Performance of different phenotypic methods compared to MBL – E test in identifying MBL + ve
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"6689",leadTitle:null,fullTitle:"Public Management and Administration",title:"Public Management and Administration",subtitle:null,reviewType:"peer-reviewed",abstract:"The public sector plays an important role for both regulation and in the delivery of services directly or indirectly. In this context, it is important to consider transformation, change, and innovation, which are the elements on which the main determinants that influence public management and the administration of economic, social, and political systems are based. This book describes the nature of the problem, its multidimensionality, and the need for original approaches, through the contribution of scholars belonging to different disciplines. This book contains nine chapters in a single section (Public Management and Administration), which, through the different approaches to the subject by the authors, help to explain the issues of the public sector.",isbn:"978-1-78923-639-2",printIsbn:"978-1-78923-638-5",pdfIsbn:"978-1-83881-645-2",doi:"10.5772/intechopen.72057",price:119,priceEur:129,priceUsd:155,slug:"public-management-and-administration",numberOfPages:148,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"ce558cd92314c50719a36e2dfdaf914d",bookSignature:"Ubaldo Comite",publishedDate:"August 29th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6689.jpg",numberOfDownloads:9105,numberOfWosCitations:1,numberOfCrossrefCitations:3,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:6,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:10,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 7th 2017",dateEndSecondStepPublish:"November 28th 2017",dateEndThirdStepPublish:"January 27th 2018",dateEndFourthStepPublish:"April 17th 2018",dateEndFifthStepPublish:"June 16th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"195399",title:"Prof.",name:"Ubaldo",middleName:null,surname:"Comite",slug:"ubaldo-comite",fullName:"Ubaldo Comite",profilePictureURL:"https://mts.intechopen.com/storage/users/195399/images/system/195399.jpg",biography:"Ubaldo Comite was born in Cosenza, Italy, on June 14, 1971. He has a degree in Law (1994) and Economics (1996) at the University of Messina (Italy) and earned his PhD degree in Public Administration at the University of Calabria (Italy), in 2005. Currently, he is a professor of Health Management, Budget and Business Organization at the University of Calabria. Furthermore, he is a professor of Business Administration at the University 'Giustino Fortunato” (Italy). He has authored several book chapters and over 60 peer-reviewed journals/proceeding papers. He served as an International Program Committee member for several conferences. His research interests are private and public management, nonprofit organizations and accounting, and health management.",institutionString:"University of Calabria",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"University of Calabria",institutionURL:null,country:{name:"Italy"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"272",title:"Management",slug:"management"}],chapters:[{id:"61823",title:"Democracy in the Middle East: The Educational Battle",doi:"10.5772/intechopen.77581",slug:"democracy-in-the-middle-east-the-educational-battle",totalDownloads:965,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"The unrest in the Middle East has created vacuums where authoritarian and democratic powers are in conflict. Education in all countries is at the heart of the challenges to leadership. In most Middle Eastern countries, graduates from middle school upward have been guaranteed employment in the government. Failure to meet this promise has left thousands of youth who are educated but unemployed. Further fueled by the overwhelming number of refugees, leaders in Jordan, Lebanon, and Israel are threatened by the unemployed and refugees’ access to technology and their democratic demands. Authoritarian countries such as Iran and Turkey are emphasizing religious education in order to increase the control of their people. Research, on-site visits and media reports provide the basis for this study which identifies three forces of the educational conflict: religious education, informal education, and access to technology. The possible solutions for future educational directions provide a roadmap for the future.",signatures:"Judith Cochran",downloadPdfUrl:"/chapter/pdf-download/61823",previewPdfUrl:"/chapter/pdf-preview/61823",authors:[{id:"212403",title:"Prof.",name:"Judith",surname:"Cochran",slug:"judith-cochran",fullName:"Judith Cochran"}],corrections:null},{id:"61576",title:"Facebook Tools and Digital Learning Achievements",doi:"10.5772/intechopen.77189",slug:"facebook-tools-and-digital-learning-achievements",totalDownloads:990,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"During recent years, there has been a significant increase in the usage of technological tools in general and in academic teaching in particular. Many programs have been developed, including online teaching and online courses, at educational institutions. In this chapter, we discuss the Facebook social network and its use at the University. The research shows that Facebook groups are used to facilitate communication between students, to foster a positive social climate, to create dialog, and to share learning material among group members. This chapter examines students’ achievements and their satisfaction with the impact of the Facebook group on the academic course, in order to examine whether the use of Facebook groups in academic courses can improve course quality and students’ achievements.",signatures:"Nitza Davidovitch and Margarita Belichenko",downloadPdfUrl:"/chapter/pdf-download/61576",previewPdfUrl:"/chapter/pdf-preview/61576",authors:[{id:"231413",title:"Prof.",name:"Nitza",surname:"Davidovitch",slug:"nitza-davidovitch",fullName:"Nitza Davidovitch"},{id:"231416",title:"Dr.",name:"Margarita",surname:"Belichenko",slug:"margarita-belichenko",fullName:"Margarita Belichenko"}],corrections:null},{id:"59667",title:"Information Security Awareness in Public Administrations",doi:"10.5772/intechopen.74572",slug:"information-security-awareness-in-public-administrations",totalDownloads:1593,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Government digital agendas worldwide go hand in hand with the digital transformation in businesses and public administrations as well as the digital changes taking place in society. Information security (IS) and awareness (ISA) must be an integrated part of these agendas. The goal of IS is to protect information of all types and origins. Here, the employees play a necessary and significant role in the success of IS, and the entire staff of an institution need to know about their specific roles and be aware of the information security management system (ISMS). As there are still fundamental strategic deficiencies in the institutions themselves, humans should not be called “the weakest link” in the security chain. Rather, sustainable awareness-raising and training for people should be established in the institutions using interactive, authentic, and game-based learning methods. Psychological studies show the great importance of emotionalization when communicating IS knowledge and the reliable exchange of experience about IS. However, in many institutions, a change in culture is becoming necessary. IS must be integrated into all (business) processes and projects, and viable safeguards must be included. This chapter summarizes the most important scientific findings and transfers them to the practice of public administrations in Germany. Moreover, it shows examples of learning methods and provides practical assistance for IS sensitization and training.",signatures:"Margit Scholl",downloadPdfUrl:"/chapter/pdf-download/59667",previewPdfUrl:"/chapter/pdf-preview/59667",authors:[{id:"235819",title:"Dr.",name:"Margit",surname:"Scholl",slug:"margit-scholl",fullName:"Margit Scholl"}],corrections:null},{id:"61851",title:"The Digital Culture within Enterprises and Public Administration: Legal Aspects and Repercussions on the Country’s Socioeconomic Fabric",doi:"10.5772/intechopen.77606",slug:"the-digital-culture-within-enterprises-and-public-administration-legal-aspects-and-repercussions-on-",totalDownloads:820,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In line with the international framework, Italy is going through a process of transformation and innovation affecting the services provided to citizens and enterprises; this process aims at administrative simplification through the use of digital technologies.",signatures:"Ida D’Ambrosio",downloadPdfUrl:"/chapter/pdf-download/61851",previewPdfUrl:"/chapter/pdf-preview/61851",authors:[{id:"235857",title:"Prof.",name:"Ida",surname:"DAmbrosio",slug:"ida-dambrosio",fullName:"Ida DAmbrosio"}],corrections:null},{id:"59713",title:"Innovation Challenges in Latin American Administration",doi:"10.5772/intechopen.74736",slug:"innovation-challenges-in-latin-american-administration",totalDownloads:941,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Faced with new challenges, public administration is searching for new levels of responsiveness and efficiency. In most emergent nations, the success of new proposals has been jeopardized by a strong popular distrust in government agencies and actions as well as an era of greater resource scarcity. This chapter deals with some new responses considering the Latin America context. We conducted a documentary survey on public administration responses in Latin America, which allowed to distinguish the possibilities to move toward an ideal of collaborative governance, new public policy values, and public-private partnership, thus reinforcing the arguments about a new logic for thinking about public administration.",signatures:"Paulo Motta and Mariana Bandeira",downloadPdfUrl:"/chapter/pdf-download/59713",previewPdfUrl:"/chapter/pdf-preview/59713",authors:[{id:"234890",title:"Prof.",name:"Paulo",surname:"Motta",slug:"paulo-motta",fullName:"Paulo Motta"},{id:"235011",title:"Dr.",name:"Mariana",surname:"Bandeira",slug:"mariana-bandeira",fullName:"Mariana Bandeira"}],corrections:null},{id:"62589",title:"Overview of Marine Stock Enhancement, Restocking and Sea Ranching in Ghana",doi:"10.5772/intechopen.79454",slug:"overview-of-marine-stock-enhancement-restocking-and-sea-ranching-in-ghana",totalDownloads:904,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Fish stocks in Ghanaian waters are on the decline. There is therefore the need to rebuild the stocks through marine stock enhancement and restocking. Stock enhancement and restocking are the guarantee routes to revive the stock declining menace of the country. Other benefits will include sustainable employment, increase fishers income, reduce poverty, ensures food security and promote national development. Species to be used for restocking is a major problem since the biology of the existing species is poorly understood. There are certain factors that must be taken into considerations if stock enhancement and restock programmes are to be successful, namely existing fisheries management schemes, socio-economic factors, institutional capacity and aquaculture development. The potential for Ghana to create sustainable, supplemental livelihoods through restocking or stock enhancement appears promising.",signatures:"Berchie Asiedu, Gyamfua Afriyie and Samuel Kwaku Konney\nAmponsah",downloadPdfUrl:"/chapter/pdf-download/62589",previewPdfUrl:"/chapter/pdf-preview/62589",authors:[{id:"236185",title:"Ph.D.",name:"Berchie",surname:"Asiedu",slug:"berchie-asiedu",fullName:"Berchie Asiedu"},{id:"253592",title:"Ms.",name:"Gyamfua",surname:"Afriyie",slug:"gyamfua-afriyie",fullName:"Gyamfua Afriyie"},{id:"253593",title:"Mr.",name:"Samuel Kwaku Konney",surname:"Amponsah",slug:"samuel-kwaku-konney-amponsah",fullName:"Samuel Kwaku Konney Amponsah"}],corrections:null},{id:"61781",title:"The Protection of Competition between National Law and EU Law: The Main Features in Public Contracts",doi:"10.5772/intechopen.76411",slug:"the-protection-of-competition-between-national-law-and-eu-law-the-main-features-in-public-contracts",totalDownloads:867,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This article provides a general analysis of competition law and then focuses on competition-related issues within public contracts. First and foremost, the article tries to highlight the economic grounds that led to the introduction of laws to protect competition, as a functional tool for production efficiency. After a critical analysis of national and EU regulations on competition, the article analyses the relation between competition and public contracts, by making a distinction between a “micro” and a “macro” view of competition. The article aims at highlighting the main features of the code of public contracts, focusing also on the relation between two different principles: the protection of EU competition, on the one side, and the power of member states to determine their internal organisation, on the other side. The article also aims at understanding to what extent can the European Union protect free competition without affecting the organisational freedom of its member states.",signatures:"Ida D’Ambrosio",downloadPdfUrl:"/chapter/pdf-download/61781",previewPdfUrl:"/chapter/pdf-preview/61781",authors:[{id:"235857",title:"Prof.",name:"Ida",surname:"DAmbrosio",slug:"ida-dambrosio",fullName:"Ida DAmbrosio"}],corrections:null},{id:"60645",title:"Crowdfunding and Civic Crowdfunding: Theoretical Features and Future Prospects",doi:"10.5772/intechopen.74739",slug:"crowdfunding-and-civic-crowdfunding-theoretical-features-and-future-prospects",totalDownloads:1073,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The aim of this work is to carefully analyze crowdfunding, an innovative financial tool based on fundraising activities intended for “crowds” of people, also meant as an antidote to the global financial crisis. After an introduction to crowdfunding, its origins and evolution, the document pinpoints the specificities of the various models. Special attention will be then reserved to civic crowdfunding, which engages the citizens in financing or co-financing public works meant to improve and preserve the territory, or to support social and cultural activities. This study focuses on critical and successful factors of the crowdfunding campaigns to then propose a research schedule meant to implement the future of this emerging tool.",signatures:"Nadia Oliva",downloadPdfUrl:"/chapter/pdf-download/60645",previewPdfUrl:"/chapter/pdf-preview/60645",authors:[{id:"229116",title:"Dr.",name:"Nadia",surname:"Oliva",slug:"nadia-oliva",fullName:"Nadia Oliva"}],corrections:null},{id:"59724",title:"The Involvement of the Taxpayer in the Public Administration Decision",doi:"10.5772/intechopen.74866",slug:"the-involvement-of-the-taxpayer-in-the-public-administration-decision",totalDownloads:952,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The relationship between taxpayers and Tax Authority and the involvement of the taxpayer in the public administration decision is a very important area of investigation in Italian tax law. This relationship is based on equity and cooperation in good faith, which stems from constitutional principles, such as the principle of sound administration (Art. 97 Italian Constitution), fairness and solidarity (Art. 3 Italian Constitution). Therefore, Tax Authority must exercise his control and assessment powers in compliance with such principles. The fundamental expression of the involvement of the taxpayer in the public administration decision is the “right to be heard”, intended as anticipation of the future activities of the administration. Precisely, it is a phase of research, acquisition and assessment of the evidence and of any other information which may facilitate a better reconstruction of the application of the tax (“presupposto”). In these terms, the “right to be heard” is an implementing tool for taxpayer’s right of defense and for best practice in the public administration. Therefore, it should be mandatory, always and in any case, in accordance with art. 3 and art. 97 of Italian Constitution, and with European law. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"46203",title:"Newer β-Lactamases and E.coli — A Cause of Concern",doi:"10.5772/57578",slug:"newer-lactamases-and-e-coli-a-cause-of-concern",body:'
In 1941, the Magic Bullet Penicillin was first used clinically in an Oxfordshire constable, Albert Alexander, but within one year Rammelkamp reported the identification of isolates of
Infact, the rising trend of developing resistance to multiple antibiotics in microbes, leads to therapeutic failure. Presently, antimicrobial resistance (AMR) is a major threat to patient care and disease control throughout the world.
The World Health Day theme on 7th April 2011 was ‘Antimicrobial resistance and its global spread’. World Health Organisation has raised the issue in 2011 that “Combat drug Resistance - No action today, No cure tomorrow” [3]. Not only the Gram positive bacteria like Methicillin Resistant
Actually, the pace in which bacteria develop resistance is much higher than the rate of development of newer antimicrobials. The antibiotic resistance is mainly developed due to inappropriate and irrational use of antibiotics. In 2011, two new terms were coined i.e. multidrug resistant (MDR) and Extreme drug resistant (XDR) organisms. MDR is defined as non-susceptibility to one or more antibiotics in three or more antibiotic classes and XDR is defined as non-susceptibility to all potentially effective antimicrobials respectively [4]. β – lactamases are the important mechanism of drug resistance among the Gram negative bacteria.
Though
About 80% cases of urinary tract infection are due to
They are classified into two types [12] – (a) Enterovirulent
Enterovirulent
Enteropathogenic
\n\t\t\t\t\t\t
Intrinsic resistance is rarely seen in genus Escherichia. Susceptibility of individual strain to different antimicrobials varies greatly, thus antibiogram is used as an epidemiological marker. This resistance pattern is plasmid mediated.
Beta lactamases are enzymes produced by wide range of Gram negative and Gram positive bacteria. This enzyme is responsible for resistance to β-lactam antibiotics like Penicillins, Cephalosporins, Cephamycins and Carbapenems. The β-lactamase enzymes break the beta-lactam ring and thus inactivate the antibacterial properties. Abraham and Chain (1940) discovered penicillinase, first β-lactamase to be identified in
Classification of β-Lactamases can be done by -
Ambler in 1980s classified β – lactamases into various groups and according to him, there are three main classes as A, C and D [19]. Metallobetalactamases belong to class B which exhibits potent hydrolyzing activity not only against Carbapenems but also to other β – lactam antibiotics.
Determination of β-lactamase production could be done by acidometric method, iodometric method and Chromogenic cephalosporin method using nitrocephin [20].
Extended spectrum beta – lactamase (ESBL) producing strains are emerging pathogens causing Health care associated infections (HAI) and pose great therapeutic challenge in recent years. ESBLs were first detected in
The ESBL in
Different confirmatory tests include Double disk approximation test, [26,27]. Comparison of Minimum inhibitory concentratin (MIC) or inhibitory zone around disk in presence or absence of β-lactamase inhibitor [28], Vitek ESBL test [29], Etest [30], three-dimentional test [31] etc. For identification of specific ESBL different molecular detection methods can be applied like DNA probes, PCR with oligonucleotide primers oligotyping, PCR followed by restriction fragment length polymorphism analysis, ligase chain reaction and nucleotide sequencing etc [32]. Commonly primers used for detecting bla genes are [33]:
CTX Forward – CGCTTTGCGATGTGCAG
Reverse - ACCGCGATATCGTTGGT
These techniques are available only in research centers and are beyond the scope of routine Clinical Microbiology Laboratories in India considering the presence of too many different types of ESBLs and the high cost.
Amp C β-lactamases were first reported in 1988. Amp C β-lactamases are found either on chromosome (inducible) or on plasmid (non-inducible). Amp C β-lactamase producing bacteria show resistance to most of Cephalosporins including Cephamycin (Cefoxitin, Cefotetan) except Carbapenems. But they also hydrolyze Penicillins and Aztreonem. These are not inhibited by beta-lactam inhibitors such as Clavulanic acid, Tazobactam and Sulbactam.
These include β – lactamases which cause Carbapenem hydrolysis, with elevated Carbapenem MICs and they belonged to molecular classes A, B and D. Molecular classes A, C and D include the β – lactamases with serine at their active site, whereas class B β – lactamases are all metalloenzymes which require Zn++ for their activation [40].
They belong to molecular class B β – lactamases, requiring one or more divalent cations (Zn++) for their activation [45] and have 3 characteristics [2] –
Hydrolyze carbapenems
Resistant to clinically used β – lactamase inhibitors and
Inhibited by EDTA, a metal ion chelator.
The first MBL detected was chromosomally encoded and was detected in
On the basis of Imipenem and other β-lactam hydrolysis, MBLs are classified into different subgroups as [47] –
Subgroup3a- possess broad spectrum activity; Subgroup3b – preferential avidity for carbapenem; Subgroup 3c – hydrolyze carbapenems poorly compared to other β-lactam substrate.
At molecular level MBLs are classified into [48] –
Class B1 – possess key Zn co-ordinating residues of three histidines and one cystein eg. IMP, VIM, GIM and SPM – 1,
Class B2 – possess asparagine instead of histidine at first position of principal Zn binding motif, NXHXD. e.g. Aeromonas species and
Class B3 – MBL L1 unique among all β-lactamases in being functionally represented as a tetramer.
The numbering scheme has been recently updated to accommodate newly discovered MBLs.
MBLs are inhibited by EDTA (Ethylene diamino tetraacetic acid), 2 Mercaptoethanol, 5-Mercaptoacetic acid, 2 Mercapto propionic acid, Copper Chloride and Ferric Chloride. MBLs are classified mainly into two types – Chromosomally encoded and Plasmid encoded or Acquired or Transmissible type. Usually metallobetalactamase producing strains are susceptible to Colistin or Polymyxin B. MBLs do not hydrolyze aztreonam very well, which characteristic is different than ESBLs or Class A β-lactamases [48].
The acquired MBLs are further classified into different types depending on their place of origin as VIM (Italy or Greece), SPM (Brazil), GIM (Germany), SIM (Korea), DIM (Dutch), NDM/PCM (New Delhi metallobetalactamases/Plasmid coded metallobetalactamases).
In March 2010, researchers from Mumbai found that most of Carbapenam resistant bacteria carried blaNDM–1 gene. The gene is carried on plasmids and is readily transferred between different strains of bacteria by horizontal gene transfer. All these strains were resistant to most of routinely used antibiotics like Aminoglycosides, β-lactams, Quinolones but sensitive to Tigecycline and Colistin [50]. Recently, Espinal et al identified a new variant of NDM-1 in
Carbapenems often used as an antibiotic of last resort for treating serious infections caused by multi-drug resistant (MDR) organism. Reduced susceptibility to any Carbapenem can be used as a screen for carbapenemases. Positive screening tests are to be followed by a confirmatory test for MBL production.
Although a variety of phenotypic methods have been proposed for the detection of carbapenemases, none have been recommended by CLSI. The classical Hodge [54], Modified Hodge test (MHT) [55] are economical approach for detection and confirmation of carbapenemase activity and Re – Modified Hodge test [56] for detection of MBL. However, the first two tests cannot differentiate between a class A carbapenemase and MBL, making a further confirmatory test necessary. Imipenem is more sensitive but less specific Carbapenem for this test allowing detection of even OXA carbapenemases.
MBL detection tests involving inhibitors such as ethylene diamine tetraacetic acids (EDTA) and 2-Mercaptopropionic acids (2-MPA) have been recommended by various workers [57]. Tris/EDTA disks can also be used in combination with a Carbapenem disk to detect Carbapenem - hydrolyzing enzymes and to differentiate between class A enzymes and MBLs. MBLs are inhibited by the Tris/EDTA disk. The inhibition of MBL can be enhanced by the addition of chelators. Double disk synergy test (DDST) [55] and Disk potentiation tests [58] are based on this principle. For detection of MBL many other methods used are MBL E-test using imipenem/imipenem-EDTA [59], reduction of MIC in presence of EDTA and polymerase chain reaction (PCR) [60].
Commonly primers used for detecting Class B metalloenzyme genes are [40]:
VIM-1 Forward – TTATGGAGCAGCAACCGATGT
Reverse - CAAAAGTCCCGCTCCAACGA
PCR is specific for gene family IMP, VIM, etc. and hence, many other specific primers can be used for different MBL genes. The main disadvantage of PCR is that it requires tailor-made DNA primers and cannot differentiate between variants and may not detect new variants.
KPCs can be mainly detected by Combined disk method using Imipenem and Imipenem with Phenyl boronic acid, Molecular methods like PCR etc.
Recently, Carbapenem Resistant Enterobacteriaceae (CRE) pose a real threat to Medical fraternity as the increased frequency with which Enterobacteriaceae cause infection and the mortality associated with infection caused by CRE. Most of the studies reported newer β- lactamases including MBL production in nonfermenters like
A total Number of 450
Antibiotic susceptibility test for all 450 strains of
Lawn culture of test strain (turbidity adjusted to 0.5 Mc Farland standard) was put on MH Agar plate. The antibiotic disks were put on inoculated plate with all aseptic precaution. Antibiotic susceptibility test was done for Aminoglycosides like Amikacin (AK-30μg), Gentamicin (GEN-10μg), Cephalosporins like Ceftazidime (CAZ-30μg), Cefotaxime (CTX-30μg), Fluoroquinolones like Ciprofloxacin (CIP–5μg), Monobactams like Aztreonam (AT-30μg), Carbapenems such as Imipenem (IPM-10μg), Etrapenem (ETP-10μg) etc. For urine sample an additional disk of Nitrofurantoin (NIT-300μg) and only for MBL producing strains, Colistin (CL-10μg) disk were used
All 450
Combined disk method as per CLSI guideline and ESBL E-test were used for ESBL detection.
In Combined disk method, lawn cultures of test strains (turbidity adjusted to McFarland 0.5 standard) were put on MH agar plates. Ceftazidime (CAZ) 30 μg disc and Ceftazidime plus Clavulanate (CAC) 30μg plus 10μg discs were put widely apart on that MH plate. After overnight incubation at 370C increase in zone diameter of ≥5 mm with CAC disk as compared to CAZ disk alone was considered positive for ESBL detection.
In ESBL E-test, lawn culture of test strain (turbidity adjusted to McFarland 0.5 standard) was done on a MH agar plate & ESBL E-test strip (AB Biomeriux) was placed. After overnight incubation at 370C, MIC ratio of ceftazidime/Ceftazidime Clavulanic acid (TZ/TZL) ≥ 8 or deformation of ellipse or phantom zone present was considered positive for ESBL production.
For, detection of Amp C β –lactamase producing strains substrate inducer combination of Imipenem (10µg) / Ceftazidime(30 μg) disks and for confirmation disk potentiation test using 3 aminophenyl boronic acid (100 mg/ml) was used.
In Disk potentiation test, lawn culture of test strain (turbidity adjusted to McFarland 0.5 standard) was done on MH agar plate. Two ceftazidime(30μg) disks with centre to centre distance of 30mm were placed on that MH plate. 3-aminophenylboronic acid (APB) was dissolved in DMSO at a concentration of 100mg/ml. 10μl of this APB solution was added to one of the ceftazidime disk. After overnight incubation at 370C, an increase in zone size of ≥5mm around the Ceftazidime - APB disc compared to Ceftazidime disc only was recorded as a positive result for Amp C β-lactamase production.
As ESBL and AMPC β – lactamase can be produced by a single strain and ESBL production is suppressed if the same strain also produces Amp C β –lactamases ,we followed the following methods.
Lawn culture of test strain (turbidity adjusted to McFarland 0.5 standard) was done on MH agar plate. To detect the strains producing both ESBL and AMPC β – lactamases, we used one disk containing Ceftazidime and Clavulanic acid (CAC) and the other 02 disks containing Ceftazidime (CAZ) only, placed widely apart. On CAC disk 10μl of 3-aminophenyl boronic acid (3 – APB) (100mg/ml) solution was put. 3 – APB inhibit the growth of AmpC β – lactamases and ESBL genes can be expressed whereas 10 μl of 3 – APB solution was also put on one of the CAZ disk. The plates were incubated 370C overnight. The zone diameter of ≥ 5 mm around CAC disk with 3 - APB compared to CAZ only was recorded as ESBL positive and increase in zone diameter of ≥5 mm around CAZ and 3 – APB disc compared to zone diameter of CAZ only was considered positive for AmpC β – lactamase production.
All 450
The MBL E-test was done and interpreted using test strains and Quality control strains according to manufacturer‘s instructions. Overnight broth culture of test strain (turbidity adjusted to 0.5 McFarland standard) was used to inoculate MH agar plate. The MBL E-test strip was put on that inoculated MH plate with a sterile forceps and plates were incubated at 370C for 18-20 hrs. After incubation, MIC ratio of Imipenem /Imipenem-EDTA (IP/IPI) of ≥8 or deformations of ellipse or phantom zone indicate MBL production.
It was done by Combined disk method [61]. Lawn culture of test strain (turbidity adjusted to 0.5 Mc Farland) was put on MH agar plate and 2 Imipenem (10 μg) disks were put widely apart. To one Imipenem disk 10 μl Phenyl boronic acid solution (400μg/disk) was put. Then the MH agar plates were incubated at 370C overnight. After incubation, the test should be considered positive when growth inhibitory zone around the disk containing Imipenem and Phenyl boronic acid was ≥ 5 mm compared to zone diameter of Imipenem alone.
Figure 1: Incidence of MBL, ESBL & Amp C β –lactamase producing
Shows incidence of different β – lactamases e.g. MBL, ESBL, AMPC β – lactamases producing
In photo 5 ESBL E Test positive shows MIC of Ceftazidime (TZ) 6 µg/ml and Ceftazidime Clavulanic acid (TZL) 0.25µg/ml respectively i.e. MIC ratio of TZ/TZL is 24. Out of 378 β - lactamase producing E.coli strains 223(59%) produced both ESBL andAmp C β –lactamases. Out of total 51 MBL producing
All 51MBL positive
Isolation of MBL producing
Out of total 450
Figure 2 shows out of total 51 MBL positive
Isolation of only MBL and MBL with other β - lactamase producing
Figure 3 shows maximum 9/51 (17.7%) MBL producing
Antibiotic resistance pattern of MBL producing
Figure 4 shows out of total 51 MBL producing
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\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
Performance of different phenotypic methods compared to MBL – E test in identifying MBL + ve
Table 1 shows Sensitivity, Specificity, Positive predictive value, Negative predictive value and Efficiency calculated for Re – Modified Hodge test (Re – MHT), Double disk synergy test (DDST) and Disk potentiation (DP) test, compared to MBL – E test in identifying MBL positive E.coli strains. MBL – E test is considered as standard phenotypic reference method for detection of MBL positive strains. The sensitivity of Re - MHT was 88.2% and specificity was 99% whereas sensitivity of DDST was 90.2% and specificity was 99.5%. DP test was having sensitivity and specificity of 100%. The efficiency of Re – MHT was 97.8%, DDST was 98.5% and DP was 100%, when compared to MBL - E test as standard reference method.
The emergence of antibiotic resistance occurs by a) spontaneous mutation and vertical gene transfer and b) horizontal gene transfer through transformation, transduction, conjugation, transposons (jumping genes) etc. The rapidity of development of antimicrobial resistance in organisms, leads to selection pressure of antibiotics like 3rd generation of cephalosporin- ESBL inhibitor combination, Monobactams and Carbapenems. Recently, Carbapenem resistant Enterobacteriaceae (CRE) pose a real threat to Medical fraternity as the increased frequency with which Enterobacteriaceae cause infection and the mortality associated with infection caused by CRE and ESBL producing bacteria. In mid1990, CTX-M 15 was first reported as ESBL in India. Now, CTX-M 15 is established as globally dominant ESBL and primary cause of acquired resistance to 3rd generation Cephalosporins in Enterobacteriaceae. Walsh TR et al in year 2005 noted that MBL genes have spread from
In the present study, 52(11.6%), 56(12.4%) and 342 (76%)
Isolation of
Isolation of
Various authors have reported MBL producing
Phenotypic detection of metallobetalactamase (MBL) producing
Walsh et al in 2002 have reported that the MBL – E test results were in 100% agreement with the results from the genotypic Polymerase chain reaction (PCR) and biochemical methods [59]. They have also reported that the E test MBL strip IP/IPI has the ability to detect MBLs both chromosomally and plasmid mediated, in aerobic and anaerobic bacteria. This novel method could be used by Clinical Laboratories to monitor the emergence of the MBL [59].
Omair et al in 2012, have reported that MBL – E test have been taken as a gold standard method for MBL detection [72]. Manoharan et al have reported that MBL - E test has taken as a phenotypic standard method for MBL detection though the test is expensive. Double disk synergy test (DDST) and Disk potentiation (DP) tests are economical and simple to perform but DDST is observer dependent while DP test is measurable with lesser chance of subjective error [45].
In the present study, we studied MBL positive
In figure 7, the venndiagram showing interrelationship of Re – modified Hodge test (Re – MHT), Double disk synergy test (DDST) and Disk potentiation test (DP) for detection of MBL producing
In the present study when results of all three phenotypic methods were compared with MBL – E test results, it was found that 45/51 (88.2%) MBL positive strains were positive by all three phenotypic method i.e. Re – Modified Hodge test (Re- MHT), Double disk synergy test (DDST) and Disk potentiation (DP) tests. 04 and 02 were false positive by Re – MHT and DDST methods respectively, whereas6/51 (11.8%) and 5/51(9.8%) were false negative by Re – MHT and DDST method respectively. Amongst all three phenotypic methods, DP was best correlated with MBL – E test. By DP test 51 MBL positive E.coli strains were detected and no false positive and false negative result was found (Sensitivity 100% and specificity 100%).
The successful outcome of clinical use of 3rd generation cephalosporines unfortunately led to the increased use and emergence of ESBL producing Enterobacteriaceae. With the emergence of ESBL and Amp C β – lactamase production in
Most common MBL found worldwide in Enterobacteriaceae were VIM (Verona integron encoded MBL) and IMP (active on imipenem). Multidrug resistant
NDM - 1 spread largely to different countries like Australia, Japan, Brazil, Belgium, Canada, Germany etc [77]. The gene encoding NDM – 1is called blaNDM-1, located on transmissible plasmid which may include other antibiotic resistance genes also leading to extensive drug resistant phenotypes (so called ‘superbugs’). A recent report from ICU and wards of Sir Gangaram hospital Delhi, India showed 8.1% NDM – 1 positive E.coli [78]. In January 2011, the name of NDM–1 was changed to PCM (Plasmid encoding Carbapenem resistant metallobetalactamases) [79].
Metallobatalactamases are also found in Carbapenem susceptible organisms. This hidden MBL gene can spread unnoticed in hospitals if isolates are reported sensitive without screening for presence of MBL [48].
The prevalence of ESBL and Amp C beta lactamases in a single isolate reduces effectiveness of beta – lactam and beta - lactamase inhibitor combinations while MBLs and Amp C beta–lactamases confer resistance to carbapenems and Cephamycin. Unfortunatenly thses enzymes usually co-exist in same isolate.
As
Phenotypic methods can be useful for routine detection of ESBLs and carbapenemase production, among Gram negative bacteria particularly when PCR is not available.
Screening of colonisation with multidrug-resistant organisms (MDROs) upon admission to hospitals has been advocated in patients who have already received healthcare in endemic countries. The CDC recommends, if previously unrecognized cases are identified of being infected with β-lactamase producing strains, a round of surveillance culture from high risk areas i.e. ICUs or wards from where detected, should be considered in any Health Care Setup. In addition prompt notification, must be made to infection control team members when CRE are identified in Clinical Microbiology Laboratories.
Antimicrobial stewardship has been suggested as the most important efforts to control multidrug resistant organisms (MDROs) [81]. It has been found to be most effective, if efforts are directed towards an overall decrease in antimicrobial use rather than targeting a specific antimicrobial class. Limiting use of invasive devices is another potentially important preventive mechanism for MDROs including β- lactamase producing organisms. Health care workers (HCW) should follow hand hygiene practices while giving patient care preferably using an alcohol based hand rubs or antimicrobial soap and water if hands are visibly soiled, and also follow Standard precautions and Additional precautions as per the indications.
In the present study, all MBL – E test positive
Beta-lactamase producing organisms are detected by E test, which is standard phenotypic method and also by Polymerase chain reaction (PCR) which is a gold standard, but both are costly and require expertise. Failure to detect these enzymes has contributed to their uncontrolled spread and commonly to therapeutic failures.
Hence to conclude, for detection of ESBL, combined disk method using Ceftazidime / Ceftazidime Clavulanic acid(CAZ/CAC), for detection of Amp C β-lactamases confirmatorty Disk potentiation test using Ceftazidime / Ceftazidime - 3-aminophenylboronic acid and for detection of Metallo β-lactamases(MBL) producing
Usage of radiopharmaceuticals has increased in recent decades, mainly for the treatment of cancer diseases [1]. However, the oncology community is still unfamiliar with radiopharmaceutical therapy (RPT). Compared with all other systemic cancer treatment options, radiopharmaceuticals have an efficacy result with minimal toxicity [2]. The radiopharmaceutical therapy application introduces new tumor-targeting agent therapy, different from external radiotherapy (Figure 1). It quantifies radioactivity distribution in tumor sites and in vivo detection [2]. The advantages of RPT are: firstly, it is targeted into tumor, included metastasis sites. Secondly, the high linear energy transfer (LET) radionuclides are effectively killed the radioresistant hypoxic cells. Thirdly, relatively lower whole-body absorbed dose [3, 4, 5]. The therapy might be used as adjuvant therapy with or after other treatment options such as chemotherapy and surgery [6, 7]. In controlling the symptoms, shrink and stabilize the tumors for systemic metastatic cancer, where conventional radiotherapy or chemotherapy is impossible, RPT can be a choice, especially for patients who no longer respond to other treatments [2, 6].
Radiopharmaceutical therapy versus external radiotherapy. In RPT, radionuclide has administrated intravenous delivery to the targeted tumor. The tumor cells will receive an absorbed dose which is exponentially decreasing over the period. The dose is delivered per cell by emissions originating from cells is influenced by the range of the emissions. When the range of the emitted particle is much longer than the dimension of the cell, periphery tumor cells of tumor mass will receive absorbed dose and crossfire dose from other target cells, and it caused a crossfire dose to normal tissue. However, the response of the normal cell will differ from the tumor cell (a). In external radiotherapy, radiation delivers the same absorbed dose per cell regardless the number of cells (b).
The radiopharmaceuticals can be in the form of radionuclides alone or radionuclides labeled (radiolabeled) for imaging or therapy. They can be labeled with molecules such as a drug, a protein, or a peptide for the therapy. Physical and biochemical characteristics of radiopharmaceuticals/radionuclides should be considered for treatment purposes. The physical characters are included physical half-life, energy radiation(s), type of emissions, daughter product(s), production method, and radionuclide purity [6, 8]. The biochemical characteristic includes tissue targeting, radioactivity retention in the tumor, in vivo stability, toxicity and the effective half-life within the patient’s body [2]. A convenience range of the physical half-life of radionuclide is between 6 hours and seven days [9]. A very short physical half-life has a limitation due to the delivery time, and a long half-life of radiopharmaceuticals will expose the surrounding environment to more time radiation. The physical half-life should not too long, but it should have sufficient retention time. So, the radiation can be delivered to the tumor efficiently [1]. On the other hand, when the biological half-life is too short, the radionuclide will be discharged with significantly high activity. Therefore, for efficient radiation delivery for therapy purposes, a balanced optimal biological and physical half-life should be considered, besides the type of tumor, method of administration, and uptake mechanism [1, 6]. Radionuclides radiations as alpha (α)-particle (50–230 keV/μm) and beta (β)-particle (0.2 keV/μm), and Äuger electrons (4–26 keV/μm) are used for therapy purposes [1, 3, 6, 10, 11]. These particles allow ionization per travel length, and they are fully deposited within a small range of tissue. The distance traveled, and the energy deposited in cells is vital that lead the most efficient route for cell destruction is the direct interaction of ionization events with DNA.
Some β-emitter radionuclides also decay γ-particle, which is used for imaging. Radionuclides that emit α or β-particles are preferred for the treatment of bulky solid tumors, and radionuclides that emit Äuger electrons are considered for the treatment of tiny clusters of cancer cells or small tumor deposits because of their high-level cytotoxicity and short-range biological effectiveness [3]. The other factor that needs to be considered is the daughter product of the radionuclides. If the daughter product is unstable, it should be short-life and may decay within hours into a stable product, and un-stable daughter nuclide will contribute to the amount of absorbed dose. Radiopharmaceuticals’ biochemical characteristics are selective tumor target concentrations and have optimal retention time in the tumor and avoid uptake in the normal cells [6, 9]. Depending on the tumor uptake mechanism, either by bone deposition, protein binding, or metabolic uptake, the ratio concentration of radionuclides on the tumor to normal tissues should be as optimal as possible [6]. The other factors that have to be considered are the radionuclides particles’ size, low toxicity, specific gravity for optimal flow and distribution, and clearance rate [6, 12, 13, 14, 15, 16].
Iodine-131 (131I) was one of the first radionuclides used for therapy in clinical oncology, especially for thyroid cancer patients. Phosphorous-32 (32P), strontium-89 (89Sr), and yttrium-90 (90Y) also have been used for the treatment of benign and malignant diseases [6, 17, 18]. Various alpha- and beta-radiation-emitting isotopes are used lately. Most of them are labeled with peptides and antibodies for specific tumor targeting, where radiopharmaceuticals are used as vehicles to deliver ionizing radiation to the tumor tissue. This review discusses radiopharmaceuticals are used for therapy and their application in the modern era of cancer therapy.
The growth in nuclear medicine has been stimulated by introducing several new radionuclides and radiopharmaceuticals. They have been used to treat benign and malignant tumors. Types of radiation that are relevant to RPT are electrons and α-particles. Electron emissions are classified by energy and by the type of decay; Auger electrons, beta (β)-particles are related to RPT [2]. Currently, β particle emitters radionuclides are mostly used for therapy purposes. However, they have a limitation of radiobiological properties. An alpha particle emitting as a new generation radionuclides is being developed, with advantages in high energy and a short path length, which show higher efficacy [19]. Below we discuss the physical differences between a beta particle, Auger electrons, and an alpha particle.
Beta particles are produced in the beta decay process, wherein an unstable nucleus, a neutron, is converted to a proton, creating an energetic electron (beta particle) [2, 19]. They are the most frequently used for RPT agents and widely available. Many of them also emit photon energy that is easily imaged. Beta particles are negatively charged and have a relatively long path length from 0.0 to 12 mm. They have low linear energy transfer (LET) of approximately 0.2 keV/μm, and more particles are required for a similar absorbed dose as alpha particles (Figure 2). For high energy beta, like 90Y and 188Re, which they energy 2.28 Mev and 2.21 MeV respectively (Table 1), they can cause crossfire doses to neighbor cells. So, they are preferable for higher volume solid tumors, poorly perfuse tumors, and less suited for targeting micro-metastases [3, 8, 23]. For the small tumor, low-energy β-rays such as lutetium-177 (177Lu) would be more β-emitting efficient [8].
Linear energy transfer alpha and beta particles and auger electron on DNA. Alpha particles have high LET (∼80 keV/μm) compared with the low LET (∼0.2 keV/μm) of beta particles, and auger electron intermediate LET 4–26 keV/μM. Thus, alpha particles result in more double-strand breaks in DNA.
Radionuclides | Mode of decay | Physical half-life | Energy (KeV) | Indication |
---|---|---|---|---|
223Ra | α | 11.44 d | 5979.2 | Bone pain palliation |
211At | α (41.8.9) EC(58.2) | 7.21 h | 5870–7450 | Clinical trials in glioblastoma, ovarian cancer, blood-borne cancers |
212Bi | α (35.9) β− (97.8) | 60.55 mins | 6051–8785 | Clinical trials in prostate cancer, ovarian cancer, pancreatic cancer, neuroendocrine tumor. |
213Bi | α (2.2) β− (64.1) | 46.61 mins | 5875–8376 | Clinical trials in acute myeloid leukemia (AML), prostate cancer, lymphoma, melanoma, glioblastoma, neuroendocrine tumor and bladder cancer. |
225Ac | α | 10 d | 5732–5830 | Clinical trial in AML, breast cancer, ovarian cancer, prostate cancer, glioblastoma, neoroblastoma. |
227Th | α | 18.68 d | 5709–6038 | Clinical trial in AML, NHL, breast cancer, ovarian cancer. |
131I | β− | 8.02 d | 606 | Hyperthyroidism, thyroid cancer, Radioimmunotherapy (RIT) for non-Hodgkin’s limphoma (NHL) and neuroblastoma, pheochromocytoma, carcinoid, medullary thyroid cancer |
32P | β− | 14.26 d | 1710 | Polycythemia vera, keloid, cystic craniopharyngioma. |
89Sr | β− | 50.53 d | 1496 | Bone pain palliation |
90Y | β− | 64.10 d | 2280 | Liver metastasis, hepatocellular carcinoma, RIT for NHL, neuroendocrine tumor |
153Sm | β− | 46.50 h | 808.2 | Bone pain palliation, synovitis |
169Er | β− | 9.4 0d | 350 | Synovitis |
177Lu | β− | 6.73 d | 497.8 | Synovitis and RIT for various cancer |
186Re | EC,β− | 3.72 d | 1069.5 | Bone pain palliation, arthritis Bone pain |
188Re | β− | 17.00 h | 2120.4 | Bone pain palliation, RIT for various cancer, rheumatoid arthritis |
The most familiar and frequent beta particle used is iodine-131 (131I) for hyperthyroidism and thyroid cancers therapy [20, 24, 25]. Subsequently, samarium-153, lutetium-177, yttrium-90 and have been introduced over the last 40 years (Table 1) [2]. Several other β-emitting radionuclides have been investigated or considered. However, those agents have not widely adopted, related to several reasons: limited availability, complex radiochemistry process, or the absence of a commercial products [26]. A variety of reasons for the shift to different radionuclides of the different β-particle emitters used over time. For example, an early evaluation of changing to different radionuclides was based on the tumor to non-tumor-absorbed dose ratio [2]. 90Y has a high-energy β-particle, and it is widely available like 131Iodine. It was used in colloidal form, mainly for rheumatoid treatment [27, 28]. 90Y labeled antibodies initially focused on ovarian cancer, followed by hematological cancers and radiopeptide therapy [2, 29, 30]. 90Y is a popular radionuclide for RPT because of the clinical impact of 90Y-impregnated microspheres used for hepatic metastases therapy [31, 32, 33]. Lutetium-177 becomes popular because it emits photons in the 100–200-keV optimal imaging range and has a β-particle energy between 131I and 90Y, which is appropriate for therapy, particularly for small tumors [2, 8]. All these factors, along with a half-life that is compatible with the pharmacokinetics of both antibodies and peptides. It is a reactor production and widely available, with relatively straightforward conjugation chemistry [2]. Samarium-153 (153Sm) is a β-emitting radionuclide that is used for palliative treatment in breast and prostate cancer with bone metastases, and other primary cancers [34, 35]. Radiopharmaceuticals therapy agent that uses the ethylenediamine-tetra-methylene-phosphonic acid (EDTMP) chelator, binding samarium-153 through six ligands (four phosphate groups and two amines) is FDA approved. 153Sm alternative formulation as 153Sm-DOTMP (1,4,7, 10-tetraazacyclododecanetetramethylenephosphonic acid), which is thought to have a more favorable chelant-to-metal ratio [2].
Auger electrons are generated from suborbital transitions. They are typically very short-range emissions, of the order of 1–1000 nm, depending on their emission energy. Auger electron is intermediate (4–26 keV/μM) of LET [3, 22, 23]. These emissions could be highly cytotoxic if the RPT drug localizes within the cell nucleus [36, 37]. Bromine-77, indium-111, iodine-123, and iodine-125 are the most commonly used Auger electron emitters. In vitro studies had shown highly effective and specific tumor cell killing when they labeled with targeting vehicles that can localize these subcellular-range radiations close to cellular DNA [38, 39]. Human studies using locoregional administration showed promise regarding tumor cell incorporation of the Auger emitters [2]. However, Auger electron-emitter RPT has not been widely adopted yet. Besides, auger electron agents must be incorporated into the DNA, and their unfavorable pharmacokinetics might be the reasons for the lack of efficacy. Technological developments that could overcome those factors will interest RPT development [2].
Alpha particles have a similar structure to a 4He nucleus without surrounding electrons (sometimes denoted as He2+) [19]. They are produced in alpha decay and emitted from the nucleus of a radioactive atom [2, 40]. Alpha particles have higher energy (4–9 MeV) and travel in tissue over a few cell diameters. Thus, the particle range is equivalent to the thickness of 1–3 cell widths (40–100 μm) [1, 2, 40]. They have high LET (~100 keV/μm) throughout their range and three times greater at the end of the path range (the Bragg peak) [19, 40]. Intracellular accumulation of the alpha particle effectively creates double-strand breaks (DSBs) in DNA [2, 40]. The cytotoxicity of α-particles is thus considered much higher than that of β-particles (Figure 2). Another advantage of α-particles compared with β-particles is the short distance traveled by the ionization products, reducing the damage to healthy surrounding cells. Moreover, the effect is not dependent on dose and oxygen concentration during any cell cycle (Table 2) [1].
Alpha particle | Beta particle | |
---|---|---|
Type of particle | 4He nucleus | Energetic electron |
Particle energy | 4–9 MeV | 50–2,300 keV |
Particle path length | 40–100 μm | 0.05–12 mm |
Linear energy transfer | ~80 keV/μm | ~0.2 keV/μm |
Hypoxic tumors | Effective | Less effective |
Toxicity | effective in creating double strand breaks (DSBs) in DNA | high dose rates (tumor survival rates close to linear exponential) low dose rates (single-strand breaks (repairable) with shouldering of the dose–response curve |
Bystander effect | Yes | Yes |
Tumor cross-fire | Low | Yes |
Tumor size | Micro/small | Solid high tumor volume |
Targeted alpha therapy (TAT) is an attractive therapeutic option for multiple micro-metastases. It has many advantages, such as easy administration, the ability to treat multiple lesions simultaneously, and the possibility of combining with other therapeutic approaches, and primarily for cancer treatment. By attaching an α-particles to a biological molecule with targeting capabilities, such as a monoclonal antibody (mAb), with the help of a bi-specific chelating agent or bonding it to a disease-targeting vector, and the vector used as a targeting agent. In this way, RPT selectively delivers a high radiation dose directly to the target, with generally limited toxicity to the surrounding normal tissues. Advances in understanding tumor biology, together with progress in mAb technology, chemical labeling techniques, and other related disciplines, provide significant advances in developing of new clinical applications of α-particles radionuclides in novel therapeutic agents [1, 2, 42].
The α-particles are used for RPT over 40 years included as bismuth-212 (212Bi), bismuth-213 (213Bi) and astatine-211 (211At), actinium-225 (225Ac), radium-223 (223Ra) and thorium-227 (227Th) as shown in Table 1 [2]. 223RaCl2 is the first alpha-emitting radiopharmaceutical for prostate and breast cancer patients’ bone pain palliation [2, 3, 8, 19, 40]. The energetic α-particles emitted by 223Ra can generate irreparable DNA DSBs in the adjacent osteoblasts and osteoclasts, leading to their death. The results in detrimental effects on the neighboring cells, inhibit abnormal bone formation, both at a cellular level and a signaling level, ultimately negatively affect tumor growth [2]. 223Ra is being studied in combination with other cytotoxic agents such as docetaxel (DORA trial), poly(ADP-ribose) polymerase inhibitors (olaparib), and new androgen axis inhibitors as enzalutamide and abiraterone citrate. It is also being explored in combination with immuno-oncology agents such as pembrolizumab and in combination with external-beam radiotherapy [2].
Bismuth-213 (213Bi) and astatine-211 (211At) labeled monoclonal antibodies in patients with leukemia and brain tumors, respectively [3, 22]. Moreover, 225Ac and 213Bi labeled somatostatin receptor (SSR) are preclinical and clinical trials [1, 19, 40]. 213Bi has a short half-life and can be produced from the generator, and because of that, it is required on-site labeling to produce TAT compound. The short half-life of 213Bi has some advantages as higher dose rates given over a short period are more effective than low dose rates given over a longer period [19, 40]. Studies reported that 213Bi had been labeled with DOTA peptides in preclinical and clinical trials with >99% purity [1, 19].
Furthermore, also there is a growing interest in using 255Ac as a therapeutic alpha particle source. It is produced via the neutron transmutation of 226Ra or decay of 233U [19]. The type of production caused 225Ac has a lack the capacity of clinical use of labeled peptide. So, production via a high-energy proton accelerator at multiple sites will overcome 225Ac labeled to treat neuroendocrine tumors. It has been labeled with PSMA with a radiochemical purity of >98% to treat prostate cancer [19]. 225Ac labeled antibodies are being tested in advanced myeloid malignancy [8]. 225Ac shows a potential appealing radionuclide for TAT, and post-therapy imaging of 225Ac is possible, although images are also suboptimal 19, 40, 41].
The results of clinical trials using TAT indicate that this treatment strategy presents a promising alternative for targeted therapy of cancer [22]. Lately, it has been gaining popularity that TAT to be a successful treatment in prostate cancer in patients refractory to 177Lu prostate-specific membrane antigen (PSMA) [19]. Therefore, alpha-emitters and Auger electron emitters (77Br, 111In, 123I, 125I) are getting more attention for targeted therapy lately. Auger electron and alpha-emitter are intermediate (4–26 keV/μM) and high (50–230 keV/μM) of LET radiation respectively. They deliver the radiation dose within the short range of the tissue (~ tens microns) have an actual tumor cell killing if they can be conjugated with suitable ligands that effectively targeted micro-metastasis therapy [3, 22, 23].
Various alpha- and beta-radiation-emitting isotopes for therapy are mostly labeled with peptides or antibodies for specific tumor targeting, which are used only as vehicles to deliver ionizing radiation to the tumor tissue. The vehicle concentrates radioactivity at the tumor tissue expressing specific tissue elements and avoiding concentrating at normal cells [2, 7, 10]. Different radioligands are being developed and investigated for uniquely targeting molecular receptors or intracellular components that currently lead to planning personal patient-tailored therapy [43]. Radionuclides are coupled to ligands that recognize and bind the tumor-associated molecules, ensuring the precise targeting of cancerous cells that can be used for therapeutic approaches and live-monitoring of treatment efficacy [43].
Radioimmunotherapy (RIT) is targeting therapy using radionuclide labeled with specific mAbs directed against tumor antigens [6, 8]. The antibody is primarily a delivery vehicle of radiation to tumors sites. Besides therapy, radionuclide combines with mAbs has been used for imaging. The imaging provides specific non-invasive information regarding the expression, location, and modulation of targets. The therapeutic effect of RIT is achieved by tissue absorption of the energies from continuous radiation emitted from the radionuclides tagged to mAbs. More specific bound between antibody and tumor antigen increase the dose delivered to tumor cells and, at the same time, reduce the dose to normal cells [6]. RIT has been evaluated in clinical trials across the full spectrum of malignancies [8].
The type of radioactive combines with mAb depends on emission characteristics, the radiolabeling chemistry, and the malignancy of cells targeted [8]. Beta and alpha emitter particles are labeled with mAbs. However, alpha emitters have limitations in practice due to mostly very short half-life (Table 1) [41]. For optimal therapy, the residence time of RIT ranges from a few days to weeks, which reach optimal tumor-to-background ratios 2–4 days post-injection. Radionuclides labeled mAbs bind several antigens and receptors expressed on the surface of tumor cells. They include CD20, prostate-specific membrane antigen (PSMA), human epidermal growth factor receptor 2+ (HER2+), mucin 1 (MUC1), epidermal growth factor receptor (EGFR), tumor necrosis factor (TNF), vascular endothelial growth factor (VEGF), and et cetera [8].
Radioimmunoconjugates targeting CD20 have been approved to treat non-Hodkin’s lymphoma (90Y-ibritumomab tiuxetan and 131I-tositumomab) [6, 8]. Both radiolabeled mAbs are more efficacious at inducing remissions than the respective unlabeled molecules and are also more effective than earlier courses of chemotherapy in these patients [8]. Other potentials of RIT include lung, pancreatic, stomach, ovarian, breast, colorectal cancers, leukemia, high-grade brain glioma [6]. On the other hand, the application of RIT for solid tumors has been less successful than in patients with malignant lymphoma. Several problems have to be addressed to its efficacy:
Higher solid tumor volume indicates lower radiosensitivity compare to small volume tumors usually.
The delivery of therapeutic radionuclide to solid tumors might be less effective. It can be by poor perfusion, elevated intra-tumoral hydrostatic pressure, and heterogeneous radionuclide uptake by tumor cells.
Furthermore, 223Ra-chloride showed that these limitations could be successfully circumvented in patients with castration-resistant prostate cancer and bone metastases. RIT therapy may become an effective treatment modality for disseminated solid tumors in the future [8].
Several radionuclides have been used for peptide therapy in neuroendocrine tumor (NET) patients. The expression of peptide receptors on various tumor cells, including NETs, was significantly higher than normal tissues or cells [25]. Over the last decade, such receptors have become recognized targets for molecular imaging and therapy because they are expressed on the cell surface. Upon binding a ligand, the receptor-ligand complex is internalized. Radiolabeled peptide ligands are known to be used for imaging and somatostatin receptor therapy (SSTR) [25].
Peptide receptor radionuclide therapy (PRRT) has been known to be an effective systemic treatment of patients with advanced, metastatic, or inoperable, slowly progressing NETs with high somatostatin receptor expression. The principles behind PRRT efficacy are the somatostatin receptor ligand that binds the specific receptor (SSTR1–5). Particularly, SSTR2 overexpressed on the surface of neuroendocrine tumor cells. The high energy of β-particle (90Y or 177Lu) labeled to a somatostatin receptor (SSTR) ligand caused cell death through direct or indirect DNA damage of target cells (self-dose) or neighboring cells (crossfire effect) [42]. The binding of the radiopharmaceutical to the targeted cells will be indispensable when using Auger emitters. Beta-particles become more effective in damaging and killing target cells that radiopharmaceutical is bound to and several cells around the target. It is the so-called “crossfire” effect. Lower tissue penetration of 177Lu favors the use in small-sized tumors, whereas, in larger tumors, 90Y might be a better choice [25]. 117Lu or 90Y labeled DOTATATE (DOTA, Tyr(3)-octreotate) was the most widely used peptide. It is a higher SSTR2 affinity compared to DOTATOC (DOTA, D-Phe1, Tyr (3)-octreotide) and DOTANOC (DOTA, 1-Nal(3)-octreotide) [43].
Furthermore, targeted peptide receptor alpha therapy with 213Bi/225Ac has been clinically tested to treat brain tumors, neuroendocrine tumors, and prostate cancer. 213Bi and 225Ac-DOTA chelated peptides developed for peptide receptor radiotherapies, such as DOTA-Substance P targeting the neurokinin-1 receptor and the widely used somatostatin-analogs (e.g., DO-TATOC, DOTATATE). The complexation efficiency, in vitro and in vivo stability of the radiopeptides is high [1, 44]. However, these promising results still need to be confirmed in further studies with therapeutic activities 213Bi and 225Ac.
After promising results with 131I-labeled prostate-specific membrane antigen (PSMA) ligands for prostate cancer therapy, it was introduced 177Lu-PSMA by the German Cancer Research Center in 2015 [45]. PSMA is known as folate hydrolase 1 (FOLH1) or glutamate carboxypeptidase II (GCP II) and is overexpressed on the membrane of prostate cancer cells [45, 46, 47]. It remains high even after multiple lines of therapy [45, 46]. Metastatic castration-resistant prostate cancer (mCRPC) patients who shown ineffective by chemotherapy, radioligand therapy targeting the PSMA is a promising therapy approach [41, 45, 46]. First data showed that 177Lu-PSMA is safe and effective in reducing tumor burden. It has been widely adopted in German and international sites, with likely more than a thousand therapy cycles performed [45].
PSMA targeting ligand using the beta emitter lutetium-177 [177Lu]Lu-PSMA-617 or [177Lu]Lu-PSMA-I&T) are currently being tested in phase III trials. It revealed encouraging data in several studies in mCRPC patients [46, 48, 49]. PSMA-targeting ligand using alpha emitters as actinium-225 may be advantageous compared to PSMA-targeting ligan with beta emitters. Clinical studies using 225Ac-labeled PSMA-ligands ([225Ac]Ac-PSMA-617 or [225Ac]Ac-PSMA-I&T) have reported remarkable therapeutic results lately. However, it shows more substantial radiobiological effect of alpha particles on the organs at risk [46]. Combining alpha emitters in adjusted doses with beta emitters called ‘tandem therapy’ may reduce these significant adverse effects compared to using alpha emitters alone [46]. Furthermore, a novel alpha therapy approach with a thorium-227-labeled PSMA antibody shows strongly in vitro potency in several PSMA-positive cell lines and in vivo efficacy in xenograft models of prostate cancer [47]. These treatment approaches need more studies for effectiveness and limited toxicity.
Radiopharmaceutical targeted therapy is a promising tumor treatment, particularly α-emitter, for effective and rapid cancer therapy due to the localized cell killing originated from high LET and short ranges of particles [8, 41]. Strategies to combine α-emitter with immunomodulators demonstrated higher tumor growth inhibition than α therapy alone [44].
Furthermore, intelligent drug delivery agents apart from peptides, small molecules, mAb, and mAb fragments can also achieve target-specific cancer therapy [41]. They are among the most searched cancer treatment issues due to their desired properties, including tumor-targeting uptake, bio-compatibility, reducing side-effects, and nonspecific uptake and distribution. So, the main problem of targeted radionuclide therapy, such as the radiation exposure effect in healthy tissues upon the emission of the particles, can be removed significantly. The number and variety of studies about the delivery of radionuclides particles by drug delivery agents are still limited. The studies will probably increase considerably in the future due to the need for effective, rapid, and personalized cancer therapy approaches.
Regarding supply issues of radionuclides also need to be address. Some main reactors in the world now are aging, which affect to constant and reliable supply globally [6]. In particular, for α-particle-emitting radionuclide (such as actinium-225), the supply is considered a potential obstacle for the growth of RPT. Some opinions suggest that the supply problems are transient technical issues that will be resolved with a more significant investment if RPT is adopted as a mainstream cancer therapy [2]. RPT is an effective cancer treatment, particularly when other standard therapeutic approaches have failed. However, even more than 40 years of clinical investigation, RPT has not become a part of cancer treatment in the same way as other therapy approaches. Even though ‘targeted’ cancer therapies are associated with clinical trial failure rates of 97%, but experience with RPT was ignored mainly or presented as a burdensome multidisciplinary endeavor [2, 50]. Additionally, public perception and fear of radioactivity and the perceived complexity of the treatment are challenges in developing and applying RPT.
Radiopharmaceutical therapy is a safe and effective targeted approach to treating many types of cancer. Compared to other systemic cancer treatment options, RPT has shown efficacy with minimal toxicity. Different types of radionuclides relevant to the purpose are β-emitters, Auger electrons, and α-emitters. However, the targeted α-emitter has potential advantages over β-emitter therapy due to the high energy and short path length of α emissions causing double-stranded breaks in DNA and the relative tolerance to cell cycle effects and hypoxic conditions. Radionuclides are coupled to ligands that recognize and bind the tumor-associated molecules, ensuring the precise targeting of cancerous cells that can be used for therapeutic approaches and live-monitoring of treatment efficacy. Different radioligands are developed for uniquely targeting molecular receptors or intracellular components that currently lead to planning personal patient-tailored therapy in modern cancer therapy management.
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\\n\\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\\n\\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\\n\\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
\\n\\n\\n"}]'},components:[{type:"htmlEditorComponent",content:'
The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\n\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\n\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\n\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\n\nOAI-PMH
\n\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\n\nLicense
\n\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
\n\nPeer Review Policies
\n\nAll scientific works are Peer Reviewed prior to publishing. Read more
\n\nOA Publishing Fees
\n\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\n\nDigital Archiving Policy
\n\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\n\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\n\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\n\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\n\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
\n\n\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{},profiles:[{id:"396",title:"Dr.",name:"Vedran",middleName:null,surname:"Kordic",slug:"vedran-kordic",fullName:"Vedran Kordic",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/396/images/7281_n.png",biography:"After obtaining his Master's degree in Mechanical Engineering he continued his education at the Vienna University of Technology where he obtained his PhD degree in 2004. He worked as a researcher at the Automation and Control Institute, Faculty of Electrical Engineering, Vienna University of Technology until 2008. His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. 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Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. In the Engineering side, Digital Signal Processing, Computer Architecture, Electronics Devices, Digital Filtering and Engineering Management.\nApart from his Academic Interest and activities he loves sport especially, Cricket, Football, Snooker and Squash. He plays cricket for Esbjerg city in the second division team as an opener wicket keeper batsman. 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Istadi, Handoko T. Wibowo, Edy Sunardi, Soffian Hadi and Nurrochmat Sawolo",authors:[{id:"60519",title:"Mr",name:"Bambang",middleName:null,surname:"Istadi",slug:"bambang-istadi",fullName:"Bambang Istadi"},{id:"60529",title:"Mr.",name:"Nurrochmat",middleName:null,surname:"Sawolo",slug:"nurrochmat-sawolo",fullName:"Nurrochmat Sawolo"},{id:"127917",title:"MSc.",name:"Handoko",middleName:"Teguh",surname:"Wibowo",slug:"handoko-wibowo",fullName:"Handoko Wibowo"},{id:"127918",title:"Dr.",name:"Edy",middleName:null,surname:"Sunardi",slug:"edy-sunardi",fullName:"Edy Sunardi"},{id:"127919",title:"Mr.",name:"Soffian",middleName:null,surname:"Hadi",slug:"soffian-hadi",fullName:"Soffian Hadi"}]},{id:"27591",doi:"10.5772/26151",title:"Self-Organization of the Khibiny Alkaline Massif (Kola Peninsula, Russia)",slug:"self-organization-of-the-khibiny-alkaline-massif-kola-peninsula-russia-",totalDownloads:2398,totalCrossrefCites:4,totalDimensionsCites:17,abstract:null,book:{id:"621",slug:"earth-sciences",title:"Earth Sciences",fullTitle:"Earth Sciences"},signatures:"Gregory Ivanyuk, Victor Yakovenchuk, Yakov Pakhomovsky, Natalya Konoplyova, Andrei Kalashnikov, Julia Mikhailova and Pavel Goryainov",authors:[{id:"65695",title:"Dr.",name:"Gregory",middleName:null,surname:"Ivanyuk",slug:"gregory-ivanyuk",fullName:"Gregory Ivanyuk"},{id:"68621",title:"Dr.",name:"Victor",middleName:null,surname:"Yakovenchuk",slug:"victor-yakovenchuk",fullName:"Victor Yakovenchuk"},{id:"68623",title:"Dr.",name:"Nataliya",middleName:null,surname:"Konoplyova",slug:"nataliya-konoplyova",fullName:"Nataliya Konoplyova"},{id:"68624",title:"Dr.",name:"Yakov",middleName:null,surname:"Pakhomovsky",slug:"yakov-pakhomovsky",fullName:"Yakov Pakhomovsky"},{id:"68625",title:"Dr.",name:"Anfdrei",middleName:null,surname:"Kalashnikov",slug:"anfdrei-kalashnikov",fullName:"Anfdrei Kalashnikov"},{id:"68626",title:"Prof.",name:"Pavel",middleName:"Michael",surname:"Goryainov",slug:"pavel-goryainov",fullName:"Pavel Goryainov"},{id:"68628",title:"Dr.",name:"Yuliya",middleName:null,surname:"Mikhailova",slug:"yuliya-mikhailova",fullName:"Yuliya Mikhailova"}]},{id:"27588",doi:"10.5772/29786",title:"Debris Flow Phenomena: A Short Overview?",slug:"debris-flow-phenomena-a-short-overview-",totalDownloads:3311,totalCrossrefCites:3,totalDimensionsCites:11,abstract:null,book:{id:"621",slug:"earth-sciences",title:"Earth Sciences",fullTitle:"Earth Sciences"},signatures:"Chiara Calligaris and Luca Zini",authors:[{id:"79309",title:"Dr.",name:"Chiara",middleName:null,surname:"Calligaris",slug:"chiara-calligaris",fullName:"Chiara Calligaris"}]},{id:"27592",doi:"10.5772/27876",title:"Seismic Imaging of Microblocks and Weak Zones in the Crust Beneath the Southeastern Margin of the Tibetan Plateau",slug:"seismic-imaging-of-microblocks-and-weak-zones-in-the-crust-beneath-the-southeastern-margin-of-the-ti",totalDownloads:1960,totalCrossrefCites:6,totalDimensionsCites:9,abstract:null,book:{id:"621",slug:"earth-sciences",title:"Earth Sciences",fullTitle:"Earth Sciences"},signatures:"Haijiang Zhang, Steve Roecker, Clifford H. Thurber and Weijun Wang",authors:[{id:"71921",title:"Dr.",name:"Haijiang",middleName:null,surname:"Zhang",slug:"haijiang-zhang",fullName:"Haijiang Zhang"}]},{id:"27599",doi:"10.5772/26179",title:"Mesothermal Lode Gold Deposit Central Belt Peninsular Malaysia",slug:"mesothermal-lode-gold-deposit-central-belt-peninsular-malaysia",totalDownloads:10822,totalCrossrefCites:1,totalDimensionsCites:8,abstract:null,book:{id:"621",slug:"earth-sciences",title:"Earth Sciences",fullTitle:"Earth Sciences"},signatures:"Kamar Shah Ariffin",authors:[{id:"65772",title:"Prof.",name:"Kamar Shah",middleName:null,surname:"Ariffin",slug:"kamar-shah-ariffin",fullName:"Kamar Shah Ariffin"}]}],mostDownloadedChaptersLast30Days:[{id:"27601",title:"Mud Volcano and Its Evolution",slug:"mud-volcano-and-its-evolution",totalDownloads:7109,totalCrossrefCites:1,totalDimensionsCites:23,abstract:null,book:{id:"621",slug:"earth-sciences",title:"Earth Sciences",fullTitle:"Earth Sciences"},signatures:"Bambang P. Istadi, Handoko T. Wibowo, Edy Sunardi, Soffian Hadi and Nurrochmat Sawolo",authors:[{id:"60519",title:"Mr",name:"Bambang",middleName:null,surname:"Istadi",slug:"bambang-istadi",fullName:"Bambang Istadi"},{id:"60529",title:"Mr.",name:"Nurrochmat",middleName:null,surname:"Sawolo",slug:"nurrochmat-sawolo",fullName:"Nurrochmat Sawolo"},{id:"127917",title:"MSc.",name:"Handoko",middleName:"Teguh",surname:"Wibowo",slug:"handoko-wibowo",fullName:"Handoko Wibowo"},{id:"127918",title:"Dr.",name:"Edy",middleName:null,surname:"Sunardi",slug:"edy-sunardi",fullName:"Edy Sunardi"},{id:"127919",title:"Mr.",name:"Soffian",middleName:null,surname:"Hadi",slug:"soffian-hadi",fullName:"Soffian Hadi"}]},{id:"56291",title:"Glaciers as an Important Element of the World Glacier Monitoring Implemented in Svalbard",slug:"glaciers-as-an-important-element-of-the-world-glacier-monitoring-implemented-in-svalbard",totalDownloads:1407,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Glaciers are not only contributors to the sea level rise but also important players in the circulation of pollutants. Over a billion people apply glacial waters for domestic purposes; hence, both the quality and quantity of this water should be monitored. In this chapter, we concentrate on the archipelago Svalbard in the Arctic, a typical target area for xenobiotics from long range atmospheric transport (LRAT), holding an important share of the Arctic glacial ice cover. Literature review has been conducted over both the cryospheric metrics and the achievements of analytical chemistry in the environmental monitoring. Svalbard is a relatively well‐monitored part of the Arctic, with 17 glaciers regularly monitored for mass balance. In the chemical records of glaciers, a variety of substances have been determined, e.g., ions, heavy metals, or persistent organic pollutants (POPs), with the use of precise analytical techniques. However, knowledge gaps persist, preventing a formation of a reliable chemical inventory of Svalbard glaciers. Moreover, detailed studies on the deposition and transport of pollutants, rather than focusing on their presence only, are crucial future research recommendations.",book:{id:"5876",slug:"glacier-evolution-in-a-changing-world",title:"Glacier Evolution in a Changing World",fullTitle:"Glacier Evolution in a Changing World"},signatures:"Sara Lehmann‐Konera, Marek Ruman, Krystyna Kozioł, Grzegorz\nGajek and Żaneta Polkowska",authors:[{id:"187026",title:"Dr.",name:"Marek",middleName:null,surname:"Ruman",slug:"marek-ruman",fullName:"Marek Ruman"},{id:"194473",title:"Prof.",name:"Żaneta",middleName:null,surname:"Polkowska",slug:"zaneta-polkowska",fullName:"Żaneta Polkowska"},{id:"204396",title:"MSc.",name:"Sara",middleName:null,surname:"Lehmann-Koneraa",slug:"sara-lehmann-koneraa",fullName:"Sara Lehmann-Koneraa"},{id:"204397",title:"Dr.",name:"Grzegorz",middleName:null,surname:"Gajek",slug:"grzegorz-gajek",fullName:"Grzegorz Gajek"},{id:"209139",title:"Dr.",name:"Krystyna",middleName:null,surname:"Kozioła",slug:"krystyna-koziola",fullName:"Krystyna Kozioła"}]},{id:"56134",title:"The Role of Microbial Ecology in Glacier Retreat",slug:"the-role-of-microbial-ecology-in-glacier-retreat",totalDownloads:1600,totalCrossrefCites:5,totalDimensionsCites:6,abstract:"Glaciers have been considered too hostile to harbor life for a long time. However, they are now recognized as unique biomes dominated by microbial communities which maintain active biochemical routes. Microbial communities inhabiting glaciers are diverse depending on the type of glacier and the area studied. Some glaciers have a marine margin and finish in a calving front, with partly or completely temperate tidewater tongues, this establishes important differences with respect to glaciers with a land margin. Depending on the glacier area studied, microorganisms are also characteristic as they establish a vertical food chain, from the surface photosynthesizers in upper illuminated layers to heterotrophs confined in the inner part. Glaciers are retreating in many areas of the world due to global warming. Microorganisms are their most abundant and unknown occupants. They play a main role, carrying out key processes in the development of soil and facilitating plant colonization when glaciers have ultimately retired. These microorganisms are perfectly adapted to their harsh environment and are very susceptible to environmental changes. This chapter summarizes the role of microbial ecology as indicator of the conservation status of glaciers.",book:{id:"5876",slug:"glacier-evolution-in-a-changing-world",title:"Glacier Evolution in a Changing World",fullTitle:"Glacier Evolution in a Changing World"},signatures:"Eva Garcia-Lopez and Cristina Cid",authors:[{id:"113044",title:"Dr.",name:"Cristina",middleName:null,surname:"Cid",slug:"cristina-cid",fullName:"Cristina Cid"},{id:"207752",title:"Dr.",name:"Eva",middleName:null,surname:"Garcia-Lopez",slug:"eva-garcia-lopez",fullName:"Eva Garcia-Lopez"}]},{id:"56963",title:"The Amazon Glaciers",slug:"the-amazon-glaciers",totalDownloads:1203,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"In this chapter, we will examine the relationship between the Andean tropical glaciers and the Amazon rainforest, presenting a comprehensive overview on those ice masses that are the headwaters of the Amazon River and examining changes in environmental processes that may affect their mass balance and how they may feedback into the Amazon lowlands environmental processes. The first part of this chapter describes the present glaciological knowledge on these Andean ice masses that flow towards the Amazon drainage basin, about 1666 km2 (of which 68% are in Peru, 24% in Bolivia and the remaining 8% in Ecuador). The mass balance of these glaciers is strongly dependent on the Amazon hydrological cycle, as water coming from the Atlantic Ocean and recycled though the rainforest is the main source of their precipitation. A second part of the chapter explores how two environmental systems are interconnected and interacted. The third part of chapter examines the present (last 50 years) human-made changes in the Amazon basin and how they may affect the Andean ice masses. These glaciers also hold the best proxy for the Amazon Holocene changes, the record left in the snow and ice chemistry. So, as a complement to this chapter, we review the information on the paleoenvironmental changes found in ice cores in Bolivia and Peru and what they may point about the future of the Andean tropical glaciers.",book:{id:"5876",slug:"glacier-evolution-in-a-changing-world",title:"Glacier Evolution in a Changing World",fullTitle:"Glacier Evolution in a Changing World"},signatures:"Rafael da Rocha Ribeiro, Jefferson Cardia Simões and Edson\nRamirez",authors:[{id:"200720",title:"Dr.",name:"Rafael",middleName:null,surname:"Ribeiro",slug:"rafael-ribeiro",fullName:"Rafael Ribeiro"},{id:"200786",title:"Prof.",name:"Edson",middleName:null,surname:"Ramirez",slug:"edson-ramirez",fullName:"Edson Ramirez"},{id:"200787",title:"Prof.",name:"Jefferson",middleName:null,surname:"Cardia Simões",slug:"jefferson-cardia-simoes",fullName:"Jefferson Cardia Simões"}]},{id:"27591",title:"Self-Organization of the Khibiny Alkaline Massif (Kola Peninsula, 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The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"May 24th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:27,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. 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He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. 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Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:50,paginationItems:[{id:"81927",title:"Purinergic System in Immune Response",doi:"10.5772/intechopen.104485",signatures:"Yerly Magnolia Useche Salvador",slug:"purinergic-system-in-immune-response",totalDownloads:0,totalCrossrefCites:null,totalDimensionsCites:null,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"80495",title:"Iron in Cell Metabolism and Disease",doi:"10.5772/intechopen.101908",signatures:"Eeka Prabhakar",slug:"iron-in-cell-metabolism-and-disease",totalDownloads:7,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Iron Metabolism - Iron a Double‐Edged Sword",coverURL:"https://cdn.intechopen.com/books/images_new/10842.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81799",title:"Cross Talk of Purinergic and Immune Signaling: Implication in Inflammatory and Pathogenic Diseases",doi:"10.5772/intechopen.104978",signatures:"Richa Rai",slug:"cross-talk-of-purinergic-and-immune-signaling-implication-in-inflammatory-and-pathogenic-diseases",totalDownloads:10,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81764",title:"Involvement of the Purinergic System in Cell Death in Models of Retinopathies",doi:"10.5772/intechopen.103935",signatures:"Douglas Penaforte Cruz, Marinna Garcia Repossi and Lucianne Fragel Madeira",slug:"involvement-of-the-purinergic-system-in-cell-death-in-models-of-retinopathies",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}}]},overviewPagePublishedBooks:{paginationCount:27,paginationItems:[{type:"book",id:"7006",title:"Biochemistry and Health Benefits of Fatty Acids",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7006.jpg",slug:"biochemistry-and-health-benefits-of-fatty-acids",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Viduranga Waisundara",hash:"c93a00abd68b5eba67e5e719f67fd20b",volumeInSeries:1,fullTitle:"Biochemistry and Health Benefits of Fatty Acids",editors:[{id:"194281",title:"Dr.",name:"Viduranga Y.",middleName:null,surname:"Waisundara",slug:"viduranga-y.-waisundara",fullName:"Viduranga Y. Waisundara",profilePictureURL:"https://mts.intechopen.com/storage/users/194281/images/system/194281.jpg",biography:"Dr. Viduranga Waisundara obtained her Ph.D. in Food Science and Technology from the Department of Chemistry, National University of Singapore, in 2010. She was a lecturer at Temasek Polytechnic, Singapore from July 2009 to March 2013. She relocated to her motherland of Sri Lanka and spearheaded the Functional Food Product Development Project at the National Institute of Fundamental Studies from April 2013 to October 2016. She was a senior lecturer on a temporary basis at the Department of Food Technology, Faculty of Technology, Rajarata University of Sri Lanka. She is currently Deputy Principal of the Australian College of Business and Technology – Kandy Campus, Sri Lanka. She is also the Global Harmonization Initiative (GHI) Ambassador to Sri Lanka.",institutionString:"Australian College of Business & Technology",institution:null}]},{type:"book",id:"6820",title:"Keratin",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6820.jpg",slug:"keratin",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Miroslav Blumenberg",hash:"6def75cd4b6b5324a02b6dc0359896d0",volumeInSeries:2,fullTitle:"Keratin",editors:[{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}}]},{type:"book",id:"7978",title:"Vitamin A",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7978.jpg",slug:"vitamin-a",publishedDate:"May 15th 2019",editedByType:"Edited by",bookSignature:"Leila Queiroz Zepka, Veridiana Vera de Rosso and Eduardo Jacob-Lopes",hash:"dad04a658ab9e3d851d23705980a688b",volumeInSeries:3,fullTitle:"Vitamin A",editors:[{id:"261969",title:"Dr.",name:"Leila",middleName:null,surname:"Queiroz Zepka",slug:"leila-queiroz-zepka",fullName:"Leila Queiroz Zepka",profilePictureURL:"https://mts.intechopen.com/storage/users/261969/images/system/261969.png",biography:"Prof. Dr. Leila Queiroz Zepka is currently an associate professor in the Department of Food Technology and Science, Federal University of Santa Maria, Brazil. 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