reliable [17]. Therefore, three LLE-procedures (C,D,E), a SPE-procedure (F), a procedure that involve evaporation and reconstitution of wine sample (B) and a direct injection of wine sample after dilution and filtration (A) were compared and the most effective method was applied to Cypriot wines. The electropherograms obtained by use of each sample preparation procedure are illustrated in Figure 2. When no extraction was performed, the electropherograms were complex, while SPE was found to be ineffective for the isolation of polyphenolic compounds from wine samples. LLE with diethyl ether, followed by evaporation of organic layer by nitrogen stream and reconstitution in ethanol proved to be the optimum sample pre-treatment method. When the optimum method was applied to Cypriot wine samples, the quantification of polyphenolic compounds was successfully achieved. It was observed that epicatechin and catechin exist in all wine samples in comparable concentrations, whereas myricetin and quercetin exist only in two of the three wine samples. Polyphenolic composition varies among different wines, because it depends on several factors, such as the type of grapes used, the vivification process used, the type of yeast that participates in the fermentation, weather variations and other biological effects [22].
Electropherograms of the wine samples obtained using six different sample preparation procedures under optimum conditions. Conditions: BGE 50 mM borate, 10 mM phosphate and 20 mM SDS (pH 9.6); pressure injection, 30 mbar for 3 sec; applied voltage, 25 kV; temperature, 25 ºC; fused-silica capillary, 64 cm (55.5 cm effective length) x 50 μm i.d.; detection, 205 nm. Peak identification: epicatechin (2), catechin (3), myricetin (7), quercetin (8) [
Another important observation was that in white wine, the only flavonoid that was detected was catechin at a concentration of 7.3 μg/mL. This was not surprising since the majority of flavonoids in wine come from the extraction derived from grape’s solids. White wine is made by pressing the juice away from the grape’s solids, and then, by allowing it to ferment. So, red wines have higher levels of polyphenolic compounds [23].
Quantification of drugs in biological fluids, like plasma, has an important role in drug discovery and development. There are two main aspects that are taken into account in order to make the identification of drugs in biological fluids possible. The first aspect is the development of an accurate analytical method, with high sensitivity, capable to identify desirable compounds in concentrations comparable to that in biological fluids. The second one is the exploration of the optimum extraction method that can effectively extract the drug from the biological matrix.
Over the years, CE coupled to electrospray ionization-mass spectrometry (ESI-MS) has been utilized as a bioanalytical tool for the analysis of drug compounds in biological samples [24-29]. Even though the most common detector in CE is the UV detector due to its easy manageability and low cost, it has the drawback of low sensitivity due to the short optical path length. An alternative to this is the use of MS. The coupling of CE with MS is a well-established technique, which combines the high efficiency and resolution that are provided by CE and the detection sensitivity and selectivity and the identification potential that are provided by MS [25,30].
In recent years, a large number of publications have been provided on the general developments and biological applications of CE-ESI-MS [24-29]. Zheng
In a 2011 study, Elhamili
The performance and usefulness of CE-MS is also demonstrated here by providing a more in-depth analysis of a research work that was performed in a blood sample obtained from a patient with Alzheimer´s Disease (AD) [24]. In this study, a CZE-ESI-MS method was developed for the analysis of the acetylcholinesterase inhibitor rivastigmine, using neostigmine bromide as an internal standard, which is highly recommended in order to avoid problems that are related to sample injection [31]. Rivastigmine is a pseudo-irreversible carbamate inhibitor of acetylcholinesterase, and it is clinically used for the symptomatic treatment of mild to moderate AD [32].
In a previous paper, MEKC coupled to a diode-array detector was used for the simultaneous separation of nine acetylcholinesterase inhibitors, including rivastigmine [33]. This method was validated and successfully applied to a real blood sample that was obtained from a patient who was not under any of this medication. The sample was spiked with rivastigmine in order to establish the ability of the method to separate the drug from other components that might exist in the blood sample. In this study, the blood sample was not directly injected into the capillary, because some components that exist in the sample can be absorbed to the capillary wall and deteriorate the performance of the column [34]. The blood sample was therefore diluted ten folds with the BGE [12.5 mM Na2HPO4 / 12.5 mM Na2B4O7 / 20 mM SDS (pH 10)], and it was then spiked with 25 μg/mL of rivastigmine. However, due to the low sensitivity obtained by CE with on-column UV detection, the identification of rivastigmine in biological fluids using CE remained a challenge. In order for the technique to be used for the quantitation of an acetylcholinesterase inhibitor in body fluids, the sensitivity, and consequently the LOD had to be improved. The increased interest in exploring CE-MS and its potential to serve as an alternative method allowed further investigation for the determination of rivastigmine and related drugs in complex biological matrices.
When the CZE-UV method was compared with the CZE-MS, the first demonstrated a shorter analysis time of approximately 2 min due to the shorter effective length, while the S/N for the peak of rivastigmine at the SIM mode was estimated to be eight times bigger than with UV detection. This, in turn, indicated the high specificity and selectivity of the ESI-MS detector [24]. In the CZE-ESI-MS study, several electrophoretic and ESI-MS parameters were also examined, which were classified in three categories: the BGE parameters, such as the concentration, the pH and the use of organic modifier, sheath liquid parameters, such as the composition, the methanol (MeOH) content and the flow rate, and finally some spray chamber parameters, such as the temperature and the flow rate of the drying gas and the nebulizer gas pressure. The effect of each parameter on the S/N, and consequently the LOD, was examined and the optimum one was chosen for further optimization.
In the case of BGE parameters, it was observed that ammonium acetate provided the most reproducible migration times, a concentration of 40 mM ammonium acetate resulted in the highest S/N, while a higher concentration decreased the ratio, probably due to the Joule heating effect that increases the level of noise (Figures 3a & 4a). When the pH was examined, it was concluded that at pH 9, where rivastigmine starts to have a negative charge (pKa=8.6), both the analysis time and resolution increased, and a higher S/N was obtained (Figures 3b & 4b).
Effect of (a) ionic strength and (b) pH of the BGE on the separation of rivastigmine (2) and I.S (1). Conditions: BGE: ammonium acetate, sheath liquid 1 % acetic acid in water:MeOH (50:50 v/v) at a flow rate of 10 μL/min, analyte and I.S. concentrations 0.3 mg/mL. Drying gas flow rate 6 L/min and temperature 200 ºC, nebulizer gas pressure 20 psi [
Effect of (a) ionic strength of the BGE and (b) pH of the BGE upon S/N ratio. Conditions: BGE: ammonium acetate, sheath liquid 1 % acetic acid in water:MeOH (50:50 v/v) at a flow rate of 10 μL/min, analyte and I.S. concentrations 0.3 mg/mL. Drying gas flow rate 6 L/min and temperature 200 ºC, nebulizer gas pressure 20 psi [
As far as the sheath liquid parameters are concerned, it was observed that its composition and its flow rate affected the ESI-MS sensitivity significantly. This was not a surprising observation since the sheath liquid plays an important role in the CE-MS system. The sheath liquid is used as the make-up liquid that can solve the flow-rate incompatibility problems between CE and MS [35]. These problems are encountered because the flow rate through the CE column is very low (nL/min), and it cannot support a stable electrospray, whose flow rate is typically a few μL/min. In addition, the sheath liquid is used for establishing an electrical connection at the cathode end of the CE capillary, and it provides the suitable solvent conditions for the electrospray, which does not depend on the CE BGE [36].
When different sheath liquids were evaluated, the one that was able to support the formation of positively charged ions, and consequently provide the highest S/N, was acetic acid (1%) (Figure 5a). The influence of methanol as an organic modifier in the sheath liquid was also examined, because the use of such solvents allows an easier protonation of the analytes, which results in a higher signal [28]. By varying the percentage of methanol, it was concluded that 50% was the optimum since the noise level was the lowest (Figure 5b). Finally, the flow rate of the sheath liquid was set at 10 μL/min (Figure 5c). Other values were either too low to establish an electric contact that is required to achieve separation, or they affected the spray stability negatively, which, in turn, lead to higher noise levels.
Effect of (a) sheath liquid composition, (b) sheath liquid organic modifier and (c) sheath liquid flow rate upon S/N ratio. Conditions: BGE: ammonium acetate 40 mM, at pH 9.0; analyte and I.S. concentrations 0.3 mg/mL. Drying gas flow rate 6 L/min and temperature 200 ºC, nebulizer gas pressure 20 psi [
The spray chamber parameters, which are the last parameters examined in this study, have an important effect on the response of the MS system. One of these parameters involves the drying gas, which is used for accelerating the buffer desolvation, increasing the MS sensitivity, and eliminating any undesirable ions from entering into the MS system. It was observed that the drying gas flow rate has an effect on the stability of the electrospray, and consequently, the levels of the noise. The flow rate was set at 6 L/min, because at this flow rate an increased number of ions come closer to the liquid-gas interface, and this increases the desolvation velocity [37] (Figure 6a). In addition, other flow rates that were examined in this study either caused an unstable electrospray or lowered the S/N. The drying gas temperature was varied from 150 °C to 350 °C, and the highest S/N was obtained at 200 °C, which was considered as the optimum (Figure 6b). The nebulizer gas pressure was the last parameter examined in this category, and based on the stability of the electrospray and the S/N, 20 psi was selected as the optimum. At 20 psi, the electrospray is more efficient, probably due to an improved ion evaporation process because smaller initial droplets are obtained with higher nebulizer gas pressure (Figure 6c).
Effect of (a) drying gas flow rate, (b) drying gas temperature and (c) nebulizer gas pressure upon S/N ratio. Conditions: BGE: ammonium acetate 40 mM at pH 9.0, sheath liquid 1 % acetic acid in water:MeOH (50:50 v/v) at a flow rate of 10 μL/min, analyte and I.S. concentrations 0.3 mg/mL [
All the parameters mentioned above are the common parameters that need to be examined in a method development process that involves a CE-MS system. These parameters affect the analysis time, resolution, response of the analyte under study, noise level, and sensitivity of the system. All these are important if the developed method is expected to be applied to biological samples for the detection and the quantification of drug and other compounds.
When the optimum conditions for the analysis of rivastigmine were determined, the method was validated in terms of linearity, precision, stability, recovery, LOD and LOQ. Two calibration curves were constructed, in human plasma and in standard solutions, and linearity was good in both cases. The precision, which was evaluated based on migration times and peak areas, was excellent, and particularly in the case where the peak area of the internal standard was also taken into consideration. The LOD and the LOQ were determined based on the standard deviation of the peak area and the slope of the calibration curve. The LOD and the LOQ were calculated as 3 and 10 times the above correlation, respectively. In the plasma sample, the LOD and the LOQ were found to be 2.8 ng/mL and 8.4 ng/mL, respectively, while in standard solutions they were 1.6 ng/mL and 5.0 ng/mL, respectively. These values are considered satisfactory for the accurate and precise quantification of rivastigmine in AD patients treated with the particular drug compound, and this is based on clinical studies that were performed in such patients [38,39].
Biological matrices are among the most difficult samples to analyze because of the big number of components they contain that they may be adsorbed onto the capillary wall or interfere in the detection and/or separation process. Therefore, before plasma analysis, it is important and necessary to perform a sample preparation procedure. In addition to this, the concentration of most of the analytes in biological samples is low; so, a preconcentration step before the detection and quantitation is required. In many cases, different sample pre-treatment methods are used and compared in order to determine the most effective one, in regard to analyte recovery, difficulty, time and reproducibility. In this study, one LLE and two different SPE procedures were examined. In the case of SPE, two different SPE cartridges were used, a C18 cartridge and an Oasis HLB cartridge. LLE proved to be inefficient for rivastigmine assay, and it was time consuming because the extraction step was followed by additional steps that involved evaporation and reconstitution of the residue in an organic solvent. When the two SPE methods were compared, the C18-SPE cartridge proved to be the optimum, because the S/N was three times higher (S/N=154) than when Oasis HLB cartridge was used (S/N=52), and it provided better recoveries.
The optimum CZE-ESI-MS parameters and the optimum sample preparation procedure were finally applied for the determination of rivastigmine in a plasma sample obtained from an AD patient following rivastigmine patch administration (dose of 9.5 mg/mL rivastigmine/24-h). Figure 7 demonstrates the SIM electropherograms of C18-SPE extract of plasma sample collected 2.0 hours post-application, at m/z 223 and 251, for I.S. and rivastigmine, respectively. The mean (± S.D.) plasma concentration obtained for rivastigmine was 14.6 (± 1.7) ng/mL.
Electropherograms of C18-SPE extracts of plasma from an AD patient following rivastigmine patch administration in a dose of 9.5 mg/mL / 24-h in the SIM-mode at (a) m/z 223 (I.S.) and (b) m/z 251 (rivastigmine). Conditions: BGE: 40 mM ammonium acetate at pH 9, sheath liquid 1 % acetic acid in water:MeOH (50:50 v/v) at a flow rate of 10 μL/min, analyte and I.S. concentrations 0.3 mg/mL. Drying gas flow rate 6 L/min and temperature 200 ºC, nebulizer gas pressure 20 psi [
Based on the studies mentioned above, the CZE-ESI-MS method proved to be a promising technique in drug and pharmaceutical analysis. The development of such a method has several advantages over HPLC-MS and GC-MS. The most important ones are the reduction of the reagents cost, the low injection volume requirements, and the avoidance of disposing large volumes of organic waste. In particular, when the study described here is compared to previous studies, where HPLC-MS and GC-MS were used for the analysis of rivastigmine, the required injection volume of plasma for a single analysis is reduced from microliters [40-43] to nanoliters.
In the last three decades, there has been a growing interest in the separation, detection and quantification of enantiomers in pharmaceutical, clinical, environmental and food analysis. It has been known that usually only one enantiomer is active while the other may be less active, inactive or has adverse effects. Among the separation techniques, HPLC [44-48] GC [44,45,49] and CE [50-55] are most often applied in chiral analysis. Temperature and derivatization are major problems encountered in GC, and poor separation efficiency is observed in HPLC. CE has proven to be a powerful separation technique in the area of chiral analysis, since it has the major advantage of low consumption of samples and solvents.
The most common modes of chiral CE are electrokinetic chromatography (EKC) in the presence of a chiral selector, MEKC, capillary electrochromatography (CEC), where the chiral selector can be either used as a coating (OT-CEC), a packing (P-CEC) or a monolithic material (M-CEC) in the capillary, and others [55-63]. The prerequisite for separation of enantiomers in CE, as in every chromatographic system, is the formation of either stable diastereoisomers by the use of a chiral derivatization agent or reversible diastereoisomeric complexes with the addition of a chiral substance, (chiral selector). In the first case, the two enantiomers are separated based on their different physicochemical properties, while in the second case, they are separated based on their different mobilities. In general, the “three point rule,” illustrated by Easson and Stedman [64], describes the interactions that are necessary for chiral discrimination. A minimum of three simultaneous interactions have to occur between the chiral selector and one of the enantiomers so that chiral separation is achieved. The other enantiomer, due to spatial restrictions, should have at least two types of interactions, which can be hydrophobic interactions between the hydrophobic core of the polymer and the analyte, electrostatic interactions between the polar head group of the polymer and the analyte, dipole-dipole forces, such as hydrogen bonding between the polar group of the chiral selector and the analyte, and secondary interactions, such as - interactions, ion-dipole bonds, and Van der Waals forces. This difference in the number and type of interactions between the enantiomers and the chiral selector generates a mobility difference between the enantiomer-chiral selector complexes, which is necessary for the achievement of a chiral separation.
A big number of chiral selectors have been widely used, over the years, in CE for improved chiral separations of various classes of analytes. These chiral selectors include cyclodextrins, polymeric surfactants, cyclofructans, macrocyclic antibiotics, crown ethers, and others. Cyclodextrins are molecules with large ring-like structures composed of α-(1,4)-linked D-(+)-glucopyranose units. Native cyclodextrins are cyclic oligosaccharides consisting of six (α-CD), seven (β-CD) and eight (γ-CD) glucopyranose units. The chiral recognition ability of cyclodextrins can be improved by their derivatization with different functional groups, such as methyl-, sulfate-, acetyl- and prolyl-, and with the modification of the hydroxyl groups, which are present on the rim of the CD. The mechanism of enantiomeric discrimination is the inclusion of the hydrophobic group of the analyte into the cavity and interactions of the hydroxyl groups of the C2 and C3 at the upper rim of the CD, such as hydrogen bonds and dipole-dipole interactions.
Navarro
Chai
The use of CE, and particularly MEKC, in chiral analysis is demonstrated further here by providing a more in-depth analysis of a research work that was performed in a pharmaceutical formulation that contained one of the enantiomers of Huperzine A [55]. Huperzine A is considered to be a potent, highly specific and reversible inhibitor of acetylcholinesterase with high efficiency and low toxicity. The mechanism of complexation of Huperzine A with acetylcholinesterase is similar to that of other pharmaceutical drugs that are used for the treatment of AD [69]. The (-)-enantiomer of Huperzine A is three times more biologically active than the synthetically racemic mixture, and only this form behaves as a potential acetylcholinesterase inhibitor. Therefore, the development of an analytical method for the enantiomeric separation of the synthetic Huperzine A is of greatest importance.
It is important here to mention that the type of the chiral selector used in this study was the polymeric surfactant. The use of polymeric surfactants in both chiral and achiral CE has attracted considerable attention. In 1994, Wang and Warner [70] were the first to report the use of a polymeric surfactant added to the BGE in MEKC. Polymeric surfactants offer several distinct advantages over conventional micelles [63,71-73]. Firstly, polymerization of the surfactant eliminates the dynamic equilibrium due to the formation of covalent bonds between the surfactant aggregates. This, in turn, enhances stability and improves resolution. Secondly, polymeric surfactants can be used at low concentrations because they do not depend on the CMC. This usually provides higher efficiencies and rapid analysis. They have, over the years, been extensively used in a BGE [74-80], in a polyelectrolyte multilayer coating [63,74,81-83], and in a CE-MS system [84-86].
In this study, the optimal conditions, in regard to resolution, efficiency and analysis time, were initially established by varying different electrophoretic parameters. The BGE type, concentration and pH are usually the first parameters to be examined in a method development procedure. Sodium acetate at acidic and neutral pHs, where the analyte exhibits cationic behavior, was chosen as the optimum. BGEs with basic pHs did not exhibit any enantiomeric discrimination, and the analysis time was very long. The optimum pH was 5.0 because it provided slightly better peak shapes, and the optimum concentration was 50 mM because it provided higher resolution (Figure 8). The very low peak efficiency, which needs to be improved, is clearly illustrated in this figure.
Effect of BGE concentration on the separation of the enantiomers of Huperzine A: (A) 20 mM, (B) 35 mM and (C) 50 mM. Separation conditions: BGE: sodium acetate (pH 5.0), 0.075% (w/v) poly-LL-SULV; pressure injection, 30 mbar for 3 s; applied voltage, 20 kV; temperature, 25 °C; fused-silica capillary, 64 cm (55.5 cm effective length) x 50 μm i.d.; detection, 230 nm [
As far as the chiral selector is concerned, different polymeric surfactants were examined, such as poly(sodium
Another parameter examined in order to improve peak efficiency and resolution was the addition of modifiers. None of the organic solvents at different concentrations were able to improve the separation. An alternative to this was the addition of a salt, such as D- and L-alanine tert-butyl ester hydrochloride (D- and L-AlaC4Cl). poly-LL-SULV became insoluble when the salt was added into the BGE. Therefore, the other polymeric surfactants mentioned above were examined at different concentrations. In each case, D- and L-AlaC4Cl were used individually as additives, the electropherograms were obtained, and resolution and efficiency were estimated. Based on this, the combination of poly-LL-SUAV at a concentration of 0.20% (w/v) with L-AlaC4Cl provided the best results.
However, the use of L-AlaC4Cl did not provide satisfactory reproducibility of the migration time and efficiency. This is probably due to the hydrolysis of the salt in an aqueous BGE solution. An alternative involved the use of tert-butanol, one of the hydrolysis products, at different concentrations. Figure 9 clearly demonstrates the improved peak efficiency, in comparison with Figure 8. Each electropherogram was obtained at a different concentration of tert-butanol. A concentration of 10% (v/v) was the optimum, because it provided the highest resolution (1.45) and the highest peak efficiency (Figure 10).
The validation of the method demonstrated good linearities and very low relative standard deviation values, indicating excellent run-to-run and day-to-day reproducibilities. In addition, the LOD and LOQ were determined to be 4.17 μg/mL and 13.92 μg/mL, respectively.
As previously shown, after method development and validation, the optimum separation conditions are applied to a real sample. In this case, the optimum parameters were applied to a pharmaceutical formulation in order to detect and quantitate the acetylcholinesterase inhibitor (-)-Huperzine A. The extraction procedure followed for extracting Huperzine A from the pharmaceutical formulation proved to be effective because the enantiomer determined in the sample was in a relatively good agreement with the amount that was stated on the bottle. Therefore, the developed MEKC-UV method is able to control the purity of (-)-Huperzine A in pharmaceutical formulations.
Effect of the concentration of tert-butanol on the separation of the enantiomers of Huperzine A: (A) 5%, (B) 7.5%, (C) 10% and (D) 12% (v/v). Separation conditions: BGE: 50 mM sodium acetate (pH 5.0), 0.2% (w/v) poly-LL-SUAV; pressure injection, 30 mbar for 3 s; applied voltage, 20 kV; temperature, 25 °C; fused-silica capillary, 64 cm (55.5 cm effective length) x 50 μm i.d.; detection, 230 nm [
Effect of the concentration of tert-butanol on the efficiency. Separation conditions: Same as
Analysis of chiral and achiral analytes in natural, pharmaceutical and biological samples can be extremely difficult. Co-migration may occur, which can cause problems in detection, and the electropherograms obtained can be very complex. In addition, the analytes of interest are usually present in the matrices at very low concentrations. Therefore, all the analytical steps, including method development, detection and sample preparation, which is an essential stage in any analysis process, have to be optimized in order to obtain the desirable sensitivity, resolution, robustness and analysis time.
Among the separation techniques that have so far been used for pharmaceutical, clinical and food analysis, CE has been established as a powerful analytical tool, which has rapidly been developed and matured since its introduction. CE and its related techniques offer a number of advantages, including low consumption of sample and solvents, high separation efficiency, rapid method development, fast migration times, versatility, and simple instrumentation. Another important aspect involves its ability to separate small and large molecules, charged and neutral species, inorganic and organic molecules, synthetic and natural compounds, along with proteins and peptides.
The coupling of CE to MS provides nowadays a promising alternative to UV detection. The combination of high sensitivity, high selectivity, and high specificity provided by MS with high resolution, and high efficiency provided by CE makes it an attractive technique in different fields, such as clinical, forensic, pharmaceutical, and others. However, chiral analysis by use of CE-MS still needs some improvement, in regard to resolution and peak capacity. In addition, contamination of the ionization source induced by the chiral selector added in the BGE is still considered a main problem, even though different procedures have, in recent years, been developed in order to overcome this limitation [87].
“Breakthrough innovations” is a hot topic aimed at stimulating industry research towards realisation of bioeconomy, sustainability, and high returns on investments. Eco-friendly inequities exist due to rapid population explosion, continuous resource exhaustion, industry biomaterial supply concerns and linear model of produce-consume-dispose [1]. Ultimately, innovative research solutions have been sought to ensure sustainability along the entire food system [2] to address the above challenges. The research solutions have been mainly in biobased industries, notably renewable resources, a component of sustainable biobased industries. However, bio-industries are subjected to considerable technological innovations and sustainable alternative challenges. Thus, the trend is geared towards developing integrated biorefineries with the goal of achieving availability and flexibility of multiple feedstocks’ low inputs and maximum outputs [3]. There are several waste resources that can be valorised to produce unmatched feedstocks for the sustainable biorefinery developments. Examples of current integrated biorefinery feedstocks and products include vegetable oils, high value-added bio-lubricants, cosmetics and bioplastics obtained from low input and under-utilised oil crops, which are not in competition with food and feed supply [4]. Others include green, clean, post-use biodegradable, compostable and efficient alternative supplies.
Cassava resources are versatile biomass supply chains that are bio-transformed into industrial feedstocks to replace fossil oil product streams [5]. Their biopolymers’ processing and products’ development using traditional techniques is accompanied by significant wastes with negative environmental impacts [6]. Cassava is a higher producer of significant wastes (peel pulp, wastewater, and leaves) during postharvest processing. Nonetheless, a comprehensive impression of cassava biomaterials, covering a wide spectrum of novel processing technologies, and underutilised and low-cost biomass, is evident.
This chapter presents a thorough discussion of bitter cassava biomaterial innovations and novel processes for bio-transforming this low-cost underexploited crop. Use of an integrated sustainable process to indirectly reduce waste streams is demonstrated. A special focus is dedicated to production of biodegradable products from intact bitter cassava waste streams of nascent sector as promising feedstocks for application in food, supplement, and packaging systems. Ultimately, concretising the concept of innovative application of cassava biomaterials can be a useful resource for academia, industry, bioeconomy, and policy.
Bitter cassava is an equivalent of sweet cassava. While sweet cassava is edible and safe for instant use in fresh and processed forms, bitter cassava is only safe for usage after intricate processing and is regarded as a staple food [6]. Bitter cassava roots contain high toxic hydrogen cyanide (HCN) levels above 100 mg/kg on fresh basis, even going beyond 900 mg/kg in tropical regions: with the minimum reference limit of 0.02 mg/kg on dry weight [7]. Increasing region-specific sweet cassava profiles as biomaterials for foods, feeds, pharmaceuticals, and confectionery industries have greatly augmented unparalleled investment into non-traditional underutilised crops [4, 8]. In East and Central Africa, bitter cassava varieties (such as Karangwa/Tongolo) have existed for decades. Anecdotal evidence points to the advantages of bitter cassava as a food and industrial crop with superior product (e.g., Flour and crude alcohol) qualities. Bitter cassava is highly preferred due to: i) its potential to be grown organically than sweet varieties because of their more toxicity levels deterring foraging rodents and pests from feasting on the crop; ii) imposing the need to process roots directly after they are harvested deters thieving from the field; and iii) as the processing adds value in terms of time invested, the social obligation of sharing cassava with neighbours is reduced [9].
Due to high potential cyanide content in bitter cassava, the code of practice allows adequate postharvest processing [10]. The appropriate postharvest processing, in particular fermentation, is effective in reducing HCN to minimum concentrations. Conversely, inadequate, notably using rudimentary techniques, leads to high HCN residuals in the final products. The peel (cortex) contains more HCN than edible portion (parenchyma) (Figure 1). As such the peels are frequently detached from the edible portion and discarded. This underutilised waste, estimated at 30% represents a great loss of feedstock and energy resources as well as potential source of eco-system contamination [4, 11, 12]. In major bitter cassava growing regions, it is transformed into primary, intermediary, and tertiary products using rudimentary fermentation processes. Traditionally, different detoxification processes, such as solid-state fermentation and retting in river ponds are used minimise HCN in bitter cassava [13]. This uncontrolled large-scale upstream and downstream process-fermentation into food and beverages contributes significantly to unsustainability, thus requiring valorisation [11, 14]. As the peel is disposed-off and its utilisation limited due to high HCN content, high fibre, and low protein; this presents exceptional opportunities to biotransformation into innovative biomaterials such as biodegradable plastics for diverse applications [4, 11, 15].
Intact root showing different components.
Cassava biomaterials are not restricted to only those produced with sweet cassava (such as food, pharmaceutical, beverage, coatings, civil works, textile industry), but emphasise biomaterials that are developed innovatively from bitter cassava wastes. Investments in bitter cassava biomaterial innovations are based on: i) the need to solve the increased environmental waste, which is caused by a linear and irreversible behavioural pattern that follows a produce-consume-dispose model; ii) innovations in biomaterial development, spurred by bitter cassava superior end-product qualities, that force nascent communities and processors to invest in the staple crop sustainably; iii) the need to reduce waste in environment and develop industrial products, in tandem, for a more competitive resource economy; and iv) solving issues of finite natural material sources and competition for food supply. Precisely, bitter cassava is a renewable resource with no competition for food supply, its valorisation minimises waste and environmental impact and is a cost-effective option.
To this end, a circular utilisation model is explored in tackling cassava biomaterial innovations. This strategy ensures that bitter cassava waste is transformed into value-added resources that later biodegrades into environment post-use, in a process of eco-designing of biomaterials for food and non-food applications.
Converting bitter cassava wastes into high premium resources demands an unusual approach, entailing departure from traditional cassava processing methods to robust processing methodologies. As such, a new systematic improved downstream processing methodology, known as “Simultaneous release recovery cyanogenesis (SRRC)” has been developed and piloted with success to ease downstream production of bitter cassava biomaterial as a template for diverse use [4]. The SRRC constitutes two main stages and unique procedures to produce a biopolymer derivatives biomaterial (Figure 2). The term “biopolymer derivatives” refers to the product recoveries from the intact root of bitter cassava, and these mainly consist of different proportions of starch, cellulose, hemicellulose, holocellulose and lignin [11, 16]. Waste derivatives are the product derivatives of waste solids and wastewaters.
Schematic flow of SRRC methodology for production of biomaterials.
Smart sourcing and preparation of starting materials is an indispensable step in the production of good quality, safe and adequate volumes of biomaterials. Bitter cassava is best sourced at maturity of 12–18 months after planting and should be designated as right harvesting time of adequate biopolymers. Using intact root (IR) is an indirect and logic approach of preventing wastes finding their way into the environment. The IR is a whole root of cassava that is composed of residues (peel, cambium, phloem, central xylem fibre) and edible parenchyma. The derivative wastes consist of the peel, internal root centre fibre (xylem bundles), unwanted trimmed solids and wastewaters. Using the SRRC methodology, intact roots are subjected to mechanical tissue rupture, biopolymer release and cyanide toxin loss. The processes typically involve feeding intact roots into automated grating machine and the resulting pulp mass obtained after mechanical tissue rupture and cell disruption (MTRCD). The MTRCD serves the twin role of actuating total cyanogens hydrolysis into release of volatile hydrogen cyanide and bringing together different biopolymer components for possible modification. In effect, the process involves crushing the intact root into finest pulp using high shear rate pulpers, which is also intended to improve the pulp texture and decrease the extraction time in the subsequent processes of release and recovery [16]. The biopolymer derivatives release is often achieved through homogenisation under the influence of extraction buffers (food grade NaCl and NaHSO3), followed by filtration, centrifugation and washing in distilled water [4]. The derivatives recovery is realised by filtration, centrifugation, washing in distilled water, wastewater recycling and drying in a convectional laminar flow dryer. Resulting biomaterial powder is cooled and stored in airtight bags to prevent post-processing absorption of moisture as the derivatives powder is highly hygroscopic. Processing intact root using SRRC produces fibre-rich derivatives, which has been confirmed to offer better mechanical and barrier properties in the biomaterials [4]. Whether to use intact root or derived wastes depends on the envisioned final product; with edible bio-products, intact root is preferred while non-edible products (e.g., goods carrier bag, derived root residues) are the choice. During SRRC, an efficient mechanical pulping is crucial to achieve good quality (finer fibrous, 30–50 μm) and non-toxic (HCN threshold levels, near 0 ppm) biomaterials. Thus, a pulping efficiency (PE) of ≥90% was found to be sufficient when applied in pulping process using a time-dependent model (Eq. (1)) [16]. The PE of this magnitude is required because of the recalcitrant nature of most cellulosic fibre mass, which succumbs at higher shear rates. The achieved finer biomaterial powder (30–50 μm) is usually a result of softer cellulosic mass when compared to other woody plants.
S, pulping time; V, pulper velocity; Ɛ, pulping efficiency.
The SRRC concept restricts between 16 and 30% wastes disposed directly into the environment. This is achieved by processing fresh bitter cassava roots, and thus avoiding underlying costs, energy, time, intended and unintended disposal efforts, of additional alternative processes for waste management. The most economic SRRC design for sustainable valorisation of bitter cassava waste into value added biomaterials avoids the need to dispose indirectly wastes into environment leading to sustainability. The SRRC processing is a unique methodology concentrated at the early stage of the design (pulping, reaction, and release) to enhance biomaterial modifications, and therefore it can be applied in processes of sweet cassava waste and most crops’ residues. The SRRC reduces the extraction time and improves biomaterial texture with nominal size of 30–50 μm (finer matrices) with potential for extensive application. The ≥90% PE confers total cells breakdown and disruption, ensuring that enzyme linamarase hydrolyses linamarin (precursor of cyanide related compounds) into HCN. Cyanogenesis process is proportional to PE, only achieved in SRRC and not common with traditional methods, ensuring the safety of biomaterials (HCN near zero) [11]. The total HCN loss can be attributed to the functionalised ionic buffers and bisulphite in solution (pH 5.0–5.5) during the reaction and release stage. The affinity of bisulphites for the ketones makes them unavailable. This creates the desired gradient leading to fast HCN loss and might explain the significant detoxification of biomaterials. Ketones are released together with HCN during linamarin hydrolysis. Concurrently, residual sulphur of the bisulphite forms complexes with HCN to form a non-toxic thiocyanate compound. This is a significant outcome of SRRC; in the absence of this process in traditional processing, there is partial detoxification with production of unsafe biomaterials that cannot be applied in industry. Strikingly, SRRC ensures better productivity of the biomaterials as illustrated by the optimised model [11]. The high yield (45.8% w/w) of biopolymer derivatives is attributed to ionic buffers converting nearly all root biomass into biomaterials.
Biopolymer derivatives, a main biomaterial of SRRC and bitter cassava outcomes, can be used as a main ingredient in food, bioplastic, and packaging industries due to its compatible, biodegradable, polysaccharide-rich (starch, cellulosic fibrous, lignin), safety (0.4–2.5 ppm HCN), colourless (white) and particle size uniformity (30–50 μm and free-flowing) properties [4, 11, 15, 16, 17]. The biopolymer derivative is made available in powder form (Figure 3). The biomaterial colour is an impurity and often removed using rudimentary means in traditional processes. Nonetheless, the colourless characteristic of the biomaterial is achieved by reaction additives (sodium salts of bisulphites and ionic buffers) (Eqs. (2) and (3)), acting as bleaching agents. As indicated previously, compatibility was realised by combination and modification of different polysaccharides in the root during pulping and reaction processes. Biodegradable, polysaccharide-rich, toxin-free, and particle size uniformity are accomplished by using intact root and SRRC downstream processing. The amylose content of the biomaterial ranges between 18 and 24%, and higher corresponding amylopectin is attributed to inclusion of the peel waste and impact of SRRC on the peel structure [4].
Biomaterial route showing (a) intact bitter cassava root; (b) periderm-free intact root; (c & d) colourless biopolymer derivatives.
The biomaterial powder is highly stable at moisture content of ≤5% but instability is often encountered when the powder is stored and handled under moisture content ≤10% because the powder is highly hygroscopic.
The biomaterial has homogeneous particle sizes with round and polygonal shapes, and with slightly bigger round granule size [11].
Filmogenic solutions are prepared by using different proportions of the bitter cassava biomaterial powder, glycerol solution and distilled water (Figure 4). The resulting mixture is heated while agitated continuously until a gel is formed and turns clear. It is important that the gel is free from bubbles as they change the microstructure of the film sheet. Immediately, a known volume of the gel is cast onto glass plates and held shortly at ambient conditions to allow them to stabilise, concurrently bubble bleeding occurs. The stabilised gel casts are heated and maintained at known temperatures. The films are peeled off the plates and stabilised under environmental conditions of temperature and relative humidity.
Schematic flow of film fabrication process.
The physico-chemical characteristics of films (Table 1) perform a critical part in diverse end use systems, and knowledge of their properties is important in assessing package perform along the distribution chain. Intact bitter cassava-based films (BCFs) are transparent, with values as low as 3.6% than those obtained from starch of all botanical origin which posts 11.9% [4]. They are comparable to most commercial NatureFlex (4.6%) and Polylactide (3.9%), and much lower than polypropylene (13.6%). The low values tending to zero and higher values leaning to 100%, determined by spectrophotometric transmission and chroma lightness index respectively, indicate more transparency (Figure 5a). It can be confirmed that intrinsic modification of the intact bitter cassava root by SRRC produces more transparent films. Transparent films are important in many applications, particularly in packaging where products in the distribution chain are required to be viewed by buyers.
Property | Bitter cassava film | Commercial PLA film |
---|---|---|
Moisture (%) | 0.19–0.45 | 0.10–0.20 |
Optical (%) | 3.43–5.29 | 1.45–1.50 |
Solubility (%) | 15.52–30.54 | 0.00 |
Water vapour permeability (gmm/(M2.24h,kPa) | 3.19–4.50 | 180.0–190.0 |
Glass transitional temperature (°C) | 44.05–56.23 | 55.0–60.0 |
Melting temperature (°C) | 193.57–213.63 | 130.0–180.0 |
Tensile strength (MPa) | 3.71–48.44 | 40.1–49.5 |
Heat of fusion (J/g) | 64.0–70.5 | 21.5–25.4 |
Degradation temperature (°C) | 370.0–380.0 | 350.0–400.0 |
Glass transition temperature (°C) | 50.0–60.0 | 60.0–65.0 |
Melting temperature (°C) | 200.0–220.0 | 170.0–230.0 |
Crystallinity (%) | 50.5–59.5 | 10.0–15.0 |
Elongation at break (%) | 17.3–18.7 | 33.4–35.0 |
Elastic modulus (MPa) | 0.11–15.95 | 2000–2300 |
Transparency (%) | 3.0–5.0 | 3.0–5.0 |
Seal strength [N/25 mm] | 305.0–325.5 | 25.5–30.5 |
Contact angle (0) | 70–105 0 | 60.0–95.0 |
Biodegradability (days) | 20–100 | 40–50 |
Characteristics of bitter cassava films in kin to commercial PLA bio-film.
Bitter cassava film depicting a) transparent nature; b) carrier bag; and c) scanning electron microscope revealed mesh structure.
BCFs are fairly water resistant after 30 days, which is explained by the relatively stable network components in the film structure imparted by the root waste and SRRC [4, 15, 17]. Intact bitter cassava biopolymer derivatives is able to produce both water soluble and resistant films which can find application in packaging fresh foods and acting as a goods carrier bag used in an environment whereby high water resistance is high (Figure 5b).
BCFs possess homogeneous surfaces, which can be attributed to complete solubilisation of biopolymer derivatives in the polymer matrix, near zero solvent migration at the interface and strong and uniform adhesion of ingredients culminating into homogeneous mesh network structures in the film matrix (Figure 5c) [4].
BCFs are either hydrophilic or hydrophobic; those characterised with contact angles (CA) 700 ≤ CA < 900 contain polar functional groups that render them hydrophilic. The CA is the measure of wettability of solids and gives an indication of the extent liquids spread over solid surface [18]. The surface energy is essential in assurance of printability, adhesion, and transparency of flexible films. The BCFs have contact angles <900 (hydrophilic) and > 900 with printability features and can be used as goods carrier bags (Figure 5b) respectively. Nonetheless, BCFs are observed to swell differently at diverse RH; lower and higher swelling is clear at higher and lower RH respectively due to differences in plasticisation.
The fluid barrier properties of biomaterials are essential for prediction of the product-package shelf-life. The BCFs accurate performance veracity is a function of their flexibility in extremely demanding distribution situations, a role of their ability to respond timely and achieve fluid barrier appropriately. The BCFs have suitable permeability to water vapour (WVP) like commercial films polylactic acid (PLA) and Natureflex (NVS) currently applied in packaging fresh foods. This is fundamentally due to their widespread pore size distributions that contribute to fluid pathways, which are tortuous and exceedingly variable [19]. Depending on the nature of the films and their intended use, their equilibrium moisture contents (EMC) increase correspondingly with relative humidity (RH) at constant temperatures. This is caused by advanced amounts of moisture resulting into augmented mobility and dissociating. By contrast, the films EMC reduces when exposed to higher temperatures at constant RH due to film adsorption behaviour [19]. At high EMC, films moisture attraction is high with enhanced capacity adsorption and faster mobility of water causing a reduction in intermolecular attractive forces. The exponential increase of films WVP at higher temperatures is linked to higher activation energy for moisture permeation but also it is due to molecular initiation triggering film section crusade with creation of hollows that ease solvents motion through permeable films.
The permeability to oxygen (OP) of BCFs is higher than those of commercial NVS films. By contrast, permeability to carbon dioxide (CDP) by films is lower than the commercial ones. This is a good indication that the BCFs are adequate to be used in packaging fresh foods that are not highly respiring. When placed in distribution chain, BCFs under highly variable temperature and RH, the OP and CDP experience slight decreases due to antagonistic nature of RH on diffusion [19]. The interference of OP at higher RH and temperature is caused by increased molecular kinetics resulting into water molecules interfering with film voids but also on chain mobility. At higher RH and temperature, crystalline films are transformed into amorphous films (due to raised glass transition temperature and crystallinity) causing decreases in OP. The ability of these films to regulate barrier properties to gas and water, implies that they can be applied as breathable films, and is important for the choice of using them in commercial applications.
BCFs are permeable to organic and inorganic solvents differently [19] Toluene and paraffin, which are common organic solvents in the distribution chain, behave differently towards films. The higher interaction of paraffin is due to forming complexes with the film but also clinging to film surfaces. The information about the behaviour of solvents in contact with films is vital for their safe handling in the distribution chain. For example, toluene permeation makes film brittle and more crystalline with reduced molecular relaxation [19].
BCFs produce strong films that can have wide-ranging applications. Experiments have shown that BCFs tensile strength (TS) compares with commercial PLA and lies in the range of NVS and orientated polypropylene (OPP). BCFs flexibility is comparable to commercial PLA [4]. Similarly, it has also been shown that BCFs can be produced as weak films when the end use is targeted.
The seal integrity plays a vital role in packages and laminations in commercial setting. The BCFs have stand-alone self-sealing abilities compared to most commercial films that require an extra coating to enhance their sealing capacity. BCFs demonstrate comparable sealing strength with NVS, PLA and OPP that have supported sealing abilities [4]. BCFs exhibit last sealing strength for 12 h under environmental conditions (15–20°C and 50–60%RH), implying that films adhered firmly naturally [4].
BCFs are thermally stable under the influence of high temperatures. Their glass transition and melting temperatures, heat of fusion and crystallinity fall within the range of commercial PLA and LLDPE [4]. They are thermally stable than commercial films with the onset of total degradation occurring at 373°C, which is higher than most polymer networks degrading at 340–360°C [19].
BCFs are highly biodegradable in varying environmental conditions, decomposing in composite pits (within 21 days), open environment during wet conditions (maximum 45 days) and open environment during dry conditions (maximum 90 days). In all disposal environments, the bio-decomposition process uses naturally occurring bacterial/fungi to biodegrade the film into carbon dioxide, water, and compost. This is important for clean environment and sustainability, in contrast with fossil-based films that take more than 1000 years to decompose. When these biofilms are kept at room temperature and away from direct sunlight and humidity, they can biodegrade beyond 365 days. This is important when they are used as goods carrier bags and reused again.
A key part of sustainability is the minimisation of wastes during the biomaterial recovery from bitter cassava environmental waste. A sustainable system is an integrated and key strategy to realise green environment and value-added biodegradable products, and thus contributing to universal sustainability perception. The approach focuses on exploring individual process and model synergies and facilitating SRRC downstream process transition to advance cassava waste feedstocks for biodegradable product innovations. The approach emphasises developing and optimising an integrated process design based on optimising the structure of SRRC with efficient production of packaging materials and sustainable utilisation of cassava waste biomass feedstocks (waste solids and waste waters), meanwhile unlocking indirect and sustainable valorisation of cassava wastes. Apart from integrating individual processes, the strategy is intended to bring them, exclusively, into better efficient levels, through modelling and optimisations, and offer increased productivity of biodegradable packaging materials, thus creating a sustainable utilisation pull to reinforce the exploitation and competitiveness of bitter cassava crop. Standardisation, though process optimisation, of producing biomaterials eases the choice and cost of processes, by defining the design space, process parameters and biomaterial functional properties. In effect, robust production processes provide standard/optimal approaches for leveraging desired biomaterials with marginal costs and maximum functionality [20]. Besides, the effort is to bring the processing technology of small to medium enterprises (SMPs) to maturity through innovations in indirect waste disposal routes; and upgrading the development of simple, convenience and attractive substitute process designs that address cassava wastes accruing using SMPs rudimentary processing technologies.
Bitter cassava wastes that are generated by independent processes are being traditionally minimised in the environment by valorisation of bagasse into organic acids, ethanol, aroma and biocomposites [20, 21]. Although the above processes are popular approaches, they have disadvantages of their fundamental high production costs, energy, and time. Optimal design models of individual processes are used as a solution, which gives best interface leverages in a sustainable cassava minimisation approach. In designing an integrated process, process modelling is used to ensure a holistic design for efficient utilisation of cassava wastes without compromising competition for food supply. Thus, to ensure efficient production of biomaterials, an integrated process design is used [16]. In this design, processes are well-defined and conceptualised before they are used in the integrated downstream processing model. In effect, only processes which add value in minimising waste at low cost, are energy efficient and time saving are selected and analysed in the integration design. Primarily, to increase the efficiency and functionality, the design is partitioned into unit operations whereby optimisations are focused. The source includes but not limited to recovering biomaterials from: i) the whole root of bitter cassava; ii) detached residue portions (peel, fibre, trimmings); and iii) wastewater streams.
The innovations to process design integration fall into three optimised and pooled processes to maximise recovery of safe biomaterials, i.e., efficient mechanical pulping; reaction and release; and recovery.
Efficiency of mechanical pulping is well explained in subsections 3.11–3.12. Precisely, the yield of biomaterials and loss of total cyanide certainly need to be augmented in optimising efficiency.
Reaction and release process is a key stage due to the need to free fully the biomaterials at minimum costs, taking into consideration protection of the environment due to released hydrogen cyanide. There are several variables to aid release, the processing conditions, and the desired biomaterial properties but their levels are highly variable. Resultantly, key buffers and bisulphates are preferred in order to infer release of biomaterials. Based on this approach, the research is done for purposes of not only releasing the biomaterials but also consider their yield, safety and customised for multiple functions.
Regarding reaction and release step, desirability function approach is used to optimise multiple response processes, which exploits optimal processing conditions and parameters and obtain the most desired yield, safety, and functionality of biomaterials. According to [16, 22], joint Pareto front and multi-objective desirability (MOD) approaches is used in the standardisation of the reaction and release process. In Pareto front/solutions, distribution to parameter choices is made in such a way that trade-offs ensure unequal distribution in which some factors are constrained in place of alternatives in order to find feasible choices that lie on the Pareto font [22]. In this case, choices are efficient and not dominated by any other choice. On the other hand, the MOD approach is used in target desirability optimisation due to its capacity predict desirables within anticipated ranges [16].
In the recovery step important processes take place, and they include: removing cyanogens and bisulphite residuals remaining in the wet biomaterials released; dehydrating released biomaterials in a safe and economic way through serial washing and recycling and optimal drying (Figure 6). In traditional washing and clarification, a lot of purified water is deployed in serial washing with implications of energy costs in purification and biomaterials carried in wastewaters. In the current innovative designs, waste solvent is recycled thus reducing greatly on the costs of purification while ensuring zero contaminated biomaterials free from unwanted solvent and other clarifying-induced defects.
Illustration of biomaterial drying process: (a) cross-sectional design of recirculating laminar flow chamber for studying optimisation and (b) mass and energy transfer.
Conventional drying involves a lot of energy spent in the process, usually involving several hours (25°C, 12–16 h) of laminar flow drying without causing defects to the biomaterials in contrast to dying in ovens [16]. During the optimal recovery stage, energy is significantly minimised by optimised conditions in the designed recirculating laminar flow chamber (Figure 6). The purpose is to minimise the resident time of the biomaterial in the chamber while attaining the required residual solvent and drying process efficiency (productivity). As such operating conditions (air temperature, heat transfer coefficient, air flow rate, solvent partial pressure and velocity distributions) of the recirculating chamber are modelled and optimised to minimise significantly the polymer-solvent concentration and biomaterial resident time. Optimal conditions for drying polymer-solvent biomaterials is an outcome of a trade-off between minimising residual solvent dose producing gradients for fast dying without changing biomaterial quality. Thus, an adequate chamber with recirculating laminar flow is designed and deployed (Figure 6) for trial studies using computational fluid dynamics and mass and energy transport modelling [23]. In trying to attain optimal drying, interactions between biomaterial properties, dying conditions, biomaterial (polymer) solvent transport and mass/energy transport are managed. The fans enable to obtain uniform air flowing through the biomaterial. For a known uniform thickness (30 microns), temperature, time and polymer solvent amount profiles evolve as air (20–30°C, 30–40%RH) circulates through chamber containing biomaterials.
Biomaterials from optimised recirculating laminar flow chamber processes are recovered and dried efficiently (high recovery, very low moisture, near zero contamination, low energy usage). The mechanism of drying biomaterial involves heat transfer from the convective air provided by external heat source and mass transfer in the biomaterial involving adsorption, diffusion, and desorption. At all stages of the drying process, drying rate is a function of solvent transport from the inside and surface of the biomaterial to the gas phase. Desorption (i.e., solvent transport from biomaterial surface) is characterised by mass transfer coefficients, gas temperature, velocity, and partial pressure, while diffusion (i.e., solvent transport within biomaterial) depends on temperature and solvent concentration [23]. Important scenarios above are modelled, optimised and outcomes presented (Table 2). The optimised drying rate in recirculating laminar flow ensures short resident time compared to laminar flow (Table 2, Figure 7), implying reduced energy in drying.
Parameters | Laminar flow | Recirculating airflow |
---|---|---|
Wet Biomaterial thickness, μm | 30 | 30 |
Dry biomaterial thickness, μm | 24 | 20 |
Initial air temperature, 0C | 25 | 25 |
Final air temperature, 0C | 30 | 30 |
Residence time, min. | 360 | 240 |
Chamber partial pressure, kPa | 102 | 102 |
Air Velocity, m/s | 1.5 | 2.1 |
Initial solvent (moisture) content, mg | 60 | 60 |
Final solvent content, mg at 240 min | 32 | 5 |
Maximum weight loss, % | 47 | 92 |
Heat transfer coefficient, cals−1 cm−2 °C−1 | 0.0033 | 0.0024 |
Parameters at optimal drying of biomaterials in Laminar flow and recirculating laminar flow.
Drying rates of biomaterials in recirculating laminar and laminar flows.
The biomaterials’ optimisation in recirculation laminar flow (RLF) chamber ensure that they are minimally degraded by heat and are more permeable to water vapour. Conversely, the RLF-based dying does not influence the structural and physico-chemical changes; this is also true for drying in laminar flow (LF) chamber [16]. By contrast, biomaterial thermal degradation increases in LF drying.
SRRC-produced biomaterials have benefits of a relatively low cost; particularly those from bitter cassava possess secondary metabolites with unrivalled properties and varied uses, and thus have an edge over commercially available starch [4]. As a multifunctional, safe and dynamic matrix, bitter cassava biomaterials have potential application in pharmaceuticals, nutraceuticals and food supplements [15, 24]. SRRC-produced bitter cassava biomaterial is used as suitable matrix in the development of novel oral tablet excipient in iron and zinc supplements [11].
In the production of iron and zinc tablets, the goal is to have a sustainable delivery system through chasing a carrier and delivery process that is inexpensive, green, and user-friendly. The manufacture follows a two-step process. Firstly, is to identify key bitter cassava biomaterial properties suitable for the development of self-sustaining excipient with important functionalities [11]. Next, based on the results from the first step, optimise the functionalities using granulation, formulate iron and zinc tablets and conduct dissolution tests.
In the preparation of biomaterial for excipient manufacture and dissolution tests, intact bitter cassava root biomass and SRRC methodology are explored [4]. In the conventional methods of producing biomaterials, peeled roots are the choice starting materials. For current innovation, tablets formation is done by exploring the capacity of biomaterial powder to produce strong tablets and is done by using both intact and peeled roots-derived biomaterials (Figure 8). Detailed procedure for tablets fabrication and dissolution tests can be found in the works of [11]. Iron and zinc are included prior to tablet formation and after granulation process. The quantities of iron and zinc included in the tablets are based on the dietary requirements of men (11 mg/day) and women (8 mg/day) while correcting for experimental loss [11, 25]. A suitable design is important if the minerals are to be distributed evenly in the tablets and an effective dissolution is needed. The design is defined based on three tablet sizes (100, 250, 500 mg), which corresponds with common pharmaceutical tablets in the market (Table 2) and the in vitro dissolution is accomplished using the US Pharmacopoeia (USP) method [11, 26]. For better elucidation of the dissolution mechanisms (behaviour, release type, application angle of tablets), mathematical models are applied [11].
Procedural investigation of excipient tablet production.
The physico-chemical properties of biomaterials play a vital role in tablet manufacture where flowability and compaction are the key properties. The biomaterials have uniform particle size and shape distribution of <3 mm, low bulk, and true densities, high tapped density and increased interparticle voids [11]. The uniform particle size is crucial in effective compaction/compression and regulated delivery matrices [11]. High tapped density is due to higher contract surface area, which is a benefit to tablet filling, higher solubility and dispersibility. Biomaterial flow properties and compressibility and solid excipient durability (desired strength, porosity and dissolution) are a function of bulk, tapped and true densities. The bulk and tapped density of the biomaterial are close to each other, which implies that it has better flow properties [11]. The biomaterial inter-particulate and intra-particulate interaction is low because of the low Carr’s index (CI) and Hausner ratio (HR). The CI indicates compressibility or flowability of a powder, while HR is the number that relates to the flowability of a powder or granular materials. It has a low angle of repose and low porosity, an indication of particle uniformity and excellent flowability, which implies that the biomaterial powder cannot cake. The angle of repose of a powder or granular material is the sharpest angle of descent or dip relative to the horizontal plane to which a material can be heaped without dropping and is between 0 and 900. The biomaterials have low water retention capacity (WRC), water holding capacity (WHC) and swelling capacity (SC) although their WRC increases and WHC and SC decreases with time. The biomaterials have higher hydration capacity due to higher surface energy. The implication is the physical structural changes and hydration properties of the biomaterials fibres and their hydrophilic nature allows maximum moisture uptake offering a hint of better disintegrating of excipients [11].
The novel Iron-Zinc excipient tablet (Figure 9) can be used extensively in developing food supplements, and as a pharmaceutical tablet with other active compounds due to its compatible, biodegradable, safe and fast dissolution properties [11]. Tablets have uniform weights (av. weight 484 ± 0.68 mg (Table 3), which is far lower than the recommended limit of 0.05. Uniformity and thickness of tablets are indication of good packing of tablets. The tablets exhibit reduced thickness corresponding to increases in compression force [11]. Tablets display adequate mechanical properties (hardness and tensile strength). The bitter cassava tablets are weak binders and strong disintegrants; these properties are crucial to the developments of fast release excipients where iron and zinc deliveries are fast demanded and in adequate amounts [24]. Tablet friability is compared to the USP standards implying that they can resist mechanical stress in the distribution chain. Tablet matrix porosity decreases as compression force is increased. Porosity is a function of particle size and shape; regular shaped particles become less and can fill up void spaces between large particles. In the low porosity tablets, small particle sizes allow flexibility for the tablets to pack more efficiently. However, the medium to high porosity biomaterials of bitter cassava does not permit flexibility in tablet packing suggesting a fast dissolution rate. Tablets exhibit higher disintegration time (DT) due to relatively medium to higher porosity, which facilitates rapid water penetration into the tablet resulting into bond rupture and disintegration [11]. The DT is the measure of time required for the tablet to disintegrate into particles under a given set of conditions.
The tablet prototypes containing biomaterial with: (a) no mineral; (b) iron; and (c) zinc.
Parameter | Biomaterial type | |||
---|---|---|---|---|
Bulk density (g/cm3) | 0.38 | |||
Tapped density (g/cm3) | 0.4 | |||
True density (g/cm3) | 1.49 | |||
Carr’s Index (%) | 9.38 | |||
Hausner’s ratio | 1.13 | |||
Flow rate (g/s2) | 20.91 | |||
Angle of repose (0) | 28.52 | |||
Porosity (%) | 68.87 | |||
Hardness (KG) | 4.32 | 4.42 | 4.64 | |
Diameter (mm) | 13.09 | 13.08 | 13.07 | |
Thickness (mm) | 3.16 | 3.14 | 3.11 | |
Weight (mg) | 546.36 | 551.48 | 542.62 | |
Tensile strength (MPa) | 0.35 | 0.37 | 0.41 | |
Disintegration time (s) | 903 | 895 | 878 | |
Friability | 0.67 | 0.56 | 0.51 |
Physical properties of bitter cassava biomaterial and excipient*.
Tablet size of 500 mg analysed at compaction pressures of 200, 500 and 700 MPa.
CP, compression pressure.
The tablet matrix morphology and microstructure are considerably homogeneous, non-aggregated and uniformly blended with iron and zinc [11]. These patterns provide hope for tablets as inert excipients for oral dosage solid forms. Nutrient analysis has shown that zinc is released faster than iron in the tablet matrix, which seems to indicate that the matrix has minor resistance to zinc release than do for iron [11]. Tablet excipients release iron and zinc better in acidic conditions than alkaline conditions within 45 minutes; this has implications for these tablets in the gastrointestinal movements and safe delivery in human body. This confirms that the nutrients have faster absorption in the stomach that in intestines. Furthermore, within 45 minutes of tablet disintegration suggests that they have one of the fastest release rates of iron and zinc nutrients and is attributed to easy tablet matrix erosion. Besides, high erosion rates of the tablet matrices are explained by high gelling, swelling and release of nutrients as fast as possible [11]. Noticeably, the low weight tablets release nutrient from the matrix faster because nutrients diffuse quicker from matrix surfaces.
Food industry packaging challenges created by the failure to maintain quality and safety of fresh and minimally processed foods in distribution have been mitigated mainly by modified atmosphere packaging (MAP). The MAP is a widely established system for the preservation of quality and managing shelf-life of fresh foods driven by the need and legislation to replace chemical preservatives. In the MAP system, the in-package environment is modified to match the requirements for storing fresh foods. While MAP is a popular packaging system, it has outstanding flaws such as design errors, which are corrected by active (gas flushing) and passive (equilibrium MAP) techniques [27]. Noticeably, Equilibrium MAP (EMAP) is universally used system for fresh respiring foods [15]. Notably, an EMAP is established inside the package when gas transmission rate matches product gas consumption rate [15]. Other current extenuation actions to the design errors include use low-cost biodegradable biomaterials for EMAP of fresh fruits and vegetables and cherry tomatoes [15, 28, 29] and joint plasma treatment and EMAP for cherry tomatoes [30]. A more robust package design was achieved using an ultimate EMAP across package distribution conditions [15]. This has an advantage of using the biomaterial film with heat sealing, heat resistance, relatively water resistance, good barrier, transparent and good mechanical properties in addition to their cost-effective, less competition with food supply biodegradability in all environments, ability to make pouches and bags, printing capacity, and non-perforation needs [4, 15, 16, 20].
When planning to design an EMAP for fresh foods, the fresh product respiration and transpiration behaviour and mass transfer of the package are important considerations and must be fully explored and understood [15]. The design trial includes defining the design requirements of bitter cassava biomaterial film EMAP that is stable in distribution chain characterised by low conditions (10°C, 75% RH). This is affected by knowing the impact of packaging parameters (perforation, RH, temperature) on gas (oxygen, carbon dioxide) composition, the optimal design parameters and gas composition and validated optimal EMAP [15]. The EMAP design follows the conceptual flow depicted in Figure 10. To design an integrated package, an active coated product is factored in the EMAP evaluation.
Practical study of an EMAP design.
The dynamics of an In-package headspace gas plays an important role in attainment of EMAP for food products. When cherry tomatoes are used in the EMAP trials and stored using BCFs, the headspace oxygen reached equilibrium (2–3%) after 180 h at 10°C for 75% RH (Figure 11). The recommended headspace oxygen is 3–5% for safe storage of tomatoes [30].
Progress of headspace oxygen (%) of stored cherry tomatoes in EMAP.
Since the shelf-life of the products is associated mainly with microbiological quality, modifying the in-package atmosphere through EMAP is often intended to limit microbial contamination.
Cherry tomatoes stored in the EMAP show visible mould around 360 h at 10°C and 75% RH and demonstrated reduced weight loss. The loss in normal EMAP is attributed to the combined effect transpiration rate of cherry tomatoes and permeability of bitter cassava films [15].
Colour is a key indicator of market value of the product. An EMAP did not have significant effect on the colour of cherry tomatoes during the 21 days of storage; however insignificant changes are apparent due to the nature of biological materials. A colour index of 1.1 was observed with cherry tomatoes storage with EMAP.
Reduced total soluble solids (TSS) is often encountered when tomatoes are stored for a long time. Like any other storage medium, EMAP decreases cherry tomato TSS (Figure 12). In this case, there is a possibility of packaging contributing to the reduced hydrolysis of insoluble polysaccharides into simple sugar [31].
Status of cherry tomato quality at different storage times: (a) weight loss; (b) TSS; (c) colour difference.
According to [32], the global cassava processing market reached a volume of 298.8 Million Tons in 2020, implying that industrial application has grown correspondingly in food, ethanol, paper and cardboard, textiles, pharmaceutical, glues and adhesives. It is reported that food industry accounts for around a half of the total global cassava consumption followed by feed industry [32]. The use of cassava in most industrial applications such as food, pharmaceuticals, beverages, civil works and textile industries is mainly done with sweet cassava starch and flour.
Food application of cassava. By improving properties of cassava flour using enzymatic and thermal modification, has been found to be acceptable in using modified flour as a key ingredient in the production of gluten-free baked products such as pasta and bread [33, 34].
Textile application of cassava. Because of starch qualities such as flexibility, resistance to abrasion and the ability to form a bond with the fibre, it is used in sizing, finishing, and printing in textile industry [35]. Of the total cassava starch used in textile, an estimated 80 percent go into sizing unit operation, which involves shaping and forming yarn fibres into warp. In this case, starch is used to coat the surfaces of the twisted warp that is then subjected to thermal treatment into a beam of warp ready for weaving. When the yarn is moisturised with cassava starch, the threads become smooth, greasy, slippery and hairless. In this case, starch behaves as a lubricant.
Pharmaceutical application of cassava. Tapioca starch, obtained from the roots of cassava by physical and chemical modifications (oxidisation, esterification, etherification, and treatment with enzyme) is applied in medicine and pharmaceuticals. Native and modified tapioca starch are used as diluents, binders and disintegrants in tablet and capsule formulations [36]. The excellent flowability and swelling power of native tapioca starch renders it useful as diluent for capsule and tablet formulations. Native tapioca starch produces tablets with higher tensile strength, less friability, least tendency to brittle fracture, longer disintegration time and slower drug dissolution rate, thus is preferred in paracetamol tablets when compared with cereal starches. Similarly, modified tapioca starch such carboxymethyl starch is generally used in medicine, pharmaceuticals, cosmetics and food due to their improved hydrophilicity, increased water absorption, reduced tendency of retrogradation, lowered gelatinization temperature, increased solubility in cold water with clear gel and higher storage stability [36, 37]. Acid-modified tapioca starch is an important filler or binder in direct compression with higher tensile strength, lower friability, faster dissolution than the native tapioca starch [38].
Application of cassava in civil works. Research has demonstrated that waste cassava is an ingredient in building materials [39]. It is demonstrated that when waste cassava, cement, charcoal and sand mixed in 2.5 kg composite and made into bricks, a denser texture of the bricks is obtained with perfect binding and compaction [39]. The relative strength is reported to be 711.5 kg/cm2 in addition to the brick being more environmentally responsive. Elsewhere, experimental trials of cassava starch modified concrete confirmed improved compressive, split tensile, flexural and elastic modulus of concrete at an optimum of 0.8% as well increased setting time and durability, with potential application in retarding admixtures [40, 41].
Application of cassava in beverages. Research trials confirm application of cassava into spirits and beers [42]. Using enzymes, cassava is liquefied and saccharified serially into, fermentable broth (circa 184 g/l of fermentable sugars), alcohol (circa10% ethanol) and spirits (40% ethanol by volume) with consumer acceptance [42].
Of recent, cassava coating is used in active packaging using both sweet and bitter varieties. Cassava-based edible coatings is used universally in preservation of foods. Trials have shown that edible cassava starch coating extended the shelf-life of Andean blackberries by 100% after 10 days in storage [43] and prevent decay and extend shelf life of black mulberries under refrigerated conditions [44].
Green environment, sustainability, resource renewability and efficiency, industry biomaterial supply, and circular produce-consume-dispose model could be spurred by exploiting innovative research solutions into cassava waste biomass. This chapter demonstrates that cassava varietal-specific waste can be transformed fully into sustainable and efficient feedstocks for bioplastics, packaging, and food supplement industries. Using innovative SRRC improved downstream processes and integrated sustainable process, up to 30% waste from bitter cassava can provide stand-alone feedstock requirements for food, medical, packaging industries. Valorisation of wastes reveals application in Iron-Zinc supplements and extending shelf life of tomatoes, which has advantage of improving nutrition status of vulnerable communities but also avoiding use of pesticides in fruit marketing. Either way, health is improved for the communities. Innovative SRRC improved processing methodology can be an alternative solution that eliminates the burden of drudgery and rudimentary process of small and medium enterprises (SMEs) to increase their market participation. As a supplementary bonus, valorisation of bitter cassava wastes into bioplastics would likely avert consequences of littering and burning of plastics (mainly carrier bags) that impact negatively on the environment and public health. Ultimately, committed used of SRRC in bitter cassava processing would help SMEs to have a sustainable non-food feedstock resource, contribute national environment programmes and improve community incomes.
Authors acknowledge the support provided by National Agricultural Research Organisation (NARO), Uganda, and School of Engineering, University College Cork, Ireland for resource provision during the doctoral studies.
Author declare no conflict of interest for this work.
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In an attempt to assist with the new therapeutic approaches to manage cancers involving the central nervous system, classical chemobiodynamic compartment and pharmacokinetic models are discussed and illustrated. In addition, strategies and approaches for penetrating the blood brain barrier (BBB) are reviewed and modeled. Finally, in support of classical pharmacology, a new anticancer agent in clinical trial for brain tumors is reviewed as an example of clinical onco-neuropharmacology.",book:{id:"5599",slug:"new-approaches-to-the-management-of-primary-and-secondary-cns-tumors",title:"New Approaches to the Management of Primary and Secondary CNS Tumors",fullTitle:"New Approaches to the Management of Primary and Secondary CNS Tumors"},signatures:"Andrew H. Rodgers and Lee Roy Morgan",authors:[{id:"158053",title:"Dr.",name:"Lee Roy",middleName:null,surname:"Morgan",slug:"lee-roy-morgan",fullName:"Lee Roy Morgan"},{id:"193557",title:"Ph.D.",name:"Andrew",middleName:null,surname:"Rodgers",slug:"andrew-rodgers",fullName:"Andrew Rodgers"}]},{id:"53555",doi:"10.5772/66207",title:"Phakomatoses and Their Tumors: Genetics and New Treatment Options",slug:"phakomatoses-and-their-tumors-genetics-and-new-treatment-options",totalDownloads:1378,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"In addition to sporadic primary neoplasms of the central nervous system, several genetic syndromes associated with CNS tumors have been identified. Tuberous sclerosis, neurofibromatosis-1 and -2, and von Hippel–Lindau syndrome belong to a collection of disorders called phakomatoses, which include both CNS tumors and cutaneous manifestations. The underlying genetics of these disorders are being elucidated and offer novel therapies for intervention.",book:{id:"5599",slug:"new-approaches-to-the-management-of-primary-and-secondary-cns-tumors",title:"New Approaches to the Management of Primary and Secondary CNS Tumors",fullTitle:"New Approaches to the Management of Primary and Secondary CNS Tumors"},signatures:"Muhammad Taimur Malik, Mohammed Faraz Majeed and Scott G.\nTurner",authors:[{id:"181611",title:"Dr.",name:"Scott",middleName:null,surname:"Turner",slug:"scott-turner",fullName:"Scott Turner"},{id:"196291",title:"Dr.",name:"Mohammed Faraz",middleName:null,surname:"Majeed",slug:"mohammed-faraz-majeed",fullName:"Mohammed Faraz Majeed"},{id:"196293",title:"Dr.",name:"Muhammad Taimur",middleName:null,surname:"Malik",slug:"muhammad-taimur-malik",fullName:"Muhammad Taimur Malik"}]},{id:"53873",doi:"10.5772/66601",title:"Primary Central Nervous System Lymphoma",slug:"primary-central-nervous-system-lymphoma-2017-03",totalDownloads:1703,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Although non-Hodgkin’s lymphoma (NHL) is a frequent cancer worldwide, primary central nervous system (CNS) lymphoma (PCNSL) is a rare presentation, with an incidence of less than 0.5 per 100,000 persons-years in the western world. In the vast majority of cases, it has the histology of a diffuse large B-cell lymphoma (DLBCL) and is a hardly curable disease with high relapse risk. Therapeutic options are limited by blood-brain barrier penetration of drugs and because of its low-incidence high-grade evidence from large studies is lacking, current management being based on reports on rather small cohorts. The current standard first-line treatment for PCNSL consists of high-dose methotrexate (HD-MTX) in combination with a variety of drugs and consolidation whole-brain radiotherapy, the latter being progressively replaced by chemotherapy. For patients relapsing after first-line treatment, intensive chemotherapy with autologous stem cell support is a feasible and relatively safe salvage therapy. In the present chapter, we briefly discuss primary central nervous system lymphoma management and review current therapeutic options and evidence-based recommendations. We discuss the role of whole-brain radiotherapy (WBRT) and new prospects to avoid this side effect-ridden approach. Also, we will look at new therapeutic approaches currently under investigation, including immunotherapy.",book:{id:"5599",slug:"new-approaches-to-the-management-of-primary-and-secondary-cns-tumors",title:"New Approaches to the Management of Primary and Secondary CNS Tumors",fullTitle:"New Approaches to the Management of Primary and Secondary CNS Tumors"},signatures:"Mihnea Zdrenghea, Delia Dima, Ciprian Tomuleasa, Horia Bumbea\nand Cristina Bagacean",authors:[{id:"73222",title:"Dr.",name:"Delia",middleName:null,surname:"Dima",slug:"delia-dima",fullName:"Delia Dima"},{id:"193180",title:"Dr.",name:"Mihnea",middleName:null,surname:"Zdrenghea",slug:"mihnea-zdrenghea",fullName:"Mihnea Zdrenghea"},{id:"198423",title:"Dr.",name:"Cristina",middleName:null,surname:"Bagacean",slug:"cristina-bagacean",fullName:"Cristina Bagacean"}]}],mostDownloadedChaptersLast30Days:[{id:"53170",title:"Current Management of Brain Metastases: Overview and Teaching Cases",slug:"current-management-of-brain-metastases-overview-and-teaching-cases",totalDownloads:1658,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Over the past two decades, increased global incidence of malignancy, improved systemic disease treatment with prolonged survival, and increased central nervous system (CNS) surveillance in cancer patients have all contributed to a rise in cerebral metastatic disease. As many patients retain good neurologic function, the approach to their management has shifted markedly; a pre-terminal prognosis and palliative treatment have been replaced by individualized care plans to prolong functional survival. However, the rapid shifts in disease characteristics, treatment options and emerging evidence can be challenging to navigate, and a rational approach to brain metastases is needed. We discuss the changing epidemiology of brain metastases and consider approaches to prognostic classification. We review current treatment modalities and discuss the significant studies pertaining to each, with emphasis on Level 1 evidence when available and cooperative group trials, as well as studies on adverse effects. To integrate the information presented, we offer case scenarios that highlight pertinent decision-making factors. The shift in care goal for cerebral metastases from symptom palliation to prolongation of survival is not only feasible, but in many cases indicated. The appropriate application of various treatment modalities must be considered in the context of individual patients and their primary cancer.",book:{id:"5599",slug:"new-approaches-to-the-management-of-primary-and-secondary-cns-tumors",title:"New Approaches to the Management of Primary and Secondary CNS Tumors",fullTitle:"New Approaches to the Management of Primary and Secondary CNS Tumors"},signatures:"Karolyn Au, Ying Meng, Suganth Suppiah, Anick Nater, Rakesh\nJalali and Gelareh Zadeh",authors:[{id:"194279",title:"M.D.",name:"Karolyn",middleName:null,surname:"Au",slug:"karolyn-au",fullName:"Karolyn Au"},{id:"197665",title:"Dr.",name:"Ying",middleName:null,surname:"Meng",slug:"ying-meng",fullName:"Ying Meng"},{id:"197666",title:"Dr.",name:"Suganth",middleName:null,surname:"Suppiah",slug:"suganth-suppiah",fullName:"Suganth Suppiah"},{id:"197667",title:"Dr.",name:"Anick",middleName:null,surname:"Nater",slug:"anick-nater",fullName:"Anick Nater"},{id:"197668",title:"Dr.",name:"Gelareh",middleName:null,surname:"Zadeh",slug:"gelareh-zadeh",fullName:"Gelareh Zadeh"},{id:"197669",title:"Dr.",name:"Rakesh",middleName:null,surname:"Jalali",slug:"rakesh-jalali",fullName:"Rakesh Jalali"}]},{id:"53032",title:"Role of Pathologist in Driver of Treatment of CNS Tumors",slug:"role-of-pathologist-in-driver-of-treatment-of-cns-tumors",totalDownloads:1622,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The incidence of Central Nervous System (CNS) tumors is gradually increasing. Furthermore, metastatic neoplasms are frequently seen in neuropathology practice as a major cause of mortality and morbidity. Pathologists try to reach a more accurate diagnosis by mentally filtering a synthesis, comprising age, radiological characteristics and microscopic findings in the sample sent, starting already from the intraoperative diagnosis process. By displaying their skills, they unveil whether a lesion in the brain parenchyma is a normal or reactive tumor and if this is a tumor, is it primary or metastatic, and if it is primary, what is the tumor type or if it is metastatic, which organ could it be associated with. Pathologists use diagnostic, prognostic and predictive markers in order to enable the patient receive the most effective and sufficient treatment. They ensure that an individualized treatment is provided via these tools, by making a histological diagnosis of the lesion according to the WHO classification, identifying the course of the disease and preventing undesired and dangerous complications. This chapter will focus on answering these questions and share the value of a multidisciplinary approach in the management of brain tumors in neurosciences, which is gradually increasing in importance, and how pathologists execute this art.",book:{id:"5599",slug:"new-approaches-to-the-management-of-primary-and-secondary-cns-tumors",title:"New Approaches to the Management of Primary and Secondary CNS Tumors",fullTitle:"New Approaches to the Management of Primary and Secondary CNS Tumors"},signatures:"Serdar Altınay",authors:[{id:"185324",title:"Associate Prof.",name:"Serdar",middleName:null,surname:"Altınay",slug:"serdar-altinay",fullName:"Serdar Altınay"}]},{id:"53873",title:"Primary Central Nervous System Lymphoma",slug:"primary-central-nervous-system-lymphoma-2017-03",totalDownloads:1702,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Although non-Hodgkin’s lymphoma (NHL) is a frequent cancer worldwide, primary central nervous system (CNS) lymphoma (PCNSL) is a rare presentation, with an incidence of less than 0.5 per 100,000 persons-years in the western world. In the vast majority of cases, it has the histology of a diffuse large B-cell lymphoma (DLBCL) and is a hardly curable disease with high relapse risk. Therapeutic options are limited by blood-brain barrier penetration of drugs and because of its low-incidence high-grade evidence from large studies is lacking, current management being based on reports on rather small cohorts. The current standard first-line treatment for PCNSL consists of high-dose methotrexate (HD-MTX) in combination with a variety of drugs and consolidation whole-brain radiotherapy, the latter being progressively replaced by chemotherapy. For patients relapsing after first-line treatment, intensive chemotherapy with autologous stem cell support is a feasible and relatively safe salvage therapy. In the present chapter, we briefly discuss primary central nervous system lymphoma management and review current therapeutic options and evidence-based recommendations. We discuss the role of whole-brain radiotherapy (WBRT) and new prospects to avoid this side effect-ridden approach. Also, we will look at new therapeutic approaches currently under investigation, including immunotherapy.",book:{id:"5599",slug:"new-approaches-to-the-management-of-primary-and-secondary-cns-tumors",title:"New Approaches to the Management of Primary and Secondary CNS Tumors",fullTitle:"New Approaches to the Management of Primary and Secondary CNS Tumors"},signatures:"Mihnea Zdrenghea, Delia Dima, Ciprian Tomuleasa, Horia Bumbea\nand Cristina Bagacean",authors:[{id:"73222",title:"Dr.",name:"Delia",middleName:null,surname:"Dima",slug:"delia-dima",fullName:"Delia Dima"},{id:"193180",title:"Dr.",name:"Mihnea",middleName:null,surname:"Zdrenghea",slug:"mihnea-zdrenghea",fullName:"Mihnea Zdrenghea"},{id:"198423",title:"Dr.",name:"Cristina",middleName:null,surname:"Bagacean",slug:"cristina-bagacean",fullName:"Cristina Bagacean"}]},{id:"53003",title:"Managing CNS Tumors: The Nanomedicine Approach",slug:"managing-cns-tumors-the-nanomedicine-approach",totalDownloads:1185,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Albeit the rapidly evolving knowledge about tumor biochemistry enables various new drug molecules to be designed as treatments, malignant central nervous system (CNS) tumors remain untreatable due to the failure to expose the entire tumor to such therapeutics at pharmacologically meaningful quantities. Therefore, drug delivery in CNS tumors must be properly addressed, as otherwise, novel therapies will continue to fail. In this regard, nanomedicine poses an appealing platform for efficient drug delivery to the CNS, since it may be targeted to improve the drug availability in the site of action, which would be translated into lower drug doses and fewer side effects. Hence, the accumulation of data about the CNS physiology and their relevant receptors, the widening therapeutic armamentarium of drugs potentially useful in CNS chemotherapy and the alternative routes for administration may envisage nanomedicines as a forthcoming routine approach. Indeed, on the basis of the promising results gathered from preclinical studies of nanomedicine-based therapy both systemically and locally administered, some nanomedicines have already been approved for clinical trials in a variety of CNS tumor conditions to serve as the first steps in the translation of nanotherapy to clinic. Their outcome will steer research directions for further improvements.",book:{id:"5599",slug:"new-approaches-to-the-management-of-primary-and-secondary-cns-tumors",title:"New Approaches to the Management of Primary and Secondary CNS Tumors",fullTitle:"New Approaches to the Management of Primary and Secondary CNS Tumors"},signatures:"Juan Aparicio-Blanco and Ana-Isabel Torres-Suárez",authors:[{id:"193558",title:"Prof.",name:"Ana Isabel",middleName:null,surname:"Torres-Suárez",slug:"ana-isabel-torres-suarez",fullName:"Ana Isabel Torres-Suárez"},{id:"195630",title:"MSc.",name:"Juan",middleName:null,surname:"Aparicio-Blanco",slug:"juan-aparicio-blanco",fullName:"Juan Aparicio-Blanco"}]},{id:"54440",title:"NeuroPharmacology: As Applied to Designing New Chemotherapeutic Agents",slug:"neuropharmacology-as-applied-to-designing-new-chemotherapeutic-agents",totalDownloads:1233,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Neurooncology anticancer drugs are no exception—their distribution and tissue interactions follow the general rules of classical pharmacology. In an attempt to assist with the new therapeutic approaches to manage cancers involving the central nervous system, classical chemobiodynamic compartment and pharmacokinetic models are discussed and illustrated. In addition, strategies and approaches for penetrating the blood brain barrier (BBB) are reviewed and modeled. Finally, in support of classical pharmacology, a new anticancer agent in clinical trial for brain tumors is reviewed as an example of clinical onco-neuropharmacology.",book:{id:"5599",slug:"new-approaches-to-the-management-of-primary-and-secondary-cns-tumors",title:"New Approaches to the Management of Primary and Secondary CNS Tumors",fullTitle:"New Approaches to the Management of Primary and Secondary CNS Tumors"},signatures:"Andrew H. Rodgers and Lee Roy Morgan",authors:[{id:"158053",title:"Dr.",name:"Lee Roy",middleName:null,surname:"Morgan",slug:"lee-roy-morgan",fullName:"Lee Roy Morgan"},{id:"193557",title:"Ph.D.",name:"Andrew",middleName:null,surname:"Rodgers",slug:"andrew-rodgers",fullName:"Andrew Rodgers"}]}],onlineFirstChaptersFilter:{topicId:"1086",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. These advances have helped foster better support for animal health, more humane animal production, and a better understanding of the physiology of endangered species to improve the assisted reproductive technologies or the pathogenesis of certain diseases, where animals can be used as models for human diseases (like cancer, degenerative diseases or fertility), and even as a guarantee of public health. Bridging Human, Animal, and Environmental health, the holistic and integrative “One Health” concept intimately associates the developments within those fields, projecting its advancements into practice. This book series aims to tackle various animal-related medicine and sciences fields, providing thematic volumes consisting of high-quality significant research directed to researchers and postgraduates. It aims to give us a glimpse into the new accomplishments in the Veterinary Medicine and Science field. 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After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"19",title:"Animal Science",coverUrl:"https://cdn.intechopen.com/series_topics/covers/19.jpg",isOpenForSubmission:!0,annualVolume:11415,editor:{id:"259298",title:"Dr.",name:"Edward",middleName:null,surname:"Narayan",slug:"edward-narayan",fullName:"Edward Narayan",profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",biography:"Dr. Edward Narayan graduated with Ph.D. degree in Biology from the University of the South Pacific and pioneered non-invasive reproductive and stress endocrinology tools for amphibians - the novel development and validation of non-invasive enzyme immunoassays for the evaluation of reproductive hormonal cycle and stress hormone responses to environmental stressors. \nDr. Narayan leads the Stress Lab (Comparative Physiology and Endocrinology) at the University of Queensland. A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null},{id:"20",title:"Animal Nutrition",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",isOpenForSubmission:!0,annualVolume:11416,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"28",title:"Animal Reproductive Biology and Technology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/28.jpg",isOpenForSubmission:!0,annualVolume:11417,editor:{id:"177225",title:"Prof.",name:"Rosa Maria Lino Neto",middleName:null,surname:"Pereira",slug:"rosa-maria-lino-neto-pereira",fullName:"Rosa Maria Lino Neto Pereira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9wkQAC/Profile_Picture_1624519982291",biography:"Rosa Maria Lino Neto Pereira (DVM, MsC, PhD and) is currently a researcher at the Genetic Resources and Biotechnology Unit of the National Institute of Agrarian and Veterinarian Research (INIAV, Portugal). 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He is an academic staff member of the Department of Reproduction and Artificial Insemination, Selçuk University, Turkey. He manages several studies on sperms and embryos and is an editorial board member for several international journals. His studies include sperm cryobiology, in vitro fertilization, and embryo production in animals.",institutionString:"Selçuk University, Faculty of Veterinary Medicine",institution:null},{id:"90846",title:"Prof.",name:"Yusuf",middleName:null,surname:"Bozkurt",slug:"yusuf-bozkurt",fullName:"Yusuf Bozkurt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/90846/images/system/90846.jpg",biography:"Yusuf Bozkurt has a BSc, MSc, and Ph.D. from Ankara University, Turkey. He is currently a Professor of Biotechnology of Reproduction in the field of Aquaculture, İskenderun Technical University, Turkey. His research interests include reproductive biology and biotechnology with an emphasis on cryo-conservation. He is on the editorial board of several international peer-reviewed journals and has published many papers. Additionally, he has participated in many international and national congresses, seminars, and workshops with oral and poster presentations. He is an active member of many local and international organizations.",institutionString:"İskenderun Technical University",institution:{name:"İskenderun Technical University",country:{name:"Turkey"}}},{id:"61139",title:"Dr.",name:"Sergey",middleName:null,surname:"Tkachev",slug:"sergey-tkachev",fullName:"Sergey Tkachev",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61139/images/system/61139.png",biography:"Dr. Sergey Tkachev is a senior research scientist at the Institute of Fundamental Medicine and Biology, Kazan Federal University, Russia, and at the Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia. He received his Ph.D. in Molecular Biology with his thesis “Genetic variability of the tick-borne encephalitis virus in natural foci of Novosibirsk city and its suburbs.” His primary field is molecular virology with research emphasis on vector-borne viruses, especially tick-borne encephalitis virus, Kemerovo virus and Omsk hemorrhagic fever virus, rabies virus, molecular genetics, biology, and epidemiology of virus pathogens.",institutionString:"Russian Academy of Sciences",institution:{name:"Russian Academy of Sciences",country:{name:"Russia"}}},{id:"310962",title:"Dr.",name:"Amlan",middleName:"Kumar",surname:"Patra",slug:"amlan-patra",fullName:"Amlan Patra",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/310962/images/system/310962.jpg",biography:"Amlan K. Patra, FRSB, obtained a Ph.D. in Animal Nutrition from Indian Veterinary Research Institute, India, in 2002. He is currently an associate professor at West Bengal University of Animal and Fishery Sciences. He has more than twenty years of research and teaching experience. He held previous positions at the American Institute for Goat Research, The Ohio State University, Columbus, USA, and Free University of Berlin, Germany. His research focuses on animal nutrition, particularly ruminants and poultry nutrition, gastrointestinal electrophysiology, meta-analysis and modeling in nutrition, and livestock–environment interaction. He has authored around 175 articles in journals, book chapters, and proceedings. Dr. Patra serves on the editorial boards of several reputed journals.",institutionString:null,institution:{name:"West Bengal University of Animal and Fishery Sciences",country:{name:"India"}}},{id:"53998",title:"Prof.",name:"László",middleName:null,surname:"Babinszky",slug:"laszlo-babinszky",fullName:"László Babinszky",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/53998/images/system/53998.png",biography:"László Babinszky is Professor Emeritus, Department of Animal Nutrition Physiology, University of Debrecen, Hungary. He has also worked in the Department of Animal Nutrition, University of Wageningen, Netherlands; the Institute for Livestock Feeding and Nutrition (IVVO), Lelystad, Netherlands; the Agricultural University of Vienna (BOKU); the Institute for Animal Breeding and Nutrition, Austria; and the Oscar Kellner Research Institute for Animal Nutrition, Rostock, Germany. In 1992, Dr. Babinszky obtained a Ph.D. in Animal Nutrition from the University of Wageningen. His main research areas are swine and poultry nutrition. He has authored more than 300 publications (papers, book chapters) and edited four books and fourteen international conference proceedings.",institutionString:"University of Debrecen",institution:{name:"University of Debrecen",country:{name:"Hungary"}}},{id:"201830",title:"Dr.",name:"Fernando",middleName:"Sanchez",surname:"Davila",slug:"fernando-davila",fullName:"Fernando Davila",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/201830/images/5017_n.jpg",biography:"I am a professor at UANL since 1988. My research lines are the development of reproductive techniques in small ruminants. We also conducted research on sexual and social behavior in males.\nI am Mexican and study my professional career as an engineer in agriculture and animal science at UANL. Then take a masters degree in science in Germany (Animal breeding). Take a doctorate in animal science at the UANL.",institutionString:null,institution:{name:"Universidad Autónoma de Nuevo León",country:{name:"Mexico"}}},{id:"309250",title:"Dr.",name:"Miguel",middleName:null,surname:"Quaresma",slug:"miguel-quaresma",fullName:"Miguel Quaresma",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309250/images/9059_n.jpg",biography:"Miguel Nuno Pinheiro Quaresma was born on May 26, 1974 in Dili, Timor Island. He is married with two children: a boy and a girl, and he is a resident in Vila Real, Portugal. He graduated in Veterinary Medicine in August 1998 and obtained his Ph.D. degree in Veterinary Sciences -Clinical Area in February 2015, both from the University of Trás-os-Montes e Alto Douro. He is currently enrolled in the Alternative Residency of the European College of Animal Reproduction. He works as a Senior Clinician at the Veterinary Teaching Hospital of UTAD (HVUTAD) with a role in clinical activity in the area of livestock and equine species as well as to support teaching and research in related areas. He teaches as an Invited Professor in Reproduction Medicine I and II of the Master\\'s in Veterinary Medicine degree at UTAD. Currently, he holds the position of Chairman of the Portuguese Buiatrics Association. He is a member of the Consultive Group on Production Animals of the OMV. He has 19 publications in indexed international journals (ISIS), as well as over 60 publications and oral presentations in both Portuguese and international journals and congresses.",institutionString:"University of Trás-os-Montes and Alto Douro",institution:{name:"University of Trás-os-Montes and Alto Douro",country:{name:"Portugal"}}},{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",country:{name:"Portugal"}}},{id:"283019",title:"Dr.",name:"Oudessa",middleName:null,surname:"Kerro Dego",slug:"oudessa-kerro-dego",fullName:"Oudessa Kerro Dego",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/283019/images/system/283019.png",biography:"Dr. Kerro Dego is a veterinary microbiologist with training in veterinary medicine, microbiology, and anatomic pathology. Dr. Kerro Dego is an assistant professor of dairy health in the department of animal science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. He received his D.V.M. (1997), M.S. (2002), and Ph.D. (2008) degrees in Veterinary Medicine, Animal Pathology and Veterinary Microbiology from College of Veterinary Medicine, Addis Ababa University, Ethiopia; College of Veterinary Medicine, Utrecht University, the Netherlands and Western College of Veterinary Medicine, University of Saskatchewan, Canada respectively. He did his Postdoctoral training in microbial pathogenesis (2009 - 2015) in the Department of Animal Science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. Dr. Kerro Dego’s research focuses on the prevention and control of infectious diseases of farm animals, particularly mastitis, improving dairy food safety, and mitigation of antimicrobial resistance. Dr. Kerro Dego has extensive experience in studying the pathogenesis of bacterial infections, identification of virulence factors, and vaccine development and efficacy testing against major bacterial mastitis pathogens. Dr. Kerro Dego conducted numerous controlled experimental and field vaccine efficacy studies, vaccination, and evaluation of immunological responses in several species of animals, including rodents (mice) and large animals (bovine and ovine).",institutionString:"University of Tennessee at Knoxville",institution:{name:"University of Tennessee at Knoxville",country:{name:"United States of America"}}},{id:"251314",title:"Dr.",name:"Juan Carlos",middleName:null,surname:"Gardón",slug:"juan-carlos-gardon",fullName:"Juan Carlos Gardón",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/251314/images/system/251314.jpeg",biography:"Juan Carlos Gardón Poggi received University degree from the Faculty of Agrarian Science in Argentina, in 1983. Also he received Masters Degree and PhD from Córdoba University, Spain. He is currently a Professor at the Catholic University of Valencia San Vicente Mártir, at the Department of Medicine and Animal Surgery. He teaches diverse courses in the field of Animal Reproduction and he is the Director of the Veterinary Farm. He also participates in academic postgraduate activities at the Veterinary Faculty of Murcia University, Spain. His research areas include animal physiology, physiology and biotechnology of reproduction either in males or females, the study of gametes under in vitro conditions and the use of ultrasound as a complement to physiological studies and development of applied biotechnologies. Routinely, he supervises students preparing their doctoral, master thesis or final degree projects.",institutionString:"Catholic University of Valencia San Vicente Mártir, Spain",institution:null},{id:"125292",title:"Dr.",name:"Katy",middleName:null,surname:"Satué Ambrojo",slug:"katy-satue-ambrojo",fullName:"Katy Satué Ambrojo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/125292/images/system/125292.jpeg",biography:"Katy Satué Ambrojo received her Veterinary Medicine degree, Master degree in Equine Technology and doctorate in Veterinary Medicine from the Faculty of Veterinary, CEU-Cardenal Herrera University in Valencia, Spain. She is a Full Professor at the Department of Medicine and Animal Surgery at the same University. She developed her research activity in the field of Endocrinology, Hematology, Biochemistry and Immunology of horses. She is a scientific reviewer of several international journals : American Journal of Obstetrics and Gynecology, Comparative Clinical Pathology, Veterinary Clinical Pathology, Journal of Equine Veterinary Science, Reproduction in Domestic Animals, Research Veterinary Science, Brazilian Journal of Medical and Biological Research, Livestock Production Science and Theriogenology. Since 2014, she has been the Head of the Clinical Analysis Laboratory of the Hospital Clínico Veterinario from the Faculty of Veterinary, CEU-Cardenal Herrera University.",institutionString:"CEU-Cardenal Herrera University",institution:{name:"CEU Cardinal Herrera University",country:{name:"Spain"}}},{id:"309529",title:"Dr.",name:"Albert",middleName:null,surname:"Rizvanov",slug:"albert-rizvanov",fullName:"Albert Rizvanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309529/images/9189_n.jpg",biography:'Albert A. Rizvanov is a Professor and Director of the Center for Precision and Regenerative Medicine at the Institute of Fundamental Medicine and Biology, Kazan Federal University (KFU), Russia. He is the Head of the Center of Excellence “Regenerative Medicine” and Vice-Director of Strategic Academic Unit \\"Translational 7P Medicine\\". Albert completed his Ph.D. at the University of Nevada, Reno, USA and Dr.Sci. at KFU. He is a corresponding member of the Tatarstan Academy of Sciences, Russian Federation. Albert is an author of more than 300 peer-reviewed journal articles and 22 patents. He has supervised 11 Ph.D. and 2 Dr.Sci. dissertations. Albert is the Head of the Dissertation Committee on Biochemistry, Microbiology, and Genetics at KFU.\nORCID https://orcid.org/0000-0002-9427-5739\nWebsite https://kpfu.ru/Albert.Rizvanov?p_lang=2',institutionString:"Kazan Federal University",institution:{name:"Kazan Federal University",country:{name:"Russia"}}},{id:"210551",title:"Dr.",name:"Arbab",middleName:null,surname:"Sikandar",slug:"arbab-sikandar",fullName:"Arbab Sikandar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210551/images/system/210551.jpg",biography:"Dr. Arbab Sikandar, PhD, M. Phil, DVM was born on April 05, 1981. He is currently working at the College of Veterinary & Animal Sciences as an Assistant Professor. He previously worked as a lecturer at the same University. \nHe is a Member/Secretory of Ethics committee (No. CVAS-9377 dated 18-04-18), Member of the QEC committee CVAS, Jhang (Regr/Gen/69/873, dated 26-10-2017), Member, Board of studies of Department of Basic Sciences (No. CVAS. 2851 Dated. 12-04-13, and No. CVAS, 9024 dated 20/11/17), Member of Academic Committee, CVAS, Jhang (No. CVAS/2004, Dated, 25-08-12), Member of the technical committee (No. CVAS/ 4085, dated 20,03, 2010 till 2016).\n\nDr. Arbab Sikandar contributed in five days hands-on-training on Histopathology at the Department of Pathology, UVAS from 12-16 June 2017. He received a Certificate of appreciation for contributions for Popularization of Science and Technology in the Society on 17-11-15. He was the resource person in the lecture series- ‘scientific writing’ at the Department of Anatomy and Histology, UVAS, Lahore on 29th October 2015. He won a full fellowship as a principal candidate for the year 2015 in the field of Agriculture, EICA, Egypt with ref. to the Notification No. 12(11) ACS/Egypt/2014 from 10 July 2015 to 25th September 2015.; he received a grant of Rs. 55000/- as research incentives from Director, Advanced Studies and Research, UVAS, Lahore upon publications of research papers in IF Journals (DR/215, dated 19-5-2014.. He obtained his PhD by winning a HEC Pakistan indigenous Scholarship, ‘Ph.D. fellowship for 5000 scholars – Phase II’ (2av1-147), 17-6/HEC/HRD/IS-II/12, November 15, 2012. \n\nDr. Sikandar is a member of numerous societies: Registered Veterinary Medical Practitioner (life member) and Registered Veterinary Medical Faculty of Pakistan Veterinary Medical Council. The Registration code of PVMC is RVMP/4298 and RVMF/ 0102.; Life member of the University of Veterinary and Animal Sciences, Lahore, Alumni Association with S# 664, dated: 6-4-12. ; Member 'Vets Care Organization Pakistan” with Reference No. VCO-605-149, dated 05-04-06. :Member 'Vet Crescent” (Society of Animal Health and Production), UVAS, Lahore.",institutionString:"University of Veterinary & Animal Science",institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}},{id:"311663",title:"Dr.",name:"Prasanna",middleName:null,surname:"Pal",slug:"prasanna-pal",fullName:"Prasanna Pal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311663/images/13261_n.jpg",biography:null,institutionString:null,institution:{name:"National Dairy Research Institute",country:{name:"India"}}},{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",country:{name:"United Kingdom"}}},{id:"283315",title:"Prof.",name:"Samir",middleName:null,surname:"El-Gendy",slug:"samir-el-gendy",fullName:"Samir El-Gendy",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRduYQAS/Profile_Picture_1606215849748",biography:"Samir El-Gendy is a Professor of anatomy and embryology at the faculty of veterinary medicine, Alexandria University, Egypt. Samir obtained his PhD in veterinary science in 2007 from the faculty of veterinary medicine, Alexandria University and has been a professor since 2017. Samir is an author on 24 articles at Scopus and 12 articles within local journals and 2 books/book chapters. His research focuses on applied anatomy, imaging techniques and computed tomography. Samir worked as a member of different local projects on E-learning and he is a board member of the African Association of Veterinary Anatomists and of anatomy societies and as an associated author at local and international journals. Orcid: https://orcid.org/0000-0002-6180-389X",institutionString:null,institution:{name:"Alexandria University",country:{name:"Egypt"}}},{id:"246149",title:"Dr.",name:"Valentina",middleName:null,surname:"Kubale",slug:"valentina-kubale",fullName:"Valentina Kubale",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246149/images/system/246149.jpg",biography:"Valentina Kubale is Associate Professor of Veterinary Medicine at the Veterinary Faculty, University of Ljubljana, Slovenia. Since graduating from the Veterinary faculty she obtained her PhD in 2007, performed collaboration with the Department of Pharmacology, University of Copenhagen, Denmark. She continued as a post-doctoral fellow at the University of Copenhagen with a Lundbeck foundation fellowship. She is the editor of three books and author/coauthor of 23 articles in peer-reviewed scientific journals, 16 book chapters, and 68 communications at scientific congresses. Since 2008 she has been the Editor Assistant for the Slovenian Veterinary Research journal. She is a member of Slovenian Biochemical Society, The Endocrine Society, European Association of Veterinary Anatomists and Society for Laboratory Animals, where she is board member.",institutionString:"University of Ljubljana",institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"258334",title:"Dr.",name:"Carlos Eduardo",middleName:null,surname:"Fonseca-Alves",slug:"carlos-eduardo-fonseca-alves",fullName:"Carlos Eduardo Fonseca-Alves",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/258334/images/system/258334.jpg",biography:"Dr. Fonseca-Alves earned his DVM from Federal University of Goias – UFG in 2008. He completed an internship in small animal internal medicine at UPIS university in 2011, earned his MSc in 2013 and PhD in 2015 both in Veterinary Medicine at Sao Paulo State University – UNESP. Dr. Fonseca-Alves currently serves as an Assistant Professor at Paulista University – UNIP teaching small animal internal medicine.",institutionString:null,institution:{name:"Universidade Paulista",country:{name:"Brazil"}}},{id:"245306",title:"Dr.",name:"María Luz",middleName:null,surname:"Garcia Pardo",slug:"maria-luz-garcia-pardo",fullName:"María Luz Garcia Pardo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/245306/images/system/245306.png",biography:"María de la Luz García Pardo is an agricultural engineer from Universitat Politècnica de València, Spain. She has a Ph.D. in Animal Genetics. Currently, she is a lecturer at the Agrofood Technology Department of Miguel Hernández University, Spain. Her research is focused on genetics and reproduction in rabbits. The major goal of her research is the genetics of litter size through novel methods such as selection by the environmental sensibility of litter size, with forays into the field of animal welfare by analysing the impact on the susceptibility to diseases and stress of the does. Details of her publications can be found at https://orcid.org/0000-0001-9504-8290.",institutionString:null,institution:{name:"Miguel Hernandez University",country:{name:"Spain"}}},{id:"350704",title:"M.Sc.",name:"Camila",middleName:"Silva Costa",surname:"Ferreira",slug:"camila-ferreira",fullName:"Camila Ferreira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/350704/images/17280_n.jpg",biography:"Graduated in Veterinary Medicine at the Fluminense Federal University, specialist in Equine Reproduction at the Brazilian Veterinary Institute (IBVET) and Master in Clinical Veterinary Medicine and Animal Reproduction at the Fluminense Federal University. She has experience in analyzing zootechnical indices in dairy cattle and organizing events related to Veterinary Medicine through extension grants. I have experience in the field of diagnostic imaging and animal reproduction in veterinary medicine through monitoring and scientific initiation scholarships. I worked at the Equus Central Reproduction Equine located in Santo Antônio de Jesus – BA in the 2016/2017 breeding season. I am currently a doctoral student with a scholarship from CAPES of the Postgraduate Program in Veterinary Medicine (Pathology and Clinical Sciences) at the Federal Rural University of Rio de Janeiro (UFRRJ) with a research project with an emphasis on equine endometritis.",institutionString:null,institution:null},{id:"41319",title:"Prof.",name:"Lung-Kwang",middleName:null,surname:"Pan",slug:"lung-kwang-pan",fullName:"Lung-Kwang Pan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41319/images/84_n.jpg",biography:null,institutionString:null,institution:null},{id:"201721",title:"Dr.",name:"Beatrice",middleName:null,surname:"Funiciello",slug:"beatrice-funiciello",fullName:"Beatrice Funiciello",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/201721/images/11089_n.jpg",biography:"Graduated from the University of Milan in 2011, my post-graduate education included CertAVP modules mainly on equines (dermatology and internal medicine) and a few on small animal (dermatology and anaesthesia) at the University of Liverpool. 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