IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
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IntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
With the desire to make book publishing more relevant for the digital age and offer innovative Open Access publishing options, we are thrilled to announce the launch of our new publishing format: IntechOpen Book Series.
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Designed to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
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After a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
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Our innovative Book Series format brings you:
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Topic Focused Publications - Each topic showcases high impact subject areas
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Renowned Editorial Expertise - Series Editors, Topic Editors, and a team of international Board Members that permanently support each Book Series
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Fast Publishing - quick turnaround which is unique for book publishing
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The benefit of ISSN and ISBN for increased citation and indexing possibilities
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IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\n
IntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
We invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
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Note: Edited in October 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"6492",leadTitle:null,fullTitle:"Vegetables - Importance of Quality Vegetables to Human Health",title:"Vegetables",subtitle:"Importance of Quality Vegetables to Human Health",reviewType:"peer-reviewed",abstract:"The book Vegetables - Importance of Quality Vegetables to Human Health provides useful and interesting information on the nutritional qualities of different vegetables and their roles in disease prevention. Quality vegetable production through hydroponic cultivation techniques is also included. The first few chapters discuss the importance of quality vegetables to human diet and health, and noncommunicable disease prevention. Nutritional qualities and bioactive compounds in freshly grown vegetables through hydroponics and soilless cultures are discussed in the middle part of the book. The final chapter describes methods of sea vegetable utilization in food formulation. This book mainly focuses on the nutritional quality of vegetables and disease prevention, their production methods, preparation, and cooking methods, making it a complete and useful resource to readers.",isbn:"978-1-78923-507-4",printIsbn:"978-1-78923-506-7",pdfIsbn:"978-1-83881-499-1",doi:"10.5772/intechopen.70972",price:119,priceEur:129,priceUsd:155,slug:"vegetables-importance-of-quality-vegetables-to-human-health",numberOfPages:112,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"c9b3988b64bc40ab0eb650fe8a2b2493",bookSignature:"Md. Asaduzzaman and Toshiki Asao",publishedDate:"August 22nd 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6492.jpg",numberOfDownloads:12962,numberOfWosCitations:14,numberOfCrossrefCitations:27,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:45,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:86,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 20th 2017",dateEndSecondStepPublish:"October 11th 2017",dateEndThirdStepPublish:"December 10th 2017",dateEndFourthStepPublish:"February 28th 2018",dateEndFifthStepPublish:"April 29th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"171564",title:"Dr.",name:"Md",middleName:null,surname:"Asaduzzaman",slug:"md-asaduzzaman",fullName:"Md Asaduzzaman",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9McQAK/Profile_Picture_1630649832129",biography:"Dr. Asaduzzaman is a native of Bangladesh and received a Ph.D. in Bioproduction Science from Tottori University, Japan. He has expertise in hydroponic crop production and is currently working as a senior researcher at the Horticulture Research Centre, Bangladesh Agricultural Research Institute. His main research focuses on the development of hydroponic techniques for horticultural crops in a greenhouse, production of specialty crops under Controlled Environment Agriculture (CEA), and development of specialty dietary components through hydroponic production of vegetables providing human health benefits beyond basic nutrition. His other research project includes studying autotoxicity, a phenomenon of intraspecific allelopathy in vegetables and ornamentals through hydroponics, and developing suitable control measures to overcome it. He has published thirty-one original research articles, five review articles, twenty-two conference proceedings, eight book chapters, and nine edited books. He was awarded the Gold Medal from Bangladesh Agricultural University in 2011 and the 2016 BAS-TWAS Prize for Young Scientists from Bangladesh.",institutionString:"Bangladesh Agricultural Research Institute",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"Bangladesh Agricultural Research Institute",institutionURL:null,country:{name:"Bangladesh"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"106510",title:"Dr.",name:"Toshiki",middleName:null,surname:"Asao",slug:"toshiki-asao",fullName:"Toshiki Asao",profilePictureURL:"https://mts.intechopen.com/storage/users/106510/images/system/106510.jpeg",biography:"Dr. Toshiki Asao is a specialist in hydroponic crop production and Professor at Department of Agriculture, Faculty of Life and Environmental Science, Shimane University, Japan. Dr. Asao is a native of Kyoto, Japan and received Ph.D. majoring Agriculture from Kyoto University. His main research focus is the development of hydroponic techniques for vegetables and ornamentals in greenhouses and also the development of specialty vegetables through hydroponics under controlled environment agriculture providing human health benefits beyond basic nutrition. His other research project is the studying autotoxicity in vegetables and ornamentals in hydroponics and developing possible control measures. He has published a number of scientific articles, book chapters, and edited books.",institutionString:"Shimane University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"Shimane University",institutionURL:null,country:{name:"Japan"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"341",title:"Olericulture",slug:"olericulture"}],chapters:[{id:"62292",title:"Introductory Chapter: Quality Vegetable Production and Human Health Benefits",doi:"10.5772/intechopen.79430",slug:"introductory-chapter-quality-vegetable-production-and-human-health-benefits",totalDownloads:1758,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Md Asaduzzaman and Toshiki Asao",downloadPdfUrl:"/chapter/pdf-download/62292",previewPdfUrl:"/chapter/pdf-preview/62292",authors:[{id:"171564",title:"Dr.",name:"Md",surname:"Asaduzzaman",slug:"md-asaduzzaman",fullName:"Md Asaduzzaman"},{id:"106510",title:"Dr.",name:"Toshiki",surname:"Asao",slug:"toshiki-asao",fullName:"Toshiki Asao"}],corrections:null},{id:"61691",title:"Role of Vegetables in Human Nutrition and Disease Prevention",doi:"10.5772/intechopen.77038",slug:"role-of-vegetables-in-human-nutrition-and-disease-prevention",totalDownloads:3270,totalCrossrefCites:12,totalDimensionsCites:22,hasAltmetrics:1,abstract:"Vegetables are important for human health because of their vitamins, minerals, phytochemical compounds, and dietary fiber content. Especially antioxidant vitamins (vitamin A, vitamin C, and vitamin E) and dietary fiber content have important roles in human health. Adequate vegetable consumption can be protective some chronic diseases such as diabetes, cancer, obesity, metabolic syndrome, cardiovascular diseases, as well as improve risk factors related with these diseases. In this chapter, basic information will be given about the classification of vegetables, preparation and cooking, and their effects on food content of vegetables and effects on health and diseases (diabetes, obesity, metabolic syndrome, cardiovascular diseases, and cancer).",signatures:"Taha Gökmen Ülger, Ayşe Nur Songur, Onur Çırak and Funda Pınar\nÇakıroğlu",downloadPdfUrl:"/chapter/pdf-download/61691",previewPdfUrl:"/chapter/pdf-preview/61691",authors:[{id:"176588",title:"Prof.",name:"Funda Pınar",surname:"Çakıroğlu",slug:"funda-pinar-cakiroglu",fullName:"Funda Pınar Çakıroğlu"},{id:"244239",title:"Dr.",name:"Onur",surname:"Çırak",slug:"onur-cirak",fullName:"Onur Çırak"},{id:"251662",title:"Dr.",name:"Ayşe Nur",surname:"Songür",slug:"ayse-nur-songur",fullName:"Ayşe Nur Songür"},{id:"251663",title:"MSc.",name:"Taha Gökmen",surname:"Ülger",slug:"taha-gokmen-ulger",fullName:"Taha Gökmen Ülger"}],corrections:null},{id:"59450",title:"Health Benefits of Fruits and Vegetables: Review from Sub-Saharan Africa",doi:"10.5772/intechopen.74472",slug:"health-benefits-of-fruits-and-vegetables-review-from-sub-saharan-africa",totalDownloads:3379,totalCrossrefCites:3,totalDimensionsCites:7,hasAltmetrics:1,abstract:"A fruit is defined as the edible part of a plant that consists of the seeds and surrounding tissues, while vegetables are plants cultivated for their edible parts. Fruits and vegetables are important sources of micronutrients and dietary fibres and are components of a healthy diet, which help in preventing major diseases. Due to the fact that fruits and vegetables have health promoting properties, they contribute to dietary guidance. This chapter defines the basic concepts related to health benefits of fruits and vegetables, reviews the previous literature on health benefits of fruits and vegetables and enumerates the health benefits of some common fruits and vegetables. It also examined the dietary recommendation of fruits and vegetables in less developed countries as well as present situation of fruits and vegetables consumption with particular reference to sub-Saharan Africa.",signatures:"Ifeoluwapo Amao",downloadPdfUrl:"/chapter/pdf-download/59450",previewPdfUrl:"/chapter/pdf-preview/59450",authors:[{id:"223341",title:"Dr.",name:"Ifeoluwapo",surname:"Amao",slug:"ifeoluwapo-amao",fullName:"Ifeoluwapo Amao"}],corrections:null},{id:"58552",title:"Hydroponic Production Systems: Impact on Nutritional Status and Bioactive Compounds of Fresh Vegetables",doi:"10.5772/intechopen.73011",slug:"hydroponic-production-systems-impact-on-nutritional-status-and-bioactive-compounds-of-fresh-vegetabl",totalDownloads:2319,totalCrossrefCites:8,totalDimensionsCites:11,hasAltmetrics:0,abstract:"Hydroponic systems for vegetable production are nowadays essential to maximize productions and increase yields. Although the technical issues concerning the production are well explored and discussed, less information is available about the impact of hydroponic methods in the nutritional status of fresh vegetables and in particularly in their levels of bioactive compounds. Therefore, the aim of the current chapter is to provide accurate and updated information about their effects on compositional and bioactive properties of vegetables, comparing with conventional production mode. This chapter will be divided as the following sections: (1) introduction (introduction to the theme), (2) hydroponics and quality of vegetable produces, and (3) conclusion. With this chapter, we hope to present an updated and credible discussion, compare hydroponic versus conventional vegetables production mode, and present new consumers and producer trends.",signatures:"Alfredo Aires",downloadPdfUrl:"/chapter/pdf-download/58552",previewPdfUrl:"/chapter/pdf-preview/58552",authors:[{id:"175895",title:"Dr.",name:"Alfredo",surname:"Aires",slug:"alfredo-aires",fullName:"Alfredo Aires"}],corrections:null},{id:"59060",title:"The Influence of Different Substrates on the Growth, Yield and Quality of Slovenian Sweetpotato Cultivars under Greenhouse Conditions",doi:"10.5772/intechopen.73118",slug:"the-influence-of-different-substrates-on-the-growth-yield-and-quality-of-slovenian-sweetpotato-culti",totalDownloads:1018,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"A greenhouse experiment was conducted to evaluate the genetic relatedness between three Slovenian sweetpotato cultivars; and to assess the effects of different growing substrates on selected agronomic and nutritional traits. Tubers of three cultivars (‘Lučka’, ‘Janja’ and ‘Martina’) with different skin/flesh color were produced in planters under glasshouse conditions in five different growing substrates (perlite, peat, expanded clay, vermiculite and garden soil) from prior raised seedlings. Genetic analysis was performed using a set of eight SSR markers. According to Nei’s genetic distance and pairwise population Fst analysis, the most related cultivars are ‘Janja’ and ‘Martina’. The following agronomic traits were evaluated: vine length, thickness of vine-base, number of branches, weight of above ground part, number of leaves plant−1, number of tubers plant−1 and tubers weight plant−1. Among nutritional traits, total phenolic content (TPC), antioxidant potential (AOP) and ascorbic acid content (AA) were determined. Significant interactions of growing substrates (factor A) × cultivar (factor B) were observed for thickness of vine-base, weight of above ground part, AOP, TPC and AA. Overall results show different response of cultivars in different growing substrate. Growing substrate provide a discriminant classification of the sweetpotato cultivars according to their agronomic and nutritional traits.",signatures:"Dragan Žnidarčič, Filip Vučanjk, Žarko M. Ilin, Barbara Pipan,\nVladimir Meglič and Lovro Sinkovič",downloadPdfUrl:"/chapter/pdf-download/59060",previewPdfUrl:"/chapter/pdf-preview/59060",authors:[{id:"179063",title:"Dr.",name:"Dragan",surname:"Znidarcic",slug:"dragan-znidarcic",fullName:"Dragan Znidarcic"}],corrections:null},{id:"60041",title:"Sea Vegetables",doi:"10.5772/intechopen.75014",slug:"sea-vegetables",totalDownloads:1220,totalCrossrefCites:3,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Sea vegetables or seaweeds have a long tradition in Asian cuisine. In Western countries, including Turkey, seaweed consumption is generally limited to sushi and other imported Asian dishes. However, seaweeds are well recognized for their richness in several nutrients such as carbohydrate, fiber, protein, lipid, and minerals. The migration of Asian population across the world has promoted the discovery of new ingredients from seaweeds and has given courage to the creation of new dishes by chefs in restaurants. Among the seaweeds traditionally consumed by Asian population, Ulva, Laminaria, and Porphyra are well-known species. Seaweed polysaccharides, such as agar, alginate, and carrageenan, are widely used in the food industry as clarifying, gelling, emulsifying, stabilizing, thickening, and flocculating agents in various food products such as ice cream, yogurt, candy, meat product, beverages, etc. The production of plant protein concentrates (PCs) is of growing interest to the food industry. Recently, PCs were also extracted from three edible green seaweed species of Enteromorpha or Ulva. Seaweed contains a wide array of nutritional compounds also possessing several functional properties that may lead to many dish and food preparation innovations. For example, a green seaweed, Ulva, may be used with or in the replacement of other commonly used vegetables to promote healthy food.",signatures:"Gamze Turan and Semra Cırık",downloadPdfUrl:"/chapter/pdf-download/60041",previewPdfUrl:"/chapter/pdf-preview/60041",authors:[{id:"228415",title:"Dr.",name:"Gamze",surname:"Turan",slug:"gamze-turan",fullName:"Gamze Turan"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"4552",title:"Soilless Culture",subtitle:"Use of Substrates for the Production of Quality Horticultural Crops",isOpenForSubmission:!1,hash:"0db90197795ffda070bec7ed97064c74",slug:"soilless-culture-use-of-substrates-for-the-production-of-quality-horticultural-crops",bookSignature:"Md. 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1. Introduction
Technological advancement has been the dominant driving force in modern society leading to a widespread diffusion of products from the rational activity as well as of scientific, technological, and administrative sources, which in turn requires new types of management [1].
This technological progress has induced a new paradigm based on the development of a set of intensive knowledge on scientific technologies, which represent many applications of scientific discoveries, whose core is to develop an increasing competence to manage information and knowledge. In this contemporary setting, the intangibles assets such as knowledge (know how), patents, and intellectual capital become increasing value strategic elements to be the center of contemporary forms of capital accumulation [2].
Biotechnology as a highly scientific sector is one of the most knowledge-intensive activities in the contemporary economy, having a direct and indirect impact on regional and national economies. The phenomenon of growth in the production of biotechnological products is relatively new, and in the long term, the growth potential is probably associated with the greater diffusion and use of your products and processes due to its convergence with nanotechnologies, information technologies, and other applied sciences [3].
In this context, biotechnology is considered as one of the most important technological tools nowadays. It is considered a key “future-bearing technology” and its applications have contributed to the structuring of new economic and social systems [4]. In this sense, biotechnology appears to have the characteristics of a core technology, with the potential to underpin a new technoeconomic paradigm.
Biotechnology represents a set of technologies “that use biological systems, living organisms, or their derivatives to produce or modify products and processes for a specific use” [5]. Biotechnology features a multidimensional nature, involving different knowledges, scientific and technological. Indeed, biotechnology can be considered as the result of a scientific revolution that involves many disciplines. In other words, it is a “constellation of scientific revolutions” [6], which is based on different areas of knowledge such as molecular biology, biochemistry, computer science, biophysics, engineering, and others.
The large set of biotechnological methods along with its different forms of application results in different interpretations about the dimensions that compose the biotechnology [7]. It has helped to generate new high-impact services in various segments such as health area with impressive revolution in the treatment of diseases as well as the use of new drugs for humans. It is also possible to verify its impact on agriculture with the development of functional foods and the reproduction of plant species; in the chemical and petrochemical industries with treatments of wastes and wastewaters; and the sustainable use of biodiversity, among other areas [2].
When assessing the potential application of modern biotechnology for the next 20 years, some authors assert that areas such as genomics, proteomics (spatial identification of protein structures), biomaterials, bioengineering, pharmacogenomics, genetic engineering, genetically modified foods, and synthetic biology will have a great impact on the future [2, 8].
In view of these future prospects, the monitoring and research of scientific advances and trends in this area of knowledge have become essential for searching opportunities in research and development (R&D), as well as for potential innovations and business opportunities, in the developed countries and mainly in countries of emerging economies such as Brazil [2]. Countries with rich biodiversity, mainly South American countries such as Brazil and Colombia, have tried to develop national capacities in science and technology (through improving their infrastructure, greater participation in network experts, training of human resources, the increase publications) that allows a better optimization of scientific resources and economics and the generation of technological products based on nationally developed biotechnology [2, 9].
In this situational scenario, in order to propose worldwide profile of knowledge management of trends in biotechnology in Brazil, this chapter presents science trends in this area, mapped out through a set of variables such as the identification of the actors involved as well as the institutional partnerships, the major journals, among others, using the analysis of all Brazilian scientific publications of international dissemination for the period of 1995–2014.
2. Biotechnology in the global market and Brazilian government programs
2.1. Biotechnology in the global market
For centuries, humans have used biotechnology in their daily lives. Biotechnology presents as the growth area and development products and technologies observed in different areas of economy, which use live microorganisms or parts of them [10], showing up as a promising area among the diverse emerging technological developments. Being a multidisciplinary area presents the possibility of new products and processes. The bioindustry has contributed to the economic and social growth by bringing new solutions to problems concerning to human and animal health, to agribusiness, the environment, and the creation of new materials. In these aspects, biotechnology is a technological innovation that also provides products or processes with social or commercial use [11].
As technological progress advances based on life sciences, the possibilities of obtaining products with higher added value or lower production costs increase. The most prospected areas of biotechnology are health (pharmaceutical) and agriculture (food) [2]. On the economic bias, biotechnology is a major focus of activities on research, development, and innovation in the developed countries and it is becoming increasingly central in developing countries due to the potential of exploiting great biodiversity [12].
For a long time, it has been emphasized about the biotechnology potential and the future full of innovations that it provides. However, today, we can observe that the largest potential innovators are in the United States and Europe (the United Kingdom, Germany, and France). Due to their investments in the chemical and pharmaceutical corporations they become owner of biotechnology companies, enlarge their capabilities of innovation, or maximized new products generation [13].
The biotechnology industry has been grown rapidly in recent years, more than doubled its worldwide revenue in the last decade, going from US$ 8 billion in 1993 to US$ 20 billion in 1999 [14]. According to the study presented in Ref. [15], the worldwide market for biotechnology resources moves expressive values of about $ 410 billion per year. The worldwide market for biotechnology between 2002 and 2006 grew at a compound annual growth rate (CAGR) of 13.4% [16]. Figures in this market are not very consistent. According to the study presented in Ref. [17], the United States alone moved the biotechnology industry resources of US$ 3.7 billion in 2009, being the market that moves much capital in this biotechnology market.
Regarding innovative effort, we can affirm that the United States is the country that spent more on R&D in biotechnology. In 2009, it spent only in entrepreneurial sector, US$ 22 billion on R&D, followed by France, Germany, and Canada, with the total expense on R&D about US$ 2.5, 1.3, and 1 billion, respectively [18].
In Asia and Pacific, among the countries that are more prominent, Japan is the most advanced in the biotechnology area, due mainly to the cooperation work developed by Japanese government, universities and private sector, directed especially to build an adequate infrastructure for innovative business start-ups [18]. After that the focus turns on Singapore, Taiwan, China, India, and Australia. The Chinese government, for example, invested about US$ 40 billion in the biotechnology industry in 2012 and, the Singapore government hopes to increase 20% biotechnology investments in the next 5 years, that is, it is intended to spend about US$ 12.5 billion in R&D in this sector [18].
2.2. Biotechnology in Brazilian government programs
The biotechnology segment holds a special place among the priorities at government policies, as much for the developed country and as for developing countries. The wide set of opportunities created by biotechnology, especially in health and agriculture areas, show the essentiality of its development as competitive strategy and expansion input in international market, mainly in developing countries such as Brazil. Brazil is a country with great potential for the development of agricultural biotechnology because it has a wide biological diversity and is rich in plants, animals, and microorganisms [19]. Since the 1970s, the biotechnology applied in agriculture has been productive and economic relevance in the country.
This chapter focuses on the characteristics and development of biotechnology in Brazil and refers to the public investment, with the main aspects of the most noteworthy programs and financing structure. There is a governmental structure in the country directed for the development of the area. This structure is composed of the following ministries: the Ministry of Science, Technology and Innovation (MST&I); Environment and Agriculture; Production and Trade; and Health and Social Development. At the same time, the government also acts through its government agencies, the private sector, and academia [2].
The government policies to support the development and financing on biotechnology in Brazil have started since 1980 with the promotion of several programs dedicated to the area, the Integrated Genetic Program, which aimed at introducing some specific actions on genetic engineering. In 1981, the government officially unveiled the National Program for Biotechnology (Pronab) which was to consolidate public investments for maintenance of the research groups in areas related to the program.
In 1984, the Ministry of Science and Technology (MST) had created a wide program in order to support, finance, and develop strategic areas in the country. This program was the development support to Scientific and Technological Program (PADCT), cofinanced by International Bank for Reconstruction and Development (BIRD). Since its beginning, biotechnology has been seen as a strategic area for the scientific development in the country and, thus, established a specific subprogram to support it, the Biotechnology Subprogram (SBIO). PADCT started in 1985 and its actions were continued until the 2000s. At first, PADCT prioritized the development of some activities such as molecular biology, genetic engineering, and biosafety, without forgetting areas such as biochemistry, microbiology, and agronomy.
From the wide vision, PADCT aimed to build physical structures for research centers and development projects in cooperation in order to attract private investment, promote dissemination, and technology transfer from academic centers to the production sector. During this period, the first biotech products emerged that were human insulin, biodegradable plastics, biofilm, genetically modified plants, among others.
Early in the 1990s, both the government and the private sector have reduced the resources applied to biotechnology due to low commercial return of biotech products developed so far.
In 1999, the government changed the pathway of financing in Brazil through the creation of sources of fiscal financing from various economic sectors, called sectoral funds. In 2001, the biotechnology sector fund was created and its main objective was to ensure the continuity of biotechnology research, especially those considered as strategic for the country. Somehow, the creation of Biotech fund strengthens the National Program of Biotechnology and Genetic, established in 2000 and under MST&I responsibility. The program emphasized actions to “conservation genetic resources and development of biotechnological products and processes with applications in industries, agriculture, and human health”. Several of these opportunities have been adopted as strategy of the project management in networking way in order to increase the flow of innovation and the results to society.
Among the many action plans applied from 2002, it is worth mentioning the following: Brazilian Genome Project, Structural Biology Network, Brazilian Proteomics Network, the development of biopharmaceuticals and immunobiology, and the development of new technological routes.
In 2004, the government using the Brazil’s Industrial, Technological and Foreign Trade Policy (PITCE) pointed out biotechnology as the “future-bearing technology.” On that political occasion, the Biotechnology Competitiveness Forum had created in order to put together all actors involved in the production chain in favor of strengthening industrial competitiveness.
Biotechnology research is funded by federal, private, and international agencies. The Organic Law of Science, Technology and Innovation (Decree No. 10.973 of 2/12/2004) defines some coordination organizations on the national level, and the Ministry for Science, Technology and Innovation (MST&I) represents the leading national organization [2].
From Biotechnology Competitiveness Forum, in 2007, begun the Biotechnology Development Policy (PDB), which established the National Biotechnology Committee (CNB). On the whole policy, structuring actions were defined in order to promote transfer of technology, investments, training of human resources, strengthen networks, regulatory framework, and to improve infrastructure for research centers and R&D. Examples of priority areas supported were: plant and animal breeding, food technology, bioinformatics and immunology, diagnosis and prospecting on biotechnology, and detection of genetically modified organisms.
3. Methodology and recovery documents
3.1. Database
The research was based on the selection of scientific publications collected in ISI/Web of KnowledgeSM database. It is international bibliographic data and is used as reference for the generation of indicators of S&T and Innovation [2].
3.2. Strategies for recovery documents
The strategy for the recovery of publications on a particular scientific topic must be carried out carefully to avoid damaging in the analysis of scientific literature. For the analysis of results in an accurate overview of the subject, ideally, the “search expression” must promote the recovery of all relevant publications on the subject present in the database, and at the same time, exclude nonrelevant publications. However, such situation is difficult to achieve since the multidisciplinary issues receive contributions from several areas of knowledge.
The solution for recovery of significant and coherent set of publications that allows an analysis of the scientific production in the biotechnology area was the elaboration of a complex search expression, consisting a large of set selected and tested keywords.
At first, we tried to develop search strategies in the mode “ISI-general search,” using keywords from the available literature and descriptors present on the Platform-Lattes/National Council for Scientific and Technological Development (CNPq) - Brazil and Portal Innovation/MSCT-Brazil related to research groups and ongoing research in the biotechnology area. These search expressions were just an exploratory character, that is, serve as a basis for elaborate more refined expressions and evaluate how the area is organized into database [20]. A selection from bibliographic references was also used.
In order to achieve the purpose of mining scientific production on biotechnology in Brazil over a period of 21 years (1995–2015), 60 distinct descriptors (Table 1) were used, selected by experts in biotechnology area, interviewed and research groups in the biotechnology area sought in the base Plataforma Lattes CNPq/Brazil and Portal Innovation/MSCT-Brazil.
Antisense
Biomaterial
Proteins engineering
GMO
Recombinant antigen
Biopolymer
Genetic engineering
Protein
Biodiversity
Bioprocess
Metabolic engineering
Recombinant protein
Biocatalyst
Bioprospection
Molecular engineering
Proteome
Biofuel
Bioreactor
Gene expression
Proteomic
Bioeconomy
Bioremediation
Pharmacogenomics
PCR
Bioengineering
Biosensor
Phytoremediation
RNA
Bioethics
Biosorption
Gene
Microarray DNA
Biofiltration
Biosurfactant
Genetic
Microarray RNA
Bioindustry
Biosulfurization
Genome
Transcriptome
Bioinformatics
Biotechnology
Genomic
Transgenic
Biolixiviation
Stem cells
Microbiota
Cellular therapy
Computational biology
Cloning
Biology modeling
Gene therapy
Biome
T cells
Nanobiotechnology
Molecular therapy
Biomass
DNA
Peptide
Vaccine
Table 1.
Biotechnology-related terms used to search articles in database ISI/Web of Science.
From our previous experiences, we found that the best way to do this recovery would be a combination of different expressions. For this, we used the advanced search mode of ISI/Web of Science and the advanced search. Once defined the strategy, we used all these keywords, and various search expression and their combinations in the database ISI/Web of Science only looking for indexed publication using document types “article.” The fields “Title, Summary, and Keyword” were used to analyze the themes of scientific publications with international dissemination [21].
The software VantagePoint® was used to perform the processing of information from articles retrieved in order to expand and enrich the results. VantagePoint® allows management of big data and information in order to present correlations of distinct variables of interest. It also allows us to identify Who, What, When, and Where, help us clarify relationships and find critical patterns, among other possibilities [2].
For visualization of the data, we used the software VOSviewer®. It is a latest free software for the representation and analysis of information, which appears as an alternative to the traditional techniques of multidimensional representation and network display. VOSviewer combines the visualization and clustering techniques, favoring analysis while bypassing unnecessary technical complications. It make possible to view the maps of collaboration between institutions, countries, and keywords [22].
After this step, macroindicators were generated for providing a global overview of the scientific production on biotechnology in Brazil and raising the main issues as follows: (1) the total number of articles published per year (1995/2015) and the trend of publication of the most frequently used terms; (2) major journals that institutions often publish their articles in this specific area; (3) key areas of knowledge and the number of articles published on the used terms; and (4) the number of papers published by institutions and maps of network (institutions and countries) for the purpose of identifying partnership [2].
The trends for biotechnology were mapped out through a set of variables such as the identification of the actors involved as well as the institutional partnerships and networking.
4. Overview of the global scientific development in biotechnology in Brazil
4.1. Analysis of results and cowords networks
Government policies to incentive and promote R&D activities in biotechnology in Brazil have started since the 1980s. However, from the late 1990s and the early 2000s, especially in 2001, with the creation of the national fund for biotechnology, the area aimed at real conditions of productivity and competitiveness in R&D. Biotechnology has its amended financing path taking up considerable resources of 97% between 2002 and 2003, with the resources allocation from the National Fund for Scientific and Technological/FNDCT, managed by the MSCT, CNPq, and Studies and Projects Financing Institution (FINEP) [23].
From the data collected in the ISI database, bibliometric indicators have been produced that will help us to understand the scientific activity in the biotechnology area.
With regard to the scientific literature on biotechnology for the period between 1995 and 2015, it was retrieved 102,326 documents containing terms selected by experts in the fields of title, abstract, and keywords, and 69,977 documents where Brazil as the home country (1st author). Figure 1 shows the evolution of publication number in biotechnology area since 1995.
Figure 1.
Historical evolution of biotechnology scientific publishing indexed in Brazil since 1995.
By analysis, the number of articles published throughout this period was possible to observe that there is an increase in publication trends, which indicates an intensive scientific activity over the past 15 years, mainly in the last 8 years. An exponential growth with increased production greater than 6500% was observed, as shown in Figure 1. However, this scenario of accelerated growth should be modified in the coming years because of the reduction of R&D investments by government agencies in recent two years (2014–2016); due to the severe economic crisis that Brazil has been facing since 2013, which will reflect in a slowdown of the scientific production in the country for the next years.
A probable cause of this growth seems to be the key role that the activities of biotechnology have gained notoriety on a worldwide scale in recent decades. In Brazil, this increase observed reflects the research government incentives, established the financial investments in the area and the implementation of government policies, as aforementioned.
With respect to the most frequently used terms to screen the biotechnology area in Brazil, it was possible to find a large dispersion in relation to them [2], which means that there are more than 7000 distinct descriptors (keywords) described by the authors in the scientific publications as examples: Vaccine, PCR, DNA, Genome, Leishmania, Trypanosoma cruzi, HIV, among others. Some of them were not used as initial descriptors when searching the database.
In the specific evaluation of these terms, we noted that terms such as DNA and PCR are often used since the beginning of the period analyzed, which means that since 1998, these are being associated with modern biotechnology techniques [2]. Other terms such as “genomic,” (72 articles) “proteomics,” (32 articles), and “stem cell” (37 articles) are further frequent, however, they are related to more advanced future-bearing technologies of modern biotechnology, being mentioned in Brazil by the National Biotechnology Committee as the frontier areas of biotechnology. This observed result is associated with the Brazil collaboration in the genome projects, as example the mapping of the Xylella fastidiosa genome in 1997, and later, working in international project such as Human Genome Project (HGP) in 1999. X. fastidiosa is a bacterium that attacks citrus agriculture producing “little yellow” and decreasing agricultural productivity, so this project was essential for the control of this pest in Brazilian farming. This project was much important because it was the first phytopathogen sequenced in the world.
According to Santana et al. [2] and Pisano [6], some areas of biotechnology will have a significant impact in the near future on the development of new technologies and its applications, which are the genomics, pharmacogenomics, transcriptomics, biomaterials, bioengineering, and synthetic biology. Some themes related to these terms were detected in this dataset. Table 2 presents the terms mentioned by the authors (keywords’ author) with more than 50 citations related to the field of biotechnology.
Articles
Top terms (keywords)
Articles
Top terms (keywords)
Articles
Top terms (keywords)
380
Vaccines
99
Cell
71
Molecular marker
324
PCR
83
Diagnosis
69
gene
232
DNA
82
Expressed gene
65
HIV
183
Genetic
85
Genotype
64
Microsatellite
134
Brazil
79
Trypanosoma cruzi
66
Chromosome
120
Genome
78
Oxidative stress
61
Apoptosis
115
Polymorphic
75
Cytokine
63
Bovine diseases
131
Leishmania
72
Genomics
57
Cancer
56
Schistosoma mansoni
56
Inflammation
54
Fish
54
Chagas disease
53
Epidemiology
50
Drugs
Table 2.
Terms with more than 50 citations used by authors in the fields title, abstract and keywords in the articles published by Brazil.
From the total of scientific publications found, it can be observed the terms like Leishmania, T. cruzi, Schistosoma mansoni, and Chagas disease, which refer to a potential application. It should be emphasized that the data collected point out that scientific research on biotechnology in Brazil is directly related to the study of some relevant social problems of a country mainly related to tropical diseases.
Neglected tropical disease (NTD) has become an extremely important issue in public health in Brazil, as they profoundly affect the quality of life and generate negative socioeconomic impacts for the population of the poorest countries. Although not unique to developing countries, they arouse little financial appeal from the large pharmaceutical industry, since they do not reach the large consumer market that is the developed countries. In Brazil, the Ministries of Health, Science and Technology and the Health Surveillance Secretariat defined seven neglected tropical diseases based on epidemiological criteria, disease impact, and demographic data. They are dengue, Chagas disease, leishmaniasis, malaria, schistosomiasis, leprosy, and tuberculosis [24].
Figure 2 presents a network map where the main lines of research stand out. This map representation was obtained using VOSviewer®, taking as the matrix of cooccurrence of the 7000 keywords’ and authors standardized by the measure of strength of association [21].
Figure 2.
Map of keywords based on a co-occurrence network on biotechnology in Brazil. Source: Map presentation software VOSviewer®.
Although the keywords, which represent the domain of cells and genome, show a highly interrelated distribution, the structure can be clearly seen. Analysis of the relations among the most frequent descriptors reveals four well-defined groups, but with a variable degree of dispersion. In the upper part (1), around the nodes infection and vaccine, we find the most compact group of the network. It includes descriptors that represent documents in the areas of immunology, infectious diseases, and tropical medicine, related fundamentally with the application and clinical research into tropical diseases.
This scenario is compounded by the lack of innovation in drug R&D programs in the area of NTD; thus, the situation requires a concentrated global for the creation and maintenance of R&D programs focused on the discovery of new alternative therapies for the control and treatment of these diseases [25, 26]. Modern biotechnological tools (e.g., genomics, functional genomics, proteomics, metabolomics, and cytometry) have provided valuable insights for the discovery and development of new drugs that are extremely useful in coping with these NTDs. Extremely important initiatives are being successfully implemented to include Brazil in an increasingly significant science and technology scenario. According to Guido et al. [25, 26], three examples are presented to illustrate the breadth and diversity of networks and partnerships that have provided great opportunities and challenges in the area of NTD.
To the right, cluster 2, the keywords genome, PCR, and DNA connect with a well-defined cluster of descriptors related to genetics, and molecular biology research related fundamentally with the application and clinical research into the genome of X. fastidiosa begun in the 1990s.
Genomics is also closely related to agriculture not only in genetic improvement of species such as transgenic crops (with resistance to pests and tolerance to pesticides), but also in the product quality changes (plants that produce hormone, eucalyptus with higher production cellulose). More recently, Brazil has been developing research on feasibility of plants, animals, and microorganisms as biofactories of molecules of agricultural, pharmaceutical and industrial interest; identification and applications of genes and biological functions that promote tolerance to abiotic and biotic stresses and elimination of contaminants in food; identification and characterization (structural and functional) of new molecules to increase the production capacity of biologically based products with low environmental impact; and identification and applications of genes and biological functions that promote tolerance to abiotic and biotic stresses and elimination of contaminants in food [27].
Meanwhile, the terms of biomass, diversity, and conversation compose the third cluster 3, far right, including areas of biotechnology and biodiversity. To the left, cluster 4, we have the keywords (cell, gene expression, and stem cell) associated with molecular biology and cell biology areas related to the processes of modern biotechnology associated with a medicine, oncology, and neuroscience therapies.
The information obtained through keywords analysis is much more comprehensive and precise. For this reason, even though the two largely coincide or overlap, subject categories (see Figure 3) are more general or superficial than the information based on keywords (Figure 2). The latter shows, with a greater level of desegregation, the distribution of the descriptors that specifically configure each thematic profile, plus the less productive or incipient research that would otherwise remain hidden [28].
Figure 3.
Percentage distribution of scientific publications on biotechnology by areas of knowledge indexed on database. Period 1995–2015.
4.2. Profile of the scientific sector: biotechnology
By its intrinsic multidisciplinary characteristics, biotechnology permeates many areas of knowledge. Therefore, when analyzing the frequency of publication of scientific areas, there is a predominance of biochemistry and molecular Biology (12.4%), followed by genetics and heredity (10.94%), immunology (8.66%), microbiology (7.57%), and veterinary science (6.22%)together representing 45.79% of total articles published. However, this study highlights the wide dispersion of scientific publications by all thematic areas. Figure 3 demonstrates the percentage distribution for all the 20 areas with the number of articles greater than 200 indexed in ISI/Web of Science.
It can be observed that most of the articles found are in the areas like life sciences and health, highlighting specific areas such as molecular biology, genetics, immunology, and microbiology. The predominance of these areas was already expected due to the characteristics of biotechnology, but it is interesting to note that areas such as molecular biology and genetics have a significant interest toward other traditional areas such as chemical and pharmaceutical industries.
Note, also, that a considerable number of articles are classified as multidisciplinary, confirming that research in biotechnology, as mentioned previously, brings together researchers from different areas of knowledge. This, probably, highlights the increasingly important role of biotechnological techniques for the development of new products.
Of the 73,125 articles published in internationally indexed journals it was possible to realize a trend of publication in two main areas: health and life science. It is worth mentioning that both thematic areas coincide with the prevailing keywords previously identified. Besides this fact, an interesting aspect observes the concerns of the regional coverage of the top 20 journals, which means that the majority of Brazilians scientific articles are submitted in Brazilian journals (60%), or particularly in indexed American journals (30%). This indicator illustrates the little dynamics of international cooperation of Brazilian research groups. Among the indexed journals, the Vaccine journal has the highest number of articles (12.65%), followed by other journals such as Memórias Instituto Oswaldo Cruz (10.98%), and genetics and molecular biology (10.58%).
Figure 4 presents the top 20 journals with a number of scientific publications greater than 40 articles. The list of journals is in accordance with classification presented in Figure 3.
Figure 4.
Main internationally indexed journals with biotechnology-related articles.
An interesting fact observed is the leadership position of Vaccine Journal, which justly gives priority, an analysis of information and knowledge about human vaccines (infectious diseases and noninfectious diseases) and veterinary vaccines, molecular biology, immunology, production and manufacturing, regulatory, and legislation aspects. It is followed by others publications in areas such as microbiology, biology, genetics, life sciences, and others.
Considering the authors´ affiliation, it is observed that there are 441 institutions, showing a high dispersion among the authors´ institutions in Brazil. It is important to highlight the significant number of articles produced by institutions such as the University of São Paulo (USP) representing 32.71%, followed by the Oswaldo Cruz Foundation (FIOCRUZ) with 8.92%, and the Federal University of Rio Grande do Sul (UFRGS) with 7.58% articles, respectively. Another significant topic to be observed is the prevalence of public governmental institutions such as research centers or universities, evidencing a concentration of activities in biotechnology by public institutions or nonprofits corporations at research levels. It is also worth mentioning a few numbers of scientific publications indexed by the Brazilian biotechnology companies in the research period, less than 1%, which indicates a small number of companies working in that area or that they are still consolidating their capacities, according Santana et al. [2]. It is should be highlighted the public institution Brazilian Agricultural Research Corporation (EMBRAPA) Genetic Resources with the 8th institution in the ranking, which is the public company with leadership in transgenic research in the agricultural area in the country. Figure 5 shows the top 20 institutions that have published more than 100 articles in the observed period.
Figure 5.
Leading Brazilian institutions with major publications in biotechnology for the period 1995–2015.
The research results present that the most of institutions are located in South/Southeast regions, which are more developed regions of the country. There is little representation of institutions in the Center-West/ Northwest regions, presented only for 4 universities: University of Brasília, Federal University of Pernambuco, University of Goiás and Federal University of Ceará.
In addition, there is the significant presence of the public universities of São Paulo (USP, UNESP, and UNICAMP), which together account for a significant share of national scientific output in the biotechnology area, that is, 46.31% of published articles in journals are from USP. This observed result was expected because since the beginning of projects development in the biotechnology area (X. fastidiosa genome and HGP/Brazil), there was an intensive participation of research groups of these universities. Furthermore, we can mention the continuous financial support from FAPESP foundation for the development of projects in the areas such biotechnology and bioprospection.
4.3. Maps of knowledge and network collaboration
According to Santana et al. [2], regarding the analysis of relationships between composing agents of the National Organizational System of S,T&I, many authors refer to the central idea of networking and the valuable interactions between system components and its main actors in order to promote the dissemination and use of new scientific knowledge [29].
In accordance with these premises, we sought to analyze the links established between the organizations by observing how these actors relate to each other using the number of publications of scientific cooperation between institutions and countries; on a macro level, the international relationships developed by these institutions for R&D. The best representation of these collaborations is the visualization of maps of knowledge, where the existence or not of correlations and the degree of its intensity are clear, which provide to decision-makers some strategic subsidies in future planning of national activities of ST&I [2].
Considering the network map of articles´ authorship in Brazil, for the biotechnology area, it is possible to verify an intensive cooperation between diverse institutions, especially among Brazilian institutions, showing that 66.9% of articles are written with internal collaboration, which subsidize the relevance to develop endogenous capacity of Brazilian groups and publish papers with little support from international cooperation [2].
It is possible to note groups with strong collaboration such as the University of São Paulo (USP), Federal University of Rio de Janeiro (UFRJ), the University of Campinas (UNICAMP), and Oswaldo Cruz Foundation (FIOCRUZ). These collaborations between Brazilian institutions demonstrate that relationship is based more heavily on the model of interaction between universities, research centers, and nongovernmental research centers and of little interaction with companies. It should be emphasized that this scenario will modify since the implementation of the Organic Law of Science, Technology and Innovation in January 2016, where the private sector was encouraged to invest more in partnerships with public institutions and/or in internal activities of ST&I, aiming to promote alliances between the private sector with scientific research center and universities [2, 29]. Figure 6 shows the collaboration network among institutions with more than 60 articles published.
Figure 6.
Map of institutional relations on biotechnology for Brazil. Source: Map presentation software VOSviewer®.
From a macro perspective, there is a large international collaboration, particularly with five countries: the United States (12.81%), the United Kingdom (2.27%), France (2.22%), Germany (1.43%), and Spain (1.30%). As seen previously, when focusing on Latin America, the block represents only 1.89% of all countries’ collaboration, it is possible to identify that Brazil has networks of scientific collaboration and research with almost all countries. Inside this block, Argentina is a major coauthored number of articles (41.94%), followed by Colombia (19.47%), Chile (12.17%), Uruguay (9.92%), and Venezuela (8.80%). Figure 7 shows the map collaboration network among 40 major countries and Brazil in the biotechnology area.
Figure 7.
Map of network based on a co-authorship between Brazil and the 40 major countries on the biotechnology area. Source: Map presentation software VOSviewer®.
5. Conclusions
Traditionally, biotechnology is a technology that is strongly dependent on the studies of the basic research area. Its great success in any country is strongly related to government policies regarding the incentive of science and its technological diffusion. This chapter presents the growing of scientific research on biotechnology in Brazil, over the number of scientific articles published in the area, showing a higher growth of 1.930%, in the last 20 years, more specifically in the last 5 years. With respect to searched terms, “Vaccine,” “PCR,” and “DNA” are among the terms most frequently applied, being cited, since 1995, by the authors as keywords in scientific journals as well as in relevant journals such as Vaccine and Mem Inst Oswaldo Cruz. Terms such as proteomics and stem cells, related to the frontier area of knowledge, have also appeared in this scientific research. This fact indicates that the research in this area in Brazil is consistent with worldwide trends. Another significant topic is that the biotechnology research in Brazil is very important for studying the country’s social problems, especially related to tropical diseases, which presents itself as an important starting point for formulating policies on ST&I, since decision-makers should encourage links between scientific institutions and companies. It is important to point out that Brazilian agricultural biotechnology research has taken significant steps toward the development and use of innovations for sustainable production systems that provide safer food (biofortified foods with vitamins, minerals, and better quality proteins).
A wide dispersion in relation to the thematic areas of biotechnology is observed, however, concentrated mainly in areas such as biochemistry and molecular biology and genetics and heredity. Three institutions are highlighted here: São Paulo University (USP), Oswaldo Cruz Foundation (FIOCRUZ), and Federal University of Rio Grande do Sul (UFRGS). It is worth mentioning that institutions that carry out scientific research in this area are primarily governmental. Regarding the analysis of relationships between agents that compose the National System of Science, Technology and Innovation in Brazil, it was found that for biotechnology, there is a large network of cooperation among international and national institutions, as well as networking among many countries that present a positive factor in the biotechnological development of a country [2]. In conclusion, it was possible to identify the United States as a major coauthor of scientific publications relating the subject, but there are also partnerships with other Latin American countries such as Colombia and Argentina.
Acknowledgments
Parts of this chapter are reproduced from the authors’ previous publications [30].
\n',keywords:"knowledge management, innovation, scientific trends, biotechnology, Brazil",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/56454.pdf",chapterXML:"https://mts.intechopen.com/source/xml/56454.xml",downloadPdfUrl:"/chapter/pdf-download/56454",previewPdfUrl:"/chapter/pdf-preview/56454",totalDownloads:1187,totalViews:265,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,impactScore:0,impactScorePercentile:6,impactScoreQuartile:1,hasAltmetrics:0,dateSubmitted:"April 27th 2016",dateReviewed:"June 19th 2017",datePrePublished:null,datePublished:"November 21st 2017",dateFinished:"July 14th 2017",readingETA:"0",abstract:"This chapter presents a study on knowledge management and innovation in biotechnology area through analysis of scientific and technological advances of biotechnology trends in Brazil, providing an overview of the science profile as well as regional development and its relation to issues on topics based on the analysis of scientific publications for the last 20 years. Given these promising prospects, the monitoring and searching of scientific advances and trends in this area of knowledge have become essential for searching opportunities in research and development and also for potential innovations and business opportunities, both in the developed countries as well as in countries of emerging economies such as Brazil. The research was realized using database Web of Science with 60 terms selected in Biotechnology area and 73,125 documents have been organized. Scientific indicators were produced using data/text mining tools. A greater number of scientific publications were found in areas such as biochemistry and molecular biology; genetics and heredity showing a greater frequency in these terms: vaccine, PCR, and genome. Results pointed out the US as the main foreign partner-country of scientific publications followed by the UK, France, and Germany. It was possible to verify cooperation network with others Latin American countries.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/56454",risUrl:"/chapter/ris/56454",book:{id:"5491",slug:"knowledge-management-strategies-and-applications"},signatures:"Maria de Fátima Ebole Santana",authors:[{id:"190174",title:"Dr.",name:"Maria De Fatima",middleName:"Ebole",surname:"Santana",fullName:"Maria De Fatima Santana",slug:"maria-de-fatima-santana",email:"mfebole@gmail.com",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190174/images/4599_n.jpg",institution:{name:"Federal University of Rio de Janeiro",institutionURL:null,country:{name:"Brazil"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Biotechnology in the global market and Brazilian government programs",level:"1"},{id:"sec_2_2",title:"2.1. Biotechnology in the global market",level:"2"},{id:"sec_3_2",title:"2.2. Biotechnology in Brazilian government programs",level:"2"},{id:"sec_5",title:"3. Methodology and recovery documents",level:"1"},{id:"sec_5_2",title:"3.1. Database",level:"2"},{id:"sec_6_2",title:"3.2. Strategies for recovery documents",level:"2"},{id:"sec_8",title:"4. Overview of the global scientific development in biotechnology in Brazil",level:"1"},{id:"sec_8_2",title:"4.1. Analysis of results and cowords networks",level:"2"},{id:"sec_9_2",title:"4.2. Profile of the scientific sector: biotechnology",level:"2"},{id:"sec_10_2",title:"4.3. Maps of knowledge and network collaboration",level:"2"},{id:"sec_12",title:"5. Conclusions",level:"1"},{id:"sec_13",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Antunes AMS, Canongia C, Bahrut E, Rodrigues HT, Pio M, Gianinne R. Prospección Tecnologica - Gestión del Conocimiento e Inteligencia Competitiva - Modelos de Gestión para la toma de decisiones y cosntrucción de futuro. In: Vásquez JM; Torres JMS, editors. 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1. Introduction
Spinocerebellar ataxia (SCA), which is included in spinocerebellar degeneration (SCD), is a genetically heterogeneous group of autosomal dominantly inherited progressive disorders [1]. Cerebellar atrophy is the most prominent clinical feature of this condition and is accompanied by spinal cord and sequential brain stem and basal ganglion damage. Therefore, coordinated movement of the eyes, head, trunk, and extremities is impaired. Therefore, the activities of daily living (ADL) and participation in social activities are limited, and the quality of life (QOL) is undisputedly impaired in these patients [2].
The effects of medication and surgery in this clinical setting depend on the cause of ataxia and the extent of neuronal damage [3, 4]; however, there is no rational effective treatment for SCA and it is difficult to slow the progression of the disease. Rehabilitation [5, 6], including physical therapy [7, 8], aimed at improving/maintaining motor function, ADL, and QOL [5] is an important intervention for patients with SCA. Here we provide a narrative review of physical rehabilitation for SCA.
2. General features
For the clinical diagnosis of cerebellar ataxia, specific blood studies and magnetic resonance imaging (MRI) have been performed [9]. Furthermore, genetic techniques improve the diagnosis of degenerative cerebellar ataxia [10]. Although the details of the findings of these genetic and blood studies are beyond the scope of this review of rehabilitation, cerebellar atrophy and cerebellar motor deficits are traditionally common observations in patients with degenerative cerebellar ataxia [9]. Furthermore, recently, the absence of motor cerebellar symptoms has also been recognized as being important for rehabilitation [11].
The cerebellum is the motor-control system in humans [12]. Clinically, the oculomotor deficit, speech deficits, ataxia in the trunk and extremities, balance disorder, and gait disturbance are the targets of rehabilitation in SCA [9, 13]. The possible underlying pathogenetic mechanisms include distorted timing, abnormal sensory acquisition, impaired sensory motor synchronization, impaired triggering of corticomotor excitability, and abnormal visuokinesthetic cerebro-cerebellar interactions [13].
Oculomotor deficits cause deoptimized vision. The vestibulo-ocular reflex and smooth pursuit [14] partially depend on motor prediction in static and dynamic movement and contribute to dynamic gazing [15]; moreover, the cerebellum contributes to the trainability of eye-head coordinated movements [16].
Abnormal excitability and modulation in the motor cortex and corticospinal tract causes a voluntary contraction deficit in [17, 18]. Cerebellar stimulation modulates the motor-evoked potential induced by transcranial magnetic stimulation (TMS) of the primary motor cortex [19, 20, 21]; however, this modulation is absent in patients with SCA [22, 23]. Furthermore, the cortical silent period, which reflects the excitability of the inhibitory GABAergic neural circuit in the primary motor cortex, is abnormal in these patients [24, 25, 26, 27, 28, 29], and this cerebellar effect on the cortical silent period is characteristic of the healthy population [30]. Before muscle contraction for movement, the corticospinal excitability increases in healthy individuals; in contrast, this facilitation is insufficient in SCA [31]. In addition, in patients with SCA, muscle tones are decreased [11] and the spinal reflex excitability is facilitated by cerebellar stimulation [32, 33, 34]. The long latency spinal reflex, which is correlated with the cortical circuit, is disturbed in SCA [35]. Although this functional cerebellum-spine connection may contribute to the preparation for muscle contraction, there is insufficient evidence that these connections contribute to motor control in healthy and cerebellar ataxia populations.
In simple movements, such as extension of the elbow, coordinated activity of the biceps and triceps is needed. For ballistic elbow-extension movement practice, the triphasic muscle agonist and antagonist contraction patterns contribute to the smooth movement, but under/overshooting appears during the uncoordinated contraction pattern of patients with SCA [36, 37]. Furthermore, this contraction pattern may be obtained by temporal electrical stimulation in these individuals [37].
The cerebellar internal model contributes to predictable/online/offline motor control and motor learning/adaptation [38]. The symptoms associated with motor learning do not appear at the onset of the cerebral atrophy [39], because several brain areas, i.e., the prefrontal cortex, primary motor cortex, and basal ganglia, compensate for cerebellar function in early-stage SCA [5, 6, 39]. Recently, the motor learning deficit at the early stage of the disorder was reportedly detected using an adaptation task [40]. Therefore, the assessment of the capacity for motor learning may be important to strategize the interventions that are concretely described in the following sections.
Representative nonataxia symptoms include hyperreflexia, areflexia, extensor plantar, spasticity, paresis, muscle atrophy, fasciculations, myoclonus, rigidity, chorea/dyskinesia, dystonia, resting tremor, sensory symptoms, urinary dysfunction, cognitive impairment, and brain stem oculomotor signs [41]. The Inventory of NonAtaxia Symptoms (INAS) [41] is used to estimate these nonataxia symptoms. The appearance of these symptoms depends on the type of SCA [41].
3. Assessment format
We should conduct assessment to detect the degree of motor dysfunction and consider more effective intervention of physical rehabilitation. The first, the imaging technology such as MRI provides us with structural information about the atrophic areas of the brain associated with the disease. We described about neuroimaging technique in Section 3.1. The next, we can use some outcome measurement to estimate the motor dysfunction and verification in the physical rehabilitation. Then, we introduce the representable outcome measures for physical rehabilitation in SCA in Section 3.2. However, we had not established method to estimate the remaining of motor learning ability, which is one of the most important factors to predict the effect of physical rehabilitation. Therefore, we propose the possible assessment of motor learning ability in Section 3.3.
3.1 Neuroimaging
Neuroimaging is a technique that is used to visualize the structural and functional activities of the brain. MRI measurements, such as diffusion tensor imaging and surface-based morphometry, visualize the brain structures. Functional activity imaging is achieved using fMRI and NIRS, which are indicators of cerebral blood flow, and electroencephalogram (EEG) and magnetoencephalography, which are indicators of electrical activity. Positron emission tomography and single-photon emission computed tomography with nuclear tracers are also used in this setting. The application of neuroimaging in the rehabilitation of cerebellar disorders includes voxel-based lesion symptom mapping in patients with stroke, to investigate the recovery of upper arm reach [42] and walking ability [43] depending on the lesion site.
Although conventional MRI [44] is widely used for the neuroimaging of spinocerebellar degeneration, to obtain diagnostic findings, few studies have used neuroimaging as a guideline or outcome of rehabilitation. The lack of reports in this context hampers the quantification of cerebellar degeneration in SCA and its correlation with motor dysfunctions. In terms of measurement techniques, the cerebellum exhibits a much tighter folding compared with the cerebral cortex, with individual cortical sheets with a thickness of 1–2 mm and a sheet area of 1500–2000 cm2, compared with a sheet area of 2200 cm2 with a thickness of 1.5–4 mm in the cerebral cortex. Therefore, the typical 2–4 mm3 spatial resolution of neuroimaging techniques is insufficient to capture local cerebellar changes. Patient factors include the difficulty in limiting the brain regions involved in movement disorders to the cerebellum, because the degenerative regions in SCD extend beyond this structure to multiple brain regions [45].
Among the neuroimaging modalities, the role of voxel-based morphometry (VBM) is notable in SCA rehabilitation. VBM is a statistical analysis of the entire brain in voxel units (1 mm3) that is used to identify the behavioral patterns and related brain morphological characteristics of patients [46]. Burciu et al. assessed the degree of cerebellar atrophy concerning motor and learning functions using VBM to evaluate brain structure changes after 2 weeks of balance training in patients with SCD; these authors reported the association between an increased volume of the dorsal premotor cortex and increased balance ability [47]. Matsgi et al. reported an association between VBM and neurophysiological markers in cerebellar brain inhibition (CBI), with atrophy of the dentate nucleus at VBM observed in cases of pure cerebellar ataxia that did not show CBI [48]. Bando et al. reported a correlation between adaptive learning ability and gray matter volume of the cerebellar IV-VII lobules and the supramarginal gyrus in a prismatic adaptation task in SCA [49]. Thus, VBM may be a biomarker to explain motor dysfunction in patients with SCA.
Conversely, VBM is not an ideal tool to show a causal relationship between brain structural changes and behavioral differences. As a solution to this problem, we can propose a combination of VBM and neurostimulation [50], as neurostimulation of the brain regions associated with the behavioral patterns obtained by VBM and the observation of behavioral changes before and after stimulation allow us to examine brain degeneration sites and behavior.
3.2 Outcome measurement
Gait disturbance is a major symptom of the cerebellar pathology in SCA [51]. The functional ambulation categories (FAC) is useful for the comprehensive assessment of walking ability; the FAC assesses gait for about 15 m and climbing stairs and classifies gait levels into 6 levels [52]. The FAC is also used in the exercise program created by Research Committee for Ataxia Disease (Research team under the jurisdiction of the Ministry of Health, Labour and Welfare in Japan, http://ataxia.umin.ne.jp/rehabilitation/).
The quantitative assessment of cerebellar ataxia is very important in clinical practice. The International Cooperative Ataxia Rating Scale (ICARS) has been used as a quantitative assessment of ataxia symptoms. However, it has been noted that the test reliability of the eye movement items is low [53]. The Scale for Assessment and Rating of Ataxia (SARA) is an 8-item performance-based scale that yields a total score of 0–40 (most severe ataxia). The minimal detectable change (MDC) for individual score difference from the baseline to the 1-year follow-up in SARA was <3.5 (n = 171; SCA1, n = 43; SCA2, n = 61; SCA3, n = 37; and SCA6, n = 30; mean age, 50.9 ± 13.5 years; mean disease duration, 11.8 ± 5.6 years) [54]. SARA does not include an eye movement section. Schmahmann et al. noted the importance of assessing oculomotor abnormalities and developed the Brief Ataxia Rating Scale, a modification of ICARS [55]. Each SCA genotype exhibits specific symptoms [56]. Therefore, these assessments should be used differently for different symptoms. However, one feature that is consistent among these assessments is that the scoring range is large and does not allow the assessment of minute symptom changes. Honda et al. developed a system to measure the evaluation of SARA using a depth sensor [57]. Using this system, the degree of ataxia can be measured numerically. In addition, because the system is inexpensive, it can be installed at the patient’s home, making it a useful tool for telemedicine.
The balance dysfunction in SCA has a significant impact on QOL [58]. The Berg Balance Scale and the Timed Up and Go test are widely used to assess balance dysfunction in SCA [59]. However, despite their widespread use, these assessments have not been examined for reliability and validity in SCA. Kondo et al. examined the test reliability of the Balance Evaluation Systems Test (BESTest) [60]. The BESTest is a multitask balance assessment tool that was developed to identify specific postural control problems (i.e., biomechanical constraints, stability limits, anticipatory postural adjustments, postural responses, sensory orientation, dynamic balance during gait, and cognitive effects) [61]. The MDC for an individual score difference from the baseline to the 4-week follow-up in BESTest was <8.7 (n = 20; SCA3, n = 4; SCA6, n = 9; SCA31, n = 7; mean age, 63.7 ± 10.1 years; age at onset, 53.9 ± 10.5 years; baseline SARA, 9.9 ± 3.5) [61]. Many types of balance function measures have been reported. However, BESTest is the only scale that is considered to have absolute reliability in SCA.
Gait speed is often used as an outcome of intervention studies in SCA [62, 63]. However, some changes in the gait pattern (e.g., base of support and gait speed) most likely reflect cerebellar-unspecific, compensatory strategies, and a high spatiotemporal gait variability appears to be a distinctive feature of ataxic gait [58, 64]. The Gait Variability Index (GVI) is a measure of gait variability that has been examined regarding reliability and validity [65]. The MDC for an individual score difference from day 1 to day 2 in GVI was <8.6 (Friedreich’s ataxia, n = 81; baseline ICARS, 70.4 ± 7.9) [65]. It has been suggested that gait instability in SCA are characterized by a stronger effect of balance-related impairments of cerebellar control during slow walking and a stronger effect of impaired intra-limb coordination during fast walking [58]. Therefore, in clinical practice, it is necessary to evaluate not only the optimal gait speed, but also slow walking and fast walking, to extract the characteristics of gait instability.
3.3 Assessment of motor learning ability
The cerebellum has the ability to compensate for tissue damage and loss of function. This is called the cerebellar reserve [6]. Mitoma et al. suggested that this is important for motor rehabilitation at a time when the cerebellar reserve is functioning [6]. Motor rehabilitation in the early stages may maintain and improve the cerebellar reserve [66, 67]. Therefore, it is important to assess this parameter.
Cerebellar ataxia is the main symptom of SCA. Ataxia symptoms may represent a compensation for predictive control using feedback control [6]. Predictive control requires a mechanism called internal model [38]. The internal model is constantly updated by motor learning [68]. In turn, motor learning is one of the most important functions of the cerebellum. Thus, a measure of motor learning ability may be useful as an assessment of the cerebellar reserve.
Prism adaptation (PA) is widely used as an assessment of motor learning ability in patients with SCA [40, 69]. The basic procedure of PA is shown in Figure 1. First, at the “baseline,” the task is performed without a prism lens. Subsequently, the prism lens is introduced and the task is performed. In the initial phase, the lens is set off to either the left or right side of the target, but the error is corrected as the number of repetitions increases. This period is called the “initial error correction phase.” Thereafter, a spatial realignment phase is performed under the prism lens. The purpose of this phase is to gather visuospatial information including the errors. Next, the prism is removed and an “after-effect phase” is performed. If the spatial information is being re-learned, errors are generated in the opposite direction to the initial error correction phase. Recently, Hashimoto et al. developed the Adaptability Index (AI), which is a composite index computed from several parameters measured PA (Figure 2). The clinical efficacy of the AI in discriminating patients with SCA from healthy individuals has been demonstrated [70]. Furthermore, Bando et al. found that a reduced AI was correlated with gray matter atrophy in the cerebellum in the SCA group [49]. In particular, the right lobule VI and the left Crus I showed the most robust correlation. These cerebellar regions are consistent with the correlates of PA detected in previous human and nonhuman primate studies [71, 72]. AI is considered as a motor learning index that reflects the cerebellar reserve (in this case, the degree of cerebellar atrophy).
Figure 1.
Overview of prism adaptation. The ordinate shows the finger-touch error represented from the target to the touch point. Three phases are generally used: (1) absence of a prism lens (prism off), (2) presence of a prism lens (prism on), and (3) absence of a prism lens (prism off).
Figure 2.
Calculation of the adaptability index (AI). The AI is calculated as follows: AI = a × b × c, where “a” is the adaptation index defined as the probability of correct touches in the last 10 trials of the spatial realignment phase 1, “b” is the retention index defined as the probability of incorrect touches in the initial 5 trials of the after-effect phase, and “c” is the extinction index designated as the probability of correct touches in the last 10 trials of the spatial realignment phase 2.
PA can be implemented using a simple system. In addition, it takes only 20 min to complete a PA. Reaching tasks can be performed even in the period during which the patient is unable to walk, and the fact that the PA can be assessed continuously over a long period is an advantage. However, only cross-sectional studies have been conducted in previous reports [40, 49, 69, 70, 73, 74]. Future studies need to be designed to examine long-term changes and intervention effects.
4. Rehabilitation
The targets of rehabilitation in cerebellar ataxia are mainly disability in ADL, gait, and motor dysfunction. Therefore, GAS, FIM, 10-m walking test, TCA, SARA, ICARS, and BESTest are used as important outcomes in rehabilitation. The most important strategies of rehabilitation for cerebellar ataxia including SCA consists in balance training (see Section 4.3), gait training (see Section 4.2), and muscle strengthening training using a high-intensity program (see Section 4.1). Further, optional possible interventions are using assistive technology (see Section 4.4) and neuromodulation technique (see Section 4.5).
4.1 Intensive and continuous training
Rehabilitation methods for cerebellar ataxia have been reported [75]. The most important strategy is the increase in the intensity of physical training, such as balancing, gait, and strength [76]. Several systematic reviews [77, 78, 79] and narrative reviews [3, 75, 80, 81] introduced and recommended intensive physical therapy for cerebellar ataxia in patients with SCA. Miyai et al. [62] reported that physical and occupational therapies of 2 h × 5 days +1 h × 2 days per week for 4 weeks were applied to inpatients and improved the SARA score and gait speed; however, the effect was carried over only up to 12 weeks after the training, and had disappeared at 24 weeks [62]. Conversely, Ilg et al. reported that intensive coordinative physiotherapy delivered over 4 weeks improved motor performance in degenerative cerebellar ataxia in a study with an intraindividual control design [63].
An outpatient rehabilitation program for 6 weeks applied to 19 participants with Friedreich’s ataxia improved the motor domain item in the FIM score and Friedreich’s Ataxia Impact Scale, but the posthome program could not maintain the effect [82]. Therefore, this finding indicates that continuous outpatient rehabilitation programs are important for maintaining the ADL in patients with Friedreich’s ataxia. Additional large-scale studies are needed to investigate the long-term effect of outpatient rehabilitation programs and identify the characteristics of patients who respond to treatment. Therefore, the development of optimal individual programs is important to obtain the effect of training, regardless of the inpatient, outpatient, or home-self-training setting [83]. The semi-order program of the Research Committee for Ataxia Disease (Research team under the jurisdiction of the Ministry of Health, Labour and Welfare in Japan, http://ataxia.umin.ne.jp/rehabilitation/) can be used for this purpose.
Subsequently, the continuity of the intensive training is an important factor, because degradation in physical function was reported. Therefore, approaches aimed at upkeeping these programs in a way that suits the patients are needed. For example, exergames contribute to the practice of exercise at home. In the future, tele-rehabilitation systems [84] should be tested for the improvement (or maintenance) of the function and continuity of exercise.
4.2 Gait training
Gait training has been reported to improve spatiotemporal gait parameters (cadence, step length/width, gait speed, etc.) [85, 86, 87], complex gait (Timed Up and Go test, Dynamic Gait Index) [85], independence (FAC) [86], ataxia (SARA) [88], and adaptive locomotor adjustments (ALA) [88]. Patients with SCA exhibit problems other than the gait disturbance itself, i.e., stiffening of the body in an attempt to avoid the occurrence of gait disturbances. Therefore, it is important to focus on gait disturbances and increasing the number of walking patterns when considering gait training in a person with SCA.
Disturbances of gait are the core features of SCA [89, 90, 91, 92], thus leading to a risk of falling down [93]. Patients with cerebellar ataxia walk with a reduced walking speed and cadence, as well as reduced step length, stride length, and swing phase; increased walking base width, stride time, step time, stance phase, and double limb support phase; and increased variability of step length, stride length, and stride time [94]. These items are affected by both balance-related impairments and deficits related to limb control and intra-limb coordination [95]. We believe that balance training and coordination training are key to the improvement of gait disturbances. Regarding the details of balance training, please refer to the Section 4.3.
In addition, stiffening of the body leads to a decrease in the number of walking patterns; as a result, ALA deteriorates [96, 97]. ALA implies that obstacle avoidance is achieved by modifying basic walking patterns in response to obstacle properties, e.g., a sloping road, stepping over an obstacle, or dynamically changing the spaces created by pedestrians in a hallway. In persons with SCA, feelings of anxiety as a result of the frequent experience of falls, as well as deficits related to limb control by ataxia, could negatively affect their ALA because of increased muscular co-contractions and reduced joint movements [98]. We will describe the approaches to improve ALA in the next paragraph.
The proposals for gait training are as follows: gait training without or with a treadmill. First, in gait training without a treadmill, we refer the reader to Section VI of the BESTest as gait adaptability training [61]. Section VI of the BESTest consists of a 7-item scale: (1) Gait Natural, (2) Change Speed, (3) Head Turns, (4) Pivot Turn, (5) Obstacles, (6) “Get Up & Go” Test, and (7) Cognitive Task “Get Up & Go” Test, aimed at evaluating the stability of the gait. These elements are important to improve ALA. As an example of gait training, persons with SCA are asked to walk while making an effort to change their walking speed according to therapist’s instructions to engage is “fast (or slow)” walking as fast (or slow) as possible. If patients need assistance when walking, you might want to change the walking speed with the support of a therapist.
Second, gait training using a treadmill has advantages in that patients can practice a relatively large amount of gait training over a short period and the therapists can control the speed and incline easily. Gait training using a treadmill has been reported as a potentially promising tool for improving ALA in a person with SCA [88], as well as gait disturbances in a person with Parkinson’s disease [99, 100]. It has been reported that variability was increased during slow and fast walking, but was normal during the preferred walking speed in a person with cerebellar ataxia [101]. Another study reported that, in ataxia, walking at the preferred speed minimizes the gait abnormalities, and the analysis of gait at a wide range of speeds is recommended [94]. For this reason, when using a treadmill in gait training, we suggest that walking be practiced at the speed at which the gait disturbance increases (i.e., slow or fast walking speed) for specific patients. When the fear of falling increases, the use of a harness is recommended, to provide a safe environment for gait without the fear of falling.
It is important to improve the balance ability and ALA during gait training in a person with SCA. Gait training is a relatively easy method; however, it is left to the therapist’s discretion and experience. By changing the task itself or adjusting the difficulty level of the task, gait training may be able to overcome the limited walking patterns of these patients.
4.3 Balance training
All patients with SCA will develop balance difficulties during the course of the disease. Balance is essential for mobility, and is very important for QOL. Although there is no effective pharmacological treatment for decreasing the ataxia or slowing disease progression, physical therapy plays an important role in controlling ataxia and improving or maintaining function through training [76]. In general, the physical therapy programs for degenerative cerebellar ataxia are based on intensive static and dynamic balance and coordination training. There is some evidence that such therapeutic training programs alleviate the ataxic symptoms and improve functional activities in a person with cerebellar ataxia [63, 78, 102]. In these patients, the disease progressively damages the cerebellar structure that plays a crucial role in motor learning [103]; however, these studies have indicated that it is necessary for highly repetitive balance training for balance impairment in SCA. For this reason, highly repetitive balance training in patients with SCA should be the focus of future studies.
More concretely, balance training exercises in early stages of the disease, i.e., ambulation, include the following categories: (1) static balance training, (2) dynamic balance training, and (3) coordination training (Figure 3). In addition, combining a dual task with balance training improves balance and reduces the number of falls in individuals with cerebellar ataxia [104].
Figure 3.
National Center of Neurology and Psychiatry (NCNP) balance training program. This balance training program was devised through consultations with patients with SCA, medical doctors, and therapists at the NCNP in Japan. In the advanced stage of SCA, it is recommended to perform the programs indicated by an asterisk.
Moreover, it is important to provide support for these approaches and make them a habit of exercising. For instance, if the patients with SCA have no habit of exercising, they should start with a small number of exercises (i.e., the minimum necessary) to get used to exercising, followed by the gradual increase in the number of exercises. If the patients with SCA have a habit of exercising, the therapist should teach them to adjust the exercise load (e.g., exercise more slowly and/or provide a small base of support). It is also important to adopt balance training that can be enjoyed, e.g., video games [105] and Tai Chi [106], as a means of continuing balance training.
In advanced stages of the disease (i.e., no ambulation), it is necessary to perform balance training under safe conditions (e.g., prone, supine, crawl, and sitting positions), to prevent the decrease in physical activity. Even in advanced stages, it has been reported that a person with degenerative ataxia may benefit from balance training [107]. In addition, it is necessary to focus on ADL and living infrastructure at this stage. If a patient with SCA requires assistance during transfer, engaging in repetitive transfer training with assistance and/or modification of the living infrastructure (e.g., installation of handrails) are necessary.
Focusing on highly repetitive balance training in patients with SCA might preserve the balance function. There is no scientific basis for the number of balance training exercises that are necessary to achieve this goal; however, we would like to recommend engaging in 30 repetitions at least per balance training session. Furthermore, the balance training must be designed to provide a significant challenge to the person’s balance. If a person with SCA wants to preserve the balance function, they have to continue engaging in repetitive balance training, “use it or lose it.” However, few studies have reported the effect of gait and balance training in persons with SCA. Therefore, further studies are needed to clarify the clinical effectiveness of gait and/or balance training.
4.4 Assistive technology
In recent years, various technologies have been used in the assessment of and treatment based on rehabilitation, as well as to support daily life in patients with SCD. Curara, a wearable robotic system, assists both hip and knee movements and supports the wearer’s rhythmic gait using a synchronization control based on a central pattern generator [108]. Gait support using the curara system has been reported to improve gait smoothness in patients with SCD [109]. In addition to these findings, a recent study addressed the effects of robotic gait training combined with noninvasive brain stimulation. This report showed that robot gait training using Lokomat-Pro in combination with cerebellar tDCS improved the functional scores on SARA, especially the scores on the subitems of gait, stance, sitting, and heel-shin slide compared with robot gait training alone [110]. Thus, hybrid training using robots and noninvasive brain stimulation will be applied to the rehabilitation treatment of patients with SCD in the future.
Accordingly, the use of walking aids is a complementary method for balance and gait impairment. In general, walking aids such as canes and walkers improve postural stability, but their improper use increases the risk of falling [111]. Because the manipulation of a cane requires coordinated upper limb movements [112], patients with SCD who have upper limb ataxia are likely to experience difficulty in using a cane. Conversely, because a walker does not require much coordinated movement of the upper limbs, technology-based walkers are being developed. Recently, a smart walker for mobility assistance and monitoring system aid, ASBGo, was developed and reported to improve gait parameters and postural stability in patients with SCA [113, 114]. In addition to technology, some studies on walking assistance using dogs and handkerchiefs have also been reported. Walking with a rehabilitation dog that has been specifically trained for goal-directed interventions or with an assistance dog that helps people with physical disability and mobility impairments has been reported to improve balance while walking in patients with SCD [115]. Furthermore, the handkerchief-guided gait, in which the patient with SCD walks along with the caregiver while maintaining light tension on a handkerchief by pulling lightly, has been shown to decrease body swaying and increase stride length and gait velocity during walking [116].
Moreover, technology is also being used as a tool to assess ataxia in patients with SCD living at home. Most of them represent attempts to evaluate SARA, which is a typical measure of ataxia, at home. In recent years, a technology aimed at objectively evaluating the speech, upper and lower limb, balance, and gait functions using wearable inertial sensors and a Kinect camera was developed, which makes it possible to discriminate between normal and abnormal functions and to detect ataxia at an early stage [117]. In addition, SaraHome has been developed to allow the remote evaluation of SARA items using Kinect and Leap Motion Controller [118]. Moreover, a spoon equipped with an inertial sensor, called Ataxia Instrumented Measurement-Spoon, has been developed, which allows the evaluation of upper limb function in ataxia while eating with a spoon [119, 120, 121]. Because SCD is an intractable neurological disease, it is difficult for many patients to leave their houses. Therefore, the contribution of technology to home-based rehabilitation is expected to increase in the future if a low-cost and easy method of assessing ataxia at home is established using the technologies and products of daily living described above.
Regarding the support of ADL, BMI studies have been reported. Patients with severe SCA often have difficulty in communicating because of language impairment. The application of BMI using event-related potentials and frequency bands of EEG is being investigated as a solution to this problem. The operational accuracy of BMI using P300 for event-related potentials was 82.9% in patients with SCA, which was similar to the accuracy observed in healthy subjects (83.2%) [122]. There are also reports of BMI manipulation in patients with SCD using the EEG frequency band associated with motor imagery [123]. BMI has a wide range of applications in diseases of the central nervous system, such as communication tools, transportation, and life support, and is expected to contribute to the QOL of patients with SCD.
4.5 Neuromodulation
Neuromodulation via noninvasive brain stimulation (NIBS) is a potential method for the treatment of cerebellar ataxia [19, 124]. A previous systematic review [125] reported the effectiveness of cerebellar neuromodulation using the TMS technique of transcranial direct current stimulation (tDCS). The SARA and ICARS scores in patients with SCA3, multiple system atrophy, and postlesion ataxia, as assessed using real cerebellar rTMS (1 Hz), were significantly lower than those detected in the sham stimulation group [125]. Furthermore, no harmful side effects were noted [125]. Cerebellar rTMS can modulate the plasticity of the vestibular reflex [16, 126]; therefore, cerebellar rTMS has potential for application in balance training to enhance vestibular contributions.
A single session of anodal cerebellar tDCS (2 mA, 20 min) significantly improved SARA, ICARS, 9-hole-peg test, and 8-m walking test scores [127]. Furthermore, combined anodal cerebellar tDCS and cathodal spinal DCS (5 days/week, 2 weeks) improved SARA score, ICARS score, 9-peg test, and 8-m walking time in patients with degenerative cerebellar ataxia [128]. There is insufficient evidence regarding whether simultaneous stimulation is more effective than single stimulation [129]; however, it is possible that this intervention method will produce improvements. Based on these findings, which were gleaned from small-sample studies, we suggest that a neuromodulation montage will improve the ataxia, balance, and gait ability. Therefore, we should perform further studies using a larger population.
5. Conclusion
Individualized physical rehabilitation programs for patients with SCA may improve/maintain their motor function, balance, gait ability, and ADL. In particular, the intensity and continuity of gait and balance training need to be considered to achieve effectiveness. Furthermore, several technologies, such as depth sensors, robotics, and NIBS, have contributed to the development of methods for the assessment and treatment of motor dysfunction in individuals with SCA. We should continue to study populations suffering from dysfunction caused by SCA.
Acknowledgments
This work was supported by Shijonawate Gakuen University and JSPS KAKENHI (Grant Number 20 K11298).
Conflict of interest
The authors declare no conflict of interest.
\n',keywords:"spinocerebellar ataxia, rehabilitation, physical therapy, ataxia, assessment, gait training, balance training, motor learning, assistive technology, neuromodulation, noninvasive brain stimulation",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/75081.pdf",chapterXML:"https://mts.intechopen.com/source/xml/75081.xml",downloadPdfUrl:"/chapter/pdf-download/75081",previewPdfUrl:"/chapter/pdf-preview/75081",totalDownloads:546,totalViews:0,totalCrossrefCites:0,dateSubmitted:"November 29th 2020",dateReviewed:"January 13th 2021",datePrePublished:"February 4th 2021",datePublished:null,dateFinished:"February 4th 2021",readingETA:"0",abstract:"Rehabilitation is an important treatment for spinocerebellar ataxia (SCA). The lack of improvement in ataxia, deficit of motor learning, and unstable balance causes disability for activities of daily living and restricts participation in social activities, further resulting in a disturbance of the restoration of quality of life. This narrative review describes physical rehabilitation, including measurement of movement disorder, associated with ataxia and possible interventions. Several lines of evidence suggest that high-intensity individualized physical rehabilitation programs, especially for gait and balance training, improve motor function. Continuous exercise at home contributes to the maintenance of the gait and balance function. Moreover, videography and mechanical technology contribute to the evaluation of ataxia and motor learning ability, and assistive robotic systems may improve gait stability. Neuromodulation montages, such as repetitive transcranial magnetic stimulation and transcranial electrical stimulation, can enhance the effect of physical rehabilitation. Further research aimed at developing a more-effective physical rehabilitation for these patients is expected.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/75081",risUrl:"/chapter/ris/75081",signatures:"Akiyoshi Matsugi, Kyota Bando, Yutaka Kikuchi, Yuki Kondo and Hideki Nakano",book:{id:"9625",type:"book",title:"Spinocerebellar Ataxia - Concepts, Particularities and Generalities",subtitle:null,fullTitle:"Spinocerebellar Ataxia - Concepts, Particularities and Generalities",slug:null,publishedDate:null,bookSignature:"Dr. Patricia Bozzetto Ambrosi",coverURL:"https://cdn.intechopen.com/books/images_new/9625.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-83880-837-2",printIsbn:"978-1-83880-836-5",pdfIsbn:"978-1-83880-967-6",isAvailableForWebshopOrdering:!0,editors:[{id:"221787",title:"Dr.",name:"Patricia",middleName:null,surname:"Bozzetto Ambrosi",slug:"patricia-bozzetto-ambrosi",fullName:"Patricia Bozzetto Ambrosi"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. General features",level:"1"},{id:"sec_3",title:"3. Assessment format",level:"1"},{id:"sec_3_2",title:"3.1 Neuroimaging",level:"2"},{id:"sec_4_2",title:"3.2 Outcome measurement",level:"2"},{id:"sec_5_2",title:"3.3 Assessment of motor learning ability",level:"2"},{id:"sec_7",title:"4. Rehabilitation",level:"1"},{id:"sec_7_2",title:"4.1 Intensive and continuous training",level:"2"},{id:"sec_8_2",title:"4.2 Gait training",level:"2"},{id:"sec_9_2",title:"4.3 Balance training",level:"2"},{id:"sec_10_2",title:"4.4 Assistive technology",level:"2"},{id:"sec_11_2",title:"4.5 Neuromodulation",level:"2"},{id:"sec_13",title:"5. Conclusion",level:"1"},{id:"sec_14",title:"Acknowledgments",level:"1"},{id:"sec_17",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Klockgether T, Mariotti C, Paulson HL. Spinocerebellar ataxia. Nat Rev Dis Primers. 2019;5(1):24. 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UK Research and Innovation (former Research Councils UK (RCUK) - including AHRC, BBSRC, ESRC, EPSRC, MRC, NERC, STFC.) Processing charges for books/book chapters can be covered through RCUK block grants which are allocated to most universities in the UK, which then handle the OA publication funding requests. It is at the discretion of the university whether it will approve the request.)
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It is present in different machines we use every day; in fact, technical systems in our homes and all the industries are hard to imagine today without these concepts. Moreover, the same theories can be used for modelling life processes as a collection of inputs, outputs, plants and control loops. Feedback is one of the main concepts behind control; in particular, several examples of physiological control mechanisms for regulating life aspects can be found in the human anatomy, for example, blood pressure, cholesterol levels, body movements, the equilibrium, etc. Those processes can be damaged by the aging effects, diseases, accidents or when the mechanism has been broken and cannot be recovered naturally; consequently, it will be required external assistance. A relative new field in control theory is related with developing technology for helping with physiological and medicals problems. However, in comparison with machines, those physiological processes are highly nonlinear, with delays and slow responses. Another problem is when human becomes the operators using their capacities of decision making to close the control loop, as they are prone to errors and mistakes. For those reasons, the biomedical system needs to be carefully designed and several aspects have to be considered. This chapter gives a small review of some internal and external control processes within the human body and discusses how to interact with them for designing biomedical devices. Under this design scheme, a practical application of a smart electric wheelchair for assisting persons with strong disabilities is presented. These assistive robotic systems are in close contact with the user, and thus, it is determinant to have a user-friendly relation between the human and the interface. Therefore, intuitive interfaces were included in the design and an intelligent navigation assistant to guarantee a collision-free path.",book:{id:"5238",slug:"automation-and-control-trends",title:"Automation and Control Trends",fullTitle:"Automation and Control Trends"},signatures:"David Balderas and Mario Rojas",authors:[{id:"183076",title:"M.Sc.",name:"David",middleName:null,surname:"Balderas Silva",slug:"david-balderas-silva",fullName:"David Balderas Silva"},{id:"184877",title:"MSc.",name:"Mario",middleName:null,surname:"Rojas",slug:"mario-rojas",fullName:"Mario Rojas"}]},{id:"51070",title:"Fuzzy PD Controller in NAO System's Platform",slug:"fuzzy-pd-controller-in-nao-system-s-platform",totalDownloads:1583,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Humanoid robotic platforms rarely achieve the desire trajectory because of the deviation generated during the robot walking. This problem is due to different circumstances such as robot manufacturing, wear and tear of mechanic parts, or variations of floor flatness. Currently, one of the humanoid robots on the market is the robotic platform developed by Aldebaran Robotics called NAO robot, and it is used for different purposes where the robot needs to navigate into controlled spaces. NAO presents the issue of deviation during walking; therefore, a Fuzzy PD Controller is developed and implemented for this platform to reduce the orientation error and to ensure reliability during navigation. Inertial sensors are used to get the orientation reference and for feedback of the closed-loop control. Consequently, a robust control was implemented and tested in different conditions of floor and velocity during the robot’s navigation such as robot races and maze resolution. 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\r\n\tScientists have long researched to understand the environment and man’s place in it. The search for this knowledge grows in importance as rapid increases in population and economic development intensify humans’ stresses on ecosystems. Fortunately, rapid increases in multiple scientific areas are advancing our understanding of environmental sciences. Breakthroughs in computing, molecular biology, ecology, and sustainability science are enhancing our ability to utilize environmental sciences to address real-world problems. \r\n\tThe four topics of this book series - Pollution; Environmental Resilience and Management; Ecosystems and Biodiversity; and Water Science - will address important areas of advancement in the environmental sciences. They will represent an excellent initial grouping of published works on these critical topics.
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International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. 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