Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
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This achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
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We are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
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Thank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
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\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{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"}]},book:{item:{type:"book",id:"10549",leadTitle:null,fullTitle:"Preclinical Animal Modeling in Medicine",title:"Preclinical Animal Modeling in Medicine",subtitle:null,reviewType:"peer-reviewed",abstract:"The results of preclinical animal research have been successfully implemented in various medical and biological practices. The use of animals in medicine is based on significant anatomical, physiological, and molecular similarities between humans and animals. Particularly, mammals that have vast biological commonalities with humans represent not only a valuable model to explore the mechanisms of varied human diseases, but also to define new diagnostic and treatment strategies. This book covers broad but important aspects of animal modeling for scientific medicine as well as for translational systems and biological sciences. Alternative methods such as cell culture and in vitro experiments that do not require the sacrifice of an animal are encouraged for scientific and medical studies.",isbn:"978-1-83968-805-8",printIsbn:"978-1-83968-804-1",pdfIsbn:"978-1-83968-806-5",doi:"10.5772/intechopen.92923",price:139,priceEur:155,priceUsd:179,slug:"preclinical-animal-modeling-in-medicine",numberOfPages:304,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"9604117cecaa0ae107ab2d03a4463148",bookSignature:"Enkhsaikhan Purevjav, Joseph F. Pierre and Lu Lu",publishedDate:"March 9th 2022",coverURL:"https://cdn.intechopen.com/books/images_new/10549.jpg",numberOfDownloads:2493,numberOfWosCitations:0,numberOfCrossrefCitations:3,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:7,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:10,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 15th 2020",dateEndSecondStepPublish:"December 2nd 2020",dateEndThirdStepPublish:"January 31st 2021",dateEndFourthStepPublish:"April 21st 2021",dateEndFifthStepPublish:"June 20th 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"231585",title:"Prof.",name:"Enkhsaikhan",middleName:null,surname:"Purevjav",slug:"enkhsaikhan-purevjav",fullName:"Enkhsaikhan Purevjav",profilePictureURL:"https://mts.intechopen.com/storage/users/231585/images/system/231585.jpg",biography:"Dr. Enkhsaikhan Purevjav earned her MD from the Leningrad Pediatric Medical Institute (LMPI), Russia in 1989, followed by an internship and residency in pediatrics at the Mongolian National Medical University, a fellowship in pediatric cardiology at LPMI, and a Ph.D. in Medical Genetics and Molecular Biology from Shimane Medical University, Japan. Dr. Purevjav joined Baylor College of Medicine and Texas Children’s Hospital as a postdoctoral trainee and instructor and then Cincinnati Children’s Hospital Medical Center as an assistant professor. She currently works as an associate professor at the University of Tennessee Health Science Center where she continues to study the genetics of heart diseases, specifically focusing on pediatric cardiomyopathies and arrhythmias.",institutionString:"University of Tennessee Health Science Center",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"University of Tennessee Health Science Center",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"337466",title:"Assistant Prof.",name:"Joseph F.",middleName:null,surname:"Pierre",slug:"joseph-f.-pierre",fullName:"Joseph F. Pierre",profilePictureURL:"https://mts.intechopen.com/storage/users/337466/images/system/337466.jpg",biography:"Dr. Joseph F. Pierre is currently an Assistant Professor of Nutritional Sciences and Surgery, University of Wisconsin-Madison. The Pierre lab addresses a range of basic, translational, and clinical research questions focused on the gastrointestinal microbiome, nutrition, and gut physiology and disease. Dr. Pierre utilizes experimental models that include bariatric surgery, parenteral and enteral nutrition, gnotobiotics, and organoid approaches. Where relevant, his research examines microbiome community composition and function to investigate host-microbial interactions. Dr. Pierre received his BS in Natural Science and Ph.D. in Nutritional Sciences from the University of Wisconsin-Madison before completing a postdoc fellowship in Gastroenterology, Hepatology, and Nutrition at the University of Chicago. He holds an adjunct faculty position at the University of Tennessee Health Science Center within the College of Medicine.",institutionString:"University of Tennessee Health Science Center",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Tennessee Health Science Center",institutionURL:null,country:{name:"United States of America"}}},coeditorTwo:{id:"346043",title:"Prof.",name:"Lu",middleName:null,surname:"Lu",slug:"lu-lu",fullName:"Lu Lu",profilePictureURL:"https://mts.intechopen.com/storage/users/346043/images/system/346043.png",biography:"Dr. Lu Lu is a professor in the Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center (UTHSC). His research focuses on the examination of genetic effects on complex traits. He and his colleagues have developed large resources for the study of systems genetics that include the largest mouse genetic reference population, which includes BXD recombinant inbred lines, high-density genotypes, thousands of phenotypes, hundreds of transcriptomic data sets, and whole-genome sequence for all 152 inbred BXD strains. All these resources provide great power for genetic analysis of complex traits and are being used by many researchers for their studies of polygenetic diseases. As Principal Investigator, he has been funded by seven NIH R01 grants and has published ~200 science papers within the last seventeen years.",institutionString:"University of Tennessee Health Science Center",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Tennessee Medical Center",institutionURL:null,country:{name:"United States of America"}}},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"694",title:"Genetic Engineering",slug:"engineering-biomedical-engineering-genetic-engineering"}],chapters:[{id:"76560",title:"Recombinant Inbred Mice as Models for Experimental Precision Medicine and Biology",doi:"10.5772/intechopen.96173",slug:"recombinant-inbred-mice-as-models-for-experimental-precision-medicine-and-biology",totalDownloads:176,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Recombinant inbred rodents form immortal genome-types that can be resampled deeply at many stages, in both sexes, and under multiple experimental conditions to model genome-environment interactions and to test genome-phenome predictions. This allows for experimental precision medicine, for which sophisticated causal models of complex interactions among DNA variants, phenotype variants at many levels, and innumerable environmental factors are required. Large families and populations of isogenic lines of mice and rats are now available and have been used across fields of biology. We will use the BXD recombinant inbred family and their derived diallel cross population as an example for predictive, experimental precision medicine and biology.",signatures:"David G. Ashbrook and Lu Lu",downloadPdfUrl:"/chapter/pdf-download/76560",previewPdfUrl:"/chapter/pdf-preview/76560",authors:[{id:"337602",title:"Assistant Prof.",name:"David G.",surname:"Ashbrook",slug:"david-g.-ashbrook",fullName:"David G. Ashbrook"},{id:"337603",title:"Prof.",name:"Lu",surname:"Lu",slug:"lu-lu",fullName:"Lu Lu"}],corrections:null},{id:"80284",title:"Parenteral Nutrition Modeling and Research Advances",doi:"10.5772/intechopen.101692",slug:"parenteral-nutrition-modeling-and-research-advances",totalDownloads:84,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Parenteral nutrition (PN) provides nutritional support intravenously to individuals who have gastrointestinal (GI) failure or contraindication to enteral feeding. Since the initial development of PN, researchers have developed specialized formulas with complete macronutrients, micronutrients, vitamins, minerals, and electrolytes to support patients’ metabolic needs. These formulas prevent malnutrition and optimize patient health, especially under long-term feeding circumstances. Although PN is commonly used and essential in preterm and malnourished patients, complications associated with PN feeding include gastrointestinal defects, infection, and other metabolic abnormalities such as liver injury and brain related disorders. In this chapter, we highlight an overview of PN and its association with abnormalities of microbiome composition as well as with gastrointestinal (GI), immune, hepatic, and neuronal disfunction. Within the gut, PN influences the number and composition of gut-associated lymphoid tissue (GALT) cells, altering adaptive immune responses. PN also modulates intestinal epithelium cell turnover, secretions, and gut barrier function, as well as the composition of the intestinal microbiome leading to changes in gut permeability. Collectively, these changes result in increased susceptibility to infection and injury. Here, we highlight animal models used to examine parenteral nutrition, changes that occur to the major organ systems, and recent advancement in using enteric nervous system (ENS) neuropeptides or microbially derived products during PN, which may improve GI, immune cell, hepatic, and neuronal function.",signatures:"Roshan Kumari, Lydia M. Henry and Joseph F. Pierre",downloadPdfUrl:"/chapter/pdf-download/80284",previewPdfUrl:"/chapter/pdf-preview/80284",authors:[{id:"337466",title:"Assistant Prof.",name:"Joseph F.",surname:"Pierre",slug:"joseph-f.-pierre",fullName:"Joseph F. Pierre"},{id:"427563",title:"Ms.",name:"Lydia M.",surname:"Henry",slug:"lydia-m.-henry",fullName:"Lydia M. Henry"},{id:"427564",title:"Mrs.",name:"Roshan",surname:"Kumari",slug:"roshan-kumari",fullName:"Roshan Kumari"}],corrections:null},{id:"75629",title:"Gut Feeding the Brain: Drosophila Gut an Animal Model for Medicine to Understand Mechanisms Mediating Food Preferences",doi:"10.5772/intechopen.96503",slug:"gut-feeding-the-brain-em-drosophila-em-gut-an-animal-model-for-medicine-to-understand-mechanisms-med",totalDownloads:358,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Fruit fly, Drosophila melanogaster is a most powerful animal model for exploring fundamental biological processes and modeling molecular and cellular aspects of human diseases. It provides the flexibility and tool box with which scientists can experimentally manipulate and study behavior as well as gene expression in specific, defined population of cells in their normal tissue contexts. The utility and increasing value of a sophisticated genetic system of flies, the tool box available for studying physiological function, functional imaging, neural circuitry from gut to brain, taste receptors expression and controlling gene expression by determining the specific cells in the intestine, makes fly gut the most useful tissue for studying the regulation of feeding behavior under changing internal state. To understand the intestine and its connectivity with the brain, Drosophila has proved an ideal model organism for studying gut brain axis aspects of human metabolic diseases. Various markers and fly lines are available to characterize the expression of transgenes in the intestine. The newly generated genetic tools aim to streamline the design of experiments to target specific cells in intestine for genetic manipulations based on their type and location within physiologically specialized intestinal regions. This chapter will be useful for understanding post-ingestive sensing system that mediate food preferences and to investigate fundamental biological processes and model human diseases at the level of single cells in the fly gut. Furthermore, the utility of adult fly gut can be extended to the study of dietary and environmental factors relevant to health and disease by screening for cells and micro circuits stimulated by internal state or the consumption of various nutrients.",signatures:"Zoha Sadaqat, Shivam Kaushik and Pinky Kain",downloadPdfUrl:"/chapter/pdf-download/75629",previewPdfUrl:"/chapter/pdf-preview/75629",authors:[{id:"306728",title:"Dr.",name:"Pinky",surname:"Kain",slug:"pinky-kain",fullName:"Pinky Kain"},{id:"335402",title:"Dr.",name:"Zoha",surname:"Sadaqat",slug:"zoha-sadaqat",fullName:"Zoha Sadaqat"},{id:"345539",title:"Mr.",name:"Shivam",surname:"Kaushik",slug:"shivam-kaushik",fullName:"Shivam Kaushik"}],corrections:null},{id:"75702",title:"Duchenne Muscular Dystrophy Animal Models",doi:"10.5772/intechopen.96738",slug:"duchenne-muscular-dystrophy-animal-models",totalDownloads:257,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Duchenne muscular dystrophy is a complex and severe orphan disease. It develops when the organism lacks the expression of dystrophin - a large structural protein. Dystrophin is transcribed from the largest gene in the human genome. At the moment, there is no cure available. Dozens of groups all over the world search for cure. Animal models are an important component of both the fundamental research and therapy development. Many animal models reproducing the features of disease were created and actively used since the late 80’s until present. The species diversity spans from invertebrates to primates and the genetic diversity of these models spans from single mutations to full gene deletions. The models are often non-interchangeable; while one model may be used for particular drug design it may be useless for another. Here we describe existing models, discuss their advantages and disadvantages and potential applications for research and therapy development.",signatures:"Tatiana V. Egorova, Ivan I. Galkin, Yulia V. Ivanova and Anna V. Polikarpova",downloadPdfUrl:"/chapter/pdf-download/75702",previewPdfUrl:"/chapter/pdf-preview/75702",authors:[{id:"340316",title:"M.Sc.",name:"Tatiana V.",surname:"Egorova",slug:"tatiana-v.-egorova",fullName:"Tatiana V. Egorova"},{id:"340335",title:"Dr.",name:"Anna V.",surname:"Polikarpova",slug:"anna-v.-polikarpova",fullName:"Anna V. Polikarpova"},{id:"340337",title:"Dr.",name:"Ivan I.",surname:"Galkin",slug:"ivan-i.-galkin",fullName:"Ivan I. Galkin"},{id:"346667",title:"MSc.",name:"Yulia V.",surname:"Ivanova",slug:"yulia-v.-ivanova",fullName:"Yulia V. Ivanova"}],corrections:null},{id:"79211",title:"Left Ventricular Noncompaction Cardiomyopathy: From Clinical Features to Animal Modeling",doi:"10.5772/intechopen.101085",slug:"left-ventricular-noncompaction-cardiomyopathy-from-clinical-features-to-animal-modeling",totalDownloads:143,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Cardiomyopathy or disease of the heart muscle involves abnormal enlargement and a thickened, stiff, or spongy-like appearance of the myocardium. As a result, the function of the myocardium is weakened and does not sufficiently pump blood throughout the body nor maintain a normal pumping rhythm, leading to heart failure. The main types of cardiomyopathies include dilated hypertrophic, restrictive, arrhythmogenic, and noncompaction cardiomyopathy. Abnormal trabeculations of the myocardium in the left ventricle are classified as left ventricular noncompaction cardiomyopathy (LVNC). Myocardial noncompaction most frequently is observed at the apex of the left ventricle and can be associated with chamber dilation or muscle hypertrophy, systolic or diastolic dysfunction, or both, or various forms of congenital heart disease. Animal models are incredibly important for uncovering the etiology and pathogenesis involved in this disease. This chapter will describe the clinical and pathological features of LVNC in humans and present the animal models that have been used for the study of the genetic basis and pathogenesis of this disease.",signatures:"Enkhsaikhan Purevjav, Michelle Chintanaphol, Buyan-Ochir Orgil, Nelly R. Alberson and Jeffrey A. Towbin",downloadPdfUrl:"/chapter/pdf-download/79211",previewPdfUrl:"/chapter/pdf-preview/79211",authors:[{id:"231585",title:"Prof.",name:"Enkhsaikhan",surname:"Purevjav",slug:"enkhsaikhan-purevjav",fullName:"Enkhsaikhan Purevjav"},{id:"345566",title:"Prof.",name:"Jeffrey A.",surname:"Towbin",slug:"jeffrey-a.-towbin",fullName:"Jeffrey A. Towbin"},{id:"425381",title:"B.Sc.",name:"Michelle",surname:"Chintanaphol",slug:"michelle-chintanaphol",fullName:"Michelle Chintanaphol"},{id:"425382",title:"Dr.",name:"Buyan-Ochir",surname:"Orgil",slug:"buyan-ochir-orgil",fullName:"Buyan-Ochir Orgil"},{id:"425383",title:"MSc.",name:"Nelly R.",surname:"Alberson",slug:"nelly-r.-alberson",fullName:"Nelly R. Alberson"}],corrections:null},{id:"76811",title:"Experimental Animal Models of Cerebral Ischemic Reperfusion Injury",doi:"10.5772/intechopen.97592",slug:"experimental-animal-models-of-cerebral-ischemic-reperfusion-injury",totalDownloads:50,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Restitution of blood flow in the ischemic region helps liberate cells from mortification in any tissue or organ. Reperfusion post cerebral ischemia worsen the condition and lead to “cerebral reperfusion injury”. In cerebral reperfusion injury, significant changes observed are infarct size, behavioural deficits, hematoma formation, inflammatory mediators, and oxidative stress markers representing the extent of brain injury. Experimental In vivo models mimicking pathological and neurological processes are key tools in researching cerebral reperfusion injury and potential therapeutic agents’ development. This review explains currently used In vivo models like middle cerebral artery occlusion model, emboli stroke model, two-vessel occlusion model of forebrain ischemia, four-vessel occlusion model of forebrain ischemia, photochemical stroke model, collagenase induced brain haemorrhage model, autologous whole blood induced haemorrhage model. This review provides contemplative facts to setup authentic and relevant animal models to study cerebral reperfusion injury.",signatures:"Prabhakar Orsu and Y. Srihari",downloadPdfUrl:"/chapter/pdf-download/76811",previewPdfUrl:"/chapter/pdf-preview/76811",authors:[{id:"341478",title:"Assistant Prof.",name:"Prabhakar",surname:"Orsu",slug:"prabhakar-orsu",fullName:"Prabhakar Orsu"},{id:"414970",title:"Dr.",name:"Y.",surname:"Srihari",slug:"y.-srihari",fullName:"Y. Srihari"}],corrections:null},{id:"76410",title:"Mouse Models of Acute Kidney Injury",doi:"10.5772/intechopen.97523",slug:"mouse-models-of-acute-kidney-injury",totalDownloads:428,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Acute Kidney Injury (AKI) is a poor prognosis in hospitalized patients that is associated with high degree of mortality. AKI is also a major risk factor for development of chronic kidney disease. Despite these serious complications associated with AKI there has not been a great amount of progress made over the last half-century. Here we have outlined and provided details on variety of mouse models of AKI. Some of the mouse models of AKI are renal pedicle clamping (ischemia reperfusion injury), Cisplatin induced nephrotoxicity, sepsis (LPS, cecal slurry, and cecal ligation and puncture), folic acid, and rhabdomyolysis. In this chapter we describe in detail the protocols that are used in our laboratories.",signatures:"Navjot Pabla, Yogesh Scindia, Joseph Gigliotti and Amandeep Bajwa",downloadPdfUrl:"/chapter/pdf-download/76410",previewPdfUrl:"/chapter/pdf-preview/76410",authors:[{id:"345349",title:"Associate Prof.",name:"Aman",surname:"Bajwa",slug:"aman-bajwa",fullName:"Aman Bajwa"},{id:"345350",title:"Dr.",name:"Navjot",surname:"Pabla",slug:"navjot-pabla",fullName:"Navjot Pabla"},{id:"345351",title:"Dr.",name:"Yogesh",surname:"Scindia",slug:"yogesh-scindia",fullName:"Yogesh Scindia"},{id:"351420",title:"Dr.",name:"Joseph",surname:"Gigliotti",slug:"joseph-gigliotti",fullName:"Joseph Gigliotti"}],corrections:null},{id:"75497",title:"Animal Pain Models for Spinal Cord Stimulation",doi:"10.5772/intechopen.96403",slug:"animal-pain-models-for-spinal-cord-stimulation",totalDownloads:241,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Spinal cord stimulation (SCS) is an electrical neuromodulation technique with proven effectiveness and safety for the treatment of intractable chronic pain in humans. Despite its widespread use, the mechanism of action is not fully understood. Animal models of chronic pain, particularly rodent-based, have been adapted to study the effect of SCS on pain-like behavior, as well as on the electrophysiology and molecular biology of neural tissues. This chapter reviews animal pain models for SCS, emphasizing on findings relevant to advancing our understanding of the mechanism of action of SCS, and highlighting the contribution of the animal model to advance clinical outcomes. The models described include those in which SCS has been coupled to neuropathic pain models in rats and sheep based on peripheral nerve injuries, including the chronic constriction injury (CCI) model and the spared nerve injury model (SNI). Other neuropathic pain models described are the spinal nerve ligation (SNL) for neuropathic pain of segmental origin, as well as the chemotherapy-induced and diabetes-induced peripheral neuropathy models. We also describe the use of SCS with inflammatory pain and ischemic pain models.",signatures:"Joseph M. Williams, Courtney A. Kelley, Ricardo Vallejo, David C. Platt and David L. Cedeño",downloadPdfUrl:"/chapter/pdf-download/75497",previewPdfUrl:"/chapter/pdf-preview/75497",authors:[{id:"337591",title:"Ph.D.",name:"David L.",surname:"Cedeño",slug:"david-l.-cedeno",fullName:"David L. Cedeño"},{id:"337596",title:"Dr.",name:"Ricardo",surname:"Vallejo",slug:"ricardo-vallejo",fullName:"Ricardo Vallejo"},{id:"346305",title:"Dr.",name:"Joseph M.",surname:"Williams",slug:"joseph-m.-williams",fullName:"Joseph M. Williams"},{id:"346306",title:"Ms.",name:"Courtney A.",surname:"Kelley",slug:"courtney-a.-kelley",fullName:"Courtney A. Kelley"},{id:"346307",title:"Mr.",name:"David C.",surname:"Platt",slug:"david-c.-platt",fullName:"David C. Platt"}],corrections:null},{id:"76040",title:"An Overview of Glaucoma: Bidirectional Translation between Humans and Pre-Clinical Animal Models",doi:"10.5772/intechopen.97145",slug:"an-overview-of-glaucoma-bidirectional-translation-between-humans-and-pre-clinical-animal-models",totalDownloads:255,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Glaucoma is a multifactorial, polygenetic disease with a shared outcome of loss of retinal ganglion cells and their axons, which ultimately results in blindness. The most common risk factor of this disease is elevated intraocular pressure (IOP), although many glaucoma patients have IOPs within the normal physiological range. Throughout disease progression, glial cells in the optic nerve head respond to glaucomatous changes, resulting in glial scar formation as a reaction to injury. This chapter overviews glaucoma as it affects humans and the quest to generate animal models of glaucoma so that we can better understand the pathophysiology of this disease and develop targeted therapies to slow or reverse glaucomatous damage. This chapter then reviews treatment modalities of glaucoma. Revealed herein is the lack of non-IOP-related modalities in the treatment of glaucoma. This finding supports the use of animal models in understanding the development of glaucoma pathophysiology and treatments.",signatures:"Sophie Pilkinton, T.J. Hollingsworth, Brian Jerkins and Monica M. Jablonski",downloadPdfUrl:"/chapter/pdf-download/76040",previewPdfUrl:"/chapter/pdf-preview/76040",authors:[{id:"342969",title:"Prof.",name:"Monica M.",surname:"Jablonski",slug:"monica-m.-jablonski",fullName:"Monica M. Jablonski"},{id:"342970",title:"Ms.",name:"Sophie",surname:"Pilkinton",slug:"sophie-pilkinton",fullName:"Sophie Pilkinton"},{id:"346686",title:"Dr.",name:"T.J.",surname:"Hollingsworth",slug:"t.j.-hollingsworth",fullName:"T.J. Hollingsworth"},{id:"349145",title:"Dr.",name:"Brian",surname:"Jerkins",slug:"brian-jerkins",fullName:"Brian Jerkins"}],corrections:null},{id:"75476",title:"An Overview of Age-Related Macular Degeneration: Clinical, Pre-Clinical Animal Models and Bidirectional Translation",doi:"10.5772/intechopen.96601",slug:"an-overview-of-age-related-macular-degeneration-clinical-pre-clinical-animal-models-and-bidirectiona",totalDownloads:356,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Age-related macular degeneration (AMD) is a multifactorial disease that results from a complex and unknown interplay among environmental, genetic, and epidemiologic factors. Risk factors include aging, family history, obesity, hypercholesterolemia, and hypertension, along with cigarette smoking, which is the most influential modifiable risk factor. Single nucleotide polymorphisms (SNPs) in numerous genes such as complement factor H (CFH) pose some of the known genetic risks. The pathophysiology in AMD is incompletely understood, but is known to involve oxidative stress, inflammation, dysregulated antioxidants, lipid metabolism, and angiogenesis. Animal models have been integral in expanding our knowledge of AMD pathology. AMD is classified as non-exudative or exudative. Because there is no perfect animal model that recapitulates all aspects of the human disease, rodents, rabbits, and non-human primates offer different advantages and disadvantages to serve as models for various aspects of the disease. Scientific advances have also allowed for the creation of polygenic pre-clinical models that may better represent the complexity of AMD, which will likely expand our knowledge of disease mechanisms and serve as platforms for testing new therapeutics. There have been, and there continues to be, many drugs in the pipeline to treat both exudative and non-exudative AMD. However, Food and Drug Administration (FDA)-approved therapies for exudative AMD that mainly target angiogenic growth factors are the only therapeutics currently being used in the clinics. There remains no FDA-approved therapy for the non-exudative form of this disease. This chapter contains a basic overview and classification of AMD and multiple animal models of AMD are highlighted. We include an overview of both current FDA-approved treatments and those in development. Lastly, we conclude with a summary of the important role of pre-clinical studies in the development of therapeutics for this highly prevalent disease.",signatures:"Jonathan Rho, Paul Percelay, Sophie Pilkinton, T.J. Hollingsworth, Ilyse Kornblau and Monica M. Jablonski",downloadPdfUrl:"/chapter/pdf-download/75476",previewPdfUrl:"/chapter/pdf-preview/75476",authors:[{id:"342969",title:"Prof.",name:"Monica M.",surname:"Jablonski",slug:"monica-m.-jablonski",fullName:"Monica M. Jablonski"},{id:"342970",title:"Ms.",name:"Sophie",surname:"Pilkinton",slug:"sophie-pilkinton",fullName:"Sophie Pilkinton"},{id:"346686",title:"Dr.",name:"T.J.",surname:"Hollingsworth",slug:"t.j.-hollingsworth",fullName:"T.J. Hollingsworth"},{id:"342971",title:"Mr.",name:"Jonathan",surname:"Rho",slug:"jonathan-rho",fullName:"Jonathan Rho"},{id:"346685",title:"Mr.",name:"Paul",surname:"Percelay",slug:"paul-percelay",fullName:"Paul Percelay"},{id:"346687",title:"Dr.",name:"Ilyse",surname:"Kornblau",slug:"ilyse-kornblau",fullName:"Ilyse Kornblau"}],corrections:null},{id:"77375",title:"Preclinical Models of Brucellar Spondylodiscitis",doi:"10.5772/intechopen.98754",slug:"preclinical-models-of-brucellar-spondylodiscitis",totalDownloads:145,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Brucellar spondylodiscitis, the most prevalent and significant osteoarticular presentation of human Brucellosis, is difficult to diagnose and usually yields irreversible neurologic deficits and spinal deformities. Relevant aspects of Brucella pathogenesis have been intensively investigated in preclinical models. Mice, rats, rabbits, and sheep are representing available models to induce Brucellosis. Evaluation of Brucellar spondylodiscitis may be performed using a large variety of methods, including plain radiography, computed tomography, magnetic resonance imaging, histological analysis, blood test, and bacteria culture. This chapter focuses on these preclinical models of Brucellar spondylodiscitis. 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1. Introduction
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Nanostructures are used in order to create specific nanodevices for the manipulation of biological systems at the molecular level, and this is what currently defines nanomedicine. So far, the integration of nanoparticles with biology has led to the development of diagnostic devices, contrast agents, advanced therapy applications, drug delivery therapy, and imaging approaches. Nanomedicine offers many advantages in everyday clinical practice, taking into consideration the non‐invasive approach of the samples used, fast reaction times, specificity, and sensitivity that nanoparticles can offer. Therein, these advantages will lead us closer to the construction of point‐of‐care mobile nanodevices. In the context of in vitro nanodiagnostics, nanotechnology allows the construction of novel sensors and in vitro tests, in order to improve the sensitivity of existing tests, to develop new diagnostic test platforms, and to allow point‐of‐care applications. Thus, Nanodiagnostics is defined as the application of nanotechnology for the diagnosis of a dysfunction and/or disease in human, at the earliest stage possible, ideally at the level of a single cell. To achieve this goal, various types of nanotechnologies are currently being explored for use in nanodiagnostic applications. Furthermore, an increase in knowledge in basic research will be seen through the development of microscopic and spectroscopic techniques towards ultrahigh spatial resolution, molecular resolution, and ultrahigh sensitivity that will also help in the creation of advanced in situ diagnostics tools. More specifically, nanotechnology‐based diagnosis techniques offer great opportunities such as\n
Rapid diagnostic test, potentially in the doctor\'s office or bedside tests, for the initial diagnosis and treatment selection and treatment monitoring to the doctor/hospital or even at home.
The early detection of several diseases in comparison with the efficiency of current techniques. The early detection is very important as it offers the opportunity for earlier diagnosis and thus more therapeutic opportunities.
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This chapter summarizes the nanostructures used in nanodiagnostic tests and their applications for the development of rapid diagnostic tests for point‐of‐care disease management and public health.
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2. Nanostructures used in nanodiagnostics
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The term nanostructures includes materials of <100 nm in size in at least one dimension. There are nanostructures in zero‐dimensional (0D), one‐dimensional, (1D), and two‐dimensional (2D) systems. The dimensions of nanostructures are advantageous for use in diagnostics because they are in the range of the size of various biomolecules such as nucleic acids, small proteins, and viruses. An in vitro diagnostic tool is always comprised of an element that is able to identify a biochemical change, activity or concentration of a specific molecule of biological importance in the solution of interest. In a nanobiosensor, a transducer is used to convert this biochemical signal into a quantifiable signal.
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The use of nanomaterials in the design of in vitro diagnostic systems is offering types of sensors that are characterized by specificity, sensitivity, and robustness. Several kinds of nanomaterials have found attractive applications in in vitro diagnostic tests, such as metallic nanoparticles, quantum dots (QDs), silica nanospheres, magnetic nanoparticles, which belong to the zero‐dimensional (0D) systems, carbon nanotubes (CNTs), silicon nanowires (SiNWs), nanopores, which belong to the one‐dimensional (1D) systems, and graphene, nanostructured surfaces, and metal films, which belong to the two‐dimensional (2D) systems.
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2.1. Metallic NPs
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Metals, especially gold and silver, have the advantageous ability to interact with external fields such as light, radiofrequency, and X‐rays. Under a specific wavelength, metals exhibit surface plasmon resonance (SPR), the oscillation of free electrons in a particle\'s surface; thus, they can successfully be combined with conventional methods such as colorimetry or absorption spectroscopy. A typical example of SPR biosensing consists of the liquid sample part and an immobilized ligand (e.g., an antibody) on an SPR‐active gold‐coated glass slide. This system can create a thin flow cell in which the sample will be able to flow in the aqueous solution, and when light (visible or near infrared) is projected through the glass slide and onto the gold surface at angles and wavelengths near the SPR condition, the optical reflectivity of the gold changes in a specific way when an actual interaction occurs between the sample and the ligand of the solid phase. The most frequent medical use of these NPs is the rapid tests, for example, pregnancy test kits, where gold nanoparticles are used as a color marker [1]. Moreover, metallic NPs are suitable for surface‐enhanced Raman spectroscopy (SERS), since they produce Raman signal. So, when molecules are in close proximity to a metal surface, they exhibit a dramatic augmentation in the electromagnetic field, yielding high Raman intensity. Thus, SERS surface biosensors are usually performed on Ag, Au, or Cu surfaces. SERS is an excellent assay for the sensitive and specific detection of low‐concentration molecules, for example, the detection of biomarkers for bacillus spores or the measurement of glucose after the appropriate chemical modifications of the SERS surfaces [2]. Another example is the molecular sentinels, which are comprised of metal NPs decorated with a Raman label‐conjugated stem‐loop DNA. Thus, when the DNA molecule is in close proximity to the metal surface, the Raman intensity is maintained high. In contrast, in the bound state, there is a disruption of the stem‐loop and the Raman label is no longer in close proximity to the metal. This approach was used to detect the gag gene of the HIV‐1 in PCR amplicons [3] and several single‐nucleotide polymorphisms (SNPs) such as BRCA1 gene of breast cancer, using plasmonic nanoprobes that detach from the Raman tag when the conjugated oligonucleotide is hybridized, thus decreasing the plasmonic effect and change the SERS [4].
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2.2. Quantum dots (QDs)
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In the field of in vitro applications, nanoparticles are mainly used as markers for biomolecules, since they have many optical advantages that make them suitable for several diagnostic assays such as PCR, for the construction of biochips or suitable for multiplexing, conversely to the traditional dyes used in every day clinical practice. To this end, inorganic fluorescent nanoparticles are being investigated such as semiconductor nanoparticles (quantum dots) or nanoparticles‐like nanophopsphors, resulting in an increase in sensitivity and specificity and the possible analysis of multiple analytes that offer opportunities of mass production [5]. Quantum dots, semiconductor nanocrystals coated with inorganic materials, are also currently used in the field of basic research of cell biology, and their use in clinical diagnostic tests is already under investigation with great progress as markers, especially in image‐guided techniques, and at the same time, some nanobiochip platforms are already in the market. More importantly, QDs are very efficient donors of energy compared to traditional organic dyes, especially dye acceptors in FRET‐based assays (fluorescence resonance energy transfer) [6].
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2.3. Silica nanospheres
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Just like QDs, inorganic dye‐loaded silica particles are characterized by good photostability, sharp emission peaks, and long‐lasting fluorescence lifetimes. They are appropriate for dispersion aqueous solutions, due to their hydrophilic surface. They are usually used to conjugate optical labels in order to increase the detection signal, such as organic or inorganic dye molecules (lanthanide‐based and ruthenium‐based) [7].
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2.4. Magnetic NPs
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Last but not least is the use of supermagnetic iron oxide nanoparticles (SPIOs), which are used for magnetic separation in several immunomagnetic applications such as cell sorting, nucleic acid extraction, purification, and detection of pathogens, cancer cells, and generally rare populations in a solution/sample [8].
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2.5. Carbon nanotubes or nanopores (CNTs–CNPs)
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There are a variety of challenges associated with the flow of liquids through carbon nanotubes and nanopores. These are small electrically insulated tubes or pores which can detect a single molecule when this passes through the tube or pore. The molecule\'s detection is based on the change of the ionic current of the electrolyte solution containing the molecules of interest, which results in a change of the electrical current (translocation event signal) [7]. The incorporation of biochips and nanofluidics with nanopores or nanotubes will be able to replace the existing sequencing approaches of DNA in the clinical practice, as each DNA base has unique molecular structure and thus a unique translocation event signal. To this aim, nanofluidic devices are developed that employ multiple measurements on single molecules to enhance the ability to size DNA molecules. Techniques to integrate membranes contain nanopores into microfluidic devices, which decrease noise and enable the design of networks containing nanopores.
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2.6. Silicon nanowires (SiNWs)
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Nanowires are currently believed to be unique and advantageous for the construction of a nanobiosensing device. Nanowires are nanoscale channels through which current is passed and can be constructed from carbon nanotubes, metal oxides or silicon, and they require high temperatures to be synthesized and are usually prepared on silicon wafers. Antibodies are usually used as detectors in the surface of the nanowire. Antibodies interact with the biological target of interest, and the conformational change results in a change in the current that passes through the nanowire, allowing a sensitive and specific detection. The use of nanowires in an array mode, where different antibodies are conjugated to each nanowire, allows the mass detection of different types of disease or the creation of a personalized molecular profile in one type of disease [7].
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2.7. Graphene, metal films and nanostructured surfaces
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Graphene, metal films, and nanostructured surfaces are all in the class of 2D nanostructures which are structures with one dimension of ∼100 nm in size. Their incorporation in nanodiagnostic is their use as racks in order to conjugate and immobilize ligands for targeted binding when the sample comes across them. They usually are sheets of a certain nanomaterial, which have special properties different from that of the corresponding bulk material. For example, metal films exhibit the same advantages with metal NPs, for example, the SPR effect, and thus, they are used in the construction of label‐free SPR biosensors. As for nanostructured surfaces, they are in reality electrodes with their surface linked with nanotubes or nanoparticles. Finally, graphene will offer great sensitivity in rapid diagnostic tests, since it is an incredibly stable one‐layer 2D surface of carbon atoms with unique optical and conductive properties [7].
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3. Nanotechnology‐on‐a‐chip or nanofluidics
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A nanobiochip is comprised of integrated biomolecules or biologically active artificial structures which are usually smaller than that of cell\'s. The chip contains microarrays, which are minitest sites, on a solid surface, and this allows for multiple tests to be carried out simultaneously. Therefore, identification of a specific molecular signature, which will be unique to the diagnosis, can be done through thousands of biochemical reactions being performed on the nanobiochip [9, 10].
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The identification and quantification of a variety of molecules will be permitted through the combination of nanotechnologies, such as nanofluids and nanobiosensors, with biochips, and this will lead to the generation of future in vitro diagnostic chip‐based devices. Nanofluidic structures have small fluidic conducts which means they are automatically applied in situations where you have extremely small quantities of the sample. This includes Coulter counting, analytical separations and determinations of biomolecules, such as proteins and DNA and facile handling of mass‐limited samples. Lab‐on‐a‐chip structures comprise one of the more promising tools of nanofluidics. The advance and production of lab‐on‐chip devices for PCR and other related techniques mean that nanofluidics have had a substantial impact in biotechnology, medicine, and clinical diagnostics. In nanofluidics, a chamber of up to a few hundred nanometers in size contains a liquid sample which is then manipulated and analyzed. As the volume of the samples are so small, this allows for a substantial reduction in the amount of sample needed for the analysis as well as allowing for the advantages of laminar flow conditions, high surface to volume rations, low concentrations, molecular confinement, and low heat capacity to be used. On the other hand, nanofluidics also generates new challenges in the device design and manufacture, the accurate control of flow and mixing, and the sensitivity of molecular detection, and they are starting to be used in many diagnostic and analytical devices [10, 11].
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An in vitro simple detection system can therefore be established, which allows hundreds of cantilever biosensors to be used simultaneously on the same array. A lab‐on‐a‐chip device could be produced through additional advances of this technique which include the complete integration with fluidic handling system, other analytical techniques and signal extraction electronic. The initial proposition, by Berger et al., was for a “laboratory‐on‐a‐tip” which described the potential combination of cantilever sensors with atomic force microscopy (AFM). In this proposed technique, a cantilever with a tip could examine and detect with nanometer resolution where the biochemical analysis is executed. Thus, in conclusion, an alternative PCR which has the potential to replace microarray detection techniques is offered through cantilever nanobiosensing for the identification of SNPs, oncogenes, viruses, bacteria, and a variety of other pathogens. Additionally, the most common in vitro application of SPR biosensor chip devices is defining the affinity parameters of biomolecular interactions, where a sensorgram is used to report the association and dissociation of the ligand and its binding partner, which is added once the ligand has been immobilized on the sensor chip. There are numerous advantages of using this technique in comparison with conventional methods for affinity measurement, and these include little material being required, it is very quick, and finally, no tracer is needed for labeling. The expanding field of proteomics has seen the most recent developments in SPR where it is combined with matrix‐assisted laser desorption/ionization time of flight mass spectrometry (MALDI‐TOF), and this permits the study of biomolecular interactions between molecules of which at least one is known. The interacting molecule cannot always be identified when a variety of proteins is used within the interaction study. However, using the MALDI‐TOF technique allows you to determine the molecule that interacts with the sensor from the mixture [10, 11].
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4. Applications of nanotechnology in in vitro nanodiagnostics
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Up to now, nanostructures are successfully incorporated to in vitro diagnostics for the construction of nanobiosensors and in vitro rapid diagnostic tests mainly in order to improve existing tests and make them more effective or create innovative diagnostic test approaches that will be able to be incorporated in point‐of‐care applications of every day clinical practice. Nanodiagnostic applications are currently focused on two main approaches, such as the use of nanoparticles as biomarkers and the development of novel nanosensors that incorporate various nanostructures, such as carbon nanotubes, lateral nanostructures or nanothin surface layers via labeled nanosensors or label‐free nanosensors. With the use of in vitro diagnostic tests based on nanotechnology, various clinical and research fields will be improved such as genotyping techniques, immunohistochemistry assays, detection of biomarkers, early cancer detection, and others. Below, we are going to describe some of these applications.
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4.1. Nanosensors for glucose monitoring
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The management of diabetes disease, besides the great progress in the maintenance of insulin, is still intriguing. In the current clinical practice, diabetes patients need to tolerate tandem blood samples in order to monitor blood glucose and therefore minimize the possibility of hyper‐ or hypoglycemia, together with the aftermaths. Thus, it is still now an essential task to design a management approach for the monitoring of blood glucose that is non‐invasive, fast, and sensitive. The use of nanotechnology for the fabrication of a rapid and portable diagnostic test offers the aforementioned advantages. However, it is difficult task to design the ideal test, since the ideal biosensor has to be small, low‐cost, with simple function, accurate in the measurement and of course portable. Furthermore, this future test will have to minimize the blood volume needed for the test and the possible contaminations and to assure the accuracy of the measurement. Even further, an implantable microfluidics biosensor could provide a more accurate management of in vivo glucose monitoring and insulin administration. Barone et al. [12] used solution‐phase optical single‐walled CNTs (SWCNTs) sensors which have a tunable near‐infrared (NIR) emission that responds to changes in the local dielectric function, but remains stable to permanent photobleaching. SWCNTs are integrated with beta‐D‐glucose sensing as a model system; for example, they are conjugated with glucose oxidase, an enzyme that degrades glucose molecules and ferricyanide a molecule that takes electrons from the NTs, quenching their capacity to glow under NIR. In order to test the in vivo capacity of the nanosensors, they implanted them in situ in a human skin tissue sample and excited with NIR. The results demonstrated that the higher the glucose concentration, the greater the fluorescence. Thus, the nanosensors were found able to modulate their emission in response to the adsorption of specific biomolecules, suggesting that nanoparticle optical sensors are an attractive solution for glucose monitoring [12]. However, such techniques that use glucose consumption turned out to have many disadvantages regarding the continuous glucose monitoring. Therefore, technique based on competitive affinity binding of glucose and subcutaneously implanted enzymatic electrochemical detection is being recently a very attractive approach, since they can be highly stable and low drift. For example, the use of a polysaccharide solution such as dextran conjugated to a glucose‐binding protein such as concanavalin A (Con A), which competitively binds glucose leading to reversible de‐cross linking of the dextran–Con A complex. In the unbound state, the changes in the fluorescence or viscosity of the solution can be detected. Alternatively, synthetic glucose‐responsive polymers have been recently fabricated from various research groups in order to substitute Con A, which is found to be cytotoxic and fast degradable. Huang et al. [13] fabricated a biocompatible, glucose‐specific polymer (PAA‐ran‐PAAPBA) in order to create a sensor based on the sensing principle of the viscosity detection changes due to affinity binding between glucose and (PAA‐ran‐PAAPBA). Microelectromechanical system (MEMS) technology was incorporated for the fabrication of the sensor device that allowed long‐term continuous glucose monitoring [14]. The device uses a magnetically responsive vibrating Parylene polymer microcantilever as sensing element, situated in a microchamber, which was filled by PAA‐ran‐PAAPBA. Glucose passes through the membrane and binds reversibly to (PAA‐ran‐PAAPBA) polymer, causing a viscosity alteration in the solution. The MEMS device was suggested as a subcutaneously implanted sensor for stable and reliable continuous monitoring of glucose in practical diabetes management [13].
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Recently, a type of miniaturized sensors called optodes has attracted the scientists’ attention. Nano‐optodes consist of a chemical that responds to an analyte, a polymer to immobilize the chemical transducer and instrumentation (optical fiber, light source, detector, and other electronics) [15]. They can be integrated with several optical measurement schemes such as reflection, absorption, evanescent wave, luminescence (fluorescence and phosphorescences) that is the most popular methodology, chemiluminescence and surface plasmon resonance. Balaconis et al. [16] used nanofiber fluorescent nano‐optodes in order to measure the dynamic changes of glucose concentrations based on the competitive binding between a hydrophobic boronic acid recognition molecule, a chromophore and glucose. The concentration change of glucose in the membrane was monitored by measuring the change of the optical signal. Nano‐optodes are proven to be functional both in vitro and in vivo and to be very sensitive, since they can detect even small molecules [15, 16].
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4.2. Detection of bacteria and viruses
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Nowadays, pathogen detection is performed using very sensitive techniques such as ELISA, PCR, and sequencing techniques. However, the aforementioned techniques are considered very expensive; they require excessive sample preparation and have long validation times with no early response; and they need expertise personnel to perform the test. Therefore, the advantageous optical, magnetic, electrical, and catalytic characteristics of nanomaterials can offer faster, more sensitive, specific, and cheaper diagnostic assays that no experts will be needed for their use, in order to detect microbial pathogenesis. Pathogens express on their membranes various molecules such as glyco‐, lipoproteins, glycopeptides, carbohydrates, and lipids. Thus, nanotechnology usually uses antibodies as targeting ligands for the development of various immunoassays. For example, gold and silver NPs have been broadly used for conjugation with affinity ligands, finding attractive applications as chemical sensors or even further for the generation of nanoscale arrays of pathogen‐targeting ligands. Moreover, NPs can also be conjugated with specific oligonucleotides sequences that bind pathogen nucleic acid sequences to generate colorimetric changes. Other nanoparticles including fluorescent QDs and CNTs have been used in various applications including DNA detection and the development of immunoassays for the detection of bacteria and viruses. Besides NPs based‐assays, miniaturized microfluidic system or lab‐on‐a‐chip (LOC) is a futuristic and attractive field of research for accurate and point of care management of microbial infections.
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Very recently, Wu et al. [17] fabricated a Microbead Quantum‐dots Detection System (MQDS) in order to identify and measure target DNAs of pathogenic microorganisms and substitute PCR amplifications. All reporter probes and internal control probes were conjugated with quantum dots that fluoresce at different emission wavelengths using the click reaction, in order to monitor the binding process by flow cytometry [17]. Zhang et al. [18] created an innovative microfluidic microbead array with QDs tags for HBV genotyping. This method detected in vitro‐transcribed RNA in serum samples with increased sensitivity of 1000 copies/mL of HBV virus. Thus, they were able to create a QDs‐based biochip of high specificity and sensitivity for virus genotyping based on DNA hybridization. This microfluidic device managed to incorporate the microarray technology with the advantages of QDs when used as fluorescent agents and thus suggested a microfluidic approach for the highly sensitive detection of virus DNA of analysis with the use of small sample amount and fast detection time [18]. Moreover, Fu et al. [19] used Raman reporter‐labeled AuNPs as SERS nanotags which target the HIV‐1 DNA marker. The oligonucleotide‐conjugated AuNPs were anchored in user‐friendly lateral flow (LF) strips that have been extensively used for point‐of‐care (POC) self‐diagnostics. They managed to analyze HIV‐1 DNA with high sensitivity by monitoring the characteristic of Raman peak intensity of the DNA‐conjugated AuNPs. The detection limit of these SERS‐based lateral flows was observed to be at least 1000 times more sensitive compared to colorimetric or fluorescent detection methods. These results demonstrate the potential feasibility of the proposed SERS‐based lateral flow assay to quantitatively detect a wide range of genetic diseases with high sensitivity [19]. Tsang et al. [20] used upconversion nanoparticles (UNPs), based on the upconversion phenomenon where the absorption of photons results in a shorter wavelength emission of light compared to the excitation wavelength. So far, the most common UNPs are the lanthanide Yb3+ to Er3+ ions as used in this study, where Yb3+ ions have the ability to convert to Er3+ ions under NIR light and emit at green, visible wavelengths. These UNPs are linked with AuNPs which are conjugated with oligonucleotide probes (AuNPs) targeting Ebola virus oligonucleotide, and this nanocomposite is anchored on a nanoporous alumina (NAAO) membrane. Taking into consideration that Ebola outbreaks are currently of great concern, it is essential to investigate the feasibility of detection nanodevices of into low‐cost, rapid, and with ultrasensitive detection of various pathogens, especially epidemic viruses [20].
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Besides DNA, antimicrobial peptides (AMPs) are promising affinity agents for the development of biosensors due to the possibility of recognizing a various pathogenic biomarkers (bacteria, fungi, toxins, viruses), in order to design biosensors that exhibit more specificity and sensitivity regarding the detection limits. In the bound state, the biosensor can be evaluated via electrochemical impedance and fluorescence spectroscopies. Mannoor et al. [21] fabricated an array electrobiosensor functionalized with the AMP magainin I on the surface of AuNPs, in order to detect pathogenic bacteria. When the specific reaction occurs between magainin I and the sample, dielectric alterations of the surface\'s properties are detected, a change that allows the selective detection of pathogenic Gram‐negative bacteria E. coli and Salmonella typhimurium related to the non‐pathogenic E. coli and the Gram‐positive species Listeria monocytogenes [21]. It is also possible to use synthetic peptides in order to maximize the selectivity like Lillehoj et al. [22] who designed a microelectromechanical sensor using two synthetic peptides (C16G2cys and G10KHc) for the detection of Streptococcus mutans and Pseudomonas aeruginosa. On the other hand, Cho and Irudayaraj [23], proposed an in situ immuno‐AuNP network‐based ELISA biosensor to detect pathogens with high sensitivity. The in situ ELISA biosensor was able to detect E. coli and S.typhimurium in real sample conditions within 2 h of inoculation pathogens at extremely low concentrations.
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As already mentioned, 2D nanostructures can offer great sensitivity in rapid diagnostic tests. Mevold et al. [24] used graphene–PDDA nanosheets absorbed with AuNPs. PDDA is a homopolymer for the dispersibility of graphene, since it charges positively the graphene and protects the solution from the aggregation of graphene. The positive charge of AuNPs/graphene–PDDA nanosheets serves to easily capture the negative charge of Staphylococcus aureus and small molecules (adenine) for SERS rapid detection [24]. Moreover, Li et al. [25] aimed to detect foodborne pathogens, such as Escherichia coli O157:H7, Salmonella enterica, Vibrio cholera, and Campylobacter jejuni, all at the same time using multiplex PCR and magnetic nanoparticle probes (MNPs). The MNPs were conjugated with streptavidin, immobilized in an oligonucleotide array and used in order to visualize the hybridization between the oligonucleotide array and the 5’ biotinylated single‐strand PCR products. Interestingly, the signal could be easily detected by naked eye or a microscope. The streptavidin–MNPs microarray detected 316 foodborne pathogens/mL and thus suggested as a sensitive, specific, and easy‐to‐use tool for the fast detection of foodborne pathogens in a modestly equipped laboratory, being an attractive approach for future rapid diagnostic tests [25].
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4.3. Nanotechnology in cancer diagnosis
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The incorporation of nanotechnology in cancer diagnosis is essential, since early detection of the disease can improve the chances of treatment. In addition, the reduction of the needed time for the nanotest will lead in more precise decision‐making in every day clinical practice and treatment costs.
\n
Up to now, several nanomaterials, such as AuNPs, semiconductor II–VI QDs, silicon nanowires (SNWs), carbon CNTs, and graphene, have been used in order to detect various cancer markers (proteins/peptides or DNA/RNA) in a sensitive and specific manner, especially when used for the construction of high‐performance nanobiosensors. For instance, FET‐SNWs have been used for the detection of several prostate cancer biomarkers, such as prostate‐specific antigen (PSA) at the level of fg/ml of PSA for monitoring prostate cancer and predicting the risk of early biochemical relapse and the prostate biomarker 8‐hydroxydeoxyguanosine (8‐OHdG) by using a SNWs functionalized with antibodies against 8‐OHdG [26]. PSA, prostate‐specific membrane antigen, platelet factor‐4, and interleukin‐6 prostate cancer biomarkers have also been detected by electrochemical NTs [27, 28].
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Furthermore, using a nanowire technology (nCounter Analysis System), ribonucleic acid (RNA) expression levels of cancer‐testis antigens (CTAs) have been measured, as biomarkers for aggressive prostate cancer. This nanowire technology offers the possibility of a sensor chip, is able to simultaneously detect more than one of cancer marker, and measures a panel of biomarkers related to a specific cancer type and/or individual, thus contributing to the personalization of cancer diagnosis [29]. Lee et al. [30] developed a nanowire substrate‐enabled laser‐scanning imaging combined with flow cytometry for the isolation and quantitation of circulating tumor cells from a human lung carcinoma sample mixture of tumor cells and leukocytes.
\n
Interestingly, CNTs and SNWs have been utilized for detection of various volatile organic compounds (VOCs) in breath samples of lung and gastric cancer patients, respectively [31]. Thus, Tran et al. [32] constructed a portable read‐out NWs on‐a‐chip device, by the addition of a complementary metal‐oxide semiconductor (CMOS) on FET‐SiNWs, creating a nanoplatform that could detect ALCAM in serum at a detection limit of 15.5 pg/ml, in <30 min. Besides cancer biomarker detection, FET‐SiNWs and zinc oxide nanowires (ZnONWs) have been used to detect ssDNA and mi‐RNAs related to the initiation and progression of various cancer types [33].
\n
Just like other nanobiosensors, nanocantilevers were demonstrated to be able to detect PSA at low levels (0.2 ng/ml–60 μg/ml) for the detection of prostate cancer. Huber et al. [34] used microcantilever arrays to detect BRAFV600E mutation nanomechanically without amplification, from total RNA samples isolated from malignant melanoma cells. Wang et al. [35] fabricated a new cantilever array‐based biosensor based on MEMS for the detection of alpha‐fetoprotein (AFP), a liver cancer biomarker, with high accuracy, while Liu et al. [36] detected the same biomarker for hepatocellular carcinoma at the level of ng/ml, using a resonant microcantilever electromagnetic resonance‐exciting and piezoresistive read‐out elements on‐chip integrated, in order to measure frequency‐shift versus specific‐adsorbed mass.
\n
So far, nanostructures such as QDs, AuNPs, and superparamagnetic NPs have been the most successfully incorporated in in vitro diagnostic applications, due to their potential to be functionalized by several biomolecules (antibodies, oligonucleotides) against the target biomolecules of interest. In the field of in vitro diagnostics, nanoparticles are mainly used as markers for biomolecules. On the other hand, conventional fluorescent dyes already used in medical laboratory tests, in PCR assays, and in biochips are not photostable or suitable for multiplexing. Jokerst et al. [37] used semiconductor nanoparticle QDs combined with a microfluidic biosensor for the multiplex quantitation of cancer biomarkers such as carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), and Her‐2/Neu (C‐erbB‐2) in serum and whole saliva specimens. This QD nanobiochip assay system resulted in a 30 times signal amplification, compared with standard molecular fluorophores [37]. Moreover, supermagnetic iron oxide nanoparticles are used, integrated with applications such as cell sorting, nucleic acid extraction and purification for the detection and isolation of circulating tumor cells of several types of cancer such as colorectal, lung, and breast cancer [38–40]. Besides circulating tumor cells, recently circulating extracellular vesicles and exosomes are demonstrated to serve as cancer biomarkers. Kanwar et al. [41] fabricated a microfluidic device (ExoChip) in polydimethylsiloxane (PDMS) and conjugated with antibodies against CD63, overexpressed mainly in exosomes. The ExoChip was able to measure fluorescent‐carbocyanine‐dyed exosomes from pancreatic cancer patients, compared to those from healthy subjects. Overall, the aim of this study was to suggest a novel approach for cancer molecular profiling that can be applied in various cancer types. Specifically, they managed to create an exosomal‐microRNA profiling that could enable the future molecular screening and diagnosis of human cancers [41].
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5. Discussion and future perspectives
\n
Up to now, the incorporation of nanostructures in medicine is offering the development of diagnostic tools of high sensitivity, advantageous contrast agents compared to traditional dyes already in use, novel personalized treatment approaches, and drug delivery vehicles. Taking into consideration small‐sized sample volumes, fast reaction times, specificity and sensitivity of nanosystems, in the near future they will be able to bring mobile testing devices into every day clinical practice. Regarding in vitro nanodiagnostics, nanotechnology allows the construction of high sensitive nanosensors and in vitro tests to develop new diagnostic nanoplatforms and to allow point of care applications. Many of the technologies described in this chapter are demonstrated to be versatile; for instance, they are suitable for DNA and protein detection, and they detect very few pathogens, such as bacteria and viruses, or molecules such as low concentration of glucose that would not be detected with conventional techniques. The incorporation of nanotechnology in medicine will lead to the development of rapid diagnostic tests, which will result in the improvement of clinical decision‐making and treatment costs. For example, rapid diagnostic nanotests offer early detection of disease such as cancer improving this way the possibilities of treatment.
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NPs are the most versatile material for developing diagnostics, since they can be conjugated with various agents and serve as tags or labels. Thus far, there are several efforts in the way in order to develop nanoparticle‐based systems for disease detection. Nanosphere, Inc. has launched the Verigene system which uses AuNPs. Verigene system is a molecular diagnostic system for rapid diagnostic evaluation that enables rapid treatment decisions regarding targeted therapy for various infections in bloodstream, respiratory tract, and gastrointestinal tract. The technology can also be applied in the future for other life‐threatening diseases such as cardiovascular, autoimmune diseases, and cancer. T2 Biosystems developed T2MR, a diagnostic detection method that uses miniaturized magnetic resonance technology in order to measure how water molecules react under magnetic fields. The T2MR technology platform offers a fast, simple, and sensitive alternative to existing diagnostic methodologies and uses magnetic nanoparticles to identify proteins, nucleic acids, and other materials. T2MR technology enables low limit of detection, as low as 1 cell/mL, compared to the 100–1000 cell/mL required by PCR‐based in vitro diagnostics. Up to now, T2Candida is in clinical trials and can identify the five clinically relevant species of Candida with 99.4% specificity and 91.1% sensitivity, directly from whole blood which enables physicians to initiate appropriate therapy on the same day. All other FDA‐cleared Candida diagnostics require a blood culture to determine the Candida species, which takes up to 6 days for species identification or negative result. On the other hand, the conjugation of virus‐specific antibodies in AuNPs can enable the rapid diagnosis of flu virus. The AuNPs–antibodies complex targets the virus in a way that larger AuNPs‐virus aggregates are formed. Subsequently, in the presence of light, the sample leads to an increase of the reflected light due to these aggregates, allowing a much faster validation and virus detection than with the tests currently used. The same notion of the formation of aggregates around the biomolecule of interest is used for the fast and specific detection of various diseases.
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Currently, QD technology is the most broadly employed nanotechnology for diagnostic developments, especially for cancer management. The only concern about QDs is the in vivo toxicity. However, researchers suggest the use of QDs composed of silicon, which is believed to be less toxic than the cadmium contained in many QDs.
\n
Regarding circulating cancer cell detection, researches have recently published the NanoFlare genetic‐based technology that enables the detection of living circulating tumor cells in bloodstream. A NanoFlare is designed to enter cells and to hybridize with cancer‐specific oligonucleotide sequences. NanoFlare has a great advantage, such as all nanoparticles due to their size: the fact that they can enter inside the cell gives the opportunity of the use of various biomolecules that are present inside the cell and not only markers anchored on the cell\'s surface. So when NanoFlare attaches to the cancer‐specific target into the cell, a reporter “flare” is released that produces a detectable fluorescent signal.
\n
Nanosensors and blood sensors capable of detecting multiple pathogens or chemical compounds are one such example. Point‐of‐care diagnostics are possible with nanosensors and also an attractive technology towards point‐of‐care diagnosis that will be easy for the patient to use at home and will enable the integration of diagnostics with therapeutics and the development of personalized treatment approaches. Blood sensors, especially cantilevers arrays, are characterized by important advantages since the technology of nanomechanical detection requires no labels and/or external probes, and optical excitation and is rapid, highly specific, sensitive, and portable. The above give the opportunity to detect pathogens or molecules in blood samples and are a great example of future point‐of‐care diagnostic tools. Furthermore, the upper goal regarding the construction of diagnostic biochips will be the miniaturization of the biosensor chips to range of “nano”‐dimensions. Thus, the use of nanotechnology in rapid diagnostic tests will lead to devices with nanodimensions, sensitive, easy to use, and non‐expensive in order to allow direct signal observation, manipulation, analysis, and result validation of a single biological molecule from a single cell. This offers new opportunities and provides powerful tools in the fields of genomics, proteomics, molecular diagnostics, and high‐throughput screening.
\n
\n',keywords:"Nanotechnology, Nanostructures, point‐of‐care devices, nanodiagnostics, low‐cost and rapid diagnosis",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/50954.pdf",chapterXML:"https://mts.intechopen.com/source/xml/50954.xml",downloadPdfUrl:"/chapter/pdf-download/50954",previewPdfUrl:"/chapter/pdf-preview/50954",totalDownloads:2245,totalViews:790,totalCrossrefCites:4,totalDimensionsCites:10,totalAltmetricsMentions:0,introChapter:null,impactScore:7,impactScorePercentile:96,impactScoreQuartile:4,hasAltmetrics:0,dateSubmitted:"October 15th 2015",dateReviewed:"April 22nd 2016",datePrePublished:null,datePublished:"September 7th 2016",dateFinished:"June 4th 2016",readingETA:"0",abstract:"Recently, various nanomaterials are used in order to develop nanotechnology‐based rapid diagnostic tests, such as metallic nanoparticles, quantum dots (QDs), silica nanospheres, magnetic nanoparticles, carbon nanotubes (CNTs), silicon nanowires (SiNWs), nanopores, graphene, nanostructured surfaces, and metal films. This novel nanodiagnostic approach will further develop point‐of‐care (POC) diagnostics and monitoring technologies. Nanobiosensors and microarrays of biosensors can create biochip systems and microfluidic platforms that are the most used nanofabrications for rapid diagnostic tests. These nanoplatforms are constructed for the rapid detection of various diseases or pathogen‐specific biomolecules/markers, such as DNA, proteins, whole cells (e.g., circulating tumor cells), and others. The fabrication of small‐scale portable devices with the incorporation of nanostructures will offer many advantages in the early detection of various diseases and health‐threatening infections by pathogens and in the treatment selection and treatment monitoring. The use of nanostructures in in vitro diagnostics gives the opportunity to augment the sensitivity and specificity required in clinical practice, lowers the cost and test time of the assays, and enables portable microfluidic platforms suitable for resource‐constrained settings. In this chapter, all the state‐of‐the‐art advantages in this field are discussed, starting with the nanostructures used for the fabrication of nanobiosensors, nanobiosensors arrays, and nanofluidic platforms and the nanodiagnostic use of rapid tests in the detection of pathogens, in cancer management, and glucose monitoring for the management of diabetes disease.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/50954",risUrl:"/chapter/ris/50954",book:{id:"5148",slug:"proof-and-concepts-in-rapid-diagnostic-tests-and-technologies"},signatures:"Anna Lyberopoulou, Efstathios P. Efstathopoulos and Maria Gazouli",authors:[{id:"179376",title:"Prof.",name:"Maria",middleName:null,surname:"Gazouli",fullName:"Maria Gazouli",slug:"maria-gazouli",email:"mgazouli@med.uoa.gr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"National and Kapodistrian University of Athens",institutionURL:null,country:{name:"Greece"}}},{id:"184280",title:"MSc.",name:"Anna",middleName:null,surname:"Lyberopoulou",fullName:"Anna Lyberopoulou",slug:"anna-lyberopoulou",email:"anna_lybero@hotmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"184281",title:"Prof.",name:"Efstathios",middleName:null,surname:"Efstathopoulos",fullName:"Efstathios Efstathopoulos",slug:"efstathios-efstathopoulos",email:"stathise@med.uoa.gr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Nanostructures used in nanodiagnostics",level:"1"},{id:"sec_2_2",title:"2.1. Metallic NPs",level:"2"},{id:"sec_3_2",title:"2.2. Quantum dots (QDs)",level:"2"},{id:"sec_4_2",title:"2.3. Silica nanospheres",level:"2"},{id:"sec_5_2",title:"2.4. Magnetic NPs",level:"2"},{id:"sec_6_2",title:"2.5. Carbon nanotubes or nanopores (CNTs–CNPs)",level:"2"},{id:"sec_7_2",title:"2.6. Silicon nanowires (SiNWs)",level:"2"},{id:"sec_8_2",title:"2.7. Graphene, metal films and nanostructured surfaces",level:"2"},{id:"sec_10",title:"3. Nanotechnology‐on‐a‐chip or nanofluidics",level:"1"},{id:"sec_11",title:"4. Applications of nanotechnology in in vitro nanodiagnostics",level:"1"},{id:"sec_11_2",title:"4.1. Nanosensors for glucose monitoring",level:"2"},{id:"sec_12_2",title:"4.2. Detection of bacteria and viruses",level:"2"},{id:"sec_13_2",title:"4.3. Nanotechnology in cancer diagnosis",level:"2"},{id:"sec_15",title:"5. 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Lab Chip. 2014 Jun 7;14(11):1891–900.\n'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Anna Lyberopoulou",address:null,affiliation:'
Department of Basic Medical Sciences, Laboratory of Biology, National and Kapodistrian University of Athens, Athens, Greece
Department of Radiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
'},{corresp:null,contributorFullName:"Efstathios P. Efstathopoulos",address:null,affiliation:'
Department of Basic Medical Sciences, Laboratory of Biology, National and Kapodistrian University of Athens, Athens, Greece
Department of Radiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
'},{corresp:"yes",contributorFullName:" Maria Gazouli",address:"mgazouli@med.uoa.gr",affiliation:'
Department of Basic Medical Sciences, Laboratory of Biology, National and Kapodistrian University of Athens, Athens, Greece
Department of Radiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
'}],corrections:null},book:{id:"5148",type:"book",title:"Proof and Concepts in Rapid Diagnostic Tests and Technologies",subtitle:null,fullTitle:"Proof and Concepts in Rapid Diagnostic Tests and Technologies",slug:"proof-and-concepts-in-rapid-diagnostic-tests-and-technologies",publishedDate:"September 7th 2016",bookSignature:"Shailendra K. Saxena",coverURL:"https://cdn.intechopen.com/books/images_new/5148.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-953-51-2581-5",printIsbn:"978-953-51-2580-8",pdfIsbn:"978-953-51-7295-6",reviewType:"peer-reviewed",numberOfWosCitations:15,isAvailableForWebshopOrdering:!0,editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. 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1. Introduction
Melatonin is a principal hormone produced by pineal cells in the pineal gland located in the cerebrum center behind the third ventricle (Figure 1). This endocrine gland consists of two cell types: pineal cells (which dominate and produce indolamines, mainly represented by melatonin, and peptides, such as arginine vasotocin) and neuroglia cells. The information received from neurons and modified by means of night and daylight intensity transforms in the pineal gland into chemical signals. Receiving the information about luminosity the pineal gland turns it into endocrine response by producing melatonin, which is a biogenic amine pertaining to the indole class, based on its chemical structure. Melatonin is a derivant of biogenic amine serotonin, which in its turn is synthesized from the amino acid tryptophan, received with food. Activity of ferments participating in serotonin transformation into melatonin is suppressed by lighting—that is why this hormone can be produced only during hours of darkness [1].
Figure 1.
Anatomical location for pineal body.
Key points
Melatonin functions in the human body are very diverse, and its normal secretion is extremely important for the preservation of somatic health.
The important role of melatonin in the formation of the reproductive function of women, the formation of a two-phase cycle, high-quality ovulation and fertilization, prevention of violations of a number of gynecological and obstetric pathologies.
Currently there are convincing data on the role of melatonin in the onset of menopause, the formation of climacteric syndrome, depression, osteoporosis, dyslipidemia, menopausal metabolic syndrome and cardiovascular diseases, and breast cancer in women in perimenopausal and postmenopausal women.
Melatonin is mainly released to the cerebrospinal fluid (liquor), getting from there to the blood flow and afterwards easily allocating itself in various organs and tissues due to good lipophilic properties [2]. Key effects of melatonin are connected with the action on membrane receptors—MT1 and MT2. They relate to a group of receptors connected with G-protein. These receptors are responsible for chronobiological effects and regulation of circadian rhythm and are widely distributed in different organs and tissues. Melatonin receptor presentation in the reproductive organs and receptors to sexual hormones in the epiphysis enables drawing the conclusion that melatonin plays an important role in regulation of reproductive aspect (Figure 2).
Figure 2.
Melatonin mechanisms of action.
In the same way, the nuclear receptors of melatonin ROR-α/RZR-β have been discovered. It is evident that many immune-stimulating and antitumoral effects are mediated by them.
Antioxidative function of melatonin is based on the receptor action, but this hormone is able to directly withdraw free radicals without receptor actuation [3].
Russian scientists discovered that apart from epiphyseal melatonin, there is an extrapineal one that is formed in different gastrointestinal tracts and other organs: liver, kidneys, supramental capsules, gall bladder, ovaries, endometrium, placenta, thymus, white blood cells, thrombocytes, and endothelium. Biologic action of the extrapineal melatonin is carried out right where it is synthesized [1].
2. Melatonin main physiological functions and its role in maintaining human health
During the recent years, new data on the mechanisms providing for the integral interaction among the nervous, immune, and endocrine systems have been received. Presumably, pineal gland is an integrator of such interaction, while its main hormone, melatonin, takes part in regulation of the activity of central and vegetative nervous systems, endocrine organs, and immune system. The performed investigations have demonstrated that melatonin fulfills an extremely wide range of physiological functions: biorhythmic and immunomodulatory processes, thermal control and sleep onset, and antioxidative and anti-stress effects [3]. Hormone secretion starts on the third month of infant development and reaches its peak during the first years (not later than at the age of 5). Before puberty, melatonin synthesis remains at a constantly high level [4]. During the age of 11–14, due to the fact that the pineal gland reduces melatonin production, the hormone mechanisms of sexual development are launched. The next significant reduction in activity occurs simultaneously with menopause onset—at the age of 45–60. With the aging progression, along with decrease in basal level, melatonin secretion peaks are getting lower [1]. During daytime melatonin concentration in the blood serum remains low (10–20 pg/ml), while during the night hours it grows considerably (80,120 pg/ml) and reaches its maximum value between midnight and 3–5 a.m. Melatonin secretion usually starts at 9 p.m. and terminates at 7–9 a.m. Melatonin metabolites are found in urine: 6-sulfatoxymelatonin (80–90%) and 6-hydroxyglucuronide (10–20%) corresponding to the circadian rhythm that is very close to the rhythm of melatonin secretion [5].
A new science, biorhythmology, introduced the notion of desynchronosis—clinically very important—that means ill-being or pathological syndrome, which is connected with the unbalance of circadian rhythms. A degree of desynchronosis is defined by the quantity and rhythm of melatonin production during the day and night. It has been determined that when a somatic disease goes hard or aggravates, melatonin production is getting worse, and its night indicator is getting closer to the day value [6]. Disturbed melatonin secretion finds its clinical manifestation in tiredness, indisposition, sleep disorder, and sometimes aggravation of a chronic disease or even appearance of a new one. Desynchronosis condition is exemplified by jet lag syndrome caused by rapid long-distance transmeridian travel [7].
It is generally known that melatonin has an antidepressant function. However, foreign colleagues stated disturbed circadian rhythm of melatonin secretion experienced by patients with depression during a menopause along with its increase during the morning hours as compared with women in good health that also has impact on sleep, level of follicle-stimulating hormone, and body mass index [8]. A connection was established between sleep disorder and melatonin reduction in female saliva during perimenopause without registering such pattern among women in postmenopause [9].
Therefore, melatonin functions in a human body are quite diversified, and its normal secretion is highly important for maintaining human health in a contemporary world.
3. Melatonin involvement into hormonal regulation of female reproductive system functions and its aging
In 1963 R.J. Wurtman et al. reported for the first time that exogenic intake of melatonin causes weight reduction in female rat ovaries. Since those times many evidences that pineal gland and its main hormone, melatonin, influence reproductive function have been received. Studies showed that neurons in preoptic and mediobasal areas of hypothalamus and hypophysis represented the main points, through which melatonin produced its reproductive action. The main physiological effect of melatonin lies in the slowdown of gonadotrophin secretion, with greater suppression of the lutenizing hormone (LH) by melatonin rather than the follicle-stimulating one. Negative correlation is registered between melatonin level at night and lutenizing hormone concentration. In addition, secretion of other tropic hormones of hypophysis anterior lobe (such as corticotrophin, thyrotropin, somatotropin) is reduced, though to a lesser extent. Melatonin can be called a universal inhibitor of endocrine function in a female body [10].
Melatonin takes part in regulation of many vital physiological processes, such as puberty and genital formation, menstrual cycle, and aging of reproductive system. High level of nocturnal melatonin was found in children with delayed puberty, while among children having accelerated puberty, a decrease in melatonin secretion at night was noted. High levels of melatonin among children produce a dominating effect on pulsatile gonadotropin secretion, ovary function, and puberty [4].
Abnormal levels of melatonin in blood are connected with a number of malfunctions in the system “hypothalamus—hypophysis—ovaries.” This gives boost to precocious puberty or its delay and formation of hypothalamic or hypergonadotropic amenorrhea. Therefore, melatonin may have indirect influence on the function of reproductive glands through its intervention into the secretion of gonadotropin-releasing hormone and/or secretion of gonadotrophins. Some data demonstrate that melatonin can also be synthesized in reproductive glands. Decreased melatonin secretion in summer coincides with higher fertility among women living in the Northern Hemisphere [11].
Based on these data, it was presupposed that melatonin could be a part of events preceding activation of hypothalamus-ovary axis during a puberty period [12]. Non-serial MRI of female head region helped register a reliable decrease in pineal gland volume during the ovulatory phase as well as while perimenopause. It indicates pineal gland involvement into “turning off” female reproductive function [13].
Melatonin may also produce direct influence on ovaries. High level of melatonin was found in preovulatory follicular fluid with triple concentration as compared to blood. Connecting areas of iodine melatonin were identified in human cells of granulosis and preovulatory follicles.
Antioxidative effect of melatonin is considered to be the most prominent one. It has been determined that melatonin ties free radicals of oxygen and at the same time stimulates enzymatic systems and SOD and possesses protective properties in relation to free-radical damage of DNA [14].
It’s generally known that macrofags, neutrophils, and vascular endothelium cells located in follicles produce AOS during ovulation. Despite the fact that AOS (active oxygen species) participate in breaking follicles, potentially they may damage an ovum and granulosis lutein cells. AOS inhibit progesterone production by lutein cells due to inhibition of steroidogenesis enzymes and transport intracellular protein. Melatonin is an important antioxidant in ovary follicles and enables progesterone synthesis by luteal cells [15]. Research outcomes have shown that melatonin intake leads to increased concentration of this hormone in follicular fluid and reduced oxidative damage inside follicles, thus raising a chance of fertilization and pregnancy [16, 17]. Melatonin intake also improved progesterone synthesis among women with infertility issues caused by insufficiency of the cycle luteal phase [18].
Pregnancy and acts of delivery are characterized by deep alterations in the endocrine profile of a female body as well as in pineal gland operation. In the case of physiological pregnancy, increased melatonin excretion with urine is marked, while just before an act of delivery its level plummets.
Decreased melatonin level is noted in the case of threatening miscarriage [4].
At the same time, many scientists speak about the great importance of melatonin in the body aging process. It is also pointed out that from the age of 45, melatonin starts to decline steadily till the end of human life. Numerous studies have demonstrated the correlation between melatonin synthesis and menopause onset [19]. The second decrease in melatonin level may be related to involutory processes in pineal gland [13].
In a placebo-controlled clinical study, it was established that there was a connection between decreased content of nocturnal melatonin in saliva and menopause onset, while intake of 3 mg of melatonin by female patients during perimenopause on a daily basis for 6 months eliminates hormonal and neurovegetative disorders and recovers menstruation cycle and thyroid function [20].
Women in postmenopause had lower concentration of melatonin in blood serum as compared to women in perimenopause, with a shorter duration of melatonin secretion in postmenopause as a rule, while melatonin synthesis peak time (acrophase) was almost the same. A pattern was determined that as melatonin secretion peak occurs later among women in perimenopause, anxiety level gets higher (p = 0.022), and as melatonin secretion continues for a longer period, the quality of life among patients gets better (p < 0.001) [21].
Some scientists suggest using melatonin drugs at the first stage of climacteric disorder treatment even before the start of hormonal therapy of menopause [4]. Moreover, in a double-blind placebo-controlled clinical study, it was determined that prescription of menopause hormonal therapy to postmenopausal women shifts melatonin secretion peak time without changing the melatonin level in the blood serum, which requires further research [21]. Other authors did not found in their research analyses devoted to alternative therapy for climacteric disorders any convincing data on hot flash arresting by melatonin drug [22].
4. Melatonin lipid metabolism
A growing number of evidences are emerging, which point to melatonin involvement into lipid metabolism. The study of H. Tamura was devoted to melatonin influence on lipid metabolism among women in perimenopause and postmenopause. A negative correlation was established between nocturnal melatonin and total cholesterol level, low-density lipoprotein, and positive correlation with high-density lipoprotein. No correlation was found between nocturnal melatonin and triglyceride level in blood. These findings show that melatonin drug prescription may represent a new approach to the correction of lipid metabolism and prevention of cardiovascular diseases during perimenopause and postmenopause [23]. Other scientists determined that melatonin improves lipid profile (leads to a reduced level of low-density lipoprotein) and fulfills antioxidant protection [24].
Under a study led by L.I. Maltseva [25], scientists analyzed melatonin role in the development of climacteric syndrome and its effectiveness for treating pathological climacterium. Russian scientists established that the level of 6-sulfatoxymelatonin in a 24-h urine among patients with severe climacteric syndrome amounts to 35.09 ± 3.5 ng/ml, medium severity (44.01 ± 7.92 ng/ml), and mild climacteric syndrome (45.91 ± 12.42 ng/ml) (1.7 times lower as compared to women in good health). Accordingly, secretory function of hypophysis is altered in various ways. Women with low level of 6-sulfatoxymelatonin in a 24-h urine show significant growth of both gonadotropic hormones—follicle-stimulating and luteinizing hormones—in a proportional way. A research showed that women had a high level of catecholamines (adrenaline and noradrenaline) with its degree being dependent on climacteric syndrome severity. It was also determined that women in perimenopausal age have increased the level of atherogenic fractions of blood lipids on the background of lower melatonin level.
Scientists came to the conclusion that melatonin acts as a modifier of alterations which occur with the development of climacteric disorders and influence hormonal, mediating, and biochemical indicators of the female body. Women with mild climacteric syndrome taking 3 mg of melatonin per day as monotherapy demonstrated during the repeated evaluation of clinical, hormonal, and biochemical indicators after 1 month a positive dynamics of all indicators. The blood hormone level was close to reference values, follicle-stimulating hormone level dropped by 2.29 times, luteinizing hormone level by 2.1 times. Values of melatonin sulfate in a 24-h urine grew by 2.64 times and were close as never to the reference values 27.95 ± 7.92…73.95 ± 24.85 ng/ml. However more significant alterations were noted for the severe climacteric syndrome without any side effects when melatonin treatment and menopause hormonal therapy were used together [25].
5. Menopause and sleep disturbance
Japanese scientists stated that estradiol level was firmly higher among women that worked night shifts and went to sleep later than 1 a.m. as compared to women that slept at night, with the level of serum testosterone and DHEA-sulfate unaffected, while 6-sulfatoxymelatonin concentration in urine was lower among the first group patients. Similar hormonal disruptions among postmenopausal women experiencing sleep disorder represent serious risk factors of breast cancer [26]. Singapore Chinese Health Study (2008) also showed that among women in postmenopause, the risk of breast cancer gets lower when sleep duration increases (p = 0.047). When sleep duration exceeds 9 h, a relative risk equals to 0.67 (95% confidence interval 0.4–1.1) as compared to women with a sleep duration of 6 h or less. At that, melatonin level was higher by 42% when sleep duration was 9 h or more. Such pattern was registered for women with normal weight (body mass index of 23.2 kg/m), p = 0.024 [27]. American scientists proved through a largescale prospective analysis that among women with 6-sulfatoxymelatonin content within the upper quartile, there were fewer with invasive breast cancer than among those whose values were within the bottom quartile [28]. It was established that the increased concentration of 6-sulfatoxymelatonin in the morning urine portion was statistically related to a lower risk of breast cancer (ratio of chances for upper and lower quartiles of 6-sulfatoxymelatonin level 0.62; 95% confidence interval 0.41–0.95; p = 0.004) [29].
C.G. Harrod and his colleagues made an assumption that a growing risk of cerebrovascular disease registered among menopausal women can be to some extent explained by changes in the level of circulating melatonin and estrogens and their modulating influence on biologic activity of endothelial cells, including vascular tone regulation, leukocytes adhesion, and angiogenesis. This hypothesis is confirmed by numerous studies demonstrating the braking effect of melatonin and estrogens on vessel tone, neuroprotection, and expression of receptors [30].
Increased melatonin secretion in the morning is more typical for menopausal patients with depression than women in good health. Moreover, menopause duration, level of the follicle-stimulating hormone, sleep end time, and body mass index may lead to alterations in melatonin secretion when suffering from depression during a menopause [8].
6. Melatonin effects on bone metabolism
At present a relation between melatonin and skeleton is known. Melatonin may produce an effect on bone tissue which manifests itself in bone tissue formation with osteoblasts and/or hindering bone resorption with osteoclasts. The study of K. Satomura et al. [31] confirms the melatonin (Mel1) receptor expression in human osteoblasts and tendency of its level reduction with aging. It is also demonstrated that melatonin can have a boosting effect on proliferation and differentiation of human osteoblasts [32]. Through a controlled randomized trial (2012), exogenous melatonin effect on bone tissue density was revealed. Bone tissue condition was controlled in two ways—bone tissue density estimation and bone marker determination. There was no considerable improvement noted in terms of bone tissue density in T points or as compared with placebo. An average change in the activity of bone resorption marker, N-telopeptide (NTX), in this study did not differ much inside and between the groups. Similarly, the average change in the activity of bone formation marker, osteocalcin, did not show any remarkable differences either inside a group or between groups. However, NTX to osteocalcin ratio followed a downward trend among the women who took melatonin as compared to placebo. It is quite important because among menopausal women, this ratio is known to increase so that osteoclasts activity outstrips osteoblast activity, which leads to a loss of bone mass. Probably, decreased level of nocturnal melatonin that occurs during a menopause causes hormonal unbalance and perimenopause symptoms, including the loss in bone mass. These data prove that melatonin intake may enable the balancing of bone resorption and formation processes, potentially preventing fast loss of bone mass attributed to a menopausal period [33].
Melatonin inhibits resorption activity by reducing RANKL-mediated osteoclastogenesis and therefore decreases bone resorption. Melatonin also protects from losing bone mass induced by free radicals, which occurs in the case of extreme bone resorption, due to its powerful antioxidative properties [34, 35]. In addition to its direct effect on the bone tissue, melatonin can produce an indirect influence on bone metabolism through the hypothalamus-pituitary axis, by suppressing levels of follicle-stimulating hormone and estrogen and increasing the level of progesterone. In contrast to the follicle-stimulating hormone, melatonin has positive correlation with progesterone level. Progesterone is known to influence on the mineral density of bone tissue, especially on osteoblast differentiation [36]. Reduced level of progesterone during a perimenopause may lead to the decreasing of bone tissue density because of osteoblasts loss.
7. Conclusion
Therefore, melatonin role in a female body is quite significant from the moment of birth till the last breath. It is revealed that up to the present time according to the literature data there is no information about the standards of secretion of melatonin for women of different age groups, and the lack of secretion of melatonin can be judged by clinical manifestations, and also when compared with groups of healthy women. The issues of using melatonin treatment for different cases of pregnancy complications and gynecological disorders remain unclear. Long-term intake of melatonin to treat pathological menopause is still to be discussed.
\n',keywords:"women, pineal gland, melatonin, 6-sulfatoxymelatonin",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/70178.pdf",chapterXML:"https://mts.intechopen.com/source/xml/70178.xml",downloadPdfUrl:"/chapter/pdf-download/70178",previewPdfUrl:"/chapter/pdf-preview/70178",totalDownloads:712,totalViews:0,totalCrossrefCites:0,dateSubmitted:"May 7th 2019",dateReviewed:"August 2nd 2019",datePrePublished:"November 23rd 2019",datePublished:"July 22nd 2020",dateFinished:"November 23rd 2019",readingETA:"0",abstract:"In the presented article, we cover the issues concerning physiology of secretion of pineal hormone melatonin and its role in the vital processes of a body. Focus is given to melatonin effect on the female reproductive system, its participation in the aging process, and formation of pathological menopause. The article also presents research data on the effectiveness of the melatonin drug when tackling climacteric syndrome. It is revealed that according to the available literature up to date there is no information about the standards of secretion of melatonin for women of different age groups, and the lack of secretion of melatonin can be judged by clinical manifestations and also when compared with groups of healthy women. The issues of the melatonin drug application at various complications of pregnancy and gynecological diseases remain unclear. Long-term intake of melatonin to treat pathologic menopause is still to be discussed.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/70178",risUrl:"/chapter/ris/70178",signatures:"Elena N. Usoltseva and Marina V. Danilova",book:{id:"7980",type:"book",title:"Hormone Therapy and Replacement in Cancer and Aging-related Diseases",subtitle:null,fullTitle:"Hormone Therapy and Replacement in Cancer and Aging-related Diseases",slug:"hormone-therapy-and-replacement-in-cancer-and-aging-related-diseases",publishedDate:"July 22nd 2020",bookSignature:"Leticia B. A. Rangel, Hephzibah Kirubamani, Ian Victor Silva and Paulo Cilas Morais Lyra Junior",coverURL:"https://cdn.intechopen.com/books/images_new/7980.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-78985-320-9",printIsbn:"978-1-78985-319-3",pdfIsbn:"978-1-83962-955-6",isAvailableForWebshopOrdering:!0,editors:[{id:"60359",title:"Dr.",name:"Letícia",middleName:null,surname:"Rangel",slug:"leticia-rangel",fullName:"Letícia Rangel"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Melatonin main physiological functions and its role in maintaining human health",level:"1"},{id:"sec_3",title:"3. Melatonin involvement into hormonal regulation of female reproductive system functions and its aging",level:"1"},{id:"sec_4",title:"4. Melatonin lipid metabolism",level:"1"},{id:"sec_5",title:"5. Menopause and sleep disturbance",level:"1"},{id:"sec_6",title:"6. Melatonin effects on bone metabolism",level:"1"},{id:"sec_7",title:"7. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Anisimov VN. Melatonin—Its Role in a Human Body, Clinical Application. SPb.: Sistema; 2007'},{id:"B2",body:'Arushanyan EB. Pregnancy and pineal gland. Ros Vestn, akush-gin. 2012;6:29-34'},{id:"B3",body:'Bespyatykh AY, Brodskiy VY, Burlakova OV, et al. In: Repport SI, Golichenkov VA, editors. Melatonin: Theory and practice. M.: Medpraktika-M; 2009'},{id:"B4",body:'Anisimov VN, Vinogradova IA. Aging of Female Reproductive System and Melatonin. SPb., Sistema; 2008'},{id:"B5",body:'Karasek M, Winczyk K. Melatonin in human. Journal of Physiology and Pharmacology. 2006;57(5):19-39'},{id:"B6",body:'Ragosin ON, Bochkarev MV. Effect of the Northern Region Modified Photoperiodism on Normal and Abnormal Human Biological Rhythms: Guide on Chronobiology and Chronomedicine. M: MIA; 2012. pp. 119-136'},{id:"B7",body:'Vosko AM, Colwell CS, Avidan AY. Jet lag syndrome: Circadian organization, pathophysiology, and management strategies. Nature and Science of Sleep. 2010;2:187-198'},{id:"B8",body:'Parry BL, Meliska CJ, Sorenson DL, et al. Increased melatonin and delayed offset in menopausal depression: Role of years past menopause, folliclestimulating hormone, sleep end time, and body mass index. Journal of Clinical Endocrinology and Metabolism. 2008;93(1):54-60'},{id:"B9",body:'Kolesnikova LI, Madaeva IM, Semenova NV, et al. Pathogenic role of melatonin in sleep disorders in menopausal women. Bulletin of Experimental Biology and Medicine. 2013;156(1):104-106'},{id:"B10",body:'Brzezinski A, Lynch HJ, Wurtman RJ, Seibel MM. Possible contribution of melatonin to the timing of the luteinizing hormone surge. New England Journal of Medicine. 1987;316:1550-1551'},{id:"B11",body:'Boczek-Leszczyk E, Juszczak M. The influence of melatonin on human reproduction. Polski Merkuriusz Lekarski. 2007;23(134):128-130'},{id:"B12",body:'Brzezinski A. Melatonin and human reproduction: Why the effect is so elusive? In: Pandi-Perumal SR, Cardinali DP, editors. Molecules to Therapy. New York: Nova Science Publishers; 2007. pp. 219-225'},{id:"B13",body:'Ivanov SV. Menopause is a key aspect of aging: Role of pineal gland. Advances in Gerontology. 2007;4(20):19-24'},{id:"B14",body:'Hardeland R. Antioxidative protection by melatonin: Multiplicity of mechanisms from radical detoxification to radical avoidance. Endocrine. 2005;27(2):119-130'},{id:"B15",body:'Tamura H, Takasaki A, Taketani T, et al. Melatonin and female reproduction. Journal of Obstetrics and Gynaecology Research. 2014;40(1):1-11'},{id:"B16",body:'Tamura H, Nakamura Y, Korkmaz A, et al. Melatonin and the ovary: Physiological and pathophysiological implications. Fertility and Sterility. 2009;92:328-343'},{id:"B17",body:'Tamura H, Takasaki A, Miwa I, et al. Oxidative stress impairs oocyte quality and melatonin protects oocytes from free radical damage and improves fertilization rate. Journal of Pineal Research. 2008;44:280-287'},{id:"B18",body:'Taketani T, Tamura H, Takasaki A, et al. Protective role of melatonin in progesterone production by human luteal cells. Journal of Pineal Research. 2011;51:207-213'},{id:"B19",body:'Diaz BL, Llaneza PC. Endocrine regulation of the course of menopause by oral melatonin: First case report. Menopause. 2008;15:388-392'},{id:"B20",body:'Bellipanni G, Di Marzo F, Blasi F, Di Marzo A. Effects of melatonin in perimenopausal and menopausal women: Our personal experience. Annals of the New York Academy of Sciences. 2005;1057:393-402'},{id:"B21",body:'Toffol E, Kalleinen N, Haukka J, et al. Melatonin in peri-menopausal and postmenopausal women: Associations with mood, sleep, climacteric symptoms, and quality of life. Menopause. 2014;21(5):493-500'},{id:"B22",body:'Kelley KW, Carroll DG. Evaluating the evidence for over-the-counter alternatives for relief of hot flashes in menopausal women. Journal of the American Pharmacists Association. 2010;50(5):106-115'},{id:"B23",body:'Tamura H, Nakamura Y, Narimatsu A, et al. Melatonin treatment in peri- and postmenopausal women elevates serum high-density lipoprotein cholesterol levels without influencing total cholesterol levels. Journal of Pineal Research. 2008;45:101-105'},{id:"B24",body:'Kozirog M, Poliwczak AR, Duchnowicz P, et al. Melatonin treatment improves blood pressure, lipid profile, and parameters of oxidative stress in patients with metabolic syndrome. Journal of Pineal Research. 2011;50:261-266'},{id:"B25",body:'Maltseva LI, Gafarova EA, Garipova GH. Melatonin role in reproductive glands function regulation and possibility of its use for pathological climacteric symptoms treatment. Advances in Gerontology. 2007;4(20):68-74'},{id:"B26",body:'Nagata C, Nagao Y, Yamamoto S, et al. Light exposure at night, urinary 6sulfatoxymelatonin, and serum estrogens and androgens in postmenopausal Japanese women. Cancer Epidemiology, Biomarkers & Prevention. 2008;17(6):1418-1423'},{id:"B27",body:'Wu AH, Wang R, Koh WP. et al, Sleep duration, melatonin and breast cancer among Chinese women in Singapore. Carcinogenesis. 2008;29(6):1244-1248'},{id:"B28",body:'Schernhammer ES, Berrino F, Krogh V, et al. Urinary 6-sulfatoxymelatonin levels and risk of breast cancer in post-menopausal women. Journal of the National Cancer Institute. 2008;100(12):898-905'},{id:"B29",body:'Schernhammer ES, Hankinson SE. Urinary melatonin levels and postmenopausal breast cancer risk in the nurses’ health study cohort. Cancer Epidemiology, Biomarkers & Prevention. 2009;18(1):74-79'},{id:"B30",body:'Harrod CG, Bendok BR, Hunt Batjer H. Interactions between mela tonin and estrogen may regulate cerebrovascular function in women: Clinical implications for the effective use of HRT during menopause and aging. Medical Hypotheses. 2008;70(1):213'},{id:"B31",body:'Satomura K, Tobiume S, Tokuyama R, Yamasaki Y, et al. Melatonin at pharmacological doses enhances human osteoblastic differentiation in vitro and promotes mouse cortical bone formation in vivo. Journal of Pineal Research. 2007 Apr;42(3):231-239'},{id:"B32",body:'Park KH, Kang JW, Lee EM, et al. Melatonin promotes osteoblastic differentiation through the BMP/ERK/Wnt signaling pathways. Journal of Pineal Research. 2011;51:187-194'},{id:"B33",body:'Kotlarczyk MP, Lassila HC, O’Neil CK, et al. Melatonin osteoporosis prevention study (MOPS): A randomized, double-blind, placebo-controlled study examining the effects of melatonin on bone health and quality of life in perimenopausal women. Journal of Pineal Research. 2012;52(4):414-426'},{id:"B34",body:'Galano A, Tan DX, Reiter RJ. Melatonin as a natural ally against oxidative stress: A physicochemical examination. Journal of Pineal Research. 2011;51:1-16'},{id:"B35",body:'Sanchez-Barcelo EJ, Mediavilla MD, Tan DX, et al. Scientific basis for the potential use of melatonin in bone diseases: Osteoporosis and adolescent idiopathic scoliosis. Journal of Osteoporosis. 1 Jun 2010;2010:830231. DOI: 10.4061/2010/830231'},{id:"B36",body:'Seifert-Klauss V, Prior JC. Progesterone and bone: Actions promoting bone health in women. Journal of Osteoporosis. 31 Oct 2010;2010:845180. DOI: 10.4061/2010/845180'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Elena N. Usoltseva",address:null,affiliation:'
Department of Obstetrics and Gynecology, South Ural State Medical University, Health Ministry of Russian Federation, Russia
'},{corresp:"yes",contributorFullName:"Marina V. Danilova",address:"danilova-mv@bk.ru",affiliation:'
City Clinical Hospital № 1, Russia
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However, interspersed, some tunnels rise to problems of instability during excavation. This chapter is a case study of the tunnel of “Djebel El Kantour” which is part of the East–West Algerian Highway. Face stability is the most critical problems that affect the subject of our research. This study is carried out via analytical and numerical methods based on the instability relationship, characteristics of the ground and the geometry of the tunnel, to draw conclusions and recommendations for overcoming this problem.",signatures:"Adel Aissi, Abdelghani Brikat, Ali Ismet Kanlı, Aissa Benselhoub and Oussama Kessal",authors:[{id:"243975",title:"Dr.",name:"Ali Ismet",surname:"Kanlı",fullName:"Ali Ismet Kanlı",slug:"ali-ismet-kanli",email:"kanli@istanbul.edu.tr"},{id:"324217",title:"Ph.D.",name:"Aissa",surname:"Benselhoub",fullName:"Aissa Benselhoub",slug:"aissa-benselhoub",email:"benselhoub@yahoo.fr"},{id:"339147",title:"Dr.",name:"Adelghani",surname:"Brikat",fullName:"Adelghani Brikat",slug:"adelghani-brikat",email:"rikat85@gmail.com"},{id:"339149",title:"Dr.",name:"Adel",surname:"Aissi",fullName:"Adel Aissi",slug:"adel-aissi",email:"adel.aissi@univ-msila.dz"},{id:"344729",title:"Dr.",name:"Oussama",surname:"Kessal",fullName:"Oussama Kessal",slug:"oussama-kessal",email:"oussama.kessal@yahoo.fr"}],book:{id:"8909",title:"Slope Engineering",slug:"slope-engineering",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"326051",title:"Dr.",name:"Masagus Ahmad",surname:"Azizi",slug:"masagus-ahmad-azizi",fullName:"Masagus Ahmad Azizi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"326644",title:"Prof.",name:"Nixon",surname:"Correa-Munoz",slug:"nixon-correa-munoz",fullName:"Nixon Correa-Munoz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Cauca",institutionURL:null,country:{name:"Colombia"}}},{id:"326647",title:"Dr.",name:"Carol Andrea",surname:"Murillo-Feo",slug:"carol-andrea-murillo-feo",fullName:"Carol Andrea Murillo-Feo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National University of Colombia",institutionURL:null,country:{name:"Colombia"}}},{id:"327586",title:"Dr.",name:"Gaurav",surname:"Singh",slug:"gaurav-singh",fullName:"Gaurav Singh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"327587",title:"Dr.",name:"Raj",surname:"Kumar",slug:"raj-kumar",fullName:"Raj Kumar",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"331111",title:"Dr.",name:"Irfan",surname:"Marwanza",slug:"irfan-marwanza",fullName:"Irfan Marwanza",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Trisakti University",institutionURL:null,country:{name:"Indonesia"}}},{id:"331112",title:"Dr.",name:"Afiat",surname:"Anugrahadi",slug:"afiat-anugrahadi",fullName:"Afiat Anugrahadi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Trisakti University",institutionURL:null,country:{name:"Indonesia"}}},{id:"331113",title:"Mr.",name:"Muhammad Kemal",surname:"Ghifari",slug:"muhammad-kemal-ghifari",fullName:"Muhammad Kemal Ghifari",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Trisakti University",institutionURL:null,country:{name:"Indonesia"}}},{id:"331673",title:"Dr.",name:"Dinesh",surname:"Jinger",slug:"dinesh-jinger",fullName:"Dinesh Jinger",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"331676",title:"Dr.",name:"Dinesh",surname:"Dhakshanamoorthy",slug:"dinesh-dhakshanamoorthy",fullName:"Dinesh Dhakshanamoorthy",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null}]},generic:{page:{slug:"open-access-funding",title:"Open Access Funding",intro:"
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The literature source was Web of Science and SSCI, SCI-EXPANDED, A&HCI, CPCI-S, CPCI-SSH, and ESCI indexes. Fifty-two articles were reviewed; however, 14 of them were not been included in the study. As a result, 38 articles were examined. Level of education, field of education, and material types of AR used in education and reported educational advantages of AR have been investigated. All articles are categorized according to target groups, which are early childhood education, primary education, secondary education, high school education, graduate education, and others. AR technology has been mostly carried out in primary and graduate education. “Science education” is the most explored field of education. Mobile applications and marker-based materials on paper have been mostly preferred. The major advantages indicated in the articles are “Learning/Academic Achievement,” “Motivation,” and “Attitude”.",book:{id:"6543",slug:"state-of-the-art-virtual-reality-and-augmented-reality-knowhow",title:"State of the Art Virtual Reality and Augmented Reality Knowhow",fullTitle:"State of the Art Virtual Reality and Augmented Reality Knowhow"},signatures:"Rabia M. Yilmaz",authors:[{id:"225838",title:"Dr.",name:"Rabia",middleName:null,surname:"Yilmaz",slug:"rabia-yilmaz",fullName:"Rabia Yilmaz"}]},{id:"63639",doi:"10.5772/intechopen.81086",title:"Cooperative Learning: The Foundation for Active Learning",slug:"cooperative-learning-the-foundation-for-active-learning",totalDownloads:3491,totalCrossrefCites:18,totalDimensionsCites:25,abstract:"The role of instructors is evolving from the presenter of information to the designer of active learning processes, environments, and experiences that maximize student engagement. The more active a lesson, the more students tend to engage intellectually and emotionally in the learning activities. Cooperative learning is the foundation on which many of the active learning procedures are based. Cooperative learning is the instructional use of small groups so that students work together to maximize their own and each other’s learning. Most of the active learning procedures, such as problem-based learning, team-learning, collaborative learning, and PALS, require that students work cooperatively in small groups to achieve joint learning goals. Cooperative learning is based on two theories: Structure-Process-Outcome theory and Social Interdependence theory. Four types of cooperative learning have been derived: formal cooperative learning, informal cooperative learning, cooperative base groups, and constructive controversy. There is considerable research confirming the effectiveness of cooperative learning. To be cooperative, however, five basic elements must be structured into the situation: positive interdependence, individual accountability, promotive interaction, social skills, and group processing.",book:{id:"6929",slug:"active-learning-beyond-the-future",title:"Active Learning",fullTitle:"Active Learning - Beyond the Future"},signatures:"David W. Johnson and Roger T. Johnson",authors:[{id:"259976",title:"Dr.",name:"David",middleName:null,surname:"Johnson",slug:"david-johnson",fullName:"David Johnson"},{id:"263004",title:"Dr.",name:"Roger",middleName:null,surname:"Johnson",slug:"roger-johnson",fullName:"Roger Johnson"}]},{id:"58060",doi:"10.5772/intechopen.72341",title:"Pedagogy of the Twenty-First Century: Innovative Teaching Methods",slug:"pedagogy-of-the-twenty-first-century-innovative-teaching-methods",totalDownloads:8833,totalCrossrefCites:17,totalDimensionsCites:23,abstract:"In the twenty-first century, significant changes are occurring related to new scientific discoveries, informatization, globalization, the development of astronautics, robotics, and artificial intelligence. This century is called the age of digital technologies and knowledge. How is the school changing in the new century? How does learning theory change? Currently, you can hear a lot of criticism that the classroom has not changed significantly compared to the last century or even like two centuries ago. Do the teachers succeed in modern changes? The purpose of the chapter is to summarize the current changes in didactics for the use of innovative teaching methods and study the understanding of changes by teachers. In this chapter, we consider four areas: the expansion of the subject of pedagogy, environmental approach to teaching, the digital generation and the changes taking place, and innovation in teaching. The theory of education, figuratively speaking, has two levels. At the macro-level, in the “education-society” relationship, decentralization and diversification, internationalization of education, and the introduction of digital technologies occur. At the micro-level in the “teacher-learner” relationship, there is an active mix of traditional and innovative methods, combination of an activity approach with an energy-informational environment approach, cognition with constructivism and connectivism.",book:{id:"5980",slug:"new-pedagogical-challenges-in-the-21st-century-contributions-of-research-in-education",title:"New Pedagogical Challenges in the 21st Century",fullTitle:"New Pedagogical Challenges in the 21st Century - Contributions of Research in Education"},signatures:"Aigerim Mynbayeva, Zukhra Sadvakassova and Bakhytkul\nAkshalova",authors:[{id:"201997",title:"Dr.",name:"Aigerim",middleName:null,surname:"Mynbayeva",slug:"aigerim-mynbayeva",fullName:"Aigerim Mynbayeva"},{id:"209208",title:"Dr.",name:"Zukhra",middleName:null,surname:"Sadvakassova",slug:"zukhra-sadvakassova",fullName:"Zukhra Sadvakassova"},{id:"209210",title:"Dr.",name:"Bakhytkul",middleName:null,surname:"Akshalova",slug:"bakhytkul-akshalova",fullName:"Bakhytkul Akshalova"}]},{id:"59468",doi:"10.5772/intechopen.74344",title:"Virtual and Augmented Reality: New Frontiers for Clinical Psychology",slug:"virtual-and-augmented-reality-new-frontiers-for-clinical-psychology",totalDownloads:2364,totalCrossrefCites:13,totalDimensionsCites:21,abstract:"In the last decades, the applied approach for the use of virtual reality (VR) and augmented reality (AR) on clinical and health psychology has grown exponentially. These technologies have been used to treat several mental disorders, for example, phobias, stress-related disorders, depression, eating disorders, and chronic pain. The importance of VR/AR for the mental health field comes from three main concepts: (1) VR/AR as an imaginal technology, people can feel “as if they are” in a reality that does not exist in external world; (2) VR/AR as an embodied technology, the experience to feel user’s body inside the virtual environment; and (3) VR/AR as connectivity technology, the “end of geography’. In this chapter, we explore the opportunities provided by VR/AR as technologies to improve people’s quality of life and to discuss new frontiers for their application in mental health and psychological well-being promotion.",book:{id:"6543",slug:"state-of-the-art-virtual-reality-and-augmented-reality-knowhow",title:"State of the Art Virtual Reality and Augmented Reality Knowhow",fullTitle:"State of the Art Virtual Reality and Augmented Reality Knowhow"},signatures:"Sara Ventura, Rosa M. Baños and Cristina Botella",authors:[{id:"106036",title:"Dr.",name:"Rosa Maria",middleName:null,surname:"Baños",slug:"rosa-maria-banos",fullName:"Rosa Maria Baños"},{id:"227763",title:"Ph.D.",name:"Sara",middleName:null,surname:"Ventura",slug:"sara-ventura",fullName:"Sara Ventura"},{id:"229056",title:"Dr.",name:"Cristina",middleName:null,surname:"Botella",slug:"cristina-botella",fullName:"Cristina Botella"}]},{id:"64583",doi:"10.5772/intechopen.81714",title:"Evaluating a Course for Teaching Advanced Programming Concepts with Scratch to Preservice Kindergarten Teachers: A Case Study in Greece",slug:"evaluating-a-course-for-teaching-advanced-programming-concepts-with-scratch-to-preservice-kindergart",totalDownloads:1422,totalCrossrefCites:13,totalDimensionsCites:18,abstract:"Coding is a new literacy for the twenty-first century, and as a literacy, coding enables new ways of thinking and new ways of communicating and expressing ideas, as well as new ways of civic participation. A growing number of countries, in Europe and beyond, have established clear policies and frameworks for introducing computational thinking (CT) and computer programming to young children. In this chapter, we discuss a game-based approach to coding education for preservice kindergarten teachers using Scratch. The aim of using Scratch was to excite students’ interest and familiarize them with the basics of programming in an open-ended, project-based, and personally meaningful environment for a semester course in the Department of Preschool Education in the University of Crete. For 13 weeks, students were introduced to the main Scratch concepts and, afterward, were asked to prepare their projects. For the projects, they were required to design their own interactive stories to teach certain concepts about mathematics or physical science to preschool-age students. The results we obtained were more satisfactory than expected and, in some regards, encouraging if one considers the fact that the research participants had no prior experiences with computational thinking.",book:{id:"6936",slug:"early-childhood-education",title:"Early Childhood Education",fullTitle:"Early Childhood Education"},signatures:"Stamatios Papadakis and Michail Kalogiannakis",authors:null}],mostDownloadedChaptersLast30Days:[{id:"58060",title:"Pedagogy of the Twenty-First Century: Innovative Teaching Methods",slug:"pedagogy-of-the-twenty-first-century-innovative-teaching-methods",totalDownloads:8832,totalCrossrefCites:17,totalDimensionsCites:23,abstract:"In the twenty-first century, significant changes are occurring related to new scientific discoveries, informatization, globalization, the development of astronautics, robotics, and artificial intelligence. This century is called the age of digital technologies and knowledge. How is the school changing in the new century? How does learning theory change? Currently, you can hear a lot of criticism that the classroom has not changed significantly compared to the last century or even like two centuries ago. Do the teachers succeed in modern changes? The purpose of the chapter is to summarize the current changes in didactics for the use of innovative teaching methods and study the understanding of changes by teachers. In this chapter, we consider four areas: the expansion of the subject of pedagogy, environmental approach to teaching, the digital generation and the changes taking place, and innovation in teaching. The theory of education, figuratively speaking, has two levels. At the macro-level, in the “education-society” relationship, decentralization and diversification, internationalization of education, and the introduction of digital technologies occur. At the micro-level in the “teacher-learner” relationship, there is an active mix of traditional and innovative methods, combination of an activity approach with an energy-informational environment approach, cognition with constructivism and connectivism.",book:{id:"5980",slug:"new-pedagogical-challenges-in-the-21st-century-contributions-of-research-in-education",title:"New Pedagogical Challenges in the 21st Century",fullTitle:"New Pedagogical Challenges in the 21st Century - Contributions of Research in Education"},signatures:"Aigerim Mynbayeva, Zukhra Sadvakassova and Bakhytkul\nAkshalova",authors:[{id:"201997",title:"Dr.",name:"Aigerim",middleName:null,surname:"Mynbayeva",slug:"aigerim-mynbayeva",fullName:"Aigerim Mynbayeva"},{id:"209208",title:"Dr.",name:"Zukhra",middleName:null,surname:"Sadvakassova",slug:"zukhra-sadvakassova",fullName:"Zukhra Sadvakassova"},{id:"209210",title:"Dr.",name:"Bakhytkul",middleName:null,surname:"Akshalova",slug:"bakhytkul-akshalova",fullName:"Bakhytkul Akshalova"}]},{id:"61746",title:"Facilitation of Teachers’ Professional Development through Principals’ Instructional Supervision and Teachers’ Knowledge- Management Behaviors",slug:"facilitation-of-teachers-professional-development-through-principals-instructional-supervision-and-t",totalDownloads:3384,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"With the rise of global competition and the focus on teacher quality, teacher professional development is becoming increasingly crucial, and the stress and challenges for principals are more severe than ever. Teachers can improve their professional abilities through principals’ instructional supervision and their own knowledge-management (KM) behaviors to benefit students. Thus, this chapter analyzes the relationship among principals’ instructional supervision, teachers’ KM, and teachers’ professional development. The author believes that principals’ instructional supervision and effective KM can facilitate the professional development of teachers. The author also believes the readers can know the relationships among them, and teachers’ professional development can be improved through principal’s instructional supervision and teachers’ KM behaviors.",book:{id:"6674",slug:"contemporary-pedagogies-in-teacher-education-and-development",title:"Contemporary Pedagogies in Teacher Education and Development",fullTitle:"Contemporary Pedagogies in Teacher Education and Development"},signatures:"Chien-Chin Chen",authors:[{id:"232569",title:"Ph.D.",name:"Chien Chih",middleName:null,surname:"Chen",slug:"chien-chih-chen",fullName:"Chien Chih Chen"}]},{id:"75908",title:"From the Classroom into Virtual Learning Environments: Essential Knowledge, Competences, Skills and Pedagogical Strategies for the 21st Century Teacher Education in Kenya",slug:"from-the-classroom-into-virtual-learning-environments-essential-knowledge-competences-skills-and-ped",totalDownloads:519,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"As teachers in Kenya begin to migrate from the classroom to virtual learning spaces following COVID 19 pandemic, there is pressing need to realign Teacher Education to requisite Knowledge, competences, skills, and attitudes that will support online teaching. This chapter explores these needs using a combination of lived experiences and literature review that captured a meta-analysis of research trends on e-learning. While trends in Teacher Education indicate progression towards adoption of technology, there are disparities between the theory and practice. Evidence from recent research and reports; and the recollected experiences confirmed knowledge, competence, skills and pedagogical gaps in the implementation of online learning, that have been exacerbated by COVID-19. The researcher recommends that teacher education should sensitize and train teacher trainees on how to access, analyze and use new knowledge emerging with technology; they also should be coached on how learners learn with technology and on fundamentals of the communication process. Particularly the course on educational technology, should focus on how to create and manage online courses. The 5-stage E-Moderator Model and Universal Design for Learning (UDL) are recommended as effective pedagogical scaffold for online teaching.",book:{id:"10229",slug:"teacher-education-in-the-21st-century-emerging-skills-for-a-changing-world",title:"Teacher Education in the 21st Century",fullTitle:"Teacher Education in the 21st Century - Emerging Skills for a Changing World"},signatures:"Catherine Adhiambo Amimo",authors:[{id:"333482",title:"Dr.",name:"Catherine Adhiambo",middleName:null,surname:"Amimo",slug:"catherine-adhiambo-amimo",fullName:"Catherine Adhiambo Amimo"}]},{id:"75224",title:"Decoding the Digital Gap in Teacher Education: Three Perspectives across the Globe",slug:"decoding-the-digital-gap-in-teacher-education-three-perspectives-across-the-globe",totalDownloads:589,totalCrossrefCites:0,totalDimensionsCites:4,abstract:"Educational use of technology is regularly assessed, and results often show a gap between educational policies and what is actually practiced. This chapter will help clarify how teacher educators experience the changing educational contexts due to the digital revolution, how their meaning-making shifts, and how outside forces influence those processes. The results are based on comparative international studies. Central for this study is practitioners’ professional digital competence, their attitudes towards digital technology and the use of digital technology in education. We found that the influence and contribution of digital practice is carried out quite differently across the globe. Our research questions were: How do practitioners experience teaching in a rapidly changing context? How do attitudes change due to top-down governing of education? and What motivates teacher educators to implement digital technology?",book:{id:"10229",slug:"teacher-education-in-the-21st-century-emerging-skills-for-a-changing-world",title:"Teacher Education in the 21st Century",fullTitle:"Teacher Education in the 21st Century - Emerging Skills for a Changing World"},signatures:"Steinar Thorvaldsen and Siri Sollied Madsen",authors:[{id:"332624",title:"Associate Prof.",name:"Siri Sollied",middleName:null,surname:"Madsen",slug:"siri-sollied-madsen",fullName:"Siri Sollied Madsen"},{id:"332626",title:"Prof.",name:"Steinar",middleName:null,surname:"Thorvaldsen",slug:"steinar-thorvaldsen",fullName:"Steinar Thorvaldsen"}]},{id:"75416",title:"Self-Study Research: Challenges and Opportunities in Teacher Education",slug:"self-study-research-challenges-and-opportunities-in-teacher-education",totalDownloads:777,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"This article aims to describe what self-study research is, why self-study can be a good approach to teacher educators’ professional development and improvements in practice and highlight some challenges and opportunities in this research approach. In addition, the article will shed light on some methodological aspects related to self-study. Self-study refers to teacher educators who in an intentionally and systematically way examine their practice to improve it, based on a deeper understanding of practice, as well as the context practice takes place. In the article, I argue that engaging in self-study is a learning and development process and an approach to developing personal professionalism, collective professionalism and improvements in practice.",book:{id:"10229",slug:"teacher-education-in-the-21st-century-emerging-skills-for-a-changing-world",title:"Teacher Education in the 21st Century",fullTitle:"Teacher Education in the 21st Century - Emerging Skills for a Changing World"},signatures:"Kåre Hauge",authors:[{id:"332053",title:"Associate Prof.",name:"Kåre",middleName:null,surname:"Hauge",slug:"kare-hauge",fullName:"Kåre Hauge"}]}],onlineFirstChaptersFilter:{topicId:"265",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:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:140,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:123,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,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:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{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"}}}},{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"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"August 2nd, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:33,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:2,paginationItems:[{id:"89",title:"Education",coverUrl:"https://cdn.intechopen.com/series_topics/covers/89.jpg",isOpenForSubmission:!1,annualVolume:null,editor:{id:"260066",title:"Associate Prof.",name:"Michail",middleName:null,surname:"Kalogiannakis",slug:"michail-kalogiannakis",fullName:"Michail Kalogiannakis",profilePictureURL:"https://mts.intechopen.com/storage/users/260066/images/system/260066.jpg",biography:"Michail Kalogiannakis is an Associate Professor of the Department of Preschool Education, University of Crete, and an Associate Tutor at School of Humanities at the Hellenic Open University. He graduated from the Physics Department of the University of Crete and continued his post-graduate studies at the University Paris 7-Denis Diderot (D.E.A. in Didactic of Physics), University Paris 5-René Descartes-Sorbonne (D.E.A. in Science Education) and received his Ph.D. degree at the University Paris 5-René Descartes-Sorbonne (PhD in Science Education). His research interests include science education in early childhood, science teaching and learning, e-learning, the use of ICT in science education, games simulations, and mobile learning. He has published over 120 articles in international conferences and journals and has served on the program committees of numerous international conferences.",institutionString:"University of Crete",institution:{name:"University of Crete",institutionURL:null,country:{name:"Greece"}}},editorTwo:{id:"422488",title:"Dr.",name:"Maria",middleName:null,surname:"Ampartzaki",slug:"maria-ampartzaki",fullName:"Maria Ampartzaki",profilePictureURL:"https://mts.intechopen.com/storage/users/422488/images/system/422488.jpg",biography:"Dr Maria Ampartzaki is an Assistant Professor in Early Childhood Education in the Department of Preschool Education at the University of Crete. Her research interests include ICT in education, science education in the early years, inquiry-based and art-based learning, teachers’ professional development, action research, and the Pedagogy of Multiliteracies, among others. 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He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. 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Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:{name:"Association for Computing Machinery",country:{name:"United States of America"}}},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"426586",title:"Dr.",name:"Oladunni A.",middleName:null,surname:"Daramola",slug:"oladunni-a.-daramola",fullName:"Oladunni A. Daramola",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Federal University of Technology",country:{name:"Nigeria"}}},{id:"357014",title:"Prof.",name:"Leon",middleName:null,surname:"Bobrowski",slug:"leon-bobrowski",fullName:"Leon Bobrowski",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Bialystok University of Technology",country:{name:"Poland"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"354126",title:"Dr.",name:"Setiawan",middleName:null,surname:"Hadi",slug:"setiawan-hadi",fullName:"Setiawan Hadi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Padjadjaran University",country:{name:"Indonesia"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"332603",title:"Prof.",name:"Kumar S.",middleName:null,surname:"Ray",slug:"kumar-s.-ray",fullName:"Kumar S. Ray",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Statistical Institute",country:{name:"India"}}},{id:"415409",title:"Prof.",name:"Maghsoud",middleName:null,surname:"Amiri",slug:"maghsoud-amiri",fullName:"Maghsoud Amiri",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Allameh Tabataba'i University",country:{name:"Iran"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}}]}},subseries:{item:{id:"18",type:"subseries",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11414,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. 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