Proposal for mapping different types of PBL initiatives along with an integral 6-year Bachelor’s and Master’s Degree in Engineering for Society 5.0.
\\n\\n
These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\\n\\n\\n\\n\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\n\n\n\n\n'}],latestNews:[{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"},{slug:"intechopen-identified-as-one-of-the-most-significant-contributor-to-oa-book-growth-in-doab-20210809",title:"IntechOpen Identified as One of the Most Significant Contributors to OA Book Growth in DOAB"}]},book:{item:{type:"book",id:"5691",leadTitle:null,fullTitle:"Evolutionary Physiology and Biochemistry - Advances and Perspectives",title:"Evolutionary Physiology and Biochemistry",subtitle:"Advances and Perspectives",reviewType:"peer-reviewed",abstract:"In 2016, it was 60 years since the eminent Soviet researcher, a disciple and a successor of Ivan Pavlov, Leon Orbeli had proclaimed the birth of a new branch of physiology, evolutionary physiology. In the same year, his ideas were embodied in the foundation in Leningrad, now Saint Petersburg, of the present Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences. This anniversary book includes the selected works carried out recently by his followers at the same institute. While addressing some hot aspects of evolutionary physiology and biochemistry, they demonstrate that this branch of physiology really represents a discipline in its own right.",isbn:"978-953-51-3858-7",printIsbn:"978-953-51-3857-0",pdfIsbn:"978-953-51-3967-6",doi:"10.5772/64635",price:119,priceEur:129,priceUsd:155,slug:"evolutionary-physiology-and-biochemistry-advances-and-perspectives",numberOfPages:242,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"1d46e40056fbbdb46c70dc255c945cf8",bookSignature:"",publishedDate:"February 19th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/5691.jpg",numberOfDownloads:16302,numberOfWosCitations:8,numberOfCrossrefCitations:11,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:0,numberOfDimensionsCitationsByBook:9,hasAltmetrics:0,numberOfTotalCitations:19,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 17th 2016",dateEndSecondStepPublish:"June 17th 2016",dateEndThirdStepPublish:"September 1st 2016",dateEndFourthStepPublish:"October 1st 2016",dateEndFifthStepPublish:"December 19th 2016",currentStepOfPublishingProcess:1,indexedIn:"1,2,3,4,5,6",editedByType:"Authored by",kuFlag:!1,featuredMarkup:null,editors:null,equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"408",title:"Applied Microbiology",slug:"biochemistry-genetics-and-molecular-biology-microbiology-applied-microbiology"}],chapters:[{id:"58997",title:"Introduction: The 60th Anniversary of the Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Saint Petersburg",doi:"10.5772/intechopen.73669",slug:"introduction-the-60th-anniversary-of-the-institute-of-evolutionary-physiology-and-biochemistry-russi",totalDownloads:862,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Alexander N. Knyazev",downloadPdfUrl:"/chapter/pdf-download/58997",previewPdfUrl:"/chapter/pdf-preview/58997",authors:[{id:"241495",title:"Ph.D.",name:"Alexander",surname:"Knyazev",slug:"alexander-knyazev",fullName:"Alexander Knyazev"}],corrections:null},{id:"58915",title:"Brain Gangliosides and Their Function as Natural Adaptogenes",doi:"10.5772/intechopen.73648",slug:"brain-gangliosides-and-their-function-as-natural-adaptogenes",totalDownloads:1066,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In brain gangliosides and phospholipids of stenothermal cold-water teleost fishes, higher content of polyenoic and monoenoic fatty acids was revealed than in brain gangliosides and phospholipids of warm-water stenothermal teleosts. The changes in fatty acid composition of lipids during adaptation of fishes to living in cold water (or at great water depth) are directed to the maintenance of liquid-crystalline state of cell membranes and their optimal fluidity, physical state, and microheterogeneity. The results of cluster analysis of the data on composition of carbohydrate component of brain gangliosides of various ectothermic vertebrates were used to create the dendrogram. This dendrogram was found to correspond appreciably to the tree of classical taxonomy of vertebrates. The changes in molecular organization of brain gangliosides in the course of evolution of vertebrates are suggested to contribute to differentiation of brain and complication of its functions in phylogenesis. The main brain gangliosides (GM1, GD1a, GD1b, GT1b) may be considered to be typical adaptogens. They protect neurons against the action of excitatory amino acids, hydrogen peroxide, amyloid β-peptide, and other toxins. Protective effect of gangliosides against these toxins depends on activation of Trk receptor tyrosine kinase and downstream protein kinases.",signatures:"Natalia F. Avrova and Yulia A. Vlasova",downloadPdfUrl:"/chapter/pdf-download/58915",previewPdfUrl:"/chapter/pdf-preview/58915",authors:[{id:"241003",title:"Dr.",name:"Natalia F.",surname:"Avrova",slug:"natalia-f.-avrova",fullName:"Natalia F. Avrova"},{id:"241004",title:"Dr.",name:"Yulia A.",surname:"Vlasova",slug:"yulia-a.-vlasova",fullName:"Yulia A. Vlasova"}],corrections:null},{id:"59070",title:"Adaptations and Disturbances of Physiological Functions in Extreme Hyperbaric Environments",doi:"10.5772/intechopen.73649",slug:"adaptations-and-disturbances-of-physiological-functions-in-extreme-hyperbaric-environments",totalDownloads:1027,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Academician E.M. Kreps founded the Laboratory of Hyperbaric Physiology in 1960. Heads of the Laboratory were G.L. Zaltsman (1960–1972), A.I. Selivra (1972–1975), I.A. Aleksandrov (1975–1982) and I.T. Demchenko (1983–2009). In 2009, the Laboratory was merged with the Laboratory of Respiratory Physiology (A.I. Krivchenko). For more than five decades, Hyperbaric Laboratory has conducted basic and applied researches dealt with CNS oxygen toxicity, the high pressure nervous syndrome and nitrogen narcosis. Main achievements of basic researches are as follows: identified key mechanisms of adaptive responses of CNS and cardiorespiratory systems to breathing gas mixtures at high pressure, neurophysiological mechanisms of CNS oxygen toxicity and high pressure nervous syndrome, and pathogenesis of nitrogen narcosis. Main achievements of the translation of hyperbaric researches are as follows: new technology for 1000 m dive of animals (monkeys) using the gas mixture (He-N2-O2), new compression and decompression profiles for free escape of monkey from a depth of 700 m, use preconditional hypoxia and hyperthermia for the protection of nitrogen narcosis. Currently, main researches are focusing on the evaluation of molecular and cellular mechanisms of biological responses to extreme hyperbaric environments.",signatures:"Olga Sergeevna Alekseeva, Alexander Ivanovich Krivchenko and\n\nIvan Timofeyevich Demchenko",downloadPdfUrl:"/chapter/pdf-download/59070",previewPdfUrl:"/chapter/pdf-preview/59070",authors:[{id:"241006",title:"Dr.",name:"I.T.",surname:"Demchenko",slug:"i.t.-demchenko",fullName:"I.T. Demchenko"}],corrections:null},{id:"59053",title:"Evolution of Thalamic Sensory Centers in Amniotes: Phylogeny and Functional Adaptation",doi:"10.5772/intechopen.73650",slug:"evolution-of-thalamic-sensory-centers-in-amniotes-phylogeny-and-functional-adaptation",totalDownloads:970,totalCrossrefCites:1,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter is a continuation of our previous study of the forebrain evolution in vertebrates using some new tests allowing evolutionary transformations to be revealed. As such tests, we chose the expression of calcium-binding proteins as neuronal functional markers and the metabolic activity of cytochrome oxidase, characterizing the level of neuronal activity. Here, we report the results of our study of the thalamic visual and auditory centers in reptiles (turtles, Emys orbicularis and Testudo horsfieldii) and birds (pigeon, Columba livia) with a special focus on differences in their parallel visual thalamofugal and tectofugal channels and auditory lemniscal and extralemniscal channels. A comparison with data obtained in other Sauropsida amniotes was drawn to elucidate the role of phylogenetic and functionally adaptive factors determining variable distribution of calcium-binding proteins and metabolic activity, as well as to identify evolutionary conservative and plastic traits in the organization of these thalamic sensory centers.",signatures:"Margarita G. Belekhova and Natalia B. Kenigfest",downloadPdfUrl:"/chapter/pdf-download/59053",previewPdfUrl:"/chapter/pdf-preview/59053",authors:[{id:"241007",title:"Dr.",name:"Margarita G.",surname:"Belekhovа",slug:"margarita-g.-belekhova",fullName:"Margarita G. Belekhovа"},{id:"241008",title:"Dr.",name:"Natalia B.",surname:"Kenigfest",slug:"natalia-b.-kenigfest",fullName:"Natalia B. Kenigfest"}],corrections:null},{id:"59065",title:"Discovery of the Phenomenon of Intracellular Development of Cardiac Stem Cell: A New Step in Understanding of Biology and Behavior of Tissue-Specific Stem Cells",doi:"10.5772/intechopen.73652",slug:"discovery-of-the-phenomenon-of-intracellular-development-of-cardiac-stem-cell-a-new-step-in-understa",totalDownloads:886,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In our experiments with an in vitro culture of rat cardiac cells, we identified and described for the first time the phenomenon of intracellular development of CSCs in mature CMs with formation of the “cell-in-cell structures” (CICSs). Recently, we have confirmed the reproducibility of our results and existence of this phenomenon in rats of different age groups, 1-year-old bull, adult mice and humans. Moreover, we demonstrated the 5–10 times increase in the amount of CICSs after exposure of in vitro cultures to hypoxia and acidosis, that is, these conditions stimulate intracellular development of CSCs. Our data strongly suggest that transitory amplifying cells (TACs), which release from CICSs, are present as a very rare cell population in adult and old rats. Therefore, we assume that TACs are important for renewal of myocardium during ontogenesis. TACs should be considered as the major source of cells that can reduce myocardial damage in adult mammals with various pathologies of the cardiovascular system. In conclusion, precise and exhaustive analysis of the phenomenon of intracellular development of CSCs, CICSs and TACs will pave the way for cell technologies of new generation in regenerative medicine.",signatures:"Galina B. Belostotskaya, Tatyana A. Golovanova, Irina V.\n\nNerubatskaya and Michael M. Galagudza",downloadPdfUrl:"/chapter/pdf-download/59065",previewPdfUrl:"/chapter/pdf-preview/59065",authors:[{id:"241009",title:"Dr.",name:"G.B.",surname:"Belostotskaya",slug:"g.b.-belostotskaya",fullName:"G.B. Belostotskaya"}],corrections:null},{id:"58933",title:"The New Pharmacological Approaches for the Regulation of Functional Activity of G Protein-Coupled Receptors",doi:"10.5772/intechopen.73322",slug:"the-new-pharmacological-approaches-for-the-regulation-of-functional-activity-of-g-protein-coupled-re",totalDownloads:861,totalCrossrefCites:1,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The G protein-coupled receptors (GPCRs), a large family of the receptors that specifically interact with a number of signal molecules, play a key role in the regulation of fundamental cell processes, and the pharmacological action of over 40% of drugs is carried out through GPCRs. In the last years, a significant progress was made in the creation of selective regulators of GPCRs interacting with their allosteric sites, such as the synthetic peptides corresponding to intracellular regions of receptors (GPCR-peptides) and the low-molecular weight agonists and antagonists of GPCRs. This review describes the recent results obtained by us and other authors in the development of GPCR-peptides and low-molecular weight agonists and the prospects of their use in clinics.",signatures:"Alexander O. Shpakov and Kira Viktorovna Derkach",downloadPdfUrl:"/chapter/pdf-download/58933",previewPdfUrl:"/chapter/pdf-preview/58933",authors:[{id:"81685",title:"Dr.",name:"Kira",surname:"Derkach",slug:"kira-derkach",fullName:"Kira Derkach"}],corrections:null},{id:"59043",title:"Ontogenetic Development of Neurophysiological Mechanisms Underlying Language Processing",doi:"10.5772/intechopen.73654",slug:"ontogenetic-development-of-neurophysiological-mechanisms-underlying-language-processing",totalDownloads:1004,totalCrossrefCites:1,totalDimensionsCites:0,hasAltmetrics:0,abstract:"During the last 20 years, new data on the neurophysiological mechanisms underlying different types of cognitive activity, especially speech and its ontogenetic formation, were obtained in the Laboratory of Children’s Neurophysiology headed by Prof. M.N. Tsitseroshin. Using the analysis of the spatial-temporal structure of regional interactions of cortical bioelectric potentials (so-called functional connectivity), we investigated how specific language levels, such as phonology, grammar, and semantics, are represented in the brain. The data obtained in children vs. adults indicate that the speech perception and production require joint and extremely coordinated activities of both hemispheres, along with the obligatory and differentiated involvement of “classic” speech centers in the left hemisphere, especially Wernicke’s area. Another line of our research is to explore the differences, which arise during verbal processing in adults and children with impaired vs. non-impaired speech, particularly with alalia, dysarthria and stuttering, using behavioral and EEG data. Our data obtained in children vs. adults allow assessing the degree of maturity in the organization of the central processes of maintaining the studied types of verbal activity in children of different ages. These data allow expanding modern concepts about the brain mechanisms of verbal activity in children in the norm and pathology.",signatures:"Diana M. Guillemard (Tsaparina), Michail N. Tsitseroshin, Alexandr N. Shepovalnikov, Elizaveta I. Galperina, Ekaterina A. Panasevich, Ekaterina E. Kats, Larisa G. Zaytseva and Olga V. Kruchinina",downloadPdfUrl:"/chapter/pdf-download/59043",previewPdfUrl:"/chapter/pdf-preview/59043",authors:[{id:"241011",title:"Dr.",name:"Diana M.",surname:"Guillemard",slug:"diana-m.-guillemard",fullName:"Diana M. Guillemard"}],corrections:null},{id:"58865",title:"Ontogenetic Development of Neural and Muscular Rhythmic Activity and Its Regulation in Mammals during Perinatal Period",doi:"10.5772/intechopen.73656",slug:"ontogenetic-development-of-neural-and-muscular-rhythmic-activity-and-its-regulation-in-mammals-durin",totalDownloads:1009,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This review covers our recent advantages in studying the ontogenetic aspects of physiological mechanisms underlying regulation of rhythmic behavior. We have revealed that excitation patterns that emerged at early stages of phylogenetic development of life forms contribute greatly to the rhythmic activity of living vertebrates and invertebrates. These patterns govern spontaneous excitation, which is easily observed during the early stage of ontogenesis. The intensity and patterns of rhythmic activity are determined by nature and kinetics of certain metabolic reactions. During perinatal and sometimes postnatal periods (as in prematurely born animals), endogenic rhythmicity of developing physiological structures is strongly pronounced due to relatively stable living conditions. This rhythmic behavior is coordinated within an entire organism. Its integration in multiple systems is driven by amplitude and frequency modulation yielding rhythms of various frequency ranges. Indeed, it is the complex and conjoint functioning of physiological systems that maintains homeostasis in developing organisms. We present the results of our authentic research concerning the evolution and ontogeny of regulatory mechanisms of motor, cardiovascular, and respiratory systems. The aspects of intact and disrupted development are considered, involving the changes in dopaminergic, norepinephrinergic, and cholinergic system activation.",signatures:"Sergey Vladimirovich Kuznetsov, Natalia D. Vdovichenko, Ludmila E. Dmitrieva, Natalia N. Kuznetsova, Vladimir A. Sizonov, Maksim A. Terpilowski and Olga P. Timofeeva",downloadPdfUrl:"/chapter/pdf-download/58865",previewPdfUrl:"/chapter/pdf-preview/58865",authors:[{id:"241013",title:"Dr.",name:"Sergey V.",surname:"Kuznetsov",slug:"sergey-v.-kuznetsov",fullName:"Sergey V. Kuznetsov"}],corrections:null},{id:"59044",title:"Development of the Biosphere in the Context of Some Fundamental Inventions of Biological Evolution",doi:"10.5772/intechopen.73297",slug:"development-of-the-biosphere-in-the-context-of-some-fundamental-inventions-of-biological-evolution",totalDownloads:1078,totalCrossrefCites:1,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Traditionally, the evolution of flora and fauna on the Earth as well as the evolution of their physical and chemical environment are considered separately. At the same time, when considering the global evolutionary changes, it becomes clear that the evolution of all these components occurs in close relationship and that they together constitute a unified evolutionary process. Thus, we should talk about their co-evolution and that the whole biosphere is a united functional system. In this chapter, we briefly discuss some of the major “inventions” of ancient life that are responsible for global biosphere transformations and which “worked” in the biosphere until now (photosynthesis, eukaryotic cell, multicellular organism, and the other findings). The evolution of the Precambrian life as well as the Phanerozoic stage of the biosphere evolution are considered in this context.",signatures:"Vladimir F. Levchenko, Alexander B. Kazansky and Marat A. Sabirov",downloadPdfUrl:"/chapter/pdf-download/59044",previewPdfUrl:"/chapter/pdf-preview/59044",authors:[{id:"193812",title:"Dr.",name:"Vladimir",surname:"Fedorovich Levchenko",slug:"vladimir-fedorovich-levchenko",fullName:"Vladimir Fedorovich Levchenko"}],corrections:null},{id:"58990",title:"Development of Multicellularity: Social/Economic Aspects",doi:"10.5772/intechopen.73658",slug:"development-of-multicellularity-social-economic-aspects",totalDownloads:1097,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This article describes a philosophy of an arising multicellularity on the basis of division of functions between cells. Laws of the division are discussed in elementary multicellularity units, called histions. There is a variety of the histions that have different social structures. Several parameters have been proposed to describe them quantitatively and to systematize them by means of a periodic table. Consideration is given to the rules that govern polymerization of histions as well as the formation of regular cellular networks using them. It is shown that these types of networks could serve as biological tissue models that enable one to predict the tissue development. It has been found that arising multicellularity can result in a drastically decreased metabolites production per cell and thus creates the need in their economically justified unequal distribution.",signatures:"Gennady A. Savostyanov",downloadPdfUrl:"/chapter/pdf-download/58990",previewPdfUrl:"/chapter/pdf-preview/58990",authors:[{id:"241014",title:"Dr.",name:"Gennady A.",surname:"Savostyanov",slug:"gennady-a.-savostyanov",fullName:"Gennady A. Savostyanov"}],corrections:null},{id:"58919",title:"Protein Reabsorption in the Amphibian Kidney: Comparative and Evolutionary Aspects",doi:"10.5772/intechopen.73659",slug:"protein-reabsorption-in-the-amphibian-kidney-comparative-and-evolutionary-aspects",totalDownloads:1185,totalCrossrefCites:1,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Protein reabsorption in the renal proximal tubule (PT) is a vitally important process which prevents the loss of filtered proteins and provides their participation in subsequent metabolism. Despite considerable changes in renal structure and function in the process of evolution, very little is known about the functional similarities or specifics of tubular protein reabsorption in the kidney of lower vertebrates compared with the mammalian and human kidney. This article presents an overview of our recent studies on protein reabsorption in the kidney of amphibians, which are used as one of the main animal models for current biological and biomedical research. In frogs, newts, and rats, the absorption capacity of epithelial PT cells was studied after the introduction of green fluorescent protein (GFP), yellow fluorescent protein (YFP), and lysozyme. Molecular mechanisms of receptor-mediated protein endocytosis were also investigated by immunohisto- and immunocytochemistry, electron, fluorescent, and laser scanning confocal microscopy.",signatures:"Elena V. Seliverstova and Natalya P. Prutskova",downloadPdfUrl:"/chapter/pdf-download/58919",previewPdfUrl:"/chapter/pdf-preview/58919",authors:[{id:"241016",title:"Dr.",name:"Elena V.",surname:"Seliverstova",slug:"elena-v.-seliverstova",fullName:"Elena V. Seliverstova"},{id:"241017",title:"Dr.",name:"Natalya P.",surname:"Prutskova",slug:"natalya-p.-prutskova",fullName:"Natalya P. Prutskova"}],corrections:null},{id:"59004",title:"The Contribution of Changes in Adenylyl Cyclase Signaling System of the Brain and Myocardium to Etiology and Pathogenesis of Diabetes Mellitus",doi:"10.5772/intechopen.73661",slug:"the-contribution-of-changes-in-adenylyl-cyclase-signaling-system-of-the-brain-and-myocardium-to-etio",totalDownloads:939,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The functional changes in hormone-sensitive adenylyl cyclase (AC) signaling system of the central nervous system (CNS) and periphery play a crucial role in etiology and pathogenesis of diabetes mellitus (DM). The identification of these changes in AC signaling system and the abnormalities in AC signaling network are necessary for creation of the new strategies to treat and prevent diabetic pathology. In this chapter, our data and the results of other authors on the changes in hormone-sensitive adenylyl cyclase signaling system (ACSS) in the diabetic brain and heart and on their contribution to etiology and pathogenesis of DM and its complications, diabetic cardiomyopathy in particular, are presented and analyzed, and the promising approaches to treat DM and its complications, which are based on the restoration of AC signaling cascades and their functional interaction, are discussed.",signatures:"Alexander Olegovich Shpakov",downloadPdfUrl:"/chapter/pdf-download/59004",previewPdfUrl:"/chapter/pdf-preview/59004",authors:[{id:"75888",title:"Dr.",name:"Alexander",surname:"Shpakov",slug:"alexander-shpakov",fullName:"Alexander Shpakov"}],corrections:null},{id:"59018",title:"Systems Evolutionary Biology of Waddington’s Canalization and Genetic Assimilation",doi:"10.5772/intechopen.73662",slug:"systems-evolutionary-biology-of-waddington-s-canalization-and-genetic-assimilation",totalDownloads:1197,totalCrossrefCites:2,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In recent years, there has been growing interest in computer modeling of the evolution of gene and cell regulatory networks, in general, and in computational studies of the classic ideas of Baldwin, Schmalhausen, Waddington, and followers, in particular. Two related aspects of Waddington’s evolutionary theories are the concepts of canalization and of genetic assimilation. Canalization is associated with the robust development of an individual to diverse perturbations and noise, though, when fluctuations in developmental factors exceed a particular limit, the normal developmental trajectory can be “thrown out” of the robust canal, resulting in an altered phenotype. If selective pressure favors the new phenotype, an initial individual loss of canalization can lead to phenotypic changes in the population (with canalization then becoming established for the new phenotype). Genetic assimilation is the subsequent genetic fixing of the new trait in the population. Recent experimental and theoretical works have established a quantitative basis for these classic concepts of Waddington; this chapter will review these new developments in systems evolutionary biology.",signatures:"Alexander V. Spirov, Marat A. Sabirov and David M. Holloway",downloadPdfUrl:"/chapter/pdf-download/59018",previewPdfUrl:"/chapter/pdf-preview/59018",authors:[{id:"103830",title:"MSc.",name:"Marat",surname:"Sabirov",slug:"marat-sabirov",fullName:"Marat Sabirov"},{id:"111296",title:"Dr.",name:"David",surname:"Holloway",slug:"david-holloway",fullName:"David Holloway"},{id:"241019",title:"Dr.",name:"Alexander V.",surname:"Spirov",slug:"alexander-v.-spirov",fullName:"Alexander V. Spirov"}],corrections:null},{id:"59010",title:"3D Structures and Molecular Evolution of Ion Channels",doi:"10.5772/intechopen.73665",slug:"3d-structures-and-molecular-evolution-of-ion-channels",totalDownloads:1106,totalCrossrefCites:1,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Ion channels mediate selective passive transport of ions across biomembranes. They participate in diverse physiological processes and belong to distinct protein families. Understanding specific roles of different channels in physiology, pathology, and pharmacology requires knowledge of their origin and evolution. Traditional approaches include experimental physiological studies and analysis of sequences and genomes. In the last two decades, availability of 3D structures of many ion channel proteins revolutionized ion channel studies, including their evolution. In this chapter, we consider examples of how 3D structures provided clues for understanding evolutionary aspects of multi-domain organization, domain folding, and roles of highly conserved and variable residues. Such achievements are important for addressing practical problems including drug design, channelopathies, and acquired resistance to insecticides.",signatures:"Denis B. Tikhonov and Boris S. Zhorov",downloadPdfUrl:"/chapter/pdf-download/59010",previewPdfUrl:"/chapter/pdf-preview/59010",authors:[{id:"241023",title:"Dr.",name:"Denis B.",surname:"Tikhonov",slug:"denis-b.-tikhonov",fullName:"Denis B. Tikhonov"}],corrections:null},{id:"59050",title:"Ontogenetic and Phylogenetic Approaches for Studying the Mechanisms of Cognitive Dysfunctions",doi:"10.5772/intechopen.73666",slug:"ontogenetic-and-phylogenetic-approaches-for-studying-the-mechanisms-of-cognitive-dysfunctions",totalDownloads:1238,totalCrossrefCites:3,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter summarizes the phylogenetic and ontogenetic approaches for studying cognitive disorders such as Alzheimer’s disease. It gives an extended example of evaluation of animal behavior and brain properties using an original model of prenatal hypoxia in rats by various physiological, behavioral, immunohistochemical, molecular biological, and biochemical techniques at different stages of postnatal development, which provide a better understanding of the pathological processes in the human brain during the development of neurodegeneration.",signatures:"Igor А. Zhuravin, Nadezhda M. Dubrovskaya, Natalia L. Tumanova,\n\nDmitrii S. Vasilev and Natalia N. Nalivaeva",downloadPdfUrl:"/chapter/pdf-download/59050",previewPdfUrl:"/chapter/pdf-preview/59050",authors:[{id:"241024",title:"Dr.",name:"Igor А.",surname:"Zhuravin",slug:"igor-a.-zhuravin",fullName:"Igor А. Zhuravin"},{id:"241026",title:"Dr.",name:"Nadezhda М.",surname:"Dubrovskaya",slug:"nadezhda-m.-dubrovskaya",fullName:"Nadezhda М. Dubrovskaya"},{id:"241027",title:"Dr.",name:"Natalia L.",surname:"Tumanova",slug:"natalia-l.-tumanova",fullName:"Natalia L. 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\r\n\tSpinal cord injury represents a relatively frequent clinical scenario that emergency doctors, neuroradiologists, and spine surgeons have to deal with in their daily practice.
\r\n\r\n\tAlthough there are many publications on this topic, a consensus on the preferred management has not been reached yet. In fact, other than clearly surgical or non-surgical patients, there is a non-negligible number of cases where an interdisciplinary discussion is strictly needed, eventually determining a case-by-case treatment selection.
\r\n\r\n\tEmergency decompression surgery, often associated with fusion, represents an effective treatment for critical compressions of the spinal cord, while its role in subacute cases is still debated. Different medical managements have been proposed for the acute, subacute, and chronic phases, respectively. Since function preservation is the primary outcome to be pursued, the multidisciplinary case discussion is a fundamental step in the decision-making process. However, a practical guide on the state of the art on spinal cord injury management may result as useful to a large audience of practitioners.
",isbn:"978-1-80355-877-6",printIsbn:"978-1-80355-876-9",pdfIsbn:"978-1-80355-878-3",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,hash:"fc1ece21c6d20adecf2b9fe16489a07d",bookSignature:"Dr. Luca Ricciardi, Dr. Giorgio Lofrese, Dr. Andrea Perna and Ph.D. Sokol Trungu",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11285.jpg",keywords:"Concussion, Medullary Edema, Paraplegia, Neurotrauma, Functional Impairment, Neurorehabilitation, Physiotherapy, Steroids, Rhiluzole, Arthrodesis, Fusion, Instrumentation",numberOfDownloads:16,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 4th 2021",dateEndSecondStepPublish:"February 24th 2022",dateEndThirdStepPublish:"April 25th 2022",dateEndFourthStepPublish:"July 14th 2022",dateEndFifthStepPublish:"September 12th 2022",remainingDaysToSecondStep:"3 months",secondStepPassed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"The clinical researcher focused on spine and spinal cord disorders. Dr. Ricciardi serves as a guest editor, editorial board member, and reviewer of many indexed journals such as the Journal of Neurosurgical Sciences and Frontiers in Neurooncology, Life, and Cell. He is a co-chairman for SPINE20, the World Congress on Spine Disorders at the G20 conference in Rome, Italy, and an individual delegate at the European Association of Neurosurgical Societies.",coeditorOneBiosketch:"A neurosurgeon specialized in craniocervical junction diseases and minimally invasive spine surgery. Dr. Lofrese was awarded the European Young Researcher Award (AOSpine) and the Young Neurosurgeon Award (WFNS). He is a member of EUROSPINE, SPINE20, and the European Association of Neurosurgical Societies.",coeditorTwoBiosketch:"Dr. Perna's main fields of study are the pathologies of the spine, with particular attention to spinal deformities, traumatological surgery, and infectious pathologies such as spondylodiscitis. His publications give particular attention to lateral surgery, while his other fields of interest are hand surgery and biomechanics applied to orthopedics.",coeditorThreeBiosketch:"Dr. Trungu completed his Ph.D. in Neuroscience and Neurosurgery at Sapienza University of Rome, Italy. His areas of special interest are Minimally Invasive Spine Surgery (MISS), complex spine surgery, spine trauma focusing on acute spinal cord injury, primary and secondary spinal tumors, and Neuro-oncology.",coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"421212",title:"Dr.",name:"Luca",middleName:null,surname:"Ricciardi",slug:"luca-ricciardi",fullName:"Luca Ricciardi",profilePictureURL:"https://mts.intechopen.com/storage/users/421212/images/system/421212.jpg",biography:"Dr. Ricciardi graduated in Medicine and Surgery in 2013 and finished his residency in Neurosurgery in 2019.\nIn 2017, he completed a fellowship in spinal deformities at the Catholic University of Rome - Italy, and in 2018 he completed a research fellowship at the Mayo Clinic, Jacksonville, Florida, US. He also completed the four-year training course of the European Association of Neurosurgical Societies and completed the European Board Exam part-1 for FEBNS.\nDr. Ricciardi has authored more than 60 papers published in peer-reviewed international journals. He has been serving as a reviewer for more than 15 scientific journals. He has been awarded as Publons Academy Mentor for training in peer-review, and he has conducted more than 80 certified peer reviews by the date. ( https://publons.com/researcher/1705851/luca-ricciardi/ ) \nIn 2021, Dr. Ricciardi was invited as Guest Editor for Systematic Reviews and Meta-analyses on the Journal of Neurosurgical Sciences, and as Invited Editor on Frontiers in Neurooncology, Life, and Cell. \nIn 2021, Dr. Ricciardi has been nominated co-Chairman and President of the Scientific Committee at SPINE20, the World Congress on Spine Disorders at the G20 conference in Rome, Italy.",institutionString:"Sapienza University of Rome",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Sapienza University of Rome",institutionURL:null,country:{name:"Italy"}}}],coeditorOne:{id:"436982",title:"Dr.",name:"Giorgio",middleName:null,surname:"Lofrese",slug:"giorgio-lofrese",fullName:"Giorgio Lofrese",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003FVMDgQAP/Profile_Picture_1633074659823",biography:"Dr. Lofrese is a neurosurgeon specialized in cranio-cervical junction diseases and minimally invasive spine surgery. As a former resident of the Catholic University in Rome, he completed his training in Milan, Bologna, and New York, concluding it in Curitiba with an AOSpine clinical fellowship. He is currently a permanent neurosurgeon at the Bufalini Hospital in Cesena, and a consultant neurosurgeon at the State Hospital of the Republic of San Marino. He was awarded with the European Young Researcher Award (AOSpine) and the Young Neurosurgeon Award (WFNS). Dr. Lofrese is in his final year as a PhD student in Neuroscience and Neurotechnologies at the University of Ferrara, developing new applications software addressed to patients with spinal cord injury.",institutionString:"University of Ferrara",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Ferrara",institutionURL:null,country:{name:"Italy"}}},coeditorTwo:{id:"436984",title:"Dr.",name:"Andrea",middleName:null,surname:"Perna",slug:"andrea-perna",fullName:"Andrea Perna",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003FVMdQQAX/Profile_Picture_1633585227288",biography:"Dr. Perna concentrates his fields of study on the pathologies of the spine, with particular attention to spinal deformities, traumatological surgery, and infectious pathologies such as spondylodiscitis. He also has numerous scientific publications relating to spinal deformity correction surgery and minimally invasive surgery, with particular attention to lateral surgery. His other fields of interest are hand surgery and biomechanics applied to orthopedics.",institutionString:"Gemelli Hospital",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorThree:{id:"440065",title:"Ph.D.",name:"Sokol",middleName:null,surname:"Trungu",slug:"sokol-trungu",fullName:"Sokol Trungu",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003FYl9aQAD/Profile_Picture_1633512850348",biography:"Dr. Trungu graduated with honors in Medicine and Surgery in 2010 and finished his residency in Neurosurgery in 2017. In 2021, he completed his PhD in Neuroscience and Neurosurgery at the Sapienza University of Rome, Italy. Currently, he is working as a consultant neurosurgeon at Cardinale G. Panico Hospital, Tricase, Italy. His areas of special interest are Minimally Invasive Spine Surgery (MISS), complex spine surgery, spine trauma focusing in acute spinal cord injury, primary and secondary spinal tumors, Neurovascular and Neuro-oncology. 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From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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Around a decade ago, the concept of “Industry 4.0” was proposed to summarize a set of industrial technologies from the fourth industrial revolution, linked to interconnected smart technologies, and evolving from the third (or digital) industrial revolution [1, 2]. Almost in parallel, the concept of “Society 5.0”, in short:
“Education 5.0” also benefits from these contemporary technological resources and aims at constructing Society 5.0, solving problems through value creation and quality education worldwide [6], in connection with the Sustainable Development Goals and the Agenda 2030 [7, 8]. Education 5.0 is bound to affect all educational levels and areas. In the engineering realm, the shift to innovative scenarios, which promote a continuously evolving engineering education, capable of adapting to these non-stop technological revolutions, is of special relevance.
Accordingly, the concept of “Engineering Education 5.0” has been also just proposed as an educational paradigm [9]. In short:
Taking into consideration recent engineering education transformations with international impacts, like the Conceive, Design, Implement, Operate (CDIO) initiative [10], it is necessary to put forward the relevance of problem- and project-based learning methodologies (PBL), which recreate the real professional life of engineers and train students for solving real-world challenges. Indeed, project-based learning has helped to reformulate engineering education over the last decades, as it has been increasingly applied worldwide, as a fundamental methodology for shifting to student-centered engineering programmes.
To enlighten the transition from Industry 4.0 to Society 5.0, and from Engineering Education 4.0 to Engineering Education 5.0, project-based learning (PBL) methodologies should also evolve:
In terms of focus and topics selected for the PBL experiences, it is necessary to put forward the relevance of global challenges and to nurture a compromise for sustainability and ethical behaviour, while bringing students as close as possible to real multifaceted engineering problems. As regards connections with other educational methodologies, PBL and service learning (SL) are clearly bound to hybridization and may benefit from innovative approaches, like the use of flipped classroom, the promotion of gamification or the support of online resources and e-/b-/m-learning tools and methods. Complete PBL experiences will also synergize with and contribute to open-source engineering movements, like the “makers” movement, and will benefit from open software and hardware tools for increased educational equity.
Towards a successful construction of “Engineering Education 5.0”, this chapter analyses and discusses trends in PBL methodologies, in connection with these new industrial and educational paradigms. Besides, basic guidelines for synergically implementing PBL experiences within engineering programmes oriented to Society 5.0 and pursuing a global promotion of students’ professional outcomes are also presented. Finally, several types of innovative PBL are described, numerous topics for implementation, covering most engineering specialties and professional roles, are presented, and useful supporting resources for professors and students are summarized. The gathered proposals are based on the author’s personal experience and views, on inspiring discussions with colleagues and a systematic search within the literature, as regards modern engineering education.
Engineering Education 5.0, according to its seminal publication [9], should be characterized by 16 interwoven key features listed in Figure 1. Some of these attributes have been also mentioned off late in relevant reports focusing on engineering education trends [11, 12, 13], which explain educational methodologies and learning styles quite connected to Education 5.0.
The 16 interwoven key features of Engineering Education 5.0.
In the author’s opinion, modern PBL should take account of these key features, to keep pace with the continuous evolutions within Engineering Education 5.0. At the same time modern PBL, built upon these elements, may liberate engineering programmes from the usually fixed frameworks and let them endlessly change, while supporting and mentoring the technological advances of Industry 5.0 for the successful construction of Society 5.0. Arguably, transforming PBL with Engineering Education 5.0 in mind, may turn out to be a very adequate strategy for empowering and deploying the technological revolutions ahead, whose positive industrial, economic, and social impacts can be essential. Counting with engineering education as one of the more relevant drivers of social change is always rewarding.
Figure 2, in alignment with other studies focused on strategies for the design and implementation of successful and transformative PBL [14, 15, 16], presents a selection of good practices for adjusting PBL methods to better consider the different pivotal aspects of Engineering Education 5.0. For instance, modern PBL in the Engineering Education 5.0 paradigm should change dynamically, evolving with technologies, as the state-of-the-art rapidly flows. To this end, annual modifications to the projects’ topics present a double intention: on the one hand keeping the PBL experiences alive, helping students to focus on avant-garde techniques and methods; on the other, avoiding malpractice and copying or taking too much inspiration from previous years’ results. Besides, modularity and flexibility are necessary for promoting resource-effective and personalized education and for swiftly spreading PBL across engineering programmes and universities. These aspects can benefit from counting with a fundamental or core module (i.e., engineering design methodologies for innovative product development), which may be central to different experiences and degrees. A combination of basic and specialization modules can foster fruitful adaptation of PBL to a wide set of programmes.
Summary of good practices for incorporating the key features of Engineering Education 5.0 to modern PBL.
Other interesting good practices deal with making PBL more holistic, taking inspiration from the engineers of the Renaissance, putting ethics in the foreground, better synergizing with key stakeholders and society, increasing societal impacts and making education more equitable. The hybridization of project-based learning and service learning [17], intensive use of e-Twinning and e-/b-/m-learning methods for supporting an affordable internationalization and for taking benefit from diversity [18], the employment of artificial intelligence tools for supporting educational practice [19] or resorting to open-source software and hardware resources [20], are also relevant strategies with synergic effects.
Ideally, through their projects, students learn how to transform society taking benefit from the ongoing technological revolutions and focusing on real needs and unsolved or partially solved societal problems. During the process, they learn to learn, feel more responsible for their learning, take decisions along a plethora of elective PBL experiences, which helps to personalize education, communicate and celebrate their results, and enjoy the process of becoming engineers. Sharing of methods and experiences, in the project-based learning field, is also fundamental towards high-quality engineering education for all.
The structures and contents of Engineering programmes in the 5.0 paradigm will necessarily suffer important transformations. A proposal for a universal engineering programme structure, considering contemporary and future engineering roles, has been recently detailed [9]. To summarizing, a whole 6-year programme, integrating a 4-year bachelor’s degree plus a 2-year master’s degree, can very adequately provide students with fundamental scientific-technological knowledge, specialized professional and transversal skills, necessary ethical values, and even give them important opportunities for personalization and professional planning. This can be achieved through modularity, through collaboration with other programmes, universities and institutions, through the promotion of international mobility and external internships and through a more flexible understanding of all the possible types of experiences that contribute to a holistic training of engineers, as already explained [9].
Let us consider the CDIO initiative, probably the most transformative and international action in the engineering education of the twenty-first century, and the current version of the CDIO standards (version 3.0) [21]. CDIO (from conceive-design-implement-operate) relies on the wise application of PBL principles for making engineering education more effective, through the engineering of different products, processes, and systems. Usually, CDIO-inspired engineering programmes benefit from at least one intensive hands-on or PBL course per training year, and the curricula are methodically designed
In the author’s belief, engineering studies in the 5.0 paradigm should rely on project-based methods even more than in current CDIO-inspired programmes. The use of PBL, not only as a methodology for fostering the ABET professional skills [22, 23], but also for delivering purposeful and continuously updated content, linked to the scientific-technological fundamentals of Industry 4.0 and 5.0, may prove strategic.
Accordingly, this section proposes a general plan for the synergic integration of PBL within engineering studies. The plan incorporates at least one intensive hands-on or PBL course or highly formative student-centered experience per semester, as schematically shown in Table 1 and further described in Table 2.
Programme level | Academic year | First semester experiences | Second semester experiences | Total PBL credits/year | ||
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Type of PBL experience | PBL credits | Type of PBL experience | PBL credits | |||
Master’s Degree in Engineering for Society 5.0 (120 ECTS) | 6th | R&D PBL | 6 | Final degree thesis | 12 | 18 |
5th | CDIO PBL | 6 | In-company PBL | 6 | 12 | |
Bachelor’s Degree in Engineering for Society 5.0 (240 ECTS) | 4th | CDIO PBL | 6 | Final degree thesis | 12 | 18 |
3rd | Synthetic PBL | 6 | International competition | 6 | 12 | |
2nd | Analytical PBL | 3 | Service-learning experience | 6 | 9 | |
1st | Descriptive PBL | 3 | Local competition | 3 | 6 |
Proposal for mapping different types of PBL initiatives along with an integral 6-year Bachelor’s and Master’s Degree in Engineering for Society 5.0.
Types of PBL experiences | Description | Implementation examples |
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Final degree thesis | Holistic and highly integrative PBL experience, in which students, normally on their own and supported by a mentor, design de novo an engineering solution or optimize an existing product or system. |
|
R&D PBL | In-depth study of a specific problem, within an ongoing R&D project of a university department and supporting project’s team. As in capstone projects, a paper based on results may be written as a conclusion. |
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In-company PBL | Immersive industrial experience, through which students live a professional practice helping to solve a real problem or trying to optimize a company’s processes, products, or solutions. |
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CDIO PBL | Highly integrative PBL experiences, in which students’ groups live through the complete conceive-design-implement-operate cycle of innovative engineering products, processes or systems. |
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Synthetic PBL | PBL experiences focused on reaching a solution proposal for an engineering problem. Typically, students detect a need, develop a concept, and reach a design of an engineering product, process, or system. |
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Analytical PBL | PBL experiences focused on the study of an existing engineering system, which is normally divided into subsystems and components for understanding and modeling its functional principles and behaviour. |
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Descriptive PBL | PBL experiences, in which students, in some cases following a case study approach, describe a relevant need and existing solutions, documenting one of the possible solutions in detail. |
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Service-learning experience | Formative experiences with a clear social purpose, in which students are connected to a real societal problem and asked to provide an engineering-related solution after interaction with key stakeholders. |
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International competition | Like the local competitions, but international and normally involving more challenging problems and requiring the delivery of a final product prototype-. |
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Local competition | Focused design competitions, usually for first-year students and with a socialization purpose, together with the formative objective, in which teams provide engineering solutions to open-ended questions. |
|
Description and implementation examples of modern PBL experiences in the Engineering Education 5.0 paradigm.
Different types of project-based activities are considered, all of them relevant and mutually supportive, from the more straightforward and descriptive, to the more complex and integrative. These are classified with some parallelism to Bloom’s taxonomy, starting with descriptive and analytical PBL experiences, following with synthetic PBL experiences, and ending up with complete CDIO approaches and final theses. There is also space for local and international competitions, as a way for promoting personalization, for more easily adapting the engineering programmes to relevant engineering trends and for promoting peer learning approaches, in a way bringing
The above-proposed mapping of PBL initiatives along an integral 6-year Bachelor’s and Master’s Degree in Engineering for Society 5.0 can be adapted to any engineering programme of the 5.0 paradigm. The initial PBL experiences (years 1st–2nd) have a clear focus on knowledge acquisition and concentrate on the promotion of analytical skills, while those from the 3rd to 6th years are directed towards knowledge application and foster more technical and professional skills.
Countless examples can be provided for each type of PBL experience and Table 2 just aims at providing a brief description, of the different types of modern PBL experiences, and some implementation examples in the context of Engineering Education 5.0. Many of the cited examples apply the techniques from Industry 4.0 and 5.0, like artificial intelligence, big data, internet of things, cyberphysical interfaces, multi-physical/chemical simulations, digital twins, additive manufacturing, collaborative robots, autonomous systems …, to solving problems in different industries and engineering fields. In other cases, the PBL initiatives are focused on designing or further developing such technologies. The redesign or reengineering of existing products, processes or systems, with sustainability principles in mind, can be also a source for highly rewarding PBL experiences, in connection with all Sustainable Development Goals.
Pioneering experiences in the PBL arena will, of course, continue enlightening the new generations of engineers. Among them, it is important to mention: the “Formula SAE/Student” automotive challenges (dating back to 1981), the “IARC” competition on aerial robotics (since 1991), the “CAN-SAT” satellite construction challenges (since 1998), the “FIRST Lego League” robotics competitions (since 1998), the “Solar Decathlon” competitions focused on efficient buildings (since 2002), the James Dyson Design Competitions (since 2007) and the “UBORA” medical device design schools (since 2017), to cite some examples in varied engineering fields. Most of them have taken benefit from the methods and techniques from Industry 4.0 and 5.0, well before the coining of such terms, and have also helped to research and develop several working methods and technologies that are central to current industrial revolutions.
The previous section has mapped the different types of PBL experiences along with an integral 6-year Bachelor’s and Master’s Degree in Engineering for Society 5.0, as an example of how any engineering programme may be transformed through truly transformative student-centered activities. Now, it is also necessary to integrate these experiences in a synergic or mutually supportive way, to systematically promote students’ outcomes.
Employing the ABET professional skills as a reference, Table 3 presents an example of how different types of PBL experiences connect with students’ outcomes, considering that each outcome should be specifically covered by at least one PBL experience of the engineering programme (see also Table 2). The more integrative PBL experiences (final theses, R&D PBL and CDIO experiences), for instance, may well synergize for fostering students’ abilities to apply knowledge from maths, science and engineering, to identify, formulate and solve engineering problems, to design systems and components to meet specifications and to understand the impacts of engineering solutions. Other more focused PBL experiences (in-company PBL, competitions, analytical/synthetic) may promote ABET’s skills d, f, g, i, j, k.
Students’ outcomes as proposed by ABET | |||||||||||
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Types of PBL experiences | a. an ability to apply knowledge of mathematics, science and engineering | b. an ability to design and conduct experiments and analyze data | c. an ability to design a system or component to meet specifications | d. an ability to function on multidisciplinary teams | e. an ability to identify, formulate and solve engineering problems | f. an understanding of professional and ethical responsibility | g. an ability to communicate effectively | h. a broad education to understand the impact of engineering solutions | i. a recognition of the need for and an ability to engage with lifelong learning | j. a knowledge of contemporary issues | k. an ability to use the techniques, skills and tools for engineering practice |
Final degree thesis | XX | X | X | XX | X | X | X | X | X | X | |
R&D PBL | X | XX | X | X | X | X | X | X | |||
In-company PBL | X | X | X | X | X | X | XX | X | X | ||
CDIO PBL | X | X | XX | X | X | X | X | XX | X | X | X |
Synthetic PBL | X | X | X | X | XX | ||||||
Analytical PBL | XX | X | X | X | |||||||
Descriptive PBL | X | X | XX | ||||||||
Service-learning experience | X | X | X | XX | X | X | X | ||||
International competition | X | XX | X | X | |||||||
Local competition | X | X | XX | X |
Different types of PBL experiences and their connections with students’ outcomes, employing the ABET professional skills as reference.
Once explained how different types of PBL experiences may be mapped along a universal 6-year engineering programme for Society 5.0 and how the different kinds of experiences support each other for the promotion of students outcomes, this section concentrates on how PBL may help to further develop the technologies from Industry 4.0 towards Society 5.0, considering also the roles of modern engineering professional practice and providing an application example of how PBL may vertebrate a specific engineering programme for Society 5.0. Table 4 presents several examples of PBL teaching-learning experiences for deploying the technologies from Industry 4.0 and hence constructing Society 5.0. Depending on the outcomes and industrial area of the specific engineering programme and on students’ wishes a myriad of combinations is possible.
Key topics | Possible PBL teaching-learning experiences for deploying Industry 4.0 and constructing Society 5.0 | Types of PBL experiences | |
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Technologies from the Industry 4.0 paradigm | Artificial intelligence |
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Big data |
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Smart factories |
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Autonomous robots |
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3D printing & flexible production |
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Internet of things |
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Cybersecurity |
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Expected transformations within Society 5.0 | Sustainable mobility |
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Better health management |
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Customized products |
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Reformed organizations |
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Improved services |
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Smart cities & environments |
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Examples of PBL teaching-learning experiences for deploying the technologies from Industry 4.0 and hence constructing Society 5.0.
Besides, the increasing connection between engineering disciplines may contribute to a progressive dissolution of borders between the classical specializations of the programmes of studies. Probably, structuring Engineering Education 5.0 programmes according to the modern professional roles of engineers, which are more stable than the continuously evolving and nascent engineering majors, may be an adequate solution for constructing universal engineering programmes [9]. With this perspective, Table 5 describes and exemplifies PBL oriented to the different professional engineering roles in Society 5.0.
Modern engineering professional roles | Description of PBL experiences and features oriented to the different roles | Possible implementation examples |
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1. Products, processes, and systems engineers | Students live through the specification, conception, design, prototyping and testing of innovative products, processes, or systems, usually employing CAD-CAE-CAM programs and AM technologies and rapid prototyping tools as resources. |
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2. Management and business engineers | Students live through the strategic planning of an enterprise and develop its business model or help to reengineer processes within existing industrial plants. |
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3. Scientific and research-oriented engineers | Students experience a research project, generally working within a university department or research center, working on basic or applied research tasks, solving a specific problem, and publishing a paper. |
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4. Political engineers and regulators | Students understand the key relevance of standards, regulations, and policies for enabling technologies to reach those needing them most safely and effectively. |
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5. Social and humanistic engineers | Students supervise the ethical implications of an innovative technology and promote human-centered design processes, working towards optimal societal impacts. |
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6. Media & arts and cultural engineers | Students experience and foster innovative connections between engineering and art by conceiving, designing, and developing new materials, designs, processes, and methods. |
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7. Environmental and urban planning engineers | Students focus on human environments focusing on well-being and living through projects linked to improving buildings, cities, and communities in general. |
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8. Biomedical and biological systems engineers | Students design and develop technologies and processes in connection with the biomedical field and with biological systems and biotechnology in general. |
|
Description of PBL experiences oriented to the different professional engineering roles in Society 5.0.
Considering all previous sections, Table 6 presents the concrete mapping of modern PBL experiences throughout an integral 6-year Bachelor’s and Master’s Degree in Biomedical Engineering for Society 5.0. In the scheme, all types of PBL experiences synergize for providing students with basic and applied knowledge, for letting them acquire technical and professional skills, liked to most areas of Industry 4.0 and several challenges of healthcare within Society 5.0.
Programme level | Academic year | First semester experiences | Second semester experiences | Total PBL credits/year | ||
---|---|---|---|---|---|---|
Type of PBL experience | PBL credits | Type of PBL experience | PBL credits | |||
Master’s Degree in Biomedical Engineering for Society 5.0 (120 ECTS) | 6th | R&D PBL: Hands-on experience linked to the development of innovative tissue engineering and biofabrication solutions | 6 | Final MSc thesis: Develop a medical technology and set the foundations for a related spin-off company | 12 | 18 |
5th | CDIO PBL: Design and prototyping of an IoT device for health management | 6 | In-company PBL: Participate in the QA/QC of production and supply chain of a medical product | 6 | 12 | |
Bachelor’s Degree in Biomedical Engineering for Society 5.0 (240 ECTS) | 4th | CDIO PBL: Design and prototyping of an AI-based diagnostic device | 6 | Final BSc thesis: Develop an app benefiting from big data for health prognosis | 12 | 18 |
3rd | Synthetic PBL: Design, simulate and 3D print a personalized medical device | 6 | International competition: Participation in an “UBORA” competition and design school [24] | 6 | 12 | |
2nd | Analytical PBL: Select a relevant medical device, check applicable standards for its safe development and propose a regulatory pathway towards commercialization | 3 | Service-learning experience: Select a hospital process, study it and propose improvements by collaborating with healthcare professionals | 6 | 9 | |
1st | Descriptive PBL: Map biomedical technologies in connection with Industry 4.0 tools and the Society 5.0 paradigm | 3 | Local competition: Ideas challenge for approaching the “healthcare of the future” | 3 | 6 |
Implementation example: concrete mapping of modern PBL experiences throughout an integral 6-year Bachelor’s and Master’s Degree in Biomedical Engineering for Society 5.0.
The presented perspective is based on an analysis of the recent evolution of PBL-experiences and engineering education, in general, and follows the findings and continuation proposals of transformative educational experiences described in the selected references. However, it also derives from the author’s personal and highly rewarding experiences in the design and implementation of different kinds of PBL experiences in six different degrees of studies at UPM, carried out at bachelor’s, master’s and doctoral levels, as well as in international onsite and online hackathons, bootcamps and engineering design schools.
Some of these successful stories, in connection with different types of PBL experiences already including some features of Engineering Education 5.0, have been previously reported [15, 19, 20, 24]. Nevertheless, the creation of a whole 6-year engineering programme, completely structured around PBL experiences focusing on the technologies from Industry 5.0, as schematically presented in Tables 1 and 6, is still an educational dream. The author intends to progress towards the implementation of this kind of educational model, which connects with the pioneering example and aims of the International CDIO Initiative, perhaps taken to the extreme, until its last consequences and interwoven with continuously evolving technologies, which requires more dynamic programmes.
Such real-life implementation can follow differently and mutually supporting strategies. A first and straightforward strategy could rely on the gathering of successful PBL experiences, across programmes of a university, and on letting students select (initially as one or two electives per year), those more in line with their interests. A second strategy, now that inter-university campuses are being created across Europe (Erasmus+ European Universities programme), would be to organize biannual international PBL events within these new communities, offering different types of PBL experiences related to Industry 5.0 and with a common credit transfer system. This would also help to vertebrate the new European universities. A third option would be to update the contents and methods of already existing engineering programmes and transform them through modern PBL. To this end, the bottom-up changes introduced by professors, already carrying out transformative PBL in their courses, can act as seminal examples. Finally, a fourth alternative is foreseen: evolving already existing PBL courses towards the concept and context of Engineering Education 5.0 (dynamically updating and incorporating new technologies, making knowledge-based and outcomes-based education compatible, focusing on the SDGs and sustainability, taking account for the human and ethical aspects of engineering, among others).
Top-down approaches and decisions might also support these directions and offer change in the mid-term future. One could foresee international accreditation agencies assuming these principles along the current decade, or a rectorate deciding to update the educational model of a whole university, which could be built around PBL and Industry 5.0. Despite these top-down possibilities, in the author’s view, the more relevant educational changes at universities tend to follow bottom-up schemes, starting with an inspiring conversation in the classroom between students and professors or with a shared dream among colleagues from a department or faculty, which act as the crystallization seeds of change.
Accordingly, to favour the proposed transition towards PBL 5.0, the following scheme of Figure 3 provides a guided set of steps and driving questions, through which PBL for Industry 5.0 experiences can be designed, managed and evaluated, with a focus on their steady integration in already existing engineering programmes, for acting as the previously cited seeds of change. Additional advice may be found in recent publications [25, 26].
Guided steps and driving issues for creating PBL 5.0 experiences.
Finally, Figure 4 presents some examples of typical behaviours (students and professors learning together, more Socratic discussions than master classes), environments (international teams, tinkering possibilities, onsite and online interactions), and results (real working prototypes solving relevant needs) expectable in PBL 5.0 experiences mentored by the author.
(a) Upper images: relaxed discussions and peer learning in international PBL experiences. (b) Lower images: PBL prototyping results of biodevices for good health and well-being (SDG3). Innovative Braille display, testing a 3D printed water filter, and face-protecting splints for safe sport practice. Courtesy of UBORA project.
Times are changing in engineering education, as a consequence of the current non-stop concatenation of scientific-technical breakthroughs and related technological revolutions. The age of untouchable decades-lasting engineering programmes is over, and dynamism, evolution, flexibility, and equity are paramount to modern engineering education. In a personal definition, modern engineering may correspond to
In consequence, strategies for enabling the continuous improvement and adjustment of engineering programmes, in a world of changing boundary conditions, are needed. To this end, PBL methodologies and experiences may vertebrate or serve as a scaffold for constructing the engineering programs in the Education 5.0 paradigm. This has been discussed and supported with varied implementation examples and methods, for the successful integration of PBL within modern engineering curricula. In this new context, PBL methodologies are not only hands-on activities for knowledge application, but play also an essential role, within the global educational strategy, for delivering purposeful and continuously updated content, for knowledge acquisition and for developing descriptive, analytical, synthetic, technical and personal skills.
The author declares no conflict of interest.
Type I interferonopathies are congenital genetic disorder of the interferon (IFN) system, characterized by certain clinical symptoms resulting from the overproduction of IFNα [1, 2, 3]. In our opinion, the term interferonopathy means a general pathology of the interferon system, congenital or acquired, which includes the following types of disorders of the IFN system:
The main role of type I interferons is to control viral infection. The synthesis and secretion of type I IFN is activated when our immune cells come in contact with viruses. Type I IFN is synthesized by epithelial cells, many cells of the immune system, including plasmacytoid dendritic cells (pDC) that recognize foreign or auto nucleic acids. Although both epithelial and pDC synthesize type I IFN simultaneously in different tissues, pDC-derived type I IFN actually exerts various immune responses through its cognate receptors on target cells. This results in modulation of diverse processes such as antigen presentation and activation of adaptive immunological process involving B and T cells [5]. For the synthesis of interferons in the body, cell activation is necessary. Toll-like receptors (TLRs); RIG-like receptors (RLRs), RIG-I; melanoma differentiation-associated protein 5 (MDA5); and cyclic GMP-AMP synthase (cGAS) participate in the recognition of foreign and host nucleic acid sites [6]. The main inducers of the synthesis of type I interferons are double-stranded and single-stranded RNA of viruses, as well as bacterial DNA [7]. RIG-like receptors recognize both single- and double-stranded viral RNAs, whereas cGAS (cyclic GMP-AMP synthase), in contrast, recognizes double-stranded DNA and RNA: DNA duplexes are formed during the replication of retroviruses and catalyze the synthesis of cGMP-AMP, which is the main agonist of the adapter protein—STING. After binding RNA, RIG-I and MDA5 bind the mitochondrial antiviral-signaling (MAVS) adapter protein. Both STING and MAVS stimulate downstream signaling cascades that include multiple kinases and finally lead to phosphorylation of IRF3 and induction of interferon synthesis [8]. Then type I IFN binds to the corresponding IFNAR receptors located on the cell membrane, which leads to the activation of Tyk2 and Jak1 kinases, which undergo phosphorylation and activate signal transduction and transcription activation proteins (STAT1 and STAT2). As a result, a heterotrimeric complex is formed, known as IFN-stimulating gene factor-3 (ISGF3), which includes IFN regulatory factor 9 (IRF9). Janus kinase (Jak) activation is negatively regulated by IFNα-inducible proteins SOCS1 and SOCS3. The binding of ISGF3 promotes interferon-stimulated genes (ISGs), which leads to their transcriptional activation and the collective actions of hundreds of ISGs, resulting in the production of a large number of induced IFN, which inhibits both viral replication and the spread of viruses. Rapid type I IFN secretion and then rapid synthesis induce activity of congenital and adaptive immunity cells by activation of pro-inflammatory cytokines that activate cellular and humoral antiviral immune response [9] (Figure 1).
Molecular mechanisms of the induction of type I and III interferon synthesis. PAMPs: dsRNA, double-stranded RNA; ssRNA, single-stranded RNA. Nucleic acid sensors: cGAS, cyclic GMP-AMP synthase;
During acute viral infection, IFN level is significantly elevated, and more than 70% of cells acquire antiviral status, i.e., they are protected against virus penetration and are able to efficiently neutralize them. Type I IFN has several very important positive effects: direct and indirect antiviral effect, protective antiviral effect, antitumor effect, and immunomodulatory effect. At the same time, it was shown that increased production of IFN can lead to negative consequences similar to autoimmune reactions.
The information presented by several authors about interferon system pathologies is vast and diverse but is not well-systematized. All known defects of IFN system, including type I and II IFN, whether congenital or acquired, including various disorders (deficiency; inadequate response to contact with viruses, bacteria, and mutated or tumor cells; IFN system paralysis; IFN overexpression), are pathologies of IFN system. All those defects of IFN system are collectively known as interferonopathies. There is an urgent need to create a classification of congenital and acquired disorders of the IFN system. We believe that the classification of IFN pathology would help in determining the correct approaches to the differentiated choice of adequate treatment tactics.
Based on our own and others’ experience, we have developed the interferonopathies classification as per the following table [1, 2, 3, 10, 11, 12, 13, 14, 15] (Table 1).
Recently several studies have presented genetic and molecular disorders accompanying rare Mendelian diseases that are associated with type I IFN overexpression resulting from defects in intracellular nucleic acid metabolism, DNAse deficiency, or defects in sensor nucleic acid recognition. Genetic disorders—Mendelian diseases (Aicardi-Goutières syndrome, familial chilblain lupus, spondyenchondromatosis, proteasome-associated autoinflammatory syndrome, Singleton-Merten syndrome)—resulting in inadequately high type I IFN overexpression accompanied by a certain range of clinical disorders are called type I interferonopathies. Interferonopathies have rare pathology; their occurrence varies from 1:10,000 to 1:1,000,000 people. According to the literature, the most common syndrome is Aicardi-Goutières [16]. The frequency of some recently described genetic disorders (e.g., PRAAS2) cannot be counted [17]. Such disorders cause a great number of own nucleic acids in cell cytoplasm to appear. It results in active DNA recognition and pathological overexpression of type I IFN which launch autoimmunity hyperactivation, thus leading to autoimmune inflammation affecting the central and peripheral nervous system. It also results to skin and vessel damage (vasculitis), lung damage, etc. Therefore rapid and efficient immune reaction to alien nucleic acids is positive when it causes type I IFN activation during pathogen invasion and antimicrobial protection. It becomes deleterious when it responds to own DNA which is due to the defect of own nucleic acid metabolism. Some neurological, vascular, and skin symptoms which are typical for type I interferonopathies are reviewed in such multifactorial diseases as exanthematous lupus erythematosus, widespread vasculitis, and autoimmune multiple myositis [6, 7, 18] (Table 2).
I. Congenital interferonopathies | II. Acquired—secondary interferonopathies |
---|---|
1.1 Interferon α deficiency (IFNα) 1.2 Interferon β deficiency (IFNβ) 1.3 Interferon γ deficiency (IFNγ) 2.1 IFNα overexpression 2.1.1 Autoinflammatory syndromes and autoimmune diseases (systemic lupus erythematosus (SLE), systemic angiitis, dermatomyositis), Down syndrome 2.1.2 Type I interferonopathies: Aicardi-Goutières syndrome (AGS), familial chilblain lupus (FCL), spondyenchondromatosis, proteasome-associated autoinflammatory syndrome (PRAAS), Singleton-Merten syndrome (SMS) | 1. 1.1 IFNα deficiency 1.2 IFNβ deficiency 1.3 IFNγ deficiency 2.1 Blockage IFNα adequate response 2.2 Blockage IFNβ adequate response 2.3 Blockage IFNγ adequate response 3.1 Cytokine storm |
Classification of interferonopathies.
Syndrome | Responsible gene | Phenotypes |
---|---|---|
Aicardi-Goutières syndrome | TREX1, RNASEH2B, RNASEH2C, RNASEH2A, SANHD, ADAR, IFIH1 | Encephalopathy, muscular dystonia, microcephaly, calcification of the basal ganglia in the substance of the brain, cramps, fever, increased acute phase blood markers, cytopenia, increased levels of interferon in the cerebrospinal fluid |
Singleton-Merten syndrome | IFIH1 DDX58 RIG-I | Cardiovascular diseases with aortic calcification, osteoporotic manifestations, dental and skeletal abnormalities, psoriatic skin lesions |
Proteasome-associated autoinflammatory syndromes Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) | PSMB4 PSMB3 PSMB8 PSMB9 POMP | Erythematous skin lesions, panniculitis, lipodystrophy, arthritis with the development of joint contractures, myalgia, hepatomegaly, splenomegaly, calcification of the basal ganglia in the brain, fever, increased acute phase blood markers Recurrent fevers in the first months of life, along with characteristic skin lesions, lipodystrophy, violaceous swollen eyelids, arthralgias, extremity contractures, and delayed physical development as well as systemic inflammation markers have been identified as CANDLE-related clinical manifestations |
STING-associated vasculopathy with onset in infancy (SAVI) | TMEM173 | Vasculopathy with the formation of distal gangrene; necrosis; erythematous rash on the face, tip of the nose, and auricles; interstitial lung disease, arthralgia, fever |
Spondyloenchondrodysplasia (SPENCD) | ACP5 | Spondylometaphyseal dysplasia, stunting, calcification of the basal ganglia in the substance of the brain, arthropathy, thrombocytopenia, deficiency of cellular and humoral immunity |
ISG15 deficiency | ISG15 | Calcification of the basal ganglia in the substance of the brain, convulsions, mycobacterial infections |
USP18 deficiency (pseudo-TORCH syndrome) | USP18 | Cerebral hemorrhage and calcification, hepatomegaly, thrombocytopenia |
Trichohepatoenteric syndrome 2 | SKIV2L | Watery diarrhea, brittle and tangled hair, liver damage, mental retardation |
Retinal vasculopathy with cerebral leukodystrophy (RVCL) | TREX1 | The main characteristics of RVCL include the middle-age onset, the progressive visual loss due to retinal vasculopathy (telangiectasias, microaneurysms, and retinal capillary obliteration around the macula), and variable neurological manifestations such as dementia or migraine |
Familial chilblain lupus | TREX1 | Rare monogenic form of cutaneous lupus erythematosus; partly ulcerating acral lesions or painful bluish-red papules located in the fingers, toes, nose, and ears; arthralgias, affecting mainly large joints, without evidence of true arthritis; photosensitivity; or mouth ulcers |
X-linked reticulate pigmentary disorder (XLPDR) | POLA1 | Generalized hyperpigmentation intermingled with small hypomelanotic macules during early childhood, a distinctive face characterized by an upswept frontal hairline and arched eyebrows, as well as severe photophobia, recurrent respiratory infections, and severe gastrointestinal disorders |
Genetic disorders associated with immune dysregulations and clinical characteristics of interferonopathies associated with type I IFN overexpression.
Data available on genetic defects of intracellular nucleic acid metabolism greatly facilitate understanding of the mechanisms of insufficient immune activation, which can help in the development of new therapeutic approaches to the treatment of autoinflammatory and autoimmune diseases [1, 2, 3]. The progress in understanding immunopathogenesis mechanism makes it possible to set the exact targets for new therapeutic strategy development [1, 2]. The immune dysregulation syndrome is characterized by a high level of IFNα, a deficiency of regulatory T-lymphocytes, impaired functioning of B cells, and low content of low-density neutrophils. These neutrophils easily form neutrophilic extracellular traps (NET), and the resulting DNA complexes provoke an increase in IFNα synthesis, and then pDC recognizes autoDNA and produces IFNα [10, 11, 19]. These disorders are observed primarily in systemic lupus erythematosus. New approaches in treatment of SLE and other type I interferonopathies have been developed. Monoclonal antibody therapy in type I interferonopathies treatment with SLE is sifalimumab, rontalizumab against IFNα, and anifrolumab against IFNα receptor (IFNAR). Baricitinib (JAK1/JAK2 inhibitor) is currently at clinical studies (phases 2 and 3) in small cohort of patients with interferonopathies [20, 21, 22]. It is also known that treatment with baricitinib decreased disease signs and symptoms and allowed a significant reduction of corticosteroid treatment in patients with CANDLE and SAVI [23] (Figure 2).
Target therapies by biologics in the treatment of type I IFN overproduction. IFNAR, IFNα receptor; ISGs, interferon-stimulated genes; Tyk, tyrosine kinase; Jak, Janus kinase; pDC, plasmacytoid dendritic cell; STAT, signal transducer and activator of transcription.
There are genetic defects in the synthesis of IFNα/IFNβ and IFNγ and defects in the receptors for IFNα and IFNγ (IFNAR and IFNGR) including genetic disorders associated with low IFN production according to recent studies. Those genetic defects of IFNs are accompanied by clinical signs of severe recurrent viral and/or mycobacterial infection.
Congenital defects of type I IFN are associated with mutation of genes participating in synthesis of IFNα/IFNβ resulting to deficiency of various molecules (STAT1, UNC93B1, MCM4, TLR3, TRAF3, TRIF, TBK1) and decline level of IFNα/IFNβ. Deficiency of IFNγ, its receptor IFNGR (IFNγR1), and IL-12 plays an important role in IFNγ regulation [12, 24, 25]. Congenital defects of type I IFN have been globally systematized in 2015 by Bousfiha et al. [24]. It has been proven that it causes severe viral and bacterial intracellular infections which are the cause of deaths. Such patients are needed in replacement therapy with recombinant IFNα2b in complex with antioxidants. Congenital defects of IFNγR1 receptor are associated with severe intracellular mycobacterial infections. Combined genetic defects leading to deficiency of IFNα and IFNγ are associated with an autosomal recessive mutation in the STAT1 gene, which causes severe viral and mycobacterial infections [12, 24, 25] (Table 3).
Predominant susceptibility to viral infection | ||
---|---|---|
Syndrome | Responsible gene | Phenotypes |
Herpes simplex encephalitis (HSE) | AR (autosomal recessive inheritance): UNC 9381 TLR3 TRIF AD (autosomal dominant inheritance): TLR3 TRIF TRAF3 TBK1 | Dominant clinical phenotype is HSE during primary infection with HSV1, usually between 3 months and 6 years of age Specific tests examining the TLR3 pathway marked decrease on the ability of patient’s fibroblasts to produce IFNβ/IFNλ in response to TLR3 agonists and HSV1 infection |
Warts, hypogammaglobulinemia, infection, myelokathexis (WHIM) syndrome | AD: CCXR4 | Warts/human papilloma virus infection Neutropenia, reduced B cell numbers |
Epidermodysplasia verruciformis | EVER1/TMC6, EVER2/TMC8 | Human papilloma virus (group B1) infection and skin cancer |
STAT1 deficiency STAT2 deficiency | Viral infections | |
CD16 deficiency | Severe viral infections | |
IRF7 deficiency | Severe influenza disease | |
Syndrome | Responsible gene | Phenotypes |
IRF8 deficiency | AR: IRF8 | Susceptibility to mycobacteria, |
RORc deficiency | RORc | Susceptibility to mycobacteria, |
MSMD IL-12-IFNγ axis deficiency | AD: IFNGR1 Complete AR IFNGR1 and AR IFNGR2 Partial STAT1 LOF (AD), partial IFNGR1, partial IFNGR2, complete IL-12R1, complete IL-12B, complete ISG15, XL CYBB, IRF8, Tyk2, XL NEMO | Mycobacterial osteomyelitis Serious disseminated BCG and environmental mycobacteria infections (soft tissue, bone marrow, lungs, skin, bones, and lymph nodes), Usually less severe |
Genetic disorders and clinical characteristics of interferonopathies associated with type I IFN deficiency.
There are secondary acquired disorders in the IFN system, which cause a weakening of antiviral resistance in adults and children [12]. Different viruses can damage synthesis and production of IFN at various interferonogenesis stages. These secondary defects of the type I IFN lead to the occurrence of severe viral infections (herpesviral encephalitis), recurrent acute respiratory viral infections (recARVI), chronic recurrent HSV1 infection, atypical chronic EBV infections, and other atypical cases of virus infection. It was shown that viruses can avoid the effects of IFN and inhibit the action and synthesis of IFN using various molecular mechanisms. Numerous studies demonstrated that a lot of viruses (all herpesviruses, majority of respiratory viruses, hepatitis B and C viruses, etc.) produce proteins capable of inhibiting synthesis and production of IFNα/IFNβ and IFNγ. Viruses can damage each stage of the expression of ISGs [9] (Figure 3).
Blockage of signaling pathways for the induction of interferon by viruses (red hexagons indicate the points of application of all herpesviruses, majority of respiratory viruses, chronic hepatitis B and C viruses, etc.). dsRNA, double-stranded RNA; IRF, IFN regulatory factor; IFNAR, IFNα receptor; ISGs, interferon-stimulated genes; Tyk, tyrosine kinase; Jak, Janus kinase; NF-kB, nuclear factor kappa-light-chain-enhancer of activated B cells; cGAS, cyclic GMP-AMP synthase; MAVS, mitochondrial antiviral-signaling protein;
Patients with recurrent acute respiratory viral infections and various chronic herpesvirus infections including recurrent herpes viral infections have secondary defects of IFN system. Immunocompromised children of various ages and adults may suffer from recARVI with the frequency of 10 to 16–24 and more times annually; almost in 100% of cases, it is associated with the presence of mono and mixed herpes viral infection. The frequency of recurrent chronic HSV1/HSV2 infection of facial and/or genital location in those patients may reach 16–24 times per year. Epstein-Barr virus may cause atypical virus infection associated with chronic fatigue syndrome [12].
The problem of developing new approaches to the treatment of congenital and acquired defects of the IFN system is very acute [12, 26, 27, 28]. Acquired defects in the IFN system (93–96%) and impaired functioning of neutrophilic granulocytes (NG) are most often detected in patients with recurrent chronic herpes virus infections.
We conducted experiment in vitro to study the effect of recombinant IFNα2b (rIFNα2b) on NG in viral (cells from patients with HSV1/HSV2 infection) and bacterial (model infection by fMLP) infections. The study showed positive regulation of the negatively charged IFNαβR1+IFNγR+TLR4+NG phenotype in patients with various chronic herpesvirus infections under the influence of rIFNα2b in vitro. It was noted that the number of NGs carrying IFNαβR1 and IFNγR and expression density of IFNαβR1 is increasing, wherein expression density of IFNγR and TLR4 is decreased [29]. rIFNα2b modulating effects on CD16+CD66b+CD33+CD11b+NG phenotype transformed by fMLP in experimental model of bacterial process in vitro, to promote remodeling of the pro-inflammatory NG phenotype into anti-inflammatory, have been shown [30]. Thus rIFNα2b has a protective effect on the NG phenotype according to experimental data.
In clinical practice, the use of parenteral IFN to correct disorders in the IFN system is very difficult due to the presence of numerous side effects. One should also bear in mind the inefficiency of short courses of IFN therapy for restoration of the normal IFN system functioning in recARVI, recurrent chronic herpes viral infection of facial or genital location, and papilloma virus infection of the skin and mucosa characterized by recurrent episodes when the frequency of recARVI and/or recurrent attacks of HSV1/HSV2 infection may reach 14–24 and more per year. For over 20 years, we have been developing interferon therapy programs using drugs in Russian production—rectal suppositories and gel of recombinant human IFNα2b (rIFNα2b+aox) in combination with antioxidants (vitamins E and C) (Viferon) [12, 13, 14, 15, 26, 27]. During that period, we managed to demonstrate safety, antiviral, and immunomodulatory efficiency of this kind of IFN therapy, total absence of any side effects that are typical for parenteral IFN therapy, and total absence of antibodies against IFNα2b. Replacement therapy with rIFNα2b + aox is prescribed to patients with primary, genetically preconditioned, congenital or acquired IFN system disorders. In case of primary IFN system disorders, patients need a basic recovery therapy making it possible to eliminate viral antigens as much as possible; and then it is required to select dosage for permanent replacement therapy with rIFNα2b+aox. In case of acquired interferon deficiency, patients are prescribed with differentiated therapy with high, medium, and low doses of rIFNα2b+aox (Figure 4).
Dynamics of changes in the system of IFN in immunocompromised children against the background of therapy with rIFNα2b+aox (Viferon).
At the same time, in case when we had treated the group of patients with combined immunodeficiency (defects of induced production of IFNα and IFNγ and dysfunctions of phagocytic and microbicidal activities of neutrophilic granulocytes) that was associated with recurrent acute respiratory viral infection and different chronic herpes viral coinfections, combined interferon and immunomodulatory therapy was used. The aim was to restore the levels of induced production of IFNα and IFNγ and to reconstruct dysfunctions of phagocytic and microbicidal activities of neutrophilic granulocytes and other deficient chains in antiviral immunity. One group of children, group 1, received an interferon therapy program (rIFNα2b+aox), and patients in group 2 received a program of combined interferon therapy (rIFNα2b+aox) and immunotherapy (glucosaminylmuramyldipeptide). The use of replacement and immunomodulatory mono-rIFNα2b+aox or in combination with immunotherapy (glucosaminylmuramyldipeptide) has helped us to receive very good clinical efficacies and has reached restoration of interferon status and normal functioning of neutrophilic granulocytes (p < 0.05) (Figure 5). At the same time, it is required to take into account both uneven viral infection syndrome manifestation and the rate of IFNα deficiency as well as peculiarities of immune system disorders in case of secondary immune deficiency [12, 13, 14, 15, 27].
The state of the interferon system in immunocompromised children with recurrent respiratory infections on the background of differentiated programs interferon and immunotherapy. Note: group 1 received an interferon therapy program (rIFNα2b+aox); group 2 received a program of combined interferon therapy (rIFNα2b+aox) and immunotherapy (glucosaminylmuramyldipeptide); (*p < 0.05, reliability in relation to control).
Here is an example illustrating the change in clinical, immune, and interferon status in immunocompromised children with recurrent acute respiratory viral infections under the influence of interferonotherapy.
Clinical case. Patient X, 3 years old. The child suffers from repeated acute respiratory viral infections 1–2 times per month (14–16 episodes per year); the duration of the acute period of respiratory viral infection is 7–10 days. The clinical symptoms of the disease were acute rhinitis, acute pharyngitis, acute laryngitis, acute tracheitis, febrile and subfebrile body temperature for 2–4 days, and severe symptoms of intoxication. The duration of the frequent incidence of acute respiratory viral infections is 2 years. The defects of the immune system are a decrease of CD3+CD4+ lymphocytes and CD3+CD8+ lymphocytes; a decrease of immunoregulatory index; neutropenia; a decrease of bacteria absorption and digestion processes by neutrophils; and a decrease of microbicidal activity of neutrophils. We tested spontaneous and Newcastle disease virus-induced IFN production during the incubation of peripheral blood (24 h, t 37°C in 5% CО2). The level of induced IFNα in the patient was 4 IU/ml versus 58 IU/ml in control. The patient was prescribed rIFNα2b+aox therapy with a total duration of 2.5 months.
Treatment program:
Local intranasal use of rIFNα2b+aox (Viferon gel, 36,000 IU/g), two to three times a day, 6 weeks.
Systemic rectal application of rIFNα2b+aox suppositories according to a “step-by-step” scheme:
300,000 IU per day, 10 days.
300,000 IU per day three times a week, 2 weeks.
300,000 IU per day two times a week, 2 weeks.
150,000 IU per day two times a week, 2 weeks.
150,000 IU per day once a week, 2 weeks.
Conducted local and systemic interferon therapy led to a reduction in the frequency of acute respiratory viral infections to three episodes per year lasting 5–7 days, proceeding in a milder form. Rehabilitation of immunity parameters occurred after 2.5 months of interferonotherapy, and the level of induced IFNα was normalized to 64 IU/ml.
Summing up the above information, we may conclude that new biological drugs based on mAb are effective and safe, and they are able to neutralize IFNα overexpression in type I interferonopathies, both in Mendelian’s diseases and in autoimmune disorders. At the same time, local and system use of rIFNα2b+aox (Viferon) in congenital and acquired IFN system defects associated with viral infection syndrome, where a differential dosage is selected individually taking into account the rate of deficiency and an adequate, extended course of therapy is optimal because it is associated with positive clinical and immunological effects without any negative and side effects. Our more than 20-year experience has shown that using recIFNα2b+aox in patients with congenital or acquired IFN system defects had demonstrated positive clinical effect and is safe [31]. IFN (rIFNα2b+aox) therapy can be used with very good clinical efficacy in cases of primary or secondary defects of induced production of IFNα and IFNγ. From the other side, it is very important that in patients with a genetic predisposition to the manifestation of autoimmune diseases, primarily vasculitis and systemic lupus erythematosus, we do not recommend to use IFN therapy.
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Among many complications, septic embolism has the potential of causing devastating sequelae and even life-threatening clinical situations. This dreaded clinico-pathologic entity is characterized by its heterogeneous presentation and the ability to affect various body systems and organs. Septic emboli to the brain, kidneys, spleen, and the pulmonary system constitute the vast majority of metastatic infections. However, other organ systems can also be affected. This chapter provides an overview of septic embolism associated with infective endocarditis, focusing on key diagnostic and therapeutic considerations in the most commonly seen and clinically relevant scenarios.",book:{id:"5351",slug:"contemporary-challenges-in-endocarditis",title:"Contemporary Challenges in Endocarditis",fullTitle:"Contemporary Challenges in Endocarditis"},signatures:"Thomas R. Wojda, Kristine Cornejo, Andrew Lin, Anthony Cipriano,\nSudip Nanda, Jose D. Amortegui, Barbara T. 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Increased vascular oxidative stress may induce non-enzymatic production of isoprostanes from AA, which, together with vasoconstrictor metabolites of AA underlie endothelial damage and impaired vascular function. The balance among vasodilator and vasoconstrictor metabolites of AA may be disturbed in cardiometabolic diseases. (e.g. hypertension,obesity,diabetes) Dietary habits significantly affect the metabolism of AA, particularly excessive kitchen salt (NaCl) intake. Control of environmental risks factors, good maintenance of the occurring diseases and balanced nutrition with restricted salt intake can significantly improve the metabolism of AA and alleviate microvascular dysfunction and subsequent organ damage. Current research on pharmacological manipulation of certain components of the AA pathways (such as 20‐HETE production inhibition or prolongation of the life of epoxyeicoatrienoic acids(EETs) by inhibitors of soluble epoxide hydrolaze (sEH)promises effective therapy of cardiovascular and cerebrovascular diseases in the future.",book:{id:"5281",slug:"microcirculation-revisited-from-molecules-to-clinical-practice",title:"Microcirculation Revisited",fullTitle:"Microcirculation Revisited - From Molecules to Clinical Practice"},signatures:"Ines Drenjančević, Ivana Jukić, Zrinka Mihaljević, Anita Ćosić and\nAleksandar Kibel",authors:[{id:"186048",title:"Prof.",name:"Ines",middleName:null,surname:"Drenjančević",slug:"ines-drenjancevic",fullName:"Ines Drenjančević"}]},{id:"35798",doi:"10.5772/39038",title:"Why, When and How Should Atrial Septal Defects Be Closed in Adults",slug:"why-when-and-how-should-atrial-septal-defects-be-closed-in-adults",totalDownloads:6744,totalCrossrefCites:1,totalDimensionsCites:8,abstract:null,book:{id:"1092",slug:"atrial-septal-defect",title:"Atrial Septal Defect",fullTitle:"Atrial Septal Defect"},signatures:"P. Syamasundar Rao",authors:[{id:"68531",title:"Dr.",name:"Syamasundar",middleName:null,surname:"Rao",slug:"syamasundar-rao",fullName:"Syamasundar Rao"}]},{id:"51006",doi:"10.5772/63515",title:"A Challenged Sympathetic System Is Associated with Retinal Vascular Calibre in a Black Male Cohort: The SABPA Study",slug:"a-challenged-sympathetic-system-is-associated-with-retinal-vascular-calibre-in-a-black-male-cohort-t",totalDownloads:1660,totalCrossrefCites:3,totalDimensionsCites:7,abstract:"Sympathetic system hyperactivity and depression are related to cardiac remodelling in Black men. We investigated whether sympathetic system hyperactivity and depressive symptoms are related to retinal vascular dysregulation. A total of 76 Black and 83 White men (23–68 years of age) from the SABPA study were included. Depressive symptoms, 24h pulse pressure (PP), fasting blood and 24-hour urinary catecholamine data were obtained. Retinal vascular calibre was quantified from digital photographs using standardized protocols. Black men demonstrated increased (p < 0.05) hyperpulsatile pressure (PP > 50 mmHg), hypertension (78.9 % vs 48.4%) and depression (34.2% vs. 13.3%) prevalence compared to White men. Despite lower epinephrine levels, epinephrine was associated with arteriolar narrowing and venular widening in the Black men [Adj R2 −0.37 (95% CI: −0.66, −0.09), p=0.013; Adj R2 0.35 (95% CI: 0.13, 0.57), p=0.003]. This might suggest ß-adrenergic hyporesponsivity to epinephrine, which was accompanied by hyperpulsatile blood pressure in the Black group. In the White group, depressive symptoms and norepinephrine were associated with retinal arteriolar narrowing. A profile of ß-adrenergic hyporesponsivity, indicative of a chronically challenged sympathetic system, was associated with retinal vascular remodelling in Black men. ß-adrenergic hyporesponsivity as a result of chronic stress emphasized central control of the brain on the circulatory system irrespective of the vascular bed.",book:{id:"5281",slug:"microcirculation-revisited-from-molecules-to-clinical-practice",title:"Microcirculation Revisited",fullTitle:"Microcirculation Revisited - From Molecules to Clinical Practice"},signatures:"Nicolaas T. Malan, Roland von Känel, Wayne Smith, Gavin W.\nLambert, Walthard Vilser, Nina Eikelis, Manja Reimann and Leoné\nMalan",authors:[{id:"183353",title:"Prof.",name:"Leoné",middleName:null,surname:"Malan",slug:"leone-malan",fullName:"Leoné Malan"},{id:"183428",title:"Prof.",name:"Gavin W",middleName:null,surname:"Lambert",slug:"gavin-w-lambert",fullName:"Gavin W Lambert"},{id:"183429",title:"Prof.",name:"Roland",middleName:null,surname:"Von Kaenel",slug:"roland-von-kaenel",fullName:"Roland Von Kaenel"},{id:"183430",title:"Prof.",name:"Nicolaas T",middleName:null,surname:"Malan",slug:"nicolaas-t-malan",fullName:"Nicolaas T Malan"},{id:"183431",title:"Dr.",name:"Wayne",middleName:null,surname:"Smith",slug:"wayne-smith",fullName:"Wayne Smith"},{id:"183432",title:"Prof.",name:"Walthard",middleName:null,surname:"Vilser",slug:"walthard-vilser",fullName:"Walthard Vilser"},{id:"183441",title:"Dr.",name:"Nina",middleName:null,surname:"Eikelis",slug:"nina-eikelis",fullName:"Nina Eikelis"},{id:"183443",title:"Dr.",name:"Manja",middleName:null,surname:"Reimann",slug:"manja-reimann",fullName:"Manja Reimann"}]},{id:"35795",doi:"10.5772/38930",title:"Historical Aspects of Transcatheter Occlusion of Atrial Septal Defects",slug:"historical-aspects-of-transcatheter-occlusion-of-atrial-septal-defects",totalDownloads:3447,totalCrossrefCites:2,totalDimensionsCites:7,abstract:null,book:{id:"1092",slug:"atrial-septal-defect",title:"Atrial Septal Defect",fullTitle:"Atrial Septal Defect"},signatures:"Srilatha Alapati and P. Syamasundar Rao",authors:[{id:"123092",title:"Dr.",name:"Srilatha",middleName:null,surname:"Alapati",slug:"srilatha-alapati",fullName:"Srilatha Alapati"}]}],mostDownloadedChaptersLast30Days:[{id:"49384",title:"Laboratory Methodology Important in the Diagnosis and Prognosis of Antiphospholipid Syndrome",slug:"laboratory-methodology-important-in-the-diagnosis-and-prognosis-of-antiphospholipid-syndrome",totalDownloads:1926,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Antiphospholipid syndrome (APS) is an autoimmune disease, characterized by thrombosis and pregnancy complications with persistently elevated levels of antiphospholipid antibodies (aPL). Recently, a unique mathematical calculation has been presented to assess the risk of thrombosis in patients with APS called antiphospholipid score or global antiphospholipid syndrome score (GAPSS). This new approach in the diagnosis of APS leads to the assessment of the risk of thrombosis considering the results of different aPL (lupus anticoagulants (LA), anticardiolipin antibodies (aCL), antibodies against β2GPI (anti-β2GPI), and phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) (isotypes IgG and IgM). This chapter provides an overview of the algorithm strategy for APS diagnosis with the aims of characterizing in detail the laboratory methodology of criteria aPL (LA, aCL, and anti-β2GPI) and noncriteria aPL, such as IgA aCL and IgA anti-β2GPI, anti-domain I β2GPI, and antiprothrombin antibodies. In order to improve APS diagnosis, several new approaches in aPL detection have recently been suggested, such as multiline immunodot assay, detection of aPL by flow cytometry using beads with particular surface properties, and the newly developed automated BioPlex system technology for parallel detection of aCL and anti-β2GPI antibodies of IgG, IgA, and IgM isotypes. A completely different and promising approach in future research lies in the potential of microRNAs as biomarkers for risk of thrombosis and/or obstetric complication.",book:{id:"4761",slug:"thrombosis-atherosclerosis-and-atherothrombosis-new-insights-and-experimental-protocols",title:"Thrombosis, Atherosclerosis and Atherothrombosis",fullTitle:"Thrombosis, Atherosclerosis and Atherothrombosis - New Insights and Experimental Protocols"},signatures:"Polona Žigon, Mojca Božič-Mijovski, Mojca Frank Bertoncelj, Aleš\nAmbrožič, Matija Tomšič, Alojzija Hočevar, Borut Božič, Snežna\nSodin Šemrl, Tanja Kveder and Saša Čučnik",authors:[{id:"31224",title:"Prof.",name:"Snežna",middleName:null,surname:"Sodin-Šemrl",slug:"snezna-sodin-semrl",fullName:"Snežna Sodin-Šemrl"},{id:"72261",title:"Dr.",name:"Mojca",middleName:null,surname:"Božič-Mijovski",slug:"mojca-bozic-mijovski",fullName:"Mojca Božič-Mijovski"},{id:"111772",title:"Prof.",name:"Borut",middleName:null,surname:"Božič",slug:"borut-bozic",fullName:"Borut Božič"},{id:"175000",title:"Dr.",name:"Polona",middleName:null,surname:"Žigon",slug:"polona-zigon",fullName:"Polona Žigon"},{id:"175001",title:"Dr.",name:"Mojca",middleName:null,surname:"Frank Bertoncelj",slug:"mojca-frank-bertoncelj",fullName:"Mojca Frank Bertoncelj"},{id:"175002",title:"Prof.",name:"Saša",middleName:null,surname:"Čučnik",slug:"sasa-cucnik",fullName:"Saša Čučnik"},{id:"175004",title:"Prof.",name:"Matija",middleName:null,surname:"Tomšič",slug:"matija-tomsic",fullName:"Matija Tomšič"},{id:"175005",title:"Dr.",name:"Aleš",middleName:null,surname:"Ambrožič",slug:"ales-ambrozic",fullName:"Aleš Ambrožič"},{id:"175884",title:"Dr.",name:"Tanja",middleName:null,surname:"Kveder",slug:"tanja-kveder",fullName:"Tanja Kveder"},{id:"175885",title:"Dr.",name:"Alojzija",middleName:null,surname:"Hočevar",slug:"alojzija-hocevar",fullName:"Alojzija Hočevar"}]},{id:"52392",title:"Ocular Manifestations of Endocarditis",slug:"ocular-manifestations-of-endocarditis",totalDownloads:1909,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"Endocarditis is an inflammation of the inside lining of the heart chambers and heart valves. Ocular manifestations are nonspecific and could reveal the disease, justifying routine ocular examination. Staphylococcus aureus is the most incriminated in ocular complications. Endophthalmitis, retinal arterial occlusion, Roth dots, or vitreal and retinal infiltrations could be seen with endocarditis. Ocular prognosis in endophthalmitis and retinal arterial occlusion is poor. Ocular involvement was independently associated with death in infective endocarditis.",book:{id:"5351",slug:"contemporary-challenges-in-endocarditis",title:"Contemporary Challenges in Endocarditis",fullTitle:"Contemporary Challenges in Endocarditis"},signatures:"Cheima Wathek and Riadh Rannen",authors:[{id:"185720",title:"M.D.",name:"Cheima",middleName:null,surname:"Wathek",slug:"cheima-wathek",fullName:"Cheima Wathek"}]},{id:"53351",title:"Infected Aortic Aneurysms",slug:"infected-aortic-aneurysms",totalDownloads:2205,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"Infected aortic aneurysms are surgical urgencies, requiring prompt management to avoid the development of catastrophic complications. Although traditional open surgery composed of radical debridement and aortic reconstruction remains the gold-standard, many favorable results of the endovascular repair strategy have been reported. In this chapter, the etiology, bacteriology, clinical manifestation, and diagnostic criteria of infected aortic aneurysms will be discussed in detail at first, followed by a comprehensive review of both traditional open surgery and endovascular repair, based on current evidences and the authors’ institutional experience. Along with long-term oral antibiotic suppression and aggressive adjunctive procedures, endovascular repair for uncomplicated infected aortic aneurysms could be a definite treatment alternative to traditional open surgery in the endovascular era.",book:{id:"5434",slug:"aortic-aneurysm",title:"Aortic Aneurysm",fullTitle:"Aortic Aneurysm"},signatures:"Ting-Wei Lin and Chung-Dann Kan",authors:[{id:"189841",title:"Ph.D.",name:"Chung-Dann",middleName:null,surname:"Kan",slug:"chung-dann-kan",fullName:"Chung-Dann Kan"},{id:"190064",title:"MSc.",name:"Ting-Wei",middleName:null,surname:"Lin",slug:"ting-wei-lin",fullName:"Ting-Wei Lin"}]},{id:"53568",title:"Isolated Aortic Root Aneurysms",slug:"isolated-aortic-root-aneurysms",totalDownloads:1927,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"The aortic root has a complex anatomy due to a combination of several anatomical structures based on simple and consistent work in it. It is a hollow cylinder with three bulges, which have the main functional effect on the aortic valve opening-closing cycle and coronary circulation. Aneurysm is defined as a dilation of a blood vessel segment having ≥50% increase in diameter, whereas annuloaortic ectasia represents a diffuse dilation <50% of the normal diameter of the related vessel segment. Aortic root aneurysms mostly occur by degenerative processes as compared with primarily atherosclerotic changes in the descending and abdominal aortas: medial fragmentation, smooth muscle cells necrosis, and elastic fiber fragmentations with cystic spaces in the media filled with mucoid material. Because of the elevated mortality risk associated with complications, an effective aortic root aneurysm management depends on reduction the risk of death, rupture, and dissection. Conventional open heart surgery is the essential procedure for isolated aortic root replacement and a type of procedure (valve replacement or sparing) could be selected due to the pathology. An extensive aortic root replacement technique is the only option to rebuild the left ventricular outflow tract due to the reconstruction of the neo aortoventricular continuity in the aortic root abscess.",book:{id:"5434",slug:"aortic-aneurysm",title:"Aortic Aneurysm",fullTitle:"Aortic Aneurysm"},signatures:"Kaan Kırali and Deniz Günay",authors:[{id:"155565",title:"Prof.",name:"Kaan",middleName:null,surname:"Kırali",slug:"kaan-kirali",fullName:"Kaan Kırali"},{id:"196017",title:"Dr.",name:"Deniz",middleName:null,surname:"Günay",slug:"deniz-gunay",fullName:"Deniz Günay"}]},{id:"52157",title:"Advanced Echocardiography for the Diagnosis and Management of Infective Endocarditis",slug:"advanced-echocardiography-for-the-diagnosis-and-management-of-infective-endocarditis",totalDownloads:3111,totalCrossrefCites:3,totalDimensionsCites:5,abstract:"Echocardiography is fundamental for the management of infective endocarditis (IE) across all stages of the illness including diagnosis, surveillance during medical therapy, identification of prognostic markers, planning perioperative intervention, postoperative assessment, and follow-up after completion of definitive therapy. Modern era echocardiography (echo) offers outstanding temporal and spatial image resolution, providing the opportunity for early diagnosis of this life-threatening infection. Emerging imaging modalities, such as real-time three-dimensional (3D) echocardiography, offer a novel way of readily visualizing the extent of intracardiac infection and the relationship of pathology to adjacent cardiac structures, well before surgical intervention, without radiation exposure or significant risk to the patient. Echocardiography can have a positive impact on the management of every stage of this disease, with the opportunity to improve outcomes.",book:{id:"5351",slug:"contemporary-challenges-in-endocarditis",title:"Contemporary Challenges in Endocarditis",fullTitle:"Contemporary Challenges in Endocarditis"},signatures:"John F. Sedgwick and Gregory M. Scalia",authors:[{id:"185698",title:"Prof.",name:"Gregory",middleName:null,surname:"Scalia",slug:"gregory-scalia",fullName:"Gregory Scalia"},{id:"205151",title:"Dr.",name:"John",middleName:"F",surname:"Sedgwick",slug:"john-sedgwick",fullName:"John Sedgwick"}]}],onlineFirstChaptersFilter:{topicId:"989",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:8,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:286,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:9,numberOfPublishedChapters:101,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:11,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,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. 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Topics will include asset liability management, financial consequences of the financial crisis and covid-19, financial accounting, mergers and acquisitions, management accounting, SMEs, financial markets, corporate finance and governance, managerial technology and innovation, resource management and sustainable development, social entrepreneurship, corporate responsibility, ethics and accountability, microeconomics, labour economics, macroeconomics, public economics, financial economics, econometrics, direct marketing, creative marketing, internet marketing, market planning and forecasting, brand management, market segmentation and targeting and other topics under business and management. This book series will focus on various aspects of business and management whose in-depth understanding is critical for business and company management to function effectively during this uncertain time of financial crisis, Covid-19 pandemic, and military activity in Europe.
",coverUrl:"https://cdn.intechopen.com/series/covers/22.jpg",latestPublicationDate:"May 11th, 2022",hasOnlineFirst:!1,numberOfPublishedBooks:1,editor:{id:"356540",title:"Prof.",name:"Taufiq",middleName:null,surname:"Choudhry",slug:"taufiq-choudhry",fullName:"Taufiq Choudhry",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000036X2hvQAC/Profile_Picture_2022-03-14T08:58:03.jpg",biography:"Prof. Choudhry holds a BSc degree in Economics from the University of Iowa, as well as a Masters and Ph.D. in Applied Economics from Clemson University, USA. In January 2006, he became a Professor of Finance at the University of Southampton Business School. He was previously a Professor of Finance at the University of Bradford Management School. He has over 80 articles published in international finance and economics journals. His research interests and specialties include financial econometrics, financial economics, international economics and finance, housing markets, financial markets, among others.",institutionString:null,institution:{name:"University of Southampton",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"86",title:"Business and Management",coverUrl:"https://cdn.intechopen.com/series_topics/covers/86.jpg",isOpenForSubmission:!0,annualVolume:11970,editor:{id:"128342",title:"Prof.",name:"Vito",middleName:null,surname:"Bobek",slug:"vito-bobek",fullName:"Vito Bobek",profilePictureURL:"https://mts.intechopen.com/storage/users/128342/images/system/128342.jpg",biography:"Dr. Vito Bobek works as an international management professor at the University of Applied Sciences FH Joanneum, Graz, Austria. He has published more than 400 works in his academic career and visited twenty-two universities worldwide as a visiting professor. Dr. Bobek is a member of the editorial boards of six international journals and a member of the Strategic Council of the Minister of Foreign Affairs of the Republic of Slovenia. He has a long history in academia, consulting, and entrepreneurship. His own consulting firm, Palemid, has managed twenty significant projects, such as Cooperation Program Interreg V-A (Slovenia-Austria) and Capacity Building for the Serbian Chamber of Enforcement Agents. He has also participated in many international projects in Italy, Germany, Great Britain, the United States, Spain, Turkey, France, Romania, Croatia, Montenegro, Malaysia, and China. Dr. Bobek is also a co-founder of the Academy of Regional Management in Slovenia.",institutionString:"Universities of Applied Sciences FH Joanneum, Austria",institution:null},editorTwo:{id:"293992",title:"Dr.",name:"Tatjana",middleName:null,surname:"Horvat",slug:"tatjana-horvat",fullName:"Tatjana Horvat",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hXb0hQAC/Profile_Picture_1642419002203",biography:"Tatjana Horvat works as a professor for accountant and auditing at the University of Primorska, Slovenia. She is a Certified State Internal Auditor (licensed by Ministry of Finance RS) and Certified Internal Auditor for Business Sector and Certified accountant (licensed by Slovenian Institute of Auditors). At the Ministry of Justice of Slovenia, she is a member of examination boards for court expert candidates and judicial appraisers in the following areas: economy/finance, valuation of companies, banking, and forensic investigation of economic operations/accounting. 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