Types of materials used in 4D printing.
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More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:{caption:"IntechOpen Maintains",originalUrl:"/media/original/113"}},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"10421",leadTitle:null,fullTitle:"Sustainable Organizations - Models, Applications, and New Perspectives",title:"Sustainable Organizations",subtitle:"Models, Applications, and New Perspectives",reviewType:"peer-reviewed",abstract:"Given the multidisciplinary nature of our object of study, sustainability, we have divided this book into twelve chapters. In the first four, we cover the content required to learn how to start a business and create companies based on sustainability. The following chapters provide guidance to help translate sustainability strategies across cultures. These processes are analyzed through the Triple Bottom Line perspective, which effectively describes the primary objectives of sustainability. The last chapters analyze current trends in sustainable development, framing education as a powerful tool to facilitate the transition to more sustainable forms of development. Through these chapters, the understanding of the theoretical concepts is facilitated and examples of sustainable enterprises are made available to the reader that serves as a reference and that allow the development of practical activities.",isbn:"978-1-83880-963-8",printIsbn:"978-1-83880-962-1",pdfIsbn:"978-1-83880-964-5",doi:"10.5772/intechopen.91607",price:119,priceEur:129,priceUsd:155,slug:"sustainable-organizations-models-applications-and-new-perspectives",numberOfPages:232,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"3580ca76579cfa211067a94148d5887d",bookSignature:"Jose C. Sánchez-García and Brizeida Hernández-Sánchez",publishedDate:"February 3rd 2021",coverURL:"https://cdn.intechopen.com/books/images_new/10421.jpg",numberOfDownloads:6368,numberOfWosCitations:1,numberOfCrossrefCitations:5,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:10,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:16,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 13th 2020",dateEndSecondStepPublish:"June 3rd 2020",dateEndThirdStepPublish:"August 2nd 2020",dateEndFourthStepPublish:"October 21st 2020",dateEndFifthStepPublish:"December 20th 2020",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"105695",title:"Dr.",name:"Jose C.",middleName:null,surname:"Sánchez-García",slug:"jose-c.-sanchez-garcia",fullName:"Jose C. Sánchez-García",profilePictureURL:"https://mts.intechopen.com/storage/users/105695/images/system/105695.png",biography:"José Carlos Sánchez-García holds a Doctoral degree in Psychology received from the Autonomous University of Madrid. He achieved his Master degrees in Clinical Psychology and later Industrial Psychology, from the Complutense University of Madrid. He is now a Professor of Entrepreneurship at the University of Salamanca where he has also served as Dean of the Faculty of Psychology for eight years. Currently Dr. Sánchez-García is the Director of Doctorate Program in Psychology, also Director of the Entrepreneurship Chair, and Director of different international postgraduate programs (masters degrees) in entrepreneurial development and innovation. He is the President of AFIDE (Association for Training, Research and Development of Entrepreneurship) and was awarded the OPA Award for his research and promotion of entrepreneurship at the university, as well as the Juan Huarte de San Juan Award for his career as a psychologist and for his promotion of psychology. He also received an award from the Municipality of Osorno (Chile) for promoting entrepreneurship in this region. Dr. Sánchez-García is an author of numerous articles published in international high-impact journals, also an author of books and book chapters of a national and international character, a member of different editorial committees of international magazines as well as a member of different international associations in the field of psychology and entrepreneurship, a visiting professor at different European and Latin American universities.",institutionString:"University of Salamanca",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"University of Salamanca",institutionURL:null,country:{name:"Spain"}}}],equalEditorOne:{id:"171418",title:"Dr.",name:"Brizeida",middleName:null,surname:"Hernandez-Sanchez",slug:"brizeida-hernandez-sanchez",fullName:"Brizeida Hernandez-Sanchez",profilePictureURL:"https://mts.intechopen.com/storage/users/171418/images/system/171418.png",biography:"Professor Brizeida Hernández Sánchez has extensive training and pedagogical experience, with focus on curricular design and teaching; specialized in project management and educational quality processes, for different academic levels; she is an expert in Information and Communication Technologies (ICT) applied to education, social pedagogy, special education, educational technology and management of public policies and educational institutions (supervising training in different master's degrees). She is currently an associate professor at the University of Salamanca, Faculty of Education.\nThis training trajectory is combined with a wide and extensive experience, academic and professional, in the field of pedagogy: in planning agile methodologies and application of actions, based on the diagnosis of needs; in the organization and management of curricular and innovation projects, in improving the teaching and learning processes; in the design of personalized educational resources, educational technology, blended learning, etc.\nShe is the Academic Coordinator of the Training Program in the Entrepreneurship Chair at the University of Salamanca, a member of the Academic Committee for international postgraduate programs (masters) in Entrepreneurial Development and Innovation, and the National Secretary of the Network for Entrepreneurship Training, Research and Development.",institutionString:"University of Salamanca",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Salamanca",institutionURL:null,country:{name:"Spain"}}},equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"79",title:"Sustainable Development",slug:"business-management-and-economics-sustainable-development"}],chapters:[{id:"73366",title:"Organizational Insights, Challenges and Impact of Sustainable Development in Developing and Developed Nations",doi:"10.5772/intechopen.93748",slug:"organizational-insights-challenges-and-impact-of-sustainable-development-in-developing-and-developed",totalDownloads:849,totalCrossrefCites:1,totalDimensionsCites:5,hasAltmetrics:0,abstract:"While developed nations can fully explore various sustainable business models to achieve sustainability, this might not be easy for developing nations because of poor governance systems, characterized by inequality, patronage, and corruption and other challenges. This chapter evaluates organizations as developing and developed nation blocs by first providing insights on how organizations can contribute to the social and environmental sustainability, and second, by highlighting the challenges and approaches for sustainable development. The chapter further unravels the potential for both blocs to grow and achieve sustainability through technology and innovative strategies alongside the opportunities offered by having fast-growing populations and natural resources. To achieve sustainability, a twofold approach comprising the 360-organizational sustainability approaches and advanced sustainability system analysis approach is used. The key societal driving forces in both blocs for exploiting sustainable business practices are governance and institutions, technology and innovation, economy and society, population and behavior, and financing for development which can unlock sustainable business opportunities for sustainable development. To address the business climate challenges, it is inferred that organizations can achieve global sustainability by integrating sustainable production and consumption, biodiversity and ecosystem services, equity and resilience sectors to attain an environmentally and socially governed systems globally.",signatures:"Katundu Imasiku",downloadPdfUrl:"/chapter/pdf-download/73366",previewPdfUrl:"/chapter/pdf-preview/73366",authors:[{id:"322704",title:"Dr.Ing.",name:"Katundu",surname:"Imasiku",slug:"katundu-imasiku",fullName:"Katundu Imasiku"}],corrections:null},{id:"73406",title:"Workplace Innovation for Social Sustainable Development",doi:"10.5772/intechopen.93791",slug:"workplace-innovation-for-social-sustainable-development",totalDownloads:795,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"The purpose of this chapter is to discuss the importance of workplace innovation to sustainable development of the organizational change process. Workplace innovation has been distinguished from the technical innovation and its significance to intangible service improvements. It has addressed how sustainable development is affected by workplace safety, health, productivity, and wellbeing at the workplace. The chapter also attempted to see the three pillars of sustainable development against the six pillars of sustainable development dimensions from prospective points of the previous studies. The previous studies’ findings considered sustainable development dimensions as economic, social, and environmental dimension, while the recent study has introduced additional three new sustainable development dimensions emanating from the existing dimension such as cultural, political and technological dimensions. Therefore, the paper tried to address the workplace innovation, its importance, model, and its impact on sustainable development of the global society.",signatures:"Kassu Jilcha",downloadPdfUrl:"/chapter/pdf-download/73406",previewPdfUrl:"/chapter/pdf-preview/73406",authors:[{id:"292841",title:"Ph.D.",name:"Kassu",surname:"Jilcha Sileyew",slug:"kassu-jilcha-sileyew",fullName:"Kassu Jilcha Sileyew"}],corrections:null},{id:"74334",title:"Entrepreneurial Momentum for Sustainable Growth",doi:"10.5772/intechopen.95099",slug:"entrepreneurial-momentum-for-sustainable-growth",totalDownloads:466,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Public and private sectors view entrepreneurship as a movement of active, creative people who exploit opportunities under uncertainty, create new products, jobs, contribute to economic development of region. Entrepreneurs with their ‘fresh’ vision and agility play an important role in creating the sustainable future for all by overcoming social and environmental challenges. Based on real cases, we illustrate the path travelled by entrepreneurs from identifying the problem and creating the platform for communication with stakeholders to building solution and scaleup. We demonstrate our ‘4A engine’ approach to maintain the momentum for startup consisting of 4 phases: Attention, Actualisation, Attraction, and Action. Even if the start is successful, statistics show that many startups fail between 18 and 24 months. Therefore, we ask startup founders about their practice and biggest surprise they came across, essential choices and important decisions they made. Readers who find this practice useful will reflect by writing a Letter from the Future.",signatures:"Ihor Katernyak and Viktoriya Loboda",downloadPdfUrl:"/chapter/pdf-download/74334",previewPdfUrl:"/chapter/pdf-preview/74334",authors:[{id:"321708",title:"Ph.D.",name:"Ihor",surname:"Katernyak",slug:"ihor-katernyak",fullName:"Ihor Katernyak"},{id:"331224",title:"Prof.",name:"Viktoriya",surname:"Loboda",slug:"viktoriya-loboda",fullName:"Viktoriya Loboda"}],corrections:null},{id:"73311",title:"Organizational Support and Sustainable Entrepreneurship Performance of SMEs, the Moderating Role of Strategic Sustainability Orientation",doi:"10.5772/intechopen.93803",slug:"organizational-support-and-sustainable-entrepreneurship-performance-of-smes-the-moderating-role-of-s",totalDownloads:445,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Small and medium sized enterprises’ (SMEs) activities have contributed significantly to environmental degradation that causes a disastrous effect on us and our future generation. Considering this, sustainable entrepreneurship has been promoted as a resolution of ecological problems capable of addressing climate change issues, public health, and safety concerns, and has become critical for competing in international markets. SMEs activities increased pollution exclusively causing environmental degradation. In response, the world is focusing on ensuring that SMEs produce products through safe and environmentally friendly practices. Literature suggests that organizational support provide SMEs with the impetus to achieve competitive advantage regarding turnover, customer attraction and market share opportunities to achieve business performance. Nonetheless, the implementation of sustainable entrepreneurship among them is still low due to numerous challenges. This paper intends to investigate the influence of organizational support on sustainable entrepreneurship towards performance among SMEs. A case study involving 300 herbal-based SMEs were surveyed using structured questionnaire. Data was analyzed using descriptive statistics, exploratory factor analysis, confirmatory factor analysis, and structural equation model. The results show that organizational support have a positive effect on sustainable entrepreneurship and performance among the SMEs, accounting for 52% and 47% variance respectively. This finding reveals that organizational support is significantly related to entrepreneurship performance, thus substantiates previous findings on the crucial roles of organizational support in enabling organizations to achieve sustainable entrepreneurship performance. This study contributes to triple bottom line literature based on incorporation of strategic choice theory, strategic sustainability orientation and resource-based view theory in entrepreneurship framework.",signatures:"Muhammad Auwal Abdullahi, Zainalabidin Mohamed, Mad Nasir Shamsudin, Juwaidah Sharifuddin and Fazlin Ali",downloadPdfUrl:"/chapter/pdf-download/73311",previewPdfUrl:"/chapter/pdf-preview/73311",authors:[{id:"321678",title:"Dr.",name:"Muhammad Auwal",surname:"Abdullahi",slug:"muhammad-auwal-abdullahi",fullName:"Muhammad Auwal Abdullahi"},{id:"328576",title:"Prof.",name:"Zainalabidin",surname:"Mohamed",slug:"zainalabidin-mohamed",fullName:"Zainalabidin Mohamed"},{id:"328577",title:"Prof.",name:"Mad Nasir",surname:"Shamsudin",slug:"mad-nasir-shamsudin",fullName:"Mad Nasir Shamsudin"},{id:"328578",title:"Dr.",name:"Juwaidah",surname:"Sharifuddin",slug:"juwaidah-sharifuddin",fullName:"Juwaidah Sharifuddin"},{id:"328579",title:"Dr.",name:"Fazlin",surname:"Ali",slug:"fazlin-ali",fullName:"Fazlin Ali"}],corrections:null},{id:"73743",title:"Institutional Structures and Women Sustainability in the Labour Market for Developing Economies",doi:"10.5772/intechopen.94262",slug:"institutional-structures-and-women-sustainability-in-the-labour-market-for-developing-economies",totalDownloads:301,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The peculiarity of women in developing economies, through changing status (marriage, widowhood, divorce, separation) and in some cases occasioned by locational vicissitudes, have continually challenged the sustainability of women in the labour market. Again, some of these challenges women face via social structures such as patriarchy, customs and traditions and unpaid household chores have particularly resulted in labour somersault, underemployment and forced unemployment which in certain cases could be temporary or of a permanent nature. Owing to this growing vulnerability of women, this chapter examine models and structures that have shaped (promoted or otherwise) women’s’ participation in the labour market. In turn, this chapter advances alternative institutional and organizational structures that can check some bewilderment of women in participating in the labour market, as well as foster the sustainability of women in the labour market.",signatures:"Oluwabunmi O. Adejumo",downloadPdfUrl:"/chapter/pdf-download/73743",previewPdfUrl:"/chapter/pdf-preview/73743",authors:[{id:"322286",title:"Dr.",name:"Oluwabunmi",surname:"Adejumo",slug:"oluwabunmi-adejumo",fullName:"Oluwabunmi Adejumo"}],corrections:null},{id:"73594",title:"Protection of Craft Products Embodied in Cultural and Creative Industries in South Africa",doi:"10.5772/intechopen.94111",slug:"protection-of-craft-products-embodied-in-cultural-and-creative-industries-in-south-africa",totalDownloads:719,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The Culture and Creative industries are commonly recognised as one of the strategic sectors. This sector has the potential for innovation and development which may lead to economic growth of a nation. Even though the culture and creative industries (CCIs) is the focus of several studies, precise consideration has not been given to the craft sectors as an essential component of the South African industrial development. The objective of this research is to identify the problems faced by crafts sectors, and to address those issues by providing policy intervention towards protection and sustainability of the sector. Also, the position of craft has been widely acknowledged, but the research regarding the protection of craft products is scarce. This gives rise to the research question: how can the crafts sectors be protected towards the sustainability and development of these sectors? This study provides an overview of the concept of craft and the CCIs focusing on the craft production and marketing activities. For this study, a qualitative research was conducted using a secondary data, and conducting an in-depth interview with crafters in the city of Durban South Africa. The results established some basic issues that need an urgent intervention towards the preservation of the craft sector in South Africa.",signatures:"Abisuga Oluwayemisi Adebola",downloadPdfUrl:"/chapter/pdf-download/73594",previewPdfUrl:"/chapter/pdf-preview/73594",authors:[{id:"247415",title:"Dr.",name:"Oluwayemisi",surname:"Abisuga",slug:"oluwayemisi-abisuga",fullName:"Oluwayemisi Abisuga"}],corrections:null},{id:"73263",title:"Sustainable Business Practices by Nigerian Organizations",doi:"10.5772/intechopen.93834",slug:"sustainable-business-practices-by-nigerian-organizations",totalDownloads:432,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Sustainability is the lifeline of any organization and it begins with its people. This paper investigates the sustainable business practices of Nigerian organizations. The pillars of sustainability, economic, social and environmental, have been linked to improve business performance when entrenched into long term strategies of a business. To address the challenges of power supply, multiple taxation, pollution and waste management faced in the business environment, it is imperative to develop solutions that will not compromise future needs yet meeting the needs of the present. Recycling, recovery and reuse, safe work initiatives, continuous learning are strategies businesses can adopt to reduce environmental waste, social and economic issues. For this purpose, this chapter examines sustainability practices of businesses from selected industries; construction, manufacturing, banking and hospitality industries were selected based on availability of sustainability reports of industry leaders. This research is expected to help business managers and policy makers understand sustainable business practices and its implications on business performance.",signatures:"Nkemdilim Iheanachor",downloadPdfUrl:"/chapter/pdf-download/73263",previewPdfUrl:"/chapter/pdf-preview/73263",authors:[{id:"322184",title:"Dr.",name:"Nkemdilim",surname:"Iheanachor",slug:"nkemdilim-iheanachor",fullName:"Nkemdilim Iheanachor"}],corrections:null},{id:"73472",title:"Evolving a Sustainable Paradigm for Harnessing Intellectual Resources in the Nigerian Space Industry",doi:"10.5772/intechopen.93905",slug:"evolving-a-sustainable-paradigm-for-harnessing-intellectual-resources-in-the-nigerian-space-industry",totalDownloads:346,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Over the years, one of the ways that have been identified as pivotal in building sustainable organisations is the manpower development component of any organisation. Such manpower development through capacity building can be gained by training and retraining to retool the workforce into having the relevant and up to date skill set that spurs competitiveness and growth. For the Nigerian space industry, this human capacity development component has been embraced, encouraged and adopted into a working model for sustainability. The Nigerian Space Industry has leveraged on its potential to harness its intellectual capital through a collaborative culture with national and international partners to provide sustainable growth in attaining technological competence in Space Science and Technology (SST). In this chapter, we present a capacity building context as a model by which Nigeria’s Space Industry mobilises its intellectual resources and collaborative efforts towards achieving sustainable development.",signatures:"Ngunan Monica Ikpaya, Ikpaya Ikpaya, Eseoghene Ovie, Chisom G. Nwokike, Sesugh Nongo and Godwin Ogor-Igbosuah",downloadPdfUrl:"/chapter/pdf-download/73472",previewPdfUrl:"/chapter/pdf-preview/73472",authors:[{id:"322642",title:"Mrs.",name:"Ngunan M.",surname:"Ikpaya",slug:"ngunan-m.-ikpaya",fullName:"Ngunan M. Ikpaya"},{id:"328859",title:"Dr.",name:"Ikpaya",surname:"Ikpaya",slug:"ikpaya-ikpaya",fullName:"Ikpaya Ikpaya"},{id:"328860",title:"Dr.",name:"Eseoghene",surname:"Ovie",slug:"eseoghene-ovie",fullName:"Eseoghene Ovie"},{id:"328861",title:"Dr.",name:"Chisom",surname:"Nwokike",slug:"chisom-nwokike",fullName:"Chisom Nwokike"},{id:"328862",title:"Dr.",name:"Sesugh",surname:"Nongo",slug:"sesugh-nongo",fullName:"Sesugh Nongo"},{id:"328863",title:"Mr.",name:"Godwin",surname:"Ogor-Igbosuah",slug:"godwin-ogor-igbosuah",fullName:"Godwin Ogor-Igbosuah"}],corrections:null},{id:"74348",title:"Sustainable Development and Islamic Ethical Tasks for Business-Organisations",doi:"10.5772/intechopen.94992",slug:"sustainable-development-and-islamic-ethical-tasks-for-business-organisations",totalDownloads:460,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The paper seeks to addresses the issues of sustainable development and it would be viewed as Islamic moral duties for business. To what level should business bodies should join in the sustainable development activities? Based on the existing literature, this study assimilates conventional as well as Islamic points about environment and sustainable development and contends that whatever explanation of sustainable development one may subscribe, ultimately, each should culminate in environmental concern. This study contends that Islamic style is more friendly to environmental protection and issues touching sustainable development have moral, social and ethical responsibility. With intense commitment of the businesses in the matter of Islamic ethics to equity, justice and wellbeing of humans, it demands that business organisations in the Islamic and other countries should participate in the sustainable development endeavours. Because of ethics of environmental aspects in Islam, the value chains of suppliers through customers, many companies may be alert for the environmental characteristics and effects of their businesses.",signatures:"Abul Hassan",downloadPdfUrl:"/chapter/pdf-download/74348",previewPdfUrl:"/chapter/pdf-preview/74348",authors:[{id:"323154",title:"Dr.",name:"Abul",surname:"Hassan",slug:"abul-hassan",fullName:"Abul Hassan"}],corrections:null},{id:"74195",title:"Teacher Professional Competencies in Education for Sustainable Development",doi:"10.5772/intechopen.94991",slug:"teacher-professional-competencies-in-education-for-sustainable-development",totalDownloads:629,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"At present, combining sustainable development with education has become one of the school’s missions. Students must master sustainable development skills. In order to explore the ideal method of K-12 teachers’ professional competence in Education for Sustainable Development and determine the talent leadership strategy can enhance the professional competence of teachers in the 21st century sustainable development education, this study uses content analysis. The author systematically reviewed and analyzed related research work on sustainable development education, teachers’ professional abilities and talent leadership strategies. According to the comprehensive results of content analysis, the ideal way for K-12 teachers to achieve professional sustainability is as follows: content focuses on sustainability with 21st century skills, collaboration with peers, active learning, and application of learning sustainability in practice Model, peer guidance, feedback and evaluation, duration, and teacher professional development. In order to achieve the second research goal, the authors found that talent leadership strategies can enhance the sustainable development of K-12 teachers’ professional capabilities, including K-12 teacher professional development methods, K-12 teacher professional capabilities, student performance and focus on student performance.",signatures:"Xiaoyao Yue and Ruixuan Ji",downloadPdfUrl:"/chapter/pdf-download/74195",previewPdfUrl:"/chapter/pdf-preview/74195",authors:[{id:"322818",title:"Dr.",name:"Xiaoyao",surname:"Yue",slug:"xiaoyao-yue",fullName:"Xiaoyao Yue"}],corrections:null},{id:"74231",title:"Driving a Sustainable University-Industry Partnership",doi:"10.5772/intechopen.94990",slug:"driving-a-sustainable-university-industry-partnership",totalDownloads:395,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"There has been a lot of emphasis on the need for academia-industry collaboration. A successful and sustainable academia-industry partnership can result from a university’s efforts in driving values in its collaboration with industry. This chapter describes a model for mainstreaming a sustainable university partnership with industry through the university’s academic curriculum. The University-Industry Innovation eXchange (UNIX) internship program is a project-based industrial training scheme that is integrated with research projects to provide students with an engaging experience of working with industry for up to one year to solve practical industrial problems. Successful implementation of UNIX projects within the Universiti Teknologi Malaysia’s (UTM) work-based curriculum contributes toward nurturing life-ready and job-ready graduates, development of resilient and sustainable organisation through improved operations, and enhanced university-industry partnership.",signatures:"Zainuddin Abd Manan and Sharifah Rafidah Wan Alwi",downloadPdfUrl:"/chapter/pdf-download/74231",previewPdfUrl:"/chapter/pdf-preview/74231",authors:[{id:"322176",title:"Prof.",name:"Zainuddin",surname:"Manan",slug:"zainuddin-manan",fullName:"Zainuddin Manan"},{id:"322179",title:"Prof.",name:"Sharifah Rafidah",surname:"Wan Alwi",slug:"sharifah-rafidah-wan-alwi",fullName:"Sharifah Rafidah Wan Alwi"}],corrections:null},{id:"73512",title:"Exploring a Culturally-Responsive Model and Theory for Sustainable Development in Education Based on Cebuano Context",doi:"10.5772/intechopen.94035",slug:"exploring-a-culturally-responsive-model-and-theory-for-sustainable-development-in-education-based-on",totalDownloads:531,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This paper explores a culturally-responsive model and theory for sustainable development in education that intertwines a seamless juxtaposition of cultural knowledge, mastery, reflections and understanding, and innovations in the Cebuano context. A multiple case analysis of selected quintains of Cebuano culture in literature reviews, and past travel observations and experiences were used as the methodology of the study. Results revealed that studies on cultural knowledge reflected a Cebuano identity of indigenous worldviews and reverence to nature. Cultural knowledge served as a basis for cultural mastery in the formulation and implementation of government policies as exemplified in the Bayanihan to Heal Act, the creation of the Inter-Agency Task Force, and other decisions of government and non-government agencies to protect people’s welfare. Cultural reflections ignited how people responded to these policies, with contrasting views and ambivalence. To prevent the furtherance of these views that would heighten possible conflict and violence, cultural innovations through a KRSP Model offers vibrant opportunities to promote and realize ESD Goal No. 4 by 2030.",signatures:"Reynaldo B. Inocian",downloadPdfUrl:"/chapter/pdf-download/73512",previewPdfUrl:"/chapter/pdf-preview/73512",authors:[{id:"321361",title:"Dr.",name:"Reynaldo",surname:"Inocian",slug:"reynaldo-inocian",fullName:"Reynaldo Inocian"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"4511",title:"Entrepreneurship",subtitle:"Education and Training",isOpenForSubmission:!1,hash:"a10958147b9a516affca89c11cdafe09",slug:"entrepreneurship-education-and-training",bookSignature:"Jose C. Sanchez-Garcia",coverURL:"https://cdn.intechopen.com/books/images_new/4511.jpg",editedByType:"Edited by",editors:[{id:"105695",title:"Dr.",name:"Jose C.",surname:"Sánchez-García",slug:"jose-c.-sanchez-garcia",fullName:"Jose C. 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by"}}},ofsBook:{item:{type:"book",id:"11867",leadTitle:null,title:"Echocardiography",subtitle:null,reviewType:"peer-reviewed",abstract:"
\r\n\tAlthough the diagnosis and overall survival of patients with various cardiac diseases have improved in the last years, there still remains a significant proportion of patients with unfavorable prognoses. The evaluation of these patients necessitates effective imaging techniques in both diagnosis and long-term follow-up. Even though Cardiac Magnetic Resonance imaging is currently the imaging modality of choice for tissue characterization, advanced echocardiography represents a modern alternative. Speckle tracking echocardiography can be used to assess myocardial deformation at both segmental and global levels. Since distinct myocardial pathologies affect deformation differently, information about the underlying tissue can be offered by strain imaging. Echocardiography advances also show promising results in the improvement of diagnostic accuracy, management, and follow-up and a major advantage of echocardiography over other imaging modalities is the ability to use it in real-time, in the cardiac catheterization laboratory, allowing for the performance of imaging immediately before, during, and after interventional procedures. Furthermore, the prevalence of adult congenital heart disease continues to grow due to advances in surgical and diagnostic techniques. Echocardiography has proven to be a useful tool in the diagnosis and follow-up of these patients, both after percutaneous and surgical procedures, and its utility has expanded significantly due to the development of better technology. In addition, stress echocardiography could be useful in the evaluation of several cardiac diseases and should be preferred over other imaging modalities due to the lower cost, wider availability, and radiation-free nature.
\r\n\tThis book intends to provide the reader with a comprehensive overview of the current state-of-the-art novel imaging techniques by focusing on the most important evidence-based developments in this area.
Vitamin D plays an important role in calcium and phosphorus metabolism, which are essential for bone health and various biological functions. In vitamin D deficiency, clinical and biochemical rickets characterized by hypocalcemia (irritability, fatigue, muscle cramps, seizures), hypophosphatemia and skeletal manifestations (delayed closure of fontanelles, craniotabes, frontal bossing, bowed legs, enlarged wrists, bone pain, and short stature) in children and adolescents or osteomalacia in adults may occur. Over the past several decades, it has been reported that the efficiency of vitamin D is not limited only to maintaining bone health by managing the calcium homeostasis, but also seems to have anti-inflamatory, immune-modulating and pro-apopitothic properties [1]. There are two different precursor molecules of vitamin D. The first is vitamin D3, or cholecalciferol, which is the main source of vitamin D in the body and is synthesized from the skin by exposure to sun. Vitamin D3 can also be obtained from dietary animal foods (fish, egg yolks) or medicines (vitamin supplements). The second precursor is vitamin D2, or ergocalciferol, which can be used as a source of vitamin D via oral medication or through enriched foods. Vitamin D3 differs in molecular structure from vitamin D2 in that it has a double bond between the 22nd and 23rd carbon atoms and a methyl group on the 24th carbon atom [2]. These structural differences in vitamin D2 affect its catabolism. Compared to vitamin D3, vitamin D2 has a lower affinity for vitamin D-binding protein (VDBP), which leads to its easy removal from the circulation, a reduced formation of 25-hydroxy vitamin D2 (25OHD2) by the 25-hydroxylase enzyme, and increased inactivation by the action of 24-hydroxylase [3, 4, 5]. Although both vitamin D2 and D3 are used as drugs, studies have shown that a higher serum 25OHD2 vitamin level is obtained when vitamin D3 is used in treatment compared to vitamin D2 [6]. In addition, it has been shown that active vitamin D obtained from vitamin D3 has a higher affinity for the vitamin D receptor (VDR) [4]. Despite these differences, vitamins D2 and D3 are both metabolized in substantially the same way and are commonly referred to as vitamin D. Vitamin D is a prohormone and inactive, and to be activated, it must go through a series of enzymatic and non-enzymatic steps.
Formation of vitamin D3, which is the first step of vitamin D synthesis, takes place in the epidermis by a non-enzymatic process (Figure 1). Vitamin D3 is the most important source of vitamin D in the body. 90–95% of vitamin D3 in the human body is produced from the skin with the effect of sunlight. Therefore, sunlight is the main source of vitamin D synthesis, and if there is sufficient exposure to sunlight, there is no need to take additional vitamin D. The mechanism of non-enzymatic photolysis of vitamin D by ultraviolet B (UVB) rays with wavelengths in the range of 290–315 nm involves the breaking of a bond in the B ring of 7-dehydrocholesterol (pro-vitamin D3), resulting in pre-vitamin D3 formation in the epidermis. Subsequently, two different double bonds are formed between the broken carbon atoms in the B ring by thermo-sensitive non-enzymatic process, and the formation of vitamin D3 from pre-vitamin D3 is completed (Figure 2) [7].
Vitamin D metabolism.
Vitamin D3 synthesis from 7-dehydrocholesterol in the epidermis.
The synthesis of vitamin D3 from pro-vitamin D3 in the skin is adjusted according to the needs of the organism. In a period of just fifteen minutes, pre-vitamin D3 is synthesized from pro-vitamin D3 with the effect of ultraviolet light. Conversion from pre-vitamin D3 to vitamin D3 occurs by isomerization in a rather slow and thermo-sensitive manner. In the case of exposure to UV rays or solar radiation for a long period, pre-vitamin D3 converts to a number of photolyzed inactive by-products, such as lumisterol (irreversible) or tachysterol (which can be converted back to pre-vitamin D3). These by-products have no biological effects (Figure 2). In other words, once pre-vitamin D3 is formed in the skin, it turns into either vitamin D3 or inactive metabolites. This is a physiological control mechanism that protects the body from vitamin D intoxication by preventing unnecessary vitamin D synthesis [8, 9].
Some conditions that prevent UVB rays from reaching the skin cause a decrease in vitamin D production. One of these reasons is the ozone (O3) layer surrounding the atmosphere, which reflects some of the sun’s rays, preventing them from reaching the Earth and their harmful carcinogenic effects on the skin. The peak UVB wavelength required for optimal vitamin D synthesis from the skin is 297 (290–315) nm [1, 8]. In addition, air pollution, aerosols, water vapors, and increased nitrogens in the air also play a role in preventing sunlight reaching the Earth, and consequently result in a potential reduced synthesis of vitamin D [8]. Another factor affecting the effectiveness of UVB rays in the synthesis of vitamin D in the skin is the solar zenith angle, which affects how UVB rays reach the world quantifiably. When the sun moves in a path closer to the horizon, which occurs in the northern latitudes in the winter season, vitamin D synthesis is more adversely affected (or reduced). In the summer time in the northern latitudes, a normal biosynthesis is more propitious or favorable. The narrowing of this angle indicates that the sun rays reach the Earth more steeply and intensely. The solar zenith angle is closely related to sunbathing time during the day, the seasons and the geographic region (latitude). Sunlight reaches the Earth most intensely in the “mid-day” when it is summer in the northern latitudes and the weather is clear. Finally, it is thought that sunlight exposure is sufficient for vitamin D synthesis in all geographic regions below 35 degrees north or south latitude all year round. In regions beyond this latitude toward the poles, especially in winter, sunlight is not sufficient for vitamin D synthesis. For example, UVB rays are not sufficient for vitamin D synthesis between October and April in Rome, which is located on 41.9 degrees north latitude, and between November and February in Berlin and Amsterdam, which are located on 52 degrees north latitude. For the reasons mentioned above, it is difficult to predict how much UVB rays reach the skin and how much of this increases serum vitamin D levels. In experimental studies, it has been reported that UVB rays that will cause minimal erythema in 25% of the skin are equivalent to 1000 units of oral vitamin D intake [2, 3, 8].
UVB rays are also affected by the individual’s clothing style, use of sunscreen, and skin colour determined by pigmentation with melanin. In dressing style, especially the type of the clothing fabric used is of great importance [10]. Non-synthetic, light-colored, and linen garments play a less preventive role in UV rays reaching the skin than do garments made of silk, nylon, polyester, and wools. For example, black-dyed cotton clothing prevents 98.6% of UVB rays from reaching the skin compared to white (undyed) cotton clothing, which blocks 47.7% of UVB. Topical sunscreens also prevent UVB rays from reaching the skin by absorbing, reflecting or dispersing them. Topical creams with a sun protection factor of 8 or higher block vitamin D synthesis above 95% [11]. Melanin is a large, opaque polymer synthesized by melanocytes in the skin through the stimulus of exposure to UVB rays. Melanin competes with dehydrocholesterol 7 in the skin to absorb UVB photons and thus inhibits vitamin D synthesis [12]. Individuals with dark skin colour have more melanin pigment in their epidermis than light-skinned individuals and require higher concentrations of sunlight for the same amount of vitamin D synthesis [12]. In addition, the 7-dehydrocholesterol level (provitamin D) in the epidermis can also affect the serum vitamin D concentration. For example, 7-dehydrocholesterol levels in scar tissue caused by the burn are reduced by 42.5% of normal. In these cases, progressive vitamin D deficiency develops, especially if supplemental dietary vitamin D is not provided. Moreover, the content of provitamin D in the skin decreases with age. Skin temperature is also important for vitamin D synthesis. Vitamin D from pre-vitamin D by isomerization whose rate of formation is temperature- dependent. The rate decreases as the skin temperature decreases. In a healthy person, the skin temperature is lower than the central body temperature and varies between 29 and 35 degrees Celcius. When the skin temperature is 37 degrees Celcius, the isomerization of vitamin D from pre-vitamin D occurs within 2.5 hours [13, 14].
Vitamin D3 synthesized in the skin is released into the systemic circulation and all forms are transported by binding to VDBP in serum. A portion of vitamin D, a fat-soluble vitamin, is stored in adipose tissue for use when necessary. The ability of vitamin D to be stored in adipose tissue extends its total half-life in the body up to approximately 2 months. When vitamin D3 is transported to the liver, it is first converted into 25OHD3 by the cytochrome P450 25-hydroxylase enzyme. 25OHD3 is the main circulating form of vitamin D, and it is the parameter that provides the best estimation about the body’s vitamin D pool [15]. Various enzymes that show 25-hydroxylase properties have been described in the body. Among these, the first one is CYP27A1 located in mitochondria, and the second is microsomally located CYP2R1 [1, 6, 16]. CYP27A1 also exerts 27-hydroxylase effect and is involved in bile acid synthesis. Although CYP27A1 is expressed in different tissues of the body, the tissues where it is most commonly found are liver and skeletal muscle tissues [1, 2]. In experimental studies, it was reported that the serum 25OHD3 levels were increased in mice which possess an inactivated CYP27A1 gene, and that rickets did not occur in these mice [17]. Interestingly, in this study, it was shown that CYP2R1 expression increased after CYP27A1 gene inactivation, and consequently 25-hydroxylation activity increased [17]. In addition, individuals with a CYP27A1-inactivating mutation develop a cerebrotendinous xanthomatosis disease with bile and cholesterol synthesis disorders, but without rickets manifestation [18]. Besides CYP27A1, different CYP-450 enzymes with 25-hydroxylase activity (CYP2D25, CYP2J2, CYP2J3, and CYP2C11) have been identified in humans and animals, with the most important one in human being CYP2R1. It is assumed that enzymes other than CYP2R1 have effects only on serum 25OHD3 levels [2].
Studies have suggested that CYP2R1 is the major enzyme responsible for 25-hydroxylation in the human body. This enzyme is expressed in many tissues, mainly liver, skin, and testis [1, 2, 17]. The 25-hydroxylase encoded by the CYP2R1 gene was first described by Cheng et al. [19]. It was first reported by Chen et al. [20] that homozygous inactivating mutations of this gene lead to clinically observed rickets (vitamin D-dependent rickets type IB) in Nigerian families. It has been reported that these cases gave suboptimal response to standard vitamin D (inactive vitamin D2 or D3 forms) treatment [21]. The CYP2R1 enzyme has equal affinity for the different forms of vitamin D precursors (D2 or D3) [19]. Studies have shown that 25-hydroxylase effect increased in male rats given estrogen, whereas this activity decreased in female rats given testosterone [21]. Despite experimental studies, the effect of sex steroids on 25-hydroxylase enzyme activity in humans is unknown. It has been shown that in CYP2R1-null mice, the level of 25OHD3 decreases by 50%, when both CYP2R1 and CYP27A1 are inactivated, and that serum 25OHD3 levels decrease by 70%, and serum 25OHD3 level remains at a measurable level in both cases [2, 17]. This supports the view that serum vitamin D level is compensated by other enzymes with recruitable 25-hydroxylase enzyme activity.
The final step of active vitamin D formation takes place in the proximal tubules of the kidney, led by the enzyme 1-alpha hydroxylase. 25OHD3, which is bound to VDBP, is taken into tubule cells and metabolized (1-alpha hydroxylation) through megalin and cubilin, which are transmembrane proteins located in renal tubules and act as surface receptors for VDBP in tubules. 25OHD3, which then undergoes 1-alpha hydroxylation [1, 2]. The 1-alpha hydroxylase enzyme hydroxylates the first carbon atom in the A ring of 25OHD3, resulting in the formation of 1,25 (OH) 2D3 [1]. CYP27B1 is the only enzyme that has 1-alpha hydroxylase activity. This enzyme, which belongs to the cytochrome P-450 enzyme system, is located in the inner mitochondrial membrane and carries out electron transport to NADPH via ferrodoxin-ferrodoxin reductase [1, 2]. The gene for the enzyme consists of nine exons and is located 12q14.1 chromosomal region. Four different groups reported the cloning and sequencing of the gene from rats, mice and humans [22, 23, 24, 25, 26]. In biallelic inactivating mutations of this enzyme, which is highly homologous to some mitochondria located cytochrome P-450 enzymes (CYP27A1 and CYP24A1), 25OHD3 cannot be converted to 1.25 (OH) 2D3, which is the active vitamin D form. In this case, the clinical picture of vitamin D-dependent rickets type 1A (also called pseudo-vitamin D deficiency rickets) occurs [23]. This disease is typically characterized by rickets, with clinically observed very low 1.25 (OH) 2D3, low serum calcium/phosphorus, and high parathyroid hormone (PTH) levels. CYP27B1 is expressed mainly in the renal proximal tubules and in the placenta during pregnancy [27]. While the expression of the gene encoding this enzyme increases with the effect of PTH, it decreases with FGF23 (fibroblast growth factor 23) and 1.25 (OH) 2D3. CYP27B1 gene is also expressed in lung, brain, breast and intestinal system epithelial cells, immune system cells (macrophage, T/B lymphocytes and dendritic cells), osteoblasts, chondrocytes, and some tumor cell types [1, 2]. The regulation of the extra-renal localized 1-alpha hydroxylase enzyme differs. In some granulomatous diseases where monocyte/macrophage cells play an important role (sarcoidosis, tuberculosis, Chron’s disease, etc.), with the effect of IL-1, TNF-α, IFN-γ, 1-alpha hydroxylase enzyme activity increases and 1,25 (OH) 2D3 is synthesized in greater quantities than normal, and consequently, hypercalcemia and hypercalciuria emerge [28, 29, 30]. Additionally, since cells in these tissues do not have PTH receptors, it is not yet understood how PTH exerts its enhancing effect on the 1-alpha hydroxylase enzyme activity in these cells. In one study, it has been suggested that this enhancing effect of PTH may have occurred through post-transcriptional effects [31]. Moreover, 1-alpha hydroxylase enzyme in these cells is not inhibited by 1,25 (OH) 2D3 or hypercalcemia, unlike the renal tubules.
The 24-hydroxylase enzyme is located in the mitochondrial inner membrane of the cells located in the proximal kidney and, like CYP27B1, uses the electron transport system that enables electron transport to NADPH via ferrodoxine-ferrodoxin reductase. It is known that CYP24A1, which is the only enzyme showing 24-hydroxylase enzyme activity in humans, can also exhibit 23-hydroxylase enzyme activity [2]. Which enzyme will be more prominent varies according to the species [32]. The 23-hydroxylase, another enzyme that degrades vitamin D, is the first step activity in the conversion of 1,25 (OH) 2D3 to 1,25 (OH) 2D3-23,26-lactone.
The CYP24A1 enzyme, encoded in 20q13 chromosomal region and having 24-hydroxylase enzyme activity, initiates catabolic processes that lead to the inactivation of vitamin D by hydroxylating the 24th carbon atom. This enzyme can use both 25OHD3 and 1.25 (OH) 2D3 as substrates, but has a higher affinity for 1.25 (OH) 2D3. As a result of a series of enzymatic reactions, calcitroic acid is formed, which becomes biologically inactive. On the other hand, it has been suggested that the 1,25 (OH) 2D3-23,26-lactone, which is formed in the 23-hydroxylase pathway, lowers serum calcium level, inhibits bone resorption induced by 1.25 (OH) 2D3, and stimulates the formation of collagen tissue in bone tissue [33]. In addition, it has been suggested that 24,25 (OH) 2D3 is not only a degradation product, but has an important role in bone metabolism, especially in endochondral bone formation [34].
There are two vitamin D response elements (VDRE) in the promoter region of the CYP24A1 gene [35]. When active vitamin D is bound to the these one of VDRE after heterodimerization with various molecules, thus initiates the inactivation process of vitamin D. In addition, it has been shown that CYP24A1 gene expression decreases with the effect of PTH, whereas it increases with increased FGF23 concentrations [1, 32, 36, 37]. Inactivating mutations in CYP24A1 lead to an idiopathic infantile hypercalcemia clinic characterized by hypercalcemia, hypercalciuria, nephrocalcinosis, low PTH, low 24.25 (OH) 2D3 and high 1.25 (OH) 2D3 levels [37]. As a result, CYP24A1 is a critical enzyme that protects the body from excessive accumulation and possible intoxication of vitamin D.
3-epimerase activity was first demonstrated in 2001, with the detection of the 3-epi form of 1,25 (OH) 2D3 in keratinocytes [38]. In the following years, epimer forms of 25OHD3 and other vitamin D metabolites were discovered. However, the enzyme or enzymes involved in epimerization has not yet been identifiedpurified or cloned. This enzyme changes the hydroxyl group in the 3rd carbon of the A ring from the alpha orientation to the beta orientation, causing the three-dimensional structure to change and consequently alter the activity of CYP27B1 and CYP24A1 enzymes on vitamin D metabolism. These epimers can be detected by special liquid chromatography-mass spectroscopy (LC-MC) measurement methods [2]. C-3 epimer forms of 25OHD3 and 1,25 (OH) 2D3 have been shown to have lower affinity for VDR and VDBP compared to non-epimer forms [38]. The C-3 epimer form of 1,25 (OH) 2D3 has been shown to cause PTH suppression similar to the non-epimer form, but its effects on bone tissue are not clear. In addition, epimer forms have also been shown to have non-calcium effects (anti-proliferative effect, surfactant synthesis) [39]. It has been shown that the serum levels of vitamin C-3 epimer forms are found to be 60% higher in the period between the neonatal period and one year old, and decrease after one year of age and decrease to very low levels in adulthood [2, 38]. The reason why epimer forms with limited biological activity are important is that they cause interference and false high results in serum 25OHD3 and 25OHD2 measurement. Therefore, it is important to prefer the method (especially LC–MS / MS) that can exclude this effect of epimer forms that cause serum vitamin D measurement interference. However, the use of LC–MS/MS method in the measurement of vitamin D has not become widespread in the world, and the use of this method is only recommended in selected cases.
The largest part of the circulating vitamin D is in the form of 25OHD3, and its serum concentration is in equilibrium with the level of vitamin D stored in muscle and adipose tissues. The parameter that gives the best information about the whole vitamin D pool in the body is 25OHD3 and its known half-life of 15–20 days. Most of all forms of vitamin D in circulation (85–88%) are transported by binding to VDBP and the remaining part (12–15%) to albumin [2, 40]. The serum concentration of VDBP is 4–8 nM and only 2% of it is bound with vitamin D metabolites [2]. Moreover, the affinity of VDBP to 25OHD3 is 20 times higher than 1.25 (OH) 2D3 [3]. 0.03% of 25OHD3 and 0.4% of 1.25 (OH) 2D3 are in free form [2]. In chronic liver disease or nephrotic syndrome, VDBP and albumin levels and thus total serum 25OHD3 and 1.25 (OH) 2D3 levels decrease, but the levels of free forms are not affected [41]. Likewise, since the VDBP level may decrease during the acute disease period, evaluating the body’s vitamin D pool by measuring the serum 25OHD3 level with standard immunoassays may lead to misinterpretations [42]. In conclusion, while the total levels of vitamin D forms are affected by the VDBP level, there is no relationship between VDBP and free vitamin D forms, which are essential for biological activity. It was shown that both 25OHD3 and 1.25 (OH) 2D3 levels in VDBP-null mice were lower than wild type mice, but serum PTH and calcium levels were similarly normal in both groups [43]. This supports the view that serum vitamin D level measured by the standard method may not be an indicator of biologically active vitamin D pool. In addition, the predisposition of VDBP-null mice to the development of osteomalacia after a vitamin D-restricted diet suggests that VDBP may play a role in maintaining the existing vitamin D pool [44]. In addition, some single nucleotide polymorphisms (GC1F, GC1S, GC2) in the
Vitamin D provides its biological effect in two different ways. The first is by directly affecting gene transcription (genomic effect) as other steroid hormones. This effect is relatively slow and usually occurs within hours or days. The second is the non-genomic pathway whose biological effect is relatively faster (within minutes). Vitamin D exerts its non-genomic effect by directly altering the trans-membrane passage of some ions (Ca, Cl) or by affecting intracellular signaling pathway activities (cAMP, PKA, PLC, PI-3 kinase and MAP kinase) [1, 2]. Genetic studies on vitamin D support that active vitamin D directly or indirectly regulates 0.8–5% of the total genome, suggesting the role of active vitamin D in many actions such as regulation of cellular growth, DNA repair, differentiation, apoptosis, membrane transport, cellular metabolism, adhesion and oxidative stress [1, 2, 3, 47].
The active form of vitamin D displays this effect through the vitamin D receptor (VDR). VDR is a member of the nuclear hormone receptor superfamily, which includes steroid, thyroid hormone, and retinoic acid receptors [48]. The VDR gene located on chromosome 12 consists of 427 amino acids encoded by. The structure of the VDR consists of a relatively short N-terminal domain compared to other nuclear receptors, two zinc-fingers that allow the receptor to bind to DNA, and a highly variable C-terminal region, and the hinge region connecting binding these domains (Figure 3) [2]. The DNA-binding region of the receptor is rich in cysteine, and the sequence of this region is largely conserved between species. The zinc-finger structure close to the C-terminal part of VDR determines the specificity for the VDRE (vitamin D response element), which is the binding site on the DNA. The other zinc-finger structure is involved in the heterodimerization of VDR with RXR (retinoid X receptor) [1, 2]. The ligand-binding part of the receptor consists of 12 α-helix structures (H1-12; the H12 part is also called AF2) and 3 β-sheet structures (S1-3) [49]. The AF-2 region located at the end of the C-terminal is the binding site of co-activator complex structures such as SRC (steroid receptor coactivator) and DRIP (vitamin D receptor interacting protein). Transcription is initiated by binding co-activators to this region [50]. Apart from these functional domains, there are NLS (nuclear localization signal) regions within the DNA binding region of VDR, which are necessary for maintaining transcriptional activity [2]. In addition, there is a hinge region between the ligand-binding and DNA-binding domains of the VDR that ensures molecule stabilization.
The structure of the Vitamin D receptor (VDR).
After active vitamin D crosses the target cell membrane, it interacts with the ligand-binding domain of its own receptor (VDR) in the cytoplasm of the cell. Vitamin D is embedded in the ligand-binding domain, and subsequently, in the H12 alpha-helix H12 (AF-2) region, which is located at the end of the ligand binding part [51]. This critical conformational change of AF-2 facilitates the binding of co-activators in later stages [52]. In the next step, vitamin D-bound VDR binds to RXRα to form a VDR/RXR heterodimer structure that binds to cognate VDR elements (VDRE) in the promoter region in the target genes with a high affinity to initiate gene activation or inhibition. There are many gene-specific VDREs associated with bone metabolism, xenobiotic detoxification, drug resistance, cell growth and differentiation, angiogenesis, mammalian hair growth cycle, lipid synthesis regulation, apoptosis, and immune functions, suggesting that vitamin D has numerous regulatory roles in various organs or tissues in the body [53].
After active vitamin D-VDR-RXR-VDRE interaction, the progression of transcription is controlled by co-activator and co-repressors. The best known co-activators are the p160 co-activator family (eg CBP/p300 and p/CAF) and SRC 1,2,3. Both bind to the AF-2 part and have histone acetyl transferase (HAT) activity, which enables the opening of the histone structure and thus facilitates gene expression [54]. The SRC complex has three NR regions that facilitate binding and contain LxxLL (L, leucine; x, any amino acid) motifs. Likewise, the DRIP complex (Mediator) also has NR regions with LxxLL motifs consisting of 15 or more amino acids [55]. Unlike SRC, DRIP complex does not have HAT activity. This suggests the fact that both protein complexes play a complementary role in the initiation of transcription. The mediator multi-protein complex DRIP205/MED1 (also known as MED1) accumulates around RNA polymerase 2of the initiation complex. This complex then interacts with the TATA region in the promoter region and enables transcription to be initiated [56]. Co-repressors (eg SMRT and NCoR) have histone de-acetylase activity and inhibit transcription by preventing unfolding of the histone core.
Some of the hormones that act on the nuclear hormone receptor can also exert their biological effects on the membrane receptor without the need for additional gene regulation [2]. The non-genomic effect occurs through messenger-mediated pathways. Estrogen, progesterone, testosterone, corticosteroids and thyroid hormones have been reported to exert their effects by using both genomic and non-genomic pathways [2]. Vitamin D has been shown to directly regulate the activation or distribution of various ion-transport channel proteins (for calcium and chloride) and of enzymes (protein kinase C and phospholipase C) through the membrane receptor in osteoblast, liver, muscle, and intestinal cells (Figure 4) [57, 58, 59, 60, 61, 62]. In order to demonstrate the non-genomic effect of vitamin D, many studies have been conducted on intestinal calcium absorption. Rapid vesicular calcium absorption (also called transcaltachia) has been shown in the chick intestinal tract [63]. Further experimental studies have shown that intestinal calcium transport cannot be blocked by the administration of actinomycin D (which inhibits the genomic effect) [64], whereas calcium absorption can be blocked by inhibition of voltage-gated L-type calcium channel proteins [65] or by protein kinase C [66].
Representation of the signal transduction pathways where Vitamin D has its non-genomic effect (2). After vitamin D binds to the membrane receptor, GDP in the G protein α-subunit turns into GTP and activation occurs. The α-subunit of the G protein is separated from other subunits and binds to phospholipase C (PLC). The PLC is then activated to convert phosphoinositol bisphosphate (PIP2) to inositol triphosphate (IP3) and diacylglycerol (DAG). Calcium release from the endoplasmic reticulum via the IP3 receptor (IP3R); DAG activates PKC. PKC, on the other hand, provides calcium entry into the cell via the L-type calcium channel in the membrane.
Apart from the intestinal system, it has been suggested that the non-genomic effect also occurs in chondrocytes in the growth plate and keratinocytes in the skin [67, 68]. Vitamin D is believed to exert its non-genomic effects through VDR analog and MARRS (also known as ERp57/GRp58/ERp60) receptors located on the cell membrane [69, 70]. These membrane receptors are located within the caveolar lipid layer [71]. In addition, research findings indicate that VDR is also necessary for the expression of membrane receptors that involve in the emergence of non-genomic effect [1, 2]. In studies evaluating the effects of vitamin D analogs (6-s-cis or 6-s-trans conformations), the 6-s-cis form can activate intestinal rapid calcium entry even though the VDR affinity is very low, whereas the 6-s-trans form has been shown to be ineffective in calcium metabolism [67].
One of the most important functions of vitamin D is to increase calcium absorption from the intestines. Calcium absorption from the intestinal tract occurs trans-cellular and para-cellular processes mediated through genomic and non-genomic effects. Among these, the trans-cellular pathway largely utilized by the intestinal system, which is regulated by vitamin D [2]. The absorption effect of vitamin D with non-genomic effect of calcium occurs directly on the membrane (transcaltachia). The channel-mediated calcium absorption effect of vitamin D occurs more slowly [2].
Calcium enters the epithelian cell by the effect of an electrical and chemical gradient via calcium channel protein TRPV6 (which has significant sequence homology to TRPV5 in the kidney), the transmembrane protein at the lumenal brush border edge of the intestinal epithelial cell. The expression of TRPV6 is activated by vitamin D [72]. Reduced intestinal calcium transport is observed in TRPV6 null mice [73]. Calcium entering the cell binds to calmodulin (CaM), which is bound with myosin 1A (also known as brush border myosin I). This formed complex allows calcium to be transported across the microvilli. Subsequently, the transport of calcium up to the basolateral membrane occurs inside the vesicle via calbindin-D9k (CaBP). The affinity of calcium for calbindinin is greater than for calmodulin, and better facilitates calcium transport inside the cell [74]. The calcium reaching the basolateral membrane is pumped out of the cell to systemic circulation via the Ca-ATPase (PMCA1b) pump located on the membrane [1, 2]. In addition, although it is less important, NCX (sodium/calcium exchanger), located in the basolateral region, also plays a role in excretion of calcium [2, 75]. Vitamin D shows its increasing effect on intestinal calcium absorption by inducing expression of TRPV6, CaBP and PMCAb and increasing the binding affinity of CaM to myosin 1A [1, 2].
Intestinal calcium absorption, serum calcium level and bone mineral content in Kalbindin D9k null mice (regardless of dietary calcium level) have been shown to be similar to normal mice [76]. Intestinal calcium absorption was found to be normal in calbindin D9k and TRPV6 null mice when a diet containing the daily requirement for calcium was given [77]. These findings indicate there is a mechanism other than the genomic effect through which vitamin D exerts its action (a non-genomic effect) in calcium absorption in the intestines when the amount of calcium in the diet is sufficient.
While trans-cellular calcium absorption is effective in compensating for a low-calcium diet, para-cellular calcium transport becomes important with the increase in calcium content in the diet [1]. Paracellular transport occurs through the extracellular space between the layer of the epithelial cells in the intestine. Although it was previously thought that vitamin D does not affect para-cellular calcium absorption, studies conducted in recent years indicate otherwise, with vitamin D still affecting calcium absorption by increasing levels of various transmembrane and adhesion proteins that control the extracellular space between cells [78, 79]. However, it is not clear at what stage of the paracellular pathway these proteins are involved.
Phosphate, another important molecule for bone mineralization, is actively absorbed mostly in the jejunum, with absorption influenced by vitamin D [2]. This absorption is provided by sodium-phosphate co-transporter IIb (NaPi IIb). In experimental studies, it has been shown that phosphate absorption is blocked when cycloheximide, which inhibits protein synthesis, is given [80]. This situation supports that phosphate absorption occurs by genomic effect. Vitamin D increases NaPi-IIb expression and thus phosphate absorption [2].
Most of the calcium that reaches the kidney tubules is absorbed from the proximal and distal tubules and approximately 1–2% of it is excreted through urine. Approximately 65% of calcium absorption in the kidney is passively absorbed para-cellularly from the proximal tubules with the sodium gradient and independent of vitamin D direct action [1]. The rest of the calcium is absorbed from the ascending limb of the loop of Henle (20%), the distal tubules (15–20%), and the collecting ducts (5%) [81]. Vitamin D plays an important role in calcium absorption in the distal tubules and provides active calcium absorption via the trans-cellular pathway with the help of an electrochemical gradient [1]. Calcium is taken into the cell by TRPV5 channel on the surface of the tubular cell and is transported inside the cell by calbindin-D9k and D28k. Transported to the basolateral part of the cell, calcium is released into the systemic circulation by NCX1 (sodium/calcium exchanger) and PMCA1b. This mechanism is similar to that in the intestinal tract. Vitamin D increases the expression of TRPV5, calbindin, NCX and PMCA1b.
Phosphate is reabsorbed by sodium-dependent phosphate carrier proteins (NaPi-IIa and NaPi-IIc) in proximal tubular cells under vitamin D control. In addition, for phosphate reabsorption, a Na/K-ATPase channel located in the basolateral membrane is also needed [1, 2]. The impact of vitamin D on transport channels is not clearly known. While PTH increases the lysosomal degradation of phosphate transport channels, FGF23 causes a decrease in the expression of these channels [1, 2, 82].
Calcium, phosphorus and vitamin D are important molecules for bone metabolism and health. Calcium is one of the most abundant minerals in the body and is obtained entirely from dietary sources. In addition to its various biological effects in the body, it is also essential for bone metabolism [83]. More than 99% of the total body calcium is found in the bone tissue as a calcium-phosphate mineral complex, while the remaining <1% is distributed between the intracellular and extracellular compartments [83]. While 40% of calcium outside bone tissue is bound to protein, 9% forms ionic complexes, and the remaining 51% is found as free ions [84, 85]. Ionized calcium balances the calcium pool in the intracellular-extracellular area and plays an important role in bone metabolism. This balance is provided by the cooperation of various hormones (PTH, vitamin D) and the organs they affect (kidney, bone and intestinal system) [83, 84, 85]. Where there is vitamin D deficiency (nutritional or genetic) or VDR-inactivating mutations, serum levels of calcium and phosphate, which play an important role in bone development and growth, are reduced and thus rickets/osteomalacia emerge. Rickets is a disease characterized by excessive osteoid tissue accumulation and defective mineralization of the epiphyseal plate, which occurs as a result of insufficient mineralization in the epiphyseal plates of growing bones [1, 2]. Osteomalacia is a disease characterized by a deterioration in the mineralization of the newly formed osteoid and a decrease in bone turnover.
There is a continuous remodeling cycle consisting bone tissue resorption and mineralization. When calcium, phosphorus, and vitamin D are sufficient, this cycle continues in a balanced manner. In the case of negative calcium balance caused by insufficient calcium intake with diet or increased renal calcium loss, vitamin D increases bone resorption in osteoblasts through VDR signaling, resulting in calcium passage from bone to blood, which leads to impaired bone mineralization. Vitamin D increases the expression of RANKL (receptor activator of NF-κB ligand), which is an osteoclastogenic factor from osteoblasts [86, 89]. RANKL stimulates osteoclastogenesis and increases osteoclast formation by binding to its related receptor, RANK [87]. In conclusion, in the case of negative calcium balance, vitamin D tries to keep the serum calcium level in a certain balance by increasing resorption and decreasing mineralization [1].
In the case of a positive calcium balance, the osteoblastogenic activity of vitamin D is prominent. In this situation where anti-resorbtive effect is in the predominant, bone mineral density increases. The occurrence of this effect has been associated with a decrease in the RANKL/OPG (osteoproteogerin) ratio and an increase in LRP-5 (LDL receptor related protein 5) expression [1]. LRP-5 is controlled by the VDR and is a necessary co-receptor for the anabolic effect of osteoblasts [88]. In addition, vitamin D plays a role in the proliferation of chondrocytes in the growth plate through genomic action.
Pro-vitamin-D3, pre-vitamin D3 and then vitamin D3 (cholecalciferol) conversion in the skin is under the control of UV radiation. Serum vitamin D concentration reaches its highest level 24–48 hours after exposure to UV radiation and then shows a gradual decrease. The half-life of serum vitamin D is 36–72 hours. Vitamin D, which is a fat-soluble vitamin, is stored in adipose tissue for later use. The ability of vitamin D to be stored in adipose tissue extends its total half-life in the body up to approximately 2 months.
There is little information on how this enzyme is regulated because of the few studies performed. What is known is that serum vitamin D level is inversely related to the rate of 25-hydroxylation in the liver, and the synthesis of 25OHD3 from vitamin D (cholecalciferol) is regulated by the 25-hydroxylase enzyme
Serum active vitamin D levels in healthy adults vary within extremely narrow ranges, so that even in cases of vitamin D intoxication, serum levels may remain normal. 1-alpha hydroxylation activity in the kidney is controlled by PTH, calcium and phosphorus. Hypocalcemia, increased PTH, and hypophosphatemia will stimulate increases in active vitamin D production through renal 1-alpha hydroxylase enzyme activation, while hypercalcemia, FGF-23 secreted from osteoblasts, and active vitamin D itself have an inhibitory effect on active vitamin D synthesis through the renal 1-alpha hydroxylase enzyme. Active vitamin D increases FGF23 synthesis from osteoblasts. FGF23 suppresses the 1-alpha hydroxylase enzyme and increases the activity of 24 hydroxylase enzymes. In addition, hypercalcemia suppressing PTH and hyperphosphatemia by increasing FGF23 levels results in 1-alpha hydroxylase enzyme activity inhbition [1, 2, 3]. It is also suggested that calcium and phosphate have a direct regulatory effect on 1-alpha hydroxylase enzyme [89].
Calcitonin is known to reduce serum calcium levels through osteoclast inhibition. In addition, this hormone has been shown to increase the expression of CYP27B1, the gene encoding the 1-alpha hydroxylase enzyme, in normocalcemic pregnant women due to the increase in calcium need. In this way, active vitamin D synthesis and consequently intestinal calcium absorption is increased [1, 90]. Apart from calcitonin, it has been suggested that prolactin also increases CYP27B1 expression, especially during lactation, and thus contributes to the increased calcium demand of the body [1, 91].
CYP3A4 enzyme in the liver and intestinal system has also been shown to be effective in the inactivation of 25OHD3 and reduction of active vitamin D [92]. Long-term use of drugs such as phenytoin, rifampicin, and carbamazepine may lead to up-regulation of the CYP3A4 enzyme and thus to a decrease in serum 25OHD3 and active vitamin D levels.
When serum calcium, phosphate and PTH levels are within normal levels, 25OHD3 and 1–25 (OH) 2 D3 are metabolized into biologically inactive forms by activation of 24-alpha hydroxylase enzyme in the kidneys (24–25 dihydroxy vitamin D3 and 1,24, 25 trihydroxy vitamin D3). This enzyme preferably binds to 1–25 (OH) 2 D3, thus limiting the effect of active vitamin D in tissues through inactivation [2]. The low level of 24-hydroxylase enzyme activity leads to high levels of 1–25 (OH) 2D3 and thus hypercalcemia. In addition, it has been suggested that a decrease in this enzyme activity may lead to impairment in intra-membranous bone mineralization [1, 2]. On the other hand, when 1–25 (OH) 2 D3 synthesis decreases, 1-alpha hydroxylase enzyme activity increases and 24-hydroxylase enzyme activity decreases. It is also known that FGF23 increases the activity of 24 hydroxylase enzymes [1, 2].
Numerous studies have shown active vitamin D synthesis by 1-alpha hydroxylase enzyme is not only a renal feature [2, 93]. The gene encoding the 1-alpha hydroxylase enzyme and the vitamin D receptor gene can be expressed in many cells or tissues such as skin, placenta, prostate, parathyroid, bone tissue, colon, lung, breast tissue, monocytes and macrophages, as well as renal cells. It has been reported that active vitamin D synthesized in the aforementioned tissues functions mostly as an intracrine or paracrine factor in the tissues where they are located, and does not contribute to the active vitamin D levels in the circulation, except for some special cases [1, 2]. Since PTH and FGF-23 receptors are not found in these tissues, they are not directly involved in controlling active vitamin D synthesis. However, it is propable that PTH increases the effect of vitamin D through posttranscriptional modification [31]. Unlike in other tissues, in activated macrophages, there is also no negative feedback of active vitamin D on 1-alpha hydroxylase enzyme [91]. Moreover, although the 24-hydroxylase enzyme is expressed in these cells, its function is not fully understood. Cytokines such as IL-1, TNF-α, IFN-γ induce the synthesis of active vitamin D in keratinocytes. Unlike macrophages, keratinocytes have a fully functional 24-hydroxylase enzyme activity and is induced by active vitamin D. In this way, active vitamin D limits its own synthesis in the epidermis through alternative catabolism [1, 2, 93].
Measurement of serum levels of vitamin D, which plays an important role in calcium and phosphorus metabolism and bone mineralization, is routinely performed worldwide. For this, it is preferred to measure the 25OHD level, which has a longer half-life (24–36 hours), can be taken exogenously, and can be synthesized endogenously. The half-life of the 1–25 (OH) 2D3 form is short (4–6 hours), and its serum levels are 1000 times lower than 25OHD. For these reasons, the active form is not preferred for routine measurement. In this section, the measurement methods of 25OHD vitamin are discussed.
To date, many methods have been developed for measuring serum vitamin D levels. These methods are basically divided into two groups. One methodology is the use of competitive binding and immunoassays: radioimmunoassay (RIA), enzyme immunoassay (EIA/ELISA), chemiluminescent immunoassay (CLIA), electrochemiluminescence assay (ECLIA), and competitive protein binding assay. The other methodology involves chemical methods. Chemical methods are based on the non-immunological direct detection methods typically after preparative chromatographic separation. Chemical methods include high performance liquid chromatography (HPLC) and LC/MS (liquid chromatography-mass spectrometer).
The first method used in the measurement of vitamin D is the competitive binding method in which VDBP binds. This method was first reported in 1971 and identifies 25OHD2 and 25OHD3 forms equally [94]. Limitations of this method include the incubation period of 10 days and its inability to separate some polar vitamin D metabolites [24,25(OH)2D, 25,26 (OH)2D ve 25,26 (OH)2D-26,23--lactone] [94]. In the late 1970s, the HPLC method was developed that can exclude the effect of polar vitamin D metabolites causing interference to the chromatographic method [95]. The advantages of this method, which uses a UV absorption technique, include the absence of lipid and polar vitamin D metabolite interference, the ability to measure 25OHD2 and 25OHD3 separated at high resolution, and a high specificity and reliability. Its disadvantages include the use of excess sample amounts, equipment cost, a need for preparative chromatography, and interference by other UV-absorbing compounds, and that the method is somewhat complex and not easily practical. It would not be considered a routine diagnostic test, as it is used in only about 2% of laboratories in the world) [94, 95]. With the later development of the RIA method, the value of quantifying vitamin levels improved. The advantages of this method type are that sample amount can be small and not pre-analytical preparative purification process is required. The assay is economical and easily applicable, and results reliable. As to the disadvantages, chemical and radioactive (with the RIA) waste are issues, and there is cross-reactivity with polar vitamin D metabolites as in the earlier competitive binding type assays. The RIA also is 100% specific for 25OHD3 and 75% specific for 25OHD2, so the final calculation requires an adjustment [94, 96]. Nonetheless automated immunoassay methods are widely used in our country and all over the world (approximately 76% of laboratories in the world) [97]. Requiring less sample volume, not requiring sample preparation, easy equipment supply, easy application, fast results, no cross-reactivity with C3-epimer forms, and low user error are among the reasons why this method is used more widely in the world [97, 98]. Despite its widespread use, this method has some significant disadvantages. In this method, 25OHD2 and 25OHD3 cannot be distinguished and both are measured as total of 25OHD. This may lead to misinterpretation in countries that use ergocalciferol in treatment (eg America) [97]. In addition, automated immunoassay results can be affected by pregnancy, whether sampled from intensive care patients, the presence of chronic disease and liver diseases, all of which affect the amount of VDBP synthesized from the liver [99, 100]. In addition, it has been reported that there is a high probability of interferences involving automated immunoassay measurement methods [97, 101].
Due to the low reliability of immunoassay measurements, this method has begun to be replaced by LC–MS/MS, which is considered to be the “gold standard” method. This method is used in approximately 18% of laboratories around the world, and it is estimated that its prevalence will increase due to its more accurate and precise results [97]. This method provides distinguishing quantitative measurements of both 25OHD2 and 25OHD3 forms in both serum and plasma [102]. Hence, 25OHD2 can be easily monitored in countries where ergocalciferol is widely used. In addition, with this method, C-3 epimer forms of vitamin D, which are present in high levels in serum in the first year, can be separated from other forms, and these metabolites are prevented from causing vitamin D measurement interference [97, 102].
In recent years, instead of measuring the level of vitamin D bound to VDBP, there is a strong belief in the need to measure free vitamin D levels as that is the form that accounts for the principal bioactivity. Routine methods measure the level of 25OHD vitamin bound to VDBP and provide information about the total body pool. In parallel with this, if the total body pool is sufficient, free vitamin D level is estimated to be sufficient. However, the situation is somewhat complex in obese patients, where a negative correlation between the amount of adipose tissue and serum vitamin D levels has been reported. In these cases, it has been reported that serum 25OHD level is lower than those with normal body weight, since large adipose tissue creates a larger pool for vitamin D sequestration [101, 102, 103, 104, 105]. In other words, serum 25OHD level in obese patients may not provide information about the body pool of vitamin D. It is thought that it would be more valuable to measure vitamin D levels that are not bound to binding protein in these cases. However, there is a serious standardization problem in the measurement of free 25OHD [103]. Also, Bikle et al. [106] proposed a method by which free 25OHD vitamin can be calculated. However, studies have shown that the results obtained with this method are not reliable [107]. Finally, direct measurement or indirect calculations of free forms of vitamin D are not yet suitable for routine use.
The process of joining materials layer upon layer from 3D digital model data or Computer-Aided Design (CAD) model is known as additive manufacturing (AM) or 3D printing as per International Organization for Standardization (ISO)/American Society for Testing and Materials (ASTM) 52900:2015 standard [1]. 3D printing has a long history of development for using it in the rapid prototyping of products for manufacturing since the 1980s. This development has since then led to also accessibility to the public. These developments started when Chuck Hull of 3D System Corp. filed their patent for a stereolithographic process eventually evolving into a 3D-printing technology boom [2]. Today 3D printer is priced as low as $100 [3] and is therefore accessible to the general public. Recent advances in 3D printing include, for example, the manufacturing of biomaterials for biomedical applications, such as tissue engineering. With recent advancements in the 3D printers, the industrial printers can build as small layers as 16 μm and thus creating a major milestone for biomedical applications [4]. 3D-printing technology can be used in various forms of materials printing, including fused deposition modeling (FDM), stereolithography (SLA), selective laser melting (SLM), and electron beam melting (EBM). The most used techniques are stereolithography and fused deposition modeling [5].
The International Organization for Standardization (ISO)/American Society for Testing and Materials (ASTM) 52900:2015 has classified the additive manufacturing (AM) process into seven categories (Figure 1) [5, 6].
Additive manufacturing processes.
There are several benefits to using 3D printing, such as [5, 7]:
Design to component translation.
Greater customization.
Manufacturing of complex, flexible, or lightweight components with no additional cost.
Potential of zero-waste manufacturing.
On-demand manufacturing.
Excellent scalability.
Although the 3D-printing industry is rapidly growing, there have been several economic, social, and environmental challenges that need to be addressed, such as recycling of materials, energy usage, organic compounds emission, high cost of raw materials, and standards and certifications [6]. The lack of printing material [8] and the high cost of thermoplastic polymers add to the barrier to the industrialization of 3D-printing technologies [9]. The market growth potential is considerable for 3D-printing as it is estimated that the filament market will be worth $ 6.6 billion by 2026 [10]. One concern for the advancement of 3D printing other than the high cost of raw material is the emission of volatile organic compounds (VOC), including iso-butanol and methyl-methacrylate [11]. To address the abovementioned economic and environmental concerns, there has been a new advancement in the additive manufacturing process which includes the addition of additives can such as diatoms [10] and biodegradable materials, such as ceramics, biomaterials, graphene, carbon fibers, binders for metals, sand, and plaster [12]. The cost of these additives is relatively much less than the thermoplastic filaments. In addition, there are added benefits including included in the addition of additives, such as improved moisture resistance that may slow down the process of decomposition of the filament material and may potentially open up other innovative functional possibilities, such as immobilization of chemical sensors and bacteria and virus-killing agents for novel biomedical applications.
In general, the structures fabricated with 3D printing either using single or multiple materials are intrinsically static, hence 3D printing cannot meet the demands where dynamic materials applications are needed including, for example, hygromorph biocomposites [13], adaptive wind turbines [14], active biocomposites [15], and self-folding microgrippers [16]. This addition of a new dimension to 3D printing has started a new era of printing known as 4D printing and includes novel materials compositions, additives, and chemical functionalization.
There are several challenges associated with manufacturing or scaling up of 3D printing mentioned as follows [17]:
Earlier 3D printing or additive manufacturing was normally used for rapid prototyping only but in the current scenario, 3D printing has already established a large pool of diverse applications, for example, in manufacturing, sociocultural, food, and biomedical sectors. There is a wide range of applications from nano to macro to large scale for 3D printing (Figure 2).
Range of applications of 3D printing.
There are several types of advancements are done recently to increase the efficiency of the additive manufacturing process, such as materials advancement, process advancement, and post-processing advancement.
There are several challenges associated with 3D printing, such as emission of volatile organic compounds, creation of voids, and high cost of thermoplastic polymers. To avoid all these issues, recent advancements have been done which include the use of fillers, such as carbon fibers, nanofibers, graphite, and diatomaceous earth [9, 10]. Carbon nanotube/polylactic acid composites (CNT/PLA) and multi-walled carbon nanotube/polylactic acid composites (MWCNT/PLA) with strong mechanical properties are being explored in microelectronics [19]. The smaller particles sizes are used in composites to produce stiffness and high density in the printed products, such as hydroxyapatite-reinforced polyethylene/polyamide composites (HA-PE/PA) [20]. Carbon black/polyamide 12 (CA/PA12) composites were fabricated which enhance the mechanical, thermal, and electrical properties of printed products [21]. Nanomaterial composites, such as nanosilica/polyamide, nanoclay/polyamide, and graphite nanoplatelets/polyamide composites, have also been fabricated leading to improved mechanical properties [9]. These composites can be used for multiple applications, such as biomedical applications, because of the high surface area of fillers present (Figure 3) [10].
3D-printed Diatoms in the PLA matrix (original work).
3D-printed titanium firefighting drone [
There is an innovative advancement that mimics the living organism’s organic cellular structure and bone growth. The world’s largest 3D-printed airplane cabin component with a “bionic partition” which separates the passenger cabin from the galley has been divulged by Autodesk and Airbus. This design has made the partition very light with a 45% reduction in weight compared to traditional designs but still very strong. It has been estimated that this design would save 465,000 metric tons of CO2 emissions per year. This new bionic partition used the second-generation alloy of scandium, aluminum, and magnesium named “Scalmalloy” created by the 3D-printing expertise of Airbus subsidiary “APWorks” (Figure 5) [24].
Airbus 3D printed bionic partition cabin [Source: Airbus].
Similarly, Airbus has collaborated with Materialise to produce the 3D-printed bionic spacer panel using FDM and Materialise’s post-production processes which made the panel 15% light in weight compared to traditional panels (Figure 6) [25, 26].
3D-printed finished spacer panel, [Source: Materialise].
Stratasys has been 3D printing more Airbus cabin components for years now [27]. Airbus A350 XWB was decided to be manufactured by 3D printing (Figure 7) [28].
Airbus 3D metal-printed bionic titanium bracket [Source: Airbus].
Alquist 3D has printed the first-ever 3D-printed house in the US which was assembled in 22 hours. The printer head was connected to the tube through which the traditional concrete was being pumped. Alquist 3D has teamed up with the nonprofit organization known as “Habitat for Humanity” where they will be providing homes to the people in need. Alquist 3D has claimed that the 3D-printed houses are 10–15% less in cost compared to traditional house building. It has saved the manpower also as according to Alquist 3D, only 3–4 humans were required to operate the printer [29]. This was not the first time 3D-printed houses have been built. In France, 3D-printed houses were built and Europe’s first 3D-printed house was built in 22 days which was later shortened to 3 days. In Dubai, there have been 3D-printed offices have been built. According to the Dubai government, it has saved them almost 50% of the total cost [30]. Initially, 3D printing was used only for prototyping the construction but now 3D printing has been used for constructing the whole buildings.
Porsche has used 3D-printing technology to produce 3D-printed pistons, spare parts, and sports seats. Porsche has developed the lightweight, better thermal resistance, high-performance pistons for the twin-turbo boxer engine of the 911GT2 RS model leading to a 30-horsepower gain. This process used the laser printing or laser metal fusion process in collaboration with MAHLE & TRUMPF which uses the high-precision machine, TruPrint 3000 with a 500-Watt fiber laser and high-purity metal special aluminum alloy powder which melted to print 1200 layers ending into the desired shape (Figure 8) [31, 32].
Pistons of the twin-turbo boxer engine of 911GT2 RS [Source: Porsche AG].
Porsche has been manufacturing spare parts using selective laser melting since 2018 but recently, Porsche has started manufacturing personalized bodyform full-bucket sports seats for Porsche 911 and 718. Porsche has also invested in 3D-printing specialist INTAMSYS (Figure 9).
3D-Printed bodyform full-bucket sports seats [Source: Porsche AG].
Porsche has also produced its first complete housing for its electric drive using the additive laser fusion process which has opened the possibilities for 3D printing in the highly stressed electric sports cars sector (Figure 10) [33].
Prototype for small series production [Source: Porsche AG].
4D printing or smart printing has a unique basic characteristic that differentiates it from the static 3D-printing structures; 4D-printing materials are dynamic and able to have functionality [8]. The well-used definition describing the 4D-printing states “It is the evolution of a 3D printed structure either in shape, property, and functionality when it is exposed to external factors such as light [38], heat [39], pH [40], and water [41]”. 4D printing can be defined as the best combination of a smart material, a 3D printer, and a well-programmed automated design (Figure 11) [8].
3D vs 4D printing.
There are five factors that influence the 4D printing which are the additive manufacturing process, feedstock material, stimuli, interaction mechanism, and modeling [42].
According to F. Momeni and J. Ni, there are three laws that define the shape-changing behavior of 4D-printed objects [43]. The first law states that “all the shapes changing behaviors such as curling, twisting, coiling, bending, etc. of multi-material 4D structures are due to the relative expansion between active and passive materials.”
The second law states that “there are four physical factors behind the shape changing ability of all multi-material 4D structures i.e., mass diffusion, thermal expansion, molecular transformation, and organic growth.”
The third law states that the “time-dependent shape-morphing behavior of nearly all multi-material 4D printed structures is governed by two “types” of time constants” (Table 1).
Types of materials | Examples | References |
---|---|---|
Responsive toward moisture: Hydrogels | Hydrogels respond to moisture or water and can expand up to 200% of their original volume. Sustainable materials, such as cellulose, can be used as hydrogel printing ink compatible with various types of printers | [8, 14, 40] |
Responsive toward light: photo-responsive | Chromophore (photosensitive) materials are inserted into smart material for which light acts as an indirect stimulus because light generates the heat which eventually changes the shape of the material. | [8, 37] |
Responsive toward temperature: thermo-responsive | Temperature (heating or cooling) is used as an external stimulus either to change the shape of material – shape change effect (SCE) or to transform the deformed shape into the original shape – shape memory effect (SME). SMEs can be polymers, metals, ceramics, alloys, and gels. These smart materials are used in biomedical applications such as orthodontics, physiotherapy, orthopedics, surgeries, etc. | [8, 38] |
Materials responsive toward pH | Polyelectrolytes are used as smart material which changes their shape as the pH changes with the release or gain of protons. It has found applications in biocatalysts, valves, actuators, drug delivery, etc. | [8, 39] |
Materials responsive toward the electric field | An electric field is also the indirect stimulus that produces the heat and causes the change in shape. For instance, origami using polypyrrole | [8] |
Materials responsive toward the magnetic field | Smart materials change their shape in the presence of a magnetic field. Magnetic nanoparticles are incorporated into hydrogels which respond in the presence of a magnetic field | [8, 41, 42] |
Piezoelectric materials | The charge is produced with mechanical stress which eventually causes the deformation. | [8, 41, 42] |
Types of materials used in 4D printing.
There are revolutionary applications associated with the 4D printing, such as biomedical applications of 4D printing in drug delivery, organ regeneration and transplantation, and tissue fabrication [44]. 4D-printed structures have great potential in soft robotics because of their capability to deform, adjust to environmental changes, and flexibility [8]. 4D-printed structures with smart materials can be used as self-evolving structures [45, 46], active origami structures [47], self-sustainable satellite manufacturing parts [8], sensors responsive toward moisture, temperature, pH, magnetic energy, etc. [8]. Despite diverse applications, 4D printing needs more research and development, especially in scaling it up. Commercializing the 4D printing is troublesome because of the high production cost, installation cost and material used and availability. Multi-materials printers could be a possible solution but need furthermore research (Figure 12).
4D printed metamaterials reconfigurable object [
Additive manufacturing was invented in the 1940s and it has developed a lot with innovative inventions since then. The different additive manufacturing process techniques have specific peculiarities and the disadvantage of one technique can lead to the innovation of a new technique. The development of different types of printers has enabled the AM to use different types of materials which include plastics, metals, and ceramics. New improvements in AM techniques allow the high filler loading in thermoplastic composites.
3D printing has diverse applications include for instance food, fashion, biomedical, health, aerospace, and cultural heritage preservation. 3D printing helps the consumer to customize the product as per their requirements. There are a few challenges that need to be addressed, such as emission of volatile organic compounds, creation of voids, high cost of thermoplastic polymers, and weak mechanical strength, of printed structures. To overcome these challenges composites with fillers have been fabricated such as carbon nanotube/polylactic acid composites, nanosilica/polyamide composites, and carbon black/polyamide composites which have increased the mechanical, electrical, and thermal properties of the composites.
Despite highly diverse applications of 3D printing and new advancements in 3D printing, there are still a few challenges that restrict the usage of 3D printing on a commercial scale. These include the resistance and adaptability of 3D-printed material’s properties and structures against the change in environmental factors, such as temperature, electric energy, and pH.
4D printing is basically the combination of a 3D printer, smart material, and well-designed programming that allows the 3D-printed object to change its shape, properties, and functionality with time. 4D-printed objects change or modify against environmental conditions. These materials can be responsive to heat, water, pH, electric energy, and magnetic field. 4D printing has increased the number of application areas for additive manufacturing and thus expanded to include aviation, self-sustaining material, sensors, active materials, and bioprinting.
There has been a tremendous amount of technological advancement and research on 3D and 4D printing, and its applications. New advancements have been, however, the commercialization and implementation at a larger stage are still in progress and therefore more research and development are needed. Importantly more sustainable materials need to be explored due to the environmental risks associated with some of the materials and techniques used. The potential to create solutions to some of the most challenging product development needs in various industries using 3D- and 4D-printing technologies remain high. These developments are many times related to niche products that cannot be manufactured otherwise.
This is a brief overview of the main steps involved in publishing with IntechOpen Compacts, Monographs and Edited Books. Once you submit your proposal you will be appointed a Author Service Manager who will be your single point of contact and lead you through all the described steps below.
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Saxena",hash:"d92a4085627bab25ddc7942fbf44cf05",volumeInSeries:2,fullTitle:"Current Perspectives in Human Papillomavirus",editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:250,paginationItems:[{id:"274452",title:"Dr.",name:"Yousif",middleName:"Mohamed",surname:"Abdallah",slug:"yousif-abdallah",fullName:"Yousif Abdallah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274452/images/8324_n.jpg",biography:"I certainly enjoyed my experience in Radiotherapy and Nuclear Medicine, particularly it has been in different institutions and hospitals with different Medical Cultures and allocated resources. Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"243698",title:"Dr.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:null,institution:null},{id:"7227",title:"Dr.",name:"Hiroaki",middleName:null,surname:"Matsui",slug:"hiroaki-matsui",fullName:"Hiroaki Matsui",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Tokyo",country:{name:"Japan"}}},{id:"312999",title:"Dr.",name:"Bernard O.",middleName:null,surname:"Asimeng",slug:"bernard-o.-asimeng",fullName:"Bernard O. 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