Efficiency of thermotherapy treatments for virus cleaning in a group of potato accessions from the field strongly infected by different viruses.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"8852",leadTitle:null,fullTitle:"Chemistry and Applications of Benzimidazole and its Derivatives",title:"Chemistry and Applications of Benzimidazole and its Derivatives",subtitle:null,reviewType:"peer-reviewed",abstract:"Finding new strategies for synthesizing benzimidazole derivatives and functionalizing the benzimidazole core has proved to be important due to the compound's various applications in medicine, chemistry, and other areas. The multitude of benzimidazole derivatives marketed as drugs has led to intensive research in the field for the discovery of new biologically active structures. The general applications of benzimidazole derivatives in materials chemistry, electronics, technology, dyes, pigments, and agriculture open up new research horizons. This book guides the rational design of benzimidazole derivatives synthesis with certain applications. Chapters cover such topics as therapeutic use of benzimidazole in conditions like diabetes, viruses, and parasitic diseases; X-ray crystal structure of selected benzimidazole derivatives; benzimidazole compounds for cancer therapy; and others.",isbn:"978-1-78984-553-2",printIsbn:"978-1-78984-552-5",pdfIsbn:"978-1-83962-241-0",doi:"10.5772/intechopen.81426",price:119,priceEur:129,priceUsd:155,slug:"chemistry-and-applications-of-benzimidazole-and-its-derivatives",numberOfPages:228,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"e95984a2b87df5a7ca051cb3345d5e7a",bookSignature:"Maria Marinescu",publishedDate:"October 2nd 2019",coverURL:"https://cdn.intechopen.com/books/images_new/8852.jpg",numberOfDownloads:11811,numberOfWosCitations:23,numberOfCrossrefCitations:14,numberOfCrossrefCitationsByBook:6,numberOfDimensionsCitations:30,numberOfDimensionsCitationsByBook:9,hasAltmetrics:1,numberOfTotalCitations:67,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 30th 2018",dateEndSecondStepPublish:"December 12th 2018",dateEndThirdStepPublish:"February 10th 2019",dateEndFourthStepPublish:"May 1st 2019",dateEndFifthStepPublish:"June 30th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"250975",title:"Ph.D.",name:"Maria",middleName:null,surname:"Marinescu",slug:"maria-marinescu",fullName:"Maria Marinescu",profilePictureURL:"https://mts.intechopen.com/storage/users/250975/images/system/250975.jpg",biography:"Maria Marinescu received her PhD in 2010 from the University of Bucharest, under the supervision of Prof. Mihaela Hillebrand, studying the chemistry and the electronic structure of the 1,2,3,4,5,6,7,8-octahydroacridine compounds, as a key structures for the new biomolecules and hydrogen-bonding receptors. Dr Maria Marinescu is currently an Assistant Professor at the University of Bucharest, Department of Organic Chemistry, Biochemistry and Catalysis and her current research interests are in organic synthesis of various heterocycles with applications in medicinal and materials chemistry, DFT studies in organic molecules related with their biological properties and applications of organic materials in art and archaeology.",institutionString:"University of Bucharest",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"University of Bucharest",institutionURL:null,country:{name:"Romania"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"384",title:"Chemical Biology",slug:"chemical-biology"}],chapters:[{id:"67827",title:"Introductory Chapter: Short Insight in Synthesis and Applications of Benzimidazole and Its Derivatives",doi:"10.5772/intechopen.87174",slug:"introductory-chapter-short-insight-in-synthesis-and-applications-of-benzimidazole-and-its-derivative",totalDownloads:994,totalCrossrefCites:2,totalDimensionsCites:4,hasAltmetrics:0,abstract:null,signatures:"Maria Marinescu",downloadPdfUrl:"/chapter/pdf-download/67827",previewPdfUrl:"/chapter/pdf-preview/67827",authors:[{id:"250975",title:"Ph.D.",name:"Maria",surname:"Marinescu",slug:"maria-marinescu",fullName:"Maria Marinescu"}],corrections:null},{id:"67843",title:"Catalytic Intermolecular Functionalization of Benzimidazoles",doi:"10.5772/intechopen.87068",slug:"catalytic-intermolecular-functionalization-of-benzimidazoles",totalDownloads:938,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"This chapter describes contemporary strategies for selective catalytic intermolecular functionalization of the benzimidazole scaffold. Functionalization at nitrogen and position C-2 is well developed employing copper, palladium, rhodium, nickel, and cobalt catalysis. Direct CH activation is the predominant approach to C-2 functionalization. Nickel-based catalysts can activate C—O bonds in conjunction with C—H activation at benzimidazole which grants access to a very broad range of phenols and enols as convenient functionalization precursors in this chemistry. The remaining carbon positions of benzimidazoles are typically functionalized via a sequential halogenation/coupling strategy to ensure selectivity. A key success factor in enabling these chemistries has been the fine-tuning of catalyst-ligand combinations.",signatures:"Jørn H. Hansen and Richard Fjellaksel",downloadPdfUrl:"/chapter/pdf-download/67843",previewPdfUrl:"/chapter/pdf-preview/67843",authors:[{id:"286179",title:"Associate Prof.",name:"Jørn H.",surname:"Hansen",slug:"jorn-h.-hansen",fullName:"Jørn H. Hansen"},{id:"305734",title:"Dr.",name:"Richard",surname:"Fjellaksel",slug:"richard-fjellaksel",fullName:"Richard Fjellaksel"}],corrections:null},{id:"66327",title:"X-Ray Crystal Structure Analysis of Selected Benzimidazole Derivatives",doi:"10.5772/intechopen.85291",slug:"x-ray-crystal-structure-analysis-of-selected-benzimidazole-derivatives",totalDownloads:898,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This chapter describes the X-ray crystal structure analysis of selected benzimidazole derivatives, viz. BIP: 2-(1H-benzimidazol-2-yl)phenol, MBMPBI: 1-(4-methylbenzyl)-2-(4-methylphenyl)-1H-benzimidazole, DPBI: 1,2-diphenyl-1H-benzimidazole, PBIP: 2-(1-phenyl-1H-benzimidazol-2-yl)phenol, FPPBI: 2-(4-fluorophenyl)-1-phenyl-1H-benzimidazole and NPBIBHS: 2-(naphthalen-1-yl)-1-phenyl-1H-benzimidazole benzene hemisolvate. The BIP molecule is planar, and in the crystal, it is arranged in parallel planes, stabilised by π-π interactions and the hydrogen bonds. In MBMPBI, benzimidazole cores of the two independent (A and B) molecules are planar. Two C▬H…N hydrogen bonds link B molecules only, forming centrosymmetric dimers with R22(8) ring motifs. In the DPBI molecule, the benzimidazole core is planar: one hydrogen-bond interaction (C▬H…N) and C▬H…π (three) interaction leading to the three-dimensional arrangement. In the PBIP molecule, the benzimidazole is nearly planar. The hydrogen bonds and a π-π stacking interaction are present in the crystal. In the FPPBI molecule, the benzimidazole unit is almost planar. The C▬H…F hydrogen bonds and weak C▬H…π interactions lead to a three-dimensional architecture in the crystal. In NPBIBHS, the naphthalene fragment lies out of the plane about the benzimidazole core unit. The C▬H…N hydrogen bonds and C▬H…π interactions lead to a three-dimensional architecture in the crystal.",signatures:"Aravazhi Amalan Thiruvalluvar, Gopalsamy Vasuki, Jayaraman Jayabharathi and Sivaraman Rosepriya",downloadPdfUrl:"/chapter/pdf-download/66327",previewPdfUrl:"/chapter/pdf-preview/66327",authors:[{id:"222223",title:"Prof.",name:"Jayabharathi",surname:"Jayaraman",slug:"jayabharathi-jayaraman",fullName:"Jayabharathi Jayaraman"},{id:"284920",title:"Dr.",name:"Aravazhi Amalan",surname:"Thiruvalluvar",slug:"aravazhi-amalan-thiruvalluvar",fullName:"Aravazhi Amalan Thiruvalluvar"},{id:"296645",title:"Dr.",name:"Sivaraman",surname:"Rosepriya",slug:"sivaraman-rosepriya",fullName:"Sivaraman Rosepriya"},{id:"297400",title:"Dr.",name:"Gopalsamy",surname:"Vasuki",slug:"gopalsamy-vasuki",fullName:"Gopalsamy Vasuki"}],corrections:null},{id:"66798",title:"Synthesis and Pharmacological Profile of Benzimidazoles",doi:"10.5772/intechopen.85229",slug:"synthesis-and-pharmacological-profile-of-benzimidazoles",totalDownloads:1689,totalCrossrefCites:6,totalDimensionsCites:7,hasAltmetrics:0,abstract:"Benzimidazoles are a class of heterocyclic, aromatic compounds which share a fundamental structural characteristic of six-membered benzene fused to five-membered imidazole moiety. Molecules having benzimidazole motifs showed promising application in biological and clinical studies. Nowadays it is a moiety of choice which possesses many pharmacological properties extensively explored with a potent inhibitor of various enzymes involved in a wide range of therapeutic uses which are antidiabetic, anticancer, antimicrobial, antiparasitic, analgesics, antiviral, and antihistamine, as well as used in cardiovascular disease, neurology, endocrinology, ophthalmology, and more. The increased interest for benzimidazole compounds has been due to their excellent properties, like increased stability, bioavailability, and significant biological activity. This book chapter mainly discussed recent synthetic methods developed for the benzimidazole derivatives and their pharmacological properties exemplified on several derivatives.",signatures:"Kantharaju Kamanna",downloadPdfUrl:"/chapter/pdf-download/66798",previewPdfUrl:"/chapter/pdf-preview/66798",authors:[{id:"284317",title:"Prof.",name:"Kantharaju",surname:"Kamanna",slug:"kantharaju-kamanna",fullName:"Kantharaju Kamanna"}],corrections:null},{id:"65847",title:"Antidiabetogenic Features of Benzimidazoles",doi:"10.5772/intechopen.84802",slug:"antidiabetogenic-features-of-benzimidazoles",totalDownloads:1050,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Literature data on the insulinogenic effect of 2-aminobenzimidazole prompted us to investigate its novel derivatives, particularly those containing an additional fused cycle in C1,2-α position, including imidazole, dihydroimidazole, or tetrahydropyrimidine ring. Consensus analysis of the hypoglycemic effect of these compounds performed with IT Microcosm and PASS system revealed that activity is mostly characteristic for N9-2,3-dihydroimidazo[1,2-a]benzimidazole derivatives. Substructural analysis of hypoglycemic activity identified substituents that determine the greatest pharmacological effect. According to the in silico assessment of the ADME properties, RU-254 was nominated as a lead compound due to the most optimal calculated and experimental activity and pharmacokinetic parameters. Preclinical studies have shown that identified compound has a pronounced insulinogenic effect and hypoglycemic effect, both in intact animals and in animals with experimental diabetes mellitus. RU-254 also reduces the level of glycated hemoglobin upon chronic administration, slightly decreases the activity of DPP-4, and increases the average number of Langerhans islets in the pancreas. Pharmaceutical drug formulation of RU-254 was developed and investigated for pharmacokinetic, pharmacodynamic, and toxicological properties. The dosage form of the drug under the name limiglidol (compound RU-254, diabenol) was evaluated in the full cycle of clinical studies that confirmed the safety, tolerability, and prominent antidiabetic properties of the drug.",signatures:"Alexander A. Spasov, Pavel M. Vassiliev, Vera A. Anisimova and Olga N. Zhukovskaya",downloadPdfUrl:"/chapter/pdf-download/65847",previewPdfUrl:"/chapter/pdf-preview/65847",authors:[{id:"286012",title:"Prof.",name:"Pavel",surname:"Vassiliev",slug:"pavel-vassiliev",fullName:"Pavel Vassiliev"},{id:"286027",title:"Prof.",name:"Alexander",surname:"Spasov",slug:"alexander-spasov",fullName:"Alexander Spasov"},{id:"286031",title:"Prof.",name:"Olga N.",surname:"Zhukovskaya",slug:"olga-n.-zhukovskaya",fullName:"Olga N. Zhukovskaya"},{id:"286074",title:"Prof.",name:"Vera A.",surname:"Anisimova",slug:"vera-a.-anisimova",fullName:"Vera A. Anisimova"}],corrections:null},{id:"67500",title:"Development of Benzimidazole Compounds for Cancer Therapy",doi:"10.5772/intechopen.86691",slug:"development-of-benzimidazole-compounds-for-cancer-therapy",totalDownloads:1092,totalCrossrefCites:4,totalDimensionsCites:10,hasAltmetrics:0,abstract:"A fact that is largely unknown in the lay press and even the scientific community is that today cancer kills more people worldwide than tuberculosis (TB), malaria, and human immunodeficiency virus (HIV) combined. Benzimidazole is a heterocyclic aromatic organic compound considered to be a useful pharmacophore in a variety of impactful drugs. The purpose of this review is to highlight the benzimidazole-containing agents that are currently in clinical use or in clinical development as anticancer drugs. It is hoped that this review would function as comprehensive working reference of research accomplishment in the field of discovery and development of benzimidazole-based anticancer drugs.",signatures:"Puranik Purushottamachar, Senthilmurugan Ramalingam and Vincent C.O. Njar",downloadPdfUrl:"/chapter/pdf-download/67500",previewPdfUrl:"/chapter/pdf-preview/67500",authors:[{id:"287305",title:"Prof.",name:"Vincent",surname:"Njar",slug:"vincent-njar",fullName:"Vincent Njar"},{id:"299412",title:"Dr.",name:"Puranik",surname:"Purushottamachar",slug:"puranik-purushottamachar",fullName:"Puranik Purushottamachar"},{id:"299413",title:"Dr.",name:"Senthilmurugan",surname:"Ramalingam",slug:"senthilmurugan-ramalingam",fullName:"Senthilmurugan Ramalingam"}],corrections:null},{id:"67074",title:"Benzimidazoles: From Antiproliferative to Multitargeted Anticancer Agents",doi:"10.5772/intechopen.86249",slug:"benzimidazoles-from-antiproliferative-to-multitargeted-anticancer-agents",totalDownloads:1054,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Benzimidazole derivatives are known to act against a range of biological targets and thus gained clinical applications in a wide spectrum of diseases. Few examples of multitargeted benzimidazole derivatives that were reported during the last decade will be described in this chapter. Multitargeting agents for serving the polypharmacology approach to combat shortcomings of the main one-drug-one target main dogma will be briefly explored. In that context, the multitargeting benzimidazole derivatives gain a special attention. This includes discovery (hit-to-lead), structure-activity relationship (SAR), and binding mode of at least one lead (or hit) in each group. Special attention will be given to two structures dovitinib and AT9283 that are reported to exhibit potent in vitro and in vivo activities against a group of kinases and non-kinase target (as shown recently for dovitinib).",signatures:"Yousef Najajreh",downloadPdfUrl:"/chapter/pdf-download/67074",previewPdfUrl:"/chapter/pdf-preview/67074",authors:[{id:"285330",title:"Dr.",name:"Yousef",surname:"Najajreh",slug:"yousef-najajreh",fullName:"Yousef Najajreh"}],corrections:null},{id:"66268",title:"Bisbenzimidazoles: Anticancer Vacuolar (H+)-ATPase Inhibitors",doi:"10.5772/intechopen.85231",slug:"bisbenzimidazoles-anticancer-vacuolar-h-sup-sup-atpase-inhibitors",totalDownloads:1094,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Small molecule chemotherapeutic agents such as Imatinib, Gefitinib, and Erlotinib have played a significant role in the treatment of cancer. Although the unprecedented progress has been achieved in cancer treatment with these targeted agents, there is a strong demand for the development of selective and highly efficacious cancer drugs. V-ATPases are emerging as important target for the identification of novel therapeutic agents for cancer. Our screening and drug discovery processes have identified the bisbenzimidazole derivative (RP-15) as a potent anticancer V-ATPase inhibitor. In the present study, bisbenzimidazoles (compound-25, RP-11 and RP-15) have been tested for proton-pump inhibition activity in human hepatoma cell line (Huh7.5). RP-15 displayed comparable proton-pump inhibition activity to the standard Bafilomycin A1. We examined the antiproliferative activity of these analogs in two highly invasive and metastatic inflammatory breast cancer (IBC) cell lines (SUM 149PT and SUM190PT) along with Huh7.5. The compound-25 (SUM190PT: IC50 = 0.43±0.11 μM) and its structural analog RP-11 (SUM190PT: IC50 = 0.49±0.09 μM) have shown significant inhibition toward IBC cell lines. Additionally, RP-11 and RP-15 have demonstrated very good cytotoxicity toward the majority of cancer cell lines in the NCI 60 cell line panel.",signatures:"Renukadevi Patil, Olivia Powrozek, Binod Kumar, William Seibel, Kenneth Beaman, Gulam Waris, Neelam Sharma-Walia and Shivaputra Patil",downloadPdfUrl:"/chapter/pdf-download/66268",previewPdfUrl:"/chapter/pdf-preview/66268",authors:[{id:"237361",title:"Dr.",name:"Gulam",surname:"Waris",slug:"gulam-waris",fullName:"Gulam Waris"},{id:"243940",title:"Dr.",name:"Binod",surname:"Kumar",slug:"binod-kumar",fullName:"Binod Kumar"},{id:"289504",title:"Dr.",name:"Shivaputra",surname:"Patil",slug:"shivaputra-patil",fullName:"Shivaputra Patil"},{id:"289506",title:"Dr.",name:"Renukadevi",surname:"Patil",slug:"renukadevi-patil",fullName:"Renukadevi Patil"},{id:"289690",title:"Dr.",name:"Olivia",surname:"Powrozek",slug:"olivia-powrozek",fullName:"Olivia Powrozek"},{id:"289691",title:"Dr.",name:"William",surname:"Seibel",slug:"william-seibel",fullName:"William Seibel"},{id:"289692",title:"Dr.",name:"Kenneth",surname:"Beaman",slug:"kenneth-beaman",fullName:"Kenneth Beaman"},{id:"289693",title:"Dr.",name:"Neelam",surname:"Sharma-Walia",slug:"neelam-sharma-walia",fullName:"Neelam Sharma-Walia"}],corrections:null},{id:"66526",title:"Optical Sensing (Nano)Materials Based on Benzimidazole Derivatives",doi:"10.5772/intechopen.85643",slug:"optical-sensing-nano-materials-based-on-benzimidazole-derivatives",totalDownloads:1224,totalCrossrefCites:1,totalDimensionsCites:5,hasAltmetrics:0,abstract:"Benzimidazole derivatives are well-known biologically active substances, and therefore, they are mostly synthesised for therapeutic purposes. However, such heteroaromatic molecular systems own structure-related properties that enable a variety of applications, especially in optical science. Multifunctionality of the benzimidazole unit, such as electron accepting ability, π-bridging, chromogenic pH sensitivity/switching and metal-ion chelating properties, makes it an exceptional structural candidate for the design of optical chemical sensors and functional materials. Development of smart molecular sensors and novel (nano)materials is the emerging trend observed in materials and optical sensing science in general, in which the benzimidazole molecular systems strongly contribute and participate. In this chapter, we summarised recent advances in optical sensing (nano)materials that incorporate the benzimidazole structural moiety. Solid-state optical sensing systems, including self-assembled molecular materials based on benzimidazoles, are reviewed and discussed. In addition, immobilisation of benzimidazole derivatives onto or into various substrates and matrices, such as organic and inorganic polymers, bulk membranes and nanoparticles, utilising different chemical and physical methods, is presented and analysed.",signatures:"Ema Horak, Robert Vianello and Ivana Murković Steinberg",downloadPdfUrl:"/chapter/pdf-download/66526",previewPdfUrl:"/chapter/pdf-preview/66526",authors:[{id:"288132",title:"Ph.D.",name:"Ema",surname:"Horak",slug:"ema-horak",fullName:"Ema Horak"},{id:"295983",title:"Dr.",name:"Robert",surname:"Vianello",slug:"robert-vianello",fullName:"Robert Vianello"},{id:"295984",title:"Dr.",name:"Ivana",surname:"Murković Steinberg",slug:"ivana-murkovic-steinberg",fullName:"Ivana Murković Steinberg"}],corrections:null},{id:"66558",title:"Benzimidazole as Solid Electrolyte Material for Fuel Cells",doi:"10.5772/intechopen.85430",slug:"benzimidazole-as-solid-electrolyte-material-for-fuel-cells",totalDownloads:964,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This chapter is focused in the application of benzimidazole, mainly in the form of poly[2,2′-(m-phenylene)-5,5′-bisbenzimidazole] (PBI) and poly(2,5-benzimidazole) (ABPBI), in the fuel cell technology. A short introduction is given of the fuel cell principles, explaining both the theory and the high importance of this technology. PBI and ABPBI are used in a certain type of fuel cells: the polymer electrolyte fuel cells and are key materials in the composition of some of the electrolyte membranes used. Commercially available membranes composed of PBI are indicated in order to give an overview of their potential performance. The synthesis of the polymers is explained. Moreover, the preparation of the different kinds of membranes, both in proton exchange membrane fuel cells (PEMFCs) and anion exchange membrane fuel cells (AEMFCs) is studied. A deep description is given about the properties that make this family of compounds so interesting for the fuel cell technology as well as an how these polymers have been characterized with the corresponding analysis. The comparison with other ion exchange membranes is also discussed. Special attention will be given to the state of the art of different kinds of PBI/ABPBI fuel cell electrolyte membranes, in which our group and others are working nowadays.",signatures:"Daniel Herranz and Pilar Ocón",downloadPdfUrl:"/chapter/pdf-download/66558",previewPdfUrl:"/chapter/pdf-preview/66558",authors:[{id:"289174",title:"Prof.",name:"Pilar",surname:"Ocon",slug:"pilar-ocon",fullName:"Pilar Ocon"},{id:"289175",title:"MSc.",name:"Daniel",surname:"Herranz",slug:"daniel-herranz",fullName:"Daniel Herranz"}],corrections:null},{id:"66205",title:"Supramolecular Assembly of Benzimidazole Derivatives and Applications",doi:"10.5772/intechopen.85333",slug:"supramolecular-assembly-of-benzimidazole-derivatives-and-applications",totalDownloads:814,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Herein, we focus on the chemical and physical properties of benzimidazole and its derivatives used for the synthesis of supramolecular materials. The design and modification of benzimidazole opens the scope of the diversity of structures (different sizes and morphologies) that can be built. The synthesized materials include not only small coordination complexes but also isolated crystals, metal-organic frameworks, metal-coordination polymers, smart nanocontainers, and more advanced macrostructures such as microflowers and nanowires. These supramolecular structures are based on noncovalent interactions, mostly on metal coordination chemistry and π-π stacking interactions. Moreover, the same molecule, due to its chemical structure, can undergo both sorts of interactions in order to induce the self-assembly into supramolecular materials. In this process, as it is shown in this chapter, the conditions used for the assembly determine the final structure and morphology of the fabricated macromolecule. Finally, we show most recent applications of these materials in the field of sensing, photoluminescence, fuel cell, and fabrication of new nanostructures.",signatures:"Ana Beloqui",downloadPdfUrl:"/chapter/pdf-download/66205",previewPdfUrl:"/chapter/pdf-preview/66205",authors:[{id:"289147",title:"Dr.",name:"Ana",surname:"Beloqui",slug:"ana-beloqui",fullName:"Ana Beloqui"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"2553",title:"Lipid Peroxidation",subtitle:null,isOpenForSubmission:!1,hash:"b39734aa940b2d63ae5e8773d3dd5280",slug:"lipid-peroxidation",bookSignature:"Angel Catala",coverURL:"https://cdn.intechopen.com/books/images_new/2553.jpg",editedByType:"Edited by",editors:[{id:"196544",title:"Prof.",name:"Angel",surname:"Catala",slug:"angel-catala",fullName:"Angel Catala"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2323",title:"Carbohydrates",subtitle:"Comprehensive Studies on Glycobiology and Glycotechnology",isOpenForSubmission:!1,hash:"f7c2e6a3566eee14c9884ad0820a6416",slug:"carbohydrates-comprehensive-studies-on-glycobiology-and-glycotechnology",bookSignature:"Chuan-Fa Chang",coverURL:"https://cdn.intechopen.com/books/images_new/2323.jpg",editedByType:"Edited by",editors:[{id:"145728",title:"Prof.",name:"Chuan-Fa",surname:"Chang",slug:"chuan-fa-chang",fullName:"Chuan-Fa Chang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"372",title:"Aflatoxins",subtitle:"Biochemistry and Molecular Biology",isOpenForSubmission:!1,hash:"b7f7359995dc5ee04e12df282495f77e",slug:"aflatoxins-biochemistry-and-molecular-biology",bookSignature:"Ramón Gerardo Guevara-González",coverURL:"https://cdn.intechopen.com/books/images_new/372.jpg",editedByType:"Edited by",editors:[{id:"62559",title:"Dr.",name:"Ramon G.",surname:"Guevara-Gonzalez",slug:"ramon-g.-guevara-gonzalez",fullName:"Ramon G. 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Potato varieties must fulfill the requirements of the market and consumer preferences, as well as to show good agronomic performance in several environments and wide adaptation to productive systems. Traits as high yield, tuber conformation, early maturity, and resistance to biotic and abiotic stresses are the most important goals for potato breeding in Chile.
The breeding of potatoes needs to deal with some complicated issues that make potato breeding a special case in genetic improvement of crops:
Most of the cultivated potatoes are tetraploid and show tetrasomic inheritance.
Tetraploidy, together with severe inbreeding depression upon repeated selfing, renders the generation of pure lines, recombinant inbred lines (RILs), or near-isogenic lines (NILs) impractical.
Tetraploid potato genotypes are therefore highly heterozygous. The heterozygous genotypes are fixed and maintained by vegetative propagation via tubers.
Current breeding of marketable varieties comprises the generation of genetic variation by crossing elite tetraploid parents, usually varieties and advanced breeding clones.
Evaluation and selection of approximately 13 main characters of plant and tuber in the recombinant F1 generation via multiyear and location trials. The selection cycle from crossing to variety release requires approximately 10–12 years.
As potato is clonally propagated, diseases are accumulated and transmitted to descendant tubers; therefore, a system for cleaning and maintaining virus-free stocks of seed is essential.
These issues make potato breeding to concentrate a large effort in developing a system of controlled crosses that generate seeds from several families producing a large F1 population that will be the source of new breeding lines with potential to become varieties. Additionally, during the process, a big expense of resources is destined to rouging and maintaining of clean seed stocks of seeds.
Under optimized agricultural practices, potato production can yield more than 40 tons per hectare within 4 months from planting to harvest. To achieve this yield, it is essential to have high-quality seeds and improved cultivars as well as good agronomic practices and pest and disease control. With low technology, average yields are much lower ranging from 5 to 20 tons per hectare.
It is expected that through applications of biotechnology such as tissue and cell culture, genetic engineering, marker-assisted technologies, genome-assisted technologies, or a combination of all the technologies for the improvement, potato has the potential to provide an increased proportion of the food intake required for the anticipated population expansion over the coming decades. Access to these biotechnological techniques is of vital importance for developing countries. However, the highly heterozygous genotypes produce a strong segregation in the progeny from controlled crosses; therefore to obtain a precise combination of characters or the improvement of some specific traits without losing other relevant genetic controlled traits is a difficult task. Genetic engineering could be the key to reach some specific gain in a particular trait preserving good genetic background to address better development of varieties. Nevertheless, GMOs are questioned for public opinion and even forbidden in numerous countries, as the case of Chile. In this way, the role of biotechnology is an assistant for the processes of classical breeding to make them more effective and to know in a better way the plant material at the genetic level.
So how is the experience of potato breeding program in Chile by using biotechnology to assist the development of Chilean varieties, specially adapted to local environments and productive systems?
Presently, 11 varieties have been released and inscribed in official system of seed certification. With the 11 varieties, it is possible to obtain 40 tons per hectare of yield in dryland conditions and 80 tons with irrigation, a good yield for Chilean conditions.
The mission of the potato breeding program in Chile is to develop potato varieties for different uses and productive systems to meet the Chilean market demand, with international projection.
The INIA uses a breeding scheme that is similar to classical potato breeding programs [3, 4, 5] with modifications according to local requirements. The potato breeding program begins with the selection of a large number of genotypes to be used as crossing parents. In the early steps of selection, around 100 crosses are made and 30,000 genotypes are evaluated. Selection of F1 progeny at early breeding stages (i.e., the primary individual selection of seedlings and the secondary individual clonal selection) is based on characteristics with high heritability and little annual variation, such as skin color, flesh color, and tuber shape, according to Chilean consumer preferences. The elimination of progeny with severe defects that can devastate potato production (e.g., hollow heart, growth cracks, and brown spots) also occurs at these stages. Progeny that is extremely susceptible to diseases as PVY, PVX, common scab, and late blight is discarded based on visual inspections of the field, although molecular markers are also available for genotype analysis. In later stages (i.e., line selection and the performance yield test), selection is carried out based on quantitative characteristics, such as yield, maturity, cooking qualities, and aptitude for chips or French fries. Molecular markers are applied in all the advanced breeding lines in order to confirm combinations of several resistance genes for diseases. A fixation process is unnecessary as they are clonally propagated.
The main objectives of the program are:
Good performance for different end uses (fresh market and processing) for national or international demand
Conformation and appearance of tuber
Good agronomic characteristics: high yield and wide adaptation to agro-climatic zones
Industrial uses
Specific objectives:
Late blight resistance
Golden nematode resistance
PVY resistance
To achieve these objectives, the activities of the program involve controlled crosses every year (around 100), with 30,000 novel genotypes that are evaluated in multiyear and locations in field conditions.
Figure 1 shows an organization chart about the role of biotechnology in the potato breeding program in Chile. In first place, the germplasm bank is the source of genetic diversity for controlled crosses. This in vitro gene banks hold the varieties developed, advanced breeding lines, and imported breeding material that can be used of donor of some characters and native landraces. With this system, the material is preserved free from pathogens and suitable to be transferred to foreign countries in case of any need of varieties and breeding lines.
Organization chart about the role of biotechnology in the Chilean potato breeding program.
Techniques to introduce the material to in vitro conditions and thermotherapy to obtain pathogen-free in vitro plants are applied. Thermotherapy in combination with previous chemotherapy can be employed successfully, but efficiency is variable depending on virus types to remove. Results of DAS ELISA test before and after thermotherapy of a group of potato accessions from the field strongly infected by different viruses are shown in Table 1, indicating that in the case of PVY, 51% of the materials could be cleaned after two rounds of thermotherapy.
Situation prior to thermotherapy treatment | Number or % | Situation after in vitro thermotherapy treatments | Number or % | Efficiency of thermotherapy (INI-FIN)/FIN × 100 |
---|---|---|---|---|
Number of accessions subjected to in vitro thermotherapy | 157 | Number of accessions cleaned after two rounds of thermotherapy | 66 | 42% |
Number of accessions infected with at least one virus | 157 | Number of accessions infected with at least one virus | 91 | |
% incidence of PVX | 26 | % incidence of PVX | 3.2 | 88% |
% incidence of PVY | 69 | % incidence of PVY | 33 | 51% |
% incidence of PVS | 78 | % incidence of PVS | 7 | 91% |
% incidence of PLRV | 86 | % incidence of PLRV | 21.7 | 75% |
% incidence of PVA | 8.9 | % incidence of PVA | 0.6 | 93% |
% incidence of PVM | 1.2 | % incidence of PVM | 0 | 100% |
Average number of viruses present per infected accession | 2.6 | Average number of viruses present per infected accession | 0.63 |
Efficiency of thermotherapy treatments for virus cleaning in a group of potato accessions from the field strongly infected by different viruses.
The materials stored in germplasm bank are analyzed by SSR markers to characterize them by molecular fingerprint. Currently, eight SSR markers are used. These markers are employed as a routine test for varietal identification since all the varieties are released with a described molecular profile that allows tracking of the varieties in the markets after available to farmers and to solve problems as mixture of varieties. These markers have been used in an overview of the genetic diversity and genotype numbers in germplasm bank of Chilean collection, including native potatoes, commercial varieties, and valuable breeding lines. It is important to notice that SSR markers must be polymorphic enough to distinguish between the different varieties that it is necessary to discriminate. In the case of using molecular markers in the process of plant propagation of potato, as a tool to assure the identity of the commercial varieties that are being propagated in vitro, it is convenient to determine the set of markers that allow to produce different allele phenotypes (band patterns) for all the commercial varieties that are multiplied by the seed program, in order to differentiate them. In the case of wild material collected and kept in germplasm bank, or breeding lines with unknown pedigree, the SSR markers could discriminate different allele phenotypes, but it depends on the numbers of markers and polymorphism detected. Always it is possible that different genotypes could not be differentiated because no polymorphism in the regions of the genomes are being analyzed, but once a different band pattern is found between some plant materials, it is proven that they are different genotypes. This is very useful when studying collections of material with similar morphological features or when not all the descriptors are available to be examined (collections of tubers, in vitro plants or others where no flowers or leaves are available, or material affected by virus that affects the phenotype). In the case of Chilean collection of native potatoes, we have found 320 different allelic phenotypes using four SSR markers, indicating that there are at least 320 different genotypes in the collections. Of these, 158 belonging to the INIA collection were not found in another collection belonging to other Chilean institutions. As expected, different genotypes were known under the same popular name by the farmers. The molecular information is useful to know the genetic structure of the material preserved or used for breeding. For more details of our results, please see [6].
There is a flow of material from the gene bank to the annual scheme of controlled crosses and selection in the plant breeding program. Some genotypes are selected in order to combine characteristics in the progeny through controlled crosses and grown to obtain flowers and used as donor of valuable traits. On the other hand, promissory breeding lines from the field are introduced to in vitro culture and kept in the bank.
During the phases of selecting/discarding clones in field plots, molecular markers are implemented. Molecular markers associated with one or few genes that have a large and heritable effect in important traits are used (e.g., disease resistance in gene per gene model). Molecular markers for golden nematode resistance, virus resistance, late blight resistance, and some markers for flesh color are involved in the battery of markers to assist the selection and verify the combination of several resistance genes (Table 2). We investigate the allele dosage in some parents by means of study segregation of the marker in an F1 population in order to know the frequency of progeny that can hold the desired character and recognize most efficient parents for controlling crosses.
Gene | Marker | Resistance to | Reference | |
---|---|---|---|---|
57R | [7] Finkers-Tomczak et al. | |||
TG689 | De Jong, W. Cornell University, (unpublished); [8] Galek et al. | |||
Gro1–4 | [9] Paal et al. | |||
U14 | [10] Jacobs et al. | |||
Ry3.3.3S/RyADG23R | PVY | [11] Kasai et al. | ||
AC15 | PVX | [12] Bendahmane et al. | ||
Ask | [13] Bendahmane et al. | |||
R1 | [14] Ballvora et al. | |||
R2 | [15] Kim et al. | |||
R3a | [16] Huang et al. | |||
R3b | [17] Rietman | |||
N° | 10 | 11 |
Molecular markers used for routine assays to select breeding lines with resistance genes to potato diseases.
Once the new variety is ready to enter to the market, it is necessary to produce the stock of seed to support the entrance in the seed certification system.
Then, in the early stages of seed production in certification system, all the mother plant materials for the new varieties are checked by molecular fingerprint, PCR, and ELISA test for pathogen diagnosis, to assure the identity and pathogen-free status of the starting seed material and then micropropagated before entering to the certification system in the field. PVY and
Test | Marker | Gene target | Reference |
---|---|---|---|
Y1/Y2 | [18] Darrasse et al., modification of protocol | ||
PVYF/PVYR | Capsid protein, strain: N | [19] Du et al., modification of protocol |
Procedures used for molecular diagnosis for
In this stage, tissue culture for massive micropropagation of new varieties is still a pivotal biotechnological technique:
Today, in the official certification system, all the varieties are propagated via in vitro culture before being multiplied in the field.
Introduction of new varieties to in vitro condition is essential to produce certificated seed and makes possible that the varieties be distributed in the market.
Currently our program keeps in vitro the 11 INIA varieties, 134 advanced breeding lines from INIA program, and 32 foreign varieties and breeding lines with research purposes.
Molecular fingerprints have been done to characterize 61 varieties, 25 advanced breeding lines, and 823 native landraces. We use the CIP identity kit for molecular profiling of the most valuable material for reliable identification and traceability during breeding process and seed production and in the future to track the presence in the market.
We use 11 molecular markers for marker-assisted selection, and at the date, we have analyzed 461 breeding lines and 33 varieties. The most important advantage of applying these markers is to allow more precision to choose parents for crossing in order to combine or pyramiding genes.
In Table 4, we can see the markers associated with resistance genes and light yellow flesh color present in the released varieties. It is possible to see that many varieties hold markers associated to golden nematode resistance, a quarantine pest in Chile but present in some areas with potato cultivation in northern part of the country. For this pest, it is not possible to conduct field trials in south of Chile, so molecular marker implementation is crucial to track resistance in the progeny from controlled crosses with appropriate donor parents able to produce offspring with different resistance genes.
Variety | Golden nematode resistance | PVX resistance | Late blight resistance | PVY resistance | Light yellow flesh/white flesh |
---|---|---|---|---|---|
Karú-INIA | |||||
Patagonia-INIA | |||||
Pukará-INIA | |||||
Puyehue-INIA | |||||
Yagana-INIA | |||||
Fueguina-INIA | |||||
Ona-INIA | |||||
Pehuenche-INIA | |||||
Purén-INIA | |||||
Kuyén-INIA | — | ||||
Rayún-INIA | |||||
R87009–28 |
Molecular markers associated with resistance genes and light yellow flesh color present in the released varieties.
The program has implemented six biotechnological techniques; these are applied in the stages of characterization of the gene bank, selection of parents, marker-assisted selection, characterization of varieties, and propagation of material for seed production. One hundred percent of the varieties have been released involving biotechnology, especially by the use of in vitro culture techniques to produce pathogen-free material for initial stages of seed production of advanced lines. Biotechnological techniques have participated in the improvement of 2 of the 13 main characteristics associated with the program objectives. Two of the 11 varieties were characterized by molecular fingerprint at the time of their release. Biotechnological techniques such as in vitro culture, molecular fingerprint, and molecular diagnosis of diseases are used to produce primary multiplication of reproductive material for 100% of the varieties released by INIA currently present on the market.
Some important facts about the use of biotechnology in breeding and development of varieties are:
Tissue culture is essential in the maintenance of varieties with the same genotype and initial steps of seed production system.
Molecular fingerprint is important for varietal identification: vital in traceability of stock plants during micropropagation, and it has possibilities to be used to track the presence of varieties in the market.
Molecular markers associated with one or few genes that have a large and heritable effect in important traits are used (e.g., disease resistance in gene per gene model).
Molecular markers allow to have more precision to choose parents for crossing in order to combine or pyramiding genes.
Markers for multigenic traits such as stress tolerance or cold tolerance have not been developed yet and remain as a big challenge to develop molecular genetic tools for multigenic traits.
In potato breeding, the selection of desirable phenotypes from a large breeding population will remain essential.
Automatic, low-cost, and high-throughput phenomic technologies would be a valuable tool for massive screening of phenotypes.
Screening methods based on next-generation sequencing technologies promise to revolutionize screening for desired genotypes, but it is necessary to solve the problem of distinguish between three different heterozygous genotypes (AAAB, AABB, and ABBB) in traits where plex number affects the character under selection.
In order to make more precise the addressing of breeding procedures to improve specific traits (i.e., compounds with nutritional value or to eliminate undesired characters), methods as the new biotechnological techniques (NBTs) could be promising in countries where GMOs are not allowed. These new technologies as CRIPSR/Cas can be used to develop a genetic engineering with no transgenic status of the final product.
Biotechnology can be easily combined with classical breeding methods with the objective to pyramiding resistance genes (R genes) to avoid the breakdown of resistance in the case of fast evolving pathogens. We will describe below our experience in developing a strategy to pyramiding R genes for late blight resistance in breeding lines.
For this purpose, we are using the Ma
The potato late blight caused by
However, only three of the 25 potato varieties used in Chile have some intermediate level of resistance to late blight. Notably, while
Eleven R gene differentials containing R genes introgressed into
Significantly, the resistance provided by the R genes is background dependent as genes that suppress R genes can also be segregated into F1 offspring plants [26]. Thus, more knowledge is needed about how R genes perform in different genetic backgrounds. Research has also focused on creating GM organisms carrying constructions with the described R genes [27]. However, this class of plant material is not allowed in many parts of the world for human or animal consumption including Europe and Chile. Furthermore, society is suspicious about its sustainable utilization because of the health, environmental, and social implications of GMOs. For this reason, it is necessary to investigate the applications of the natural stacking of several R genes to overcome
The objectives of our work are:
To combine multiple R genes that confer resistance to late blight in new lines of the potato breeding program of INIA Remehue, Chile
To evaluate the level of resistance to
Controlled crosses were performed between five commercial varieties and the genotypes Ma
Ten progenies from each cross were randomly selected for molecular analysis and phenotypic evaluations in order to assay for the presence of R genes. The performance of these genotypes was monitored under pathogenic pressure in field conditions.
During the 2013–2014 season, 90 randomly selected progenies were evaluated for pathogen resistance. We calculated the area under disease progress curve (AUDPC) in individual plants under natural infections in the field. To promote infections, the progeny was watered by a spray system twice a week although the natural inoculum was high in Osorno, Chile.
For the molecular analysis, DNA extractions and PCR amplification were performed using genetic markers as described in Table 2 for
Progeny was also phenotypically evaluated. We determined the percentage of leaves affected by late blight during plant development by visually estimating the green and non-green portions of the leaves. The estimations were integrated into the AUDPC or area under the disease progress curve. AUDPC is obtained by the repeated visual inspections and estimation of the percentage of the leaf affected in a set of plants. The value is calculated by the formula used by Jo et al. [28]. Percentages of damaged foliage are plotted through a period of time. AUDPC was calculated for the 10 randomly selected individuals from each cross in the field.
For the following 2014–2015 season, the tubers of 71 genotypes that were not damaged by late blight were harvested. The experiment was designed with three replicates in randomized blocks. We planted three plants of each genotype that hold R genes in front of three plants of the susceptible Atlantic cultivar (susceptible control) per each replicate.
Rows of the susceptible Atlantic cultivar were also planted in the border and interspersed in the complete area of the assay. AUDPC values were calculated for all genotypes and susceptible control plots. A pairwise comparison was performed between each genotype and the respective control plot. We calculated the AUDPC from the visual estimation of the percentage of infected foliage.
In the 2013–2014 season, an evaluation of randomly selected individual plants from the progeny of Ma
In the second season, we utilized undamaged plants from the first season. Most of the plants carrying R genes again had lower AUDPC values than the control plots. Interestingly, plants carrying the
In conclusion, we found that plants carrying R genes were only slightly affected by late blight in conditions of high pathogenic pressure, with the exception of the
Number of genotypes tested | % genotypes significantly different to susceptible | |
---|---|---|
Genotypes carrying 1 R genes | 5 | 60 |
Genotypes carrying 2 R genes | 21 | 71 |
Genotypes carrying 3 R genes | 18 | 94 |
Genotypes carrying 4 R genes | 13 | 92 |
Any genotype carrying R1 | 27 | 96 |
Any genotype carrying R2 | 17 | 88 |
Genotypes carrying only R3a or R3b | 20 | 55 |
Genotypes harboring different numbers of R genes and % showing an AUDPC value significantly lower than the susceptible control plots.
The Ma
A major challenge remains to develop an efficient and reliable system of phenotyping for late blight damage and for large-scale screening of breeding lines.
Financial support: Subsecretary of the Chilean Ministry of Agriculture through Potato Breeding Program project and Conservation of Genetic Resources program (501453-70). CORFO (Corporación de Fomento a la Producción) through INNOVA-Public Goods 14BPC4-28525.
Considered the second most commonly performed operation after cesarean section worldwide, hysterectomy may be classified as abdominal (laparotomy, laparoscopy, or robotic assistance) and vaginal (via an incision through the superior part of the vagina).
The most common indications for hysterectomy are benign conditions such as uterine fibroids, endometriosis, genital prolapse, pelvic pain, heavy menstrual bleeding, but the technique is also used for gynecological malignancy (usually ovarian, uterine, or cervical) and risk-reducing surgery (in cases of BRCA 1 or 2 mutations or Lynch syndrome) [1, 2, 3, 4].
Actually, there are three types of hysterectomy—total hysterectomy (the uterus and cervix are removed), subtotal or partial hysterectomy (the uterus is removed, but the cervix is left in place), and total hysterectomy with bilateral salpingo-oophorectomy (uterus, fallopian tubes, ovaries, and cervix are removed) [1, 2, 3, 4]. The term radical hysterectomy (removal of the uterus, cervix, parametrium, vaginal cuff, and fallopian tubes) is used to describe a wide range of procedures universally applicable to cervical cancer. However, the degree of radicality clearly depends on preoperative estimation of tumor location, surgical margins and the risk of occult lymphatic spread. Moreover, the ovaries may or may not be removed according to the patient age [1, 2, 3, 4]. In addition, supracervical hysterectomy is sometimes preferred to diminish the intraoperative complications and surgical times, as well as to limit the possibility of lower urinary tract issues and maintain normal sexual function [1, 2, 3, 4].
The best route for hysterectomy is multifactorial, depending not only on the surgeon’s skills and patient safety (minimally invasive procedures as vaginal, laparoscopic, laparoscopic-assisted, and robotic-assisted hysterectomies) but also on economic reasons [1, 2, 3, 4].
Hemorrhage after hysterectomy is recognized as an occasional life-threatening complication in modern gynecological surgery, assuming appropriate medical and surgical management [2, 3, 4, 5, 6, 7, 8, 9].
Classified as “reactionary” (postoperative bleeding within the first 24 hours following surgery) and secondary (bleeding occurring in the interval 3–22 days after surgery), unexpected hemorrhage may arise regardless of the route or subtype of hysterectomy [5, 6, 9]. Early recognition and prompt intervention (reoperation or arterial embolization) to arrest bleeding are essential strategies for the suitable outcome of the patient [2, 3, 4, 5, 6, 7, 8, 9, 10].
While the role of risk factors for “reactionary” hemorrhage is emerging and critical for a correct assessment of the patient, operative laparoscopy is still ideal to treat hemorrhage after vaginal hysterectomy, laparoscopic hysterectomy, laparoscopic-assisted vaginal hysterectomy, and laparotomy being necessary only in selected cases [2, 3, 4, 6, 9].
Secondary hemorrhage presents with varying degrees of severity and tends to be more common after laparoscopic hysterectomy, especially total laparoscopic hysterectomy than after the other hysterectomy approaches [5, 9]. Factors potentially responsible are vaginal vault infection, vault hematoma, a poor surgical technique including excessive thermal injury by electrocoagulation, and early resumption of physical activity, large uterus size, excessive use of an energy source for the uterine artery, and culdotomy [2, 3, 4, 5, 7, 9, 10].
Ultimately, the management of secondary hemorrhage is challenging and involves diverse approaches based on the exact cause of bleeding, comprising vaginal packing with or without vault suturing, laparoscopic coagulation of the uterine artery if the source of bleeding could not be identified vaginally or arterial embolization [6, 9, 10].
Because of elective gynecologic surgery, we encourage selective patients to donate their own blood before surgery [6, 11]. Several definitions are actually used:
autologous blood transfusion, when is done with the patient’s own blood; blood is stored and can be transfused during surgery;
homologous transfusion or transfusion from another woman;
parachute pack or umbrella pack is a useful tool for pelvic bleeding after pelvic exenteration;
peanut dissector; this tool is indicated for blunt pressure dissection of small places;
total blood volume; estimated blood volume of total body weight is 8% or 4.5–5.0 liters in the average women. When intraoperative blood loss exceeds 15% of the blood volume, blood transfusion must be taken into consideration in combating hypovolemic shock. About 15% of an adult blood volume can be calculated by amplification a patient’s weight in kg 10 times. The usual method of performing abdominal hysterectomy involved the use of clamps or forceps on vessels.
The present chapter will give an overview on different aspects of bleeding after hysterectomy such as incidence rate, risk factors, mechanisms, and management techniques aiming to expand our knowledge and skills in recognizing and treating this unexpected potentially serious complication. Furthermore, we intend to offer a guide toward standardizing treatment practice across bleeding issues following hysterectomy considering clear recommendations and algorithms.
Postoperative hemorrhage represents a significant potential complication of contemporary gynecological surgery. Despite normal hemostasis, appropriate/suitable surgical technique and close monitoring, postoperative bleeding may occur, leading to the different clinical and operative scenarios and challenging even the most experienced operative team [2, 3, 4, 9, 11, 12].
Based on their timing to surgery, two main subtypes of postoperative hemorrhage are actually recognized [5, 6, 7, 8, 9]:
Although the incidence of postoperative hemorrhage basically varies according to surgery, the difference between abdominal, laparoscopic, and vaginal hysterectomy remains statistically insignificant [5, 6, 7]. Indeed, some authors postulate that postoperative bleeding occurs more frequently after abdominal and laparoscopic than after vaginal hysterectomy, but overall, the incidence of hemorrhagic events after a hysterectomy varies from 0.2 to 3.1%, irrespective of surgical route [5, 6, 7, 8, 10, 13, 14].
On the other hand, the true frequency of delayed bleeding complications is still unknown, although the consequences can be particularly significant in women undergoing outpatient surgery [5, 6, 7, 8, 10, 13, 14]. Paul et al. reported an overall cumulative incidence of secondary hemorrhage after a total laparoscopic hysterectomy of 1.3% [5]. Although secondary hemorrhage is rare, it is more often reported after total laparoscopic hysterectomy than after other hysterectomy approaches [5, 6, 7, 8, 10, 13, 14].
Table 1 summarizes data on the incidence of postoperative hemorrhage reported by several authors.
Authors | Type of study, no of cases | Incidence postoperative hemorrhage |
---|---|---|
Makinen et al. [15] |
|
|
Wilke et al. [13] |
|
|
Holub and Jabor [7] |
|
|
Erian et al. [6] | 719 patients between November 1990 and March 2007: 476 VH, 243 LH |
|
Paul et al. [5] |
|
|
Incidence of postoperative hemorrhage in gynecological surgery.*
AH, abdominal hysterectomy; LH, laparoscopic hysterectomy; VH, vaginal hysterectomy; L-AVH, laparoscopic-assisted vaginal hysterectomy.
Hemorrhage is responsible for about half of the postoperative complications following gynecological surgery, ranging from persistent venous oozing to massive blood loss from injury to retroperitoneal vessels [5, 6, 7, 12, 13].
Main bleeding sites comprise the anterior abdominal wall (both the suprapubic and the umbilical incision), the vaginal cuff (after laparoscopic hysterectomy and laparoscopic-assisted vaginal hysterectomy), and intraabdominal bleeding. Abdominal wall vessel injury occurs with increasing frequency, as the practice of laparoscopic surgery becomes wider and trocars become sharper [2, 3, 4, 7, 9].
The source of bleeding in secondary hemorrhage can be the uterine vessels or descending cervical/vaginal vessels; occasionally, uterine artery pseudoaneurysm can cause delayed heavy vaginal bleeding after laparoscopic hysterectomy [2, 3, 4, 7, 9]; additionally, the technique of vaginal vault closure may also contribute to the occurrence of secondary hemorrhage [5, 9].
Postoperative hemorrhage can result from failure to control vascular injury during surgery. Accurate clamp placement, gentle handling of tissues, and the accuracy of dissection are all important and contribute to maximum efficiency with minimum blood loss and minimum tissue damage when abdominal hysterectomy is performed [9].
The electrosurgical instrument can be used for a precise incision of the abdominal wall with minimal tissue injury. By holding the electrode close to the tissue or touching the metal clamp and pressing the coagulation button, superficial coagulation can be achieved [2, 3, 4, 9].
Intra- and post-operative bleeding generally develops in younger women or those with a more vascular pelvis who underwent a hysterectomy, especially laparoscopic hysterectomy in the presence of fibroids [6, 16].
Possible rationales for secondary hemorrhage comprise a bleeding vessel missed at the end of the procedure, effects of pneumoperitoneum, Trendelenburg position, low intraoperative pressure, wearing off the effect of vasopressin, subacute infection, postoperative analgesia, as well as bleeding disorders [2, 3, 4, 5, 7, 9].
Other potential factors accounting for delayed postsurgical bleeding are vaginal vault infection, vault hematoma, poor surgical technique with excessive thermal injury by electrocoagulation, and early resumption of physical activity [5, 7, 9]. A large-sized uterus, high vascularity, large-sized vessels, excessive use of an energy source for the uterine artery, and culdotomy also play a role in this hemorrhagic event [5, 7, 9].
Most of the complications during or after hysterectomy are preventable or treatable. Other complications may exist as medical conditions before hysterectomy but are worsened during surgery, especially if not managed as part of holistic woman’s care.
Complications after surgery include [2, 3, 4, 9, 12]:
In Romania, the mortality rate following a hysterectomy is very low.
Contemporary management of surgical interventions includes postoperative bleeding and the possibility of blood transfusion with risks of HIV transmission (in 1.9 million cases), the transmission of hepatitis B (one in every 180.000 cases), or a febrile reaction to transfusion (1% cases) [2]. Most experts recommend acute normovolemic hemodilution and cell salvage in women undergoing hysterectomy section who will not accept blood products.
Hypovolemic shock can occur after major bleeding as a direct result of uncontrolled hemorrhage. Depending on the total blood volume lost, hypovolemic shock may be divided into four classes: I (< 75 mL or 15%), II (750–1500 mL, or 15–30%), III (1500–2000 mL or 30–40%) and IV (>2000 mL or > 40%) [6].
The clinical manifestations of class I hypovolemia are not measurable and compensatory mechanisms restore plasma volume within a day. In class II hypovolemia, tachycardia is the most frequent clinical finding as a result of inadequate circulatory volume. The distinction between class I and II hypovolemic shock is made by recording blood pressure and pulse in the standing, sitting, or reclining position. Postural hypotension is observed as result of cardiac failure. Compensatory mechanisms begin to fail with the class III hypovolemic shock. This results in an increase in the arterial and venous oxygen difference with classic signs including worked tachycardia, tachypnea, oliguria, and cold skin. With the class IV hypovolemic shock, a patient’s survival depends on rapid transfusion of blood and immediate surgical intervention before cardiovascular collapse and death or organ system failure.
After initial resuscitative measures are instituted, it is highly recommended for patients to be carried out in a critical care unit. Use of sympathomimetic agents after sufficient hydration and vasodilator is normally preferred in the management of patients with hemorrhagic shock who have arterial pressure higher than 70 mm Hg.
Once restoration of the intravascular volume has been completed, it is important to reassess the patient’s response to blood transfusion when managing women with severe blood loss, especially in those patients who have pulmonary edema, myocardial infarction, or congestive heart failure [12].
Transfusion for patients with hemoglobin of 8–10 mg/dL is no longer recommended.
When major surgery is anticipated and transfusion is massive, platelets in addition to packed cell transfusion are required. It is recommended that cryoprecipitate be reserved for patients with deficiencies in von Willebrand factor, factor VIII, and fibrinogen factor XIII.
Recognized as an uncommon complication of hysterectomy, postoperative hemorrhage represents a true challenge in routine practice [8]; irrespective of the procedure, a close follow-up of the patient in a high-dependency unit is indicated in order to exclude recurrence of bleeding [6, 7].
The key to successful management is timely intervention meaning prompt diagnosis, urgent resuscitation if necessary and rapid decision for either arterial embolization or reoperation according to the severity of bleeding and the hemodynamic stability of the patient. Both techniques are highly effective to control bleeding; nevertheless, if the patient is hemodynamically unstable or of the interval since surgery is under 24 hours suggesting rapid hemorrhage, the emergency return to the operating theater to arrest the bleeding is preferred [6, 7, 9].
Current options for managing hemorrhage include [6, 7, 9]:
every patient should be carefully monitored postoperatively for signs of bleeding (hypotension, tachycardia, tachypnea, abdominal distension);
ultrasound can confirm intraperitoneal bleeding; more ways to determine intraabdominal hemorrhage include abdominal and pelvic CT scan; a routine coagulation profile should be done immediately for the patient with a rapid pulse, low blood pressure, and/or low urine output. The surgeon must take charge of the problem and execute the technical steps necessary to treat hemorrhagic shock in the operating room. Intraperitoneal bleeding can be hidden by incisional pain and analgesic medications. Despite adequate dissection, a small vessel may bleed or the suture may cut through tissue. Skeletonized vessels and small sutures should be used for significantly reducing the incidence of postoperative hemorrhage. Venous bleeding can be more life-threatening than arterial hemorrhage which can be clearly seen and controlled with fast small sutures or clamps.
the presence of unexpected drop in hematocrit or hemoglobin postoperatively.
A simplified algorithm to describe steps after gynecological surgery and potential post-surgery bleeding is provided in Figure 1.
A simplified algorithm of post-surgery bleeding approach.
A closer look at the holistic management of postoperative blood should also underpin the following [9]:
to assess blood value and coagulation mechanisms;
to identify changes in the coagulation components, and to initiate replacement therapy in order to achieve adequate hemostasis. In assessing the patient’s coagulation status, it is very important to avoid such a situation known as the trauma triad of death consisting of—hypothermia, metabolic acidosis, and coagulopathy. In some patients with benign disease, blood transfusion is rarely indicated. Experience has shown that blood transfusion may be significant in women with malignant disease;
to establish the therapeutic strategy by measuring the level of prothrombin time < 14 sec, activated partial thromboplastin time (aptt) < 40 sec, fibrinogen >100 mg/dL, platelets >80 × 103 mL.
In hemodynamically unstable women (rapid pulse, falling blood pressure, with or without renal impairment) or if the bleeding occurs shortly in post-surgery (the so-called reactionary hemorrhage), it is desirable to return to the operating room [5, 6, 7, 8, 9].
A preoperative abdominal and pelvic ultrasound or CT scan is routinely required to visualize the source of bleeding as being intra- or retro-peritoneal, as well as adequate local examination without or under anesthesia. Moreover, the operative procedure should be mentally revised to identify any potential bleeding issue [9].
Surgical revision for postoperative bleeding may be performed transvaginally, laparoscopically, or both [5, 6, 7, 8, 9, 13, 14].
Postoperative hemorrhage from the vaginal vault recurrently originates from the vaginal artery in the lateral vaginal fornix or from one of its branches, since the lateral vaginal angle which includes the vaginal artery may not be accurately protected or turn into disligated [9, 13, 14]. Excessive vaginal bleeding needs to be objectively measured; since the vagina is a distensible organ, clots obstructing the vaginal introitus may lead to a large amount of blood accumulating and distending the vagina, subsequently covering the true significance of hemorrhage [9, 13, 14]. Vaginal bleeding can be controlled by clamping and ligating the bleeding point as well as by delayed-absorbable transfixion suturing of the vaginal mucosa and paravaginal tissue [9, 13, 14]. If such techniques are not enough or bleeding vessels have retracted, other tactics should be intended [8].
When no noticeable vaginal source, bleeding after abdominal or vaginal hysterectomy is traditionally treated by laparotomy or laparoscopy [7, 9]. While laparotomy is recommended in cases of intraperitoneal bleeding or unsuccessful conservative transvaginal treatment, operative laparoscopy is clearly indicated if the source of bleeding cannot be identified by the means of vaginal examination and/or if an intraabdominal bleeding source is suspected [7, 9, 13].
Post-surgery bleeding requires laparotomy in two situations.
Firstly, if the surgical hemostasis cannot be achieved transvaginally, laparotomy may be necessary [9].
Secondly, if the patient underwent an abdominal hysterectomy, the incision should be reopened, succeeding the following steps (i) clots and blood evacuation from the abdomen and pelvic area; (ii) searching of the potential bleeding sites, commencing with the most expected places; (iii) ligating, suturing, or clipping of the identified bleeding sites; (iv) verifying the ureteral integrity as high risk of ureteral damage during reoperation; and (v) closing second time after a completely dry abdomen and pelvis [9].
The laparoscopic approach to postoperative bleeding following laparoscopic hysterectomy, vaginal hysterectomy, or laparoscopic-assisted vaginal hysterectomy is an attractive alternative to the abdominal surgical approach in the majority of patients [6, 7, 9, 13]. The procedure can be used to adequately evaluate the pelvis and the abdominal wall, which is occasionally the source of hemorrhage after laparoscopic hysterectomy. Moreover, whether the bleeding is from the abdominal wall, the surgical pedicles, or the vaginal cuff, it can be managed laparoscopically [8, 9]. Evidently, hemostasis can be more easily obtained in laparoscopic surgery because of magnification, close inspection, routine use of suction irrigation, and bipolar coagulation [7, 9]. Besides, bipolar coagulation, a Foley catheter introduced in the port-site bleeding, or a collagen-fibrin agent can be used to achieve local hemostasis during laparoscopy [7, 9].
Following laparoscopic irrigation/suction using Ringer’s solution to clear the operative field, a combination of laparoscopic suturing using absorbable suture material and laparoscopic bipolar coagulation is commonly recommended [6, 8, 9]. Also, electrosurgery is effective in controlling bleeding during laparoscopic surgery. Furthermore, different forms of fibrin adhesive are tested in gynecologic open surgery in order to stop oozing hemorrhages after primary hemostatic treatment with a high efficacy rate (98%) [6]. Holub and Kliment reported successful treatment of hemorrhage from damaged tissue near important pelvic structures using the laparoscope to apply collagen fleece combined with fibrin glue [7, 17].
To avoid further risk of injury to the abdominal wall and to improve the recovery time from surgery,
Conversely, if the patient is reasonably stable and there is not abrupt early bleeding (based on the volume of blood in the abdomen or retroperitoneal space as estimated by ultrasound and the time from surgery), it seems realistic to try to identify the bleeding artery and embolize it by transcatheter interventional radiological techniques [2, 3, 4, 9, 10].
Arterial embolization remains an important minimally invasive option for the management of delayed postoperative hemorrhage [2, 3, 4, 8, 9, 18]. Transcatheter arterial embolization has been shown to be an effective tool for the management of postoperative hemorrhage after gynecologic laparoscopy, but also after abdominal and vaginal hysterectomy [8, 9]. Selective angiographic arterial embolization is a quite simple and safe procedure with a clinical success rate up to 90% in routine practice and usually a low complication rate less than 10%, including a mild postembolization syndrome with pain, fever, high leucocyte count related to vascular thrombosis and tissue necrosis [8, 9]. Bladder necrosis, vesicovaginal fistula, neuropathies as well as renal toxicity are uncommon, isolated side effects [9].
Arterial embolization technique comprises the following main steps—(i) identification of the site of bleeding by angiofluoroscopy if more than 2–3 mL/min bleeding rate; (ii) percutaneous catheterization of the femoral artery or, uncommonly, brachial artery under local anesthesia with retrograde direct access to the hypogastric artery; (iii) canulation of the hypogastric artery or specific collateral vessel if appropriate; (iv) injection of the embolization material under angiographic observation (metal coins, autologous clot, small pieces of gelfoam, small silastic spheres, subcutaneous tissue, or other hemostatic materials; (v) repeat angiography to demonstrate the occlusion of the bleeding vessel; (vi) remove of the catheter followed by careful monitoring for further bleeding [8, 9, 10].
Although second surgery is often the initial choice for postoperative hemorrhage, for a patient who is hemodynamically stable but is experiencing postoperative hemorrhage, transcatheter arterial embolization is a welcome alternative to a second surgery [8, 9]. However, if rapid access to interventional radiology is not available or if transcatheter arterial embolization is unsuccessful, laparoscopy can still be considered [8, 9]. Besides, a potential advantage of surgical management of postoperative hemorrhage over transcatheter arterial embolization is the ability to evacuate the hemoperitoneum, which may decrease postoperative pain, the risk of infection, and the risk of ileus [8, 9].
It is typical to expect some bleeding after hysterectomy in the 6–8 weeks following the procedure; the discharge may be red, brown, or pink. Bleeding should steadily decrease in the days and weeks following the surgery and should never be excessive at any point of recovery [18]. The exception is menstruation in women who have undergone a subtotal hysterectomy [18, 19]. In case of bleeding after hysterectomy, it is more likely to be of some pathologic cause instead of menstruation which needs to be ruled out [19].
However, a sudden and significant increase in bleeding during recovery should be considered abnormal. Points of concern comprise but are not limited to—bright red vaginal bleeding (indicating active bleed), temperature over 100.4°F, severe nausea or vomiting, increasing pelvic pain, a local complication such as redness, swelling, or drainage at the incision site as well as difficulty in urinating or pain with urination suggesting either an infection or a neurogenic bladder [18].
Delayed vaginal hemorrhage after laparoscopic supracervical hysterectomy usually requires emergent reoperation. Several studies have described continued cyclical bleeding from the cervical stump after supracervical hysterectomy in 0–25% of cases [20].
Effective interventions addressing hemorrhage after hysterectomy are needed to reduce women’s mortality worldwide.
Prior to hysterectomy, these women should be offered specific counseling and have a prospective plan for the management of their disease, developed by gynecologists of how their condition and hysterectomy interact. Prehysterectomy counseling services starting for all women planning this surgical intervention are a key part of hospital services and should be an integral part of the local health services network. They could be provided by general practitioners or specialist clinicians or surgeons, all of whom should be suitably trained or may require different management or specialized services before hysterectomy. There are special circumstances as congenital or acquired coagulation disorders that should be considered to evaluate by a thorough history and lab tests.
Professional interpretation services for women who do not speak English.
It is not clear how much the specific medical terminology is conveyed to the patient. Healthcare providers have to invest in technology, security, specialists, and translators to ensure healthcare becomes world-class. Medical tourism is growing each year. Romania provides the highest quality healthcare at the lowest price. Also, the cost of hysterectomy in Romania is lower than the same treatment in UK or UE. In developed countries as the USA, UE countries or Canada patients have to wait a long time for major surgeries. The cost involved in treating a patient depends upon factors like—type of hysterectomy needed, hospital and physician selected for it, and duration of staying.
Communication and referrals among professionals.
Good communication among professionals is essential. Referral between specialties involved should be rapid. They can use a variety of communication methods including—mobile phone, email, fax, Whatsapp, Instagram, Tik Tok, Facebook, etc. In many cases, junior trainees in the front line did not have proper support and need to have clear guidelines about when to seek senior help.
Women with serious medical conditions
They require immediate and appropriate multidisciplinary specialist care; women will require referral to tertiary or specialist medical centers for their preexisting medical or mental conditions before hysterectomy. Conditions that require prehysterectomy counseling and advice include—epilepsy, diabetes, asthma, congenital or known acquired cardiac disease, autoimmune disorders, renal and liver disease, obesity (BMI > 30), severe mental illness, or psychiatric conditions that require a change of medication, HIV infection. Women with potential serious underlying preexisting medical on mental health conditions should be immediately referred to appropriate specialist centers of expertise as soon as their symptoms develop.
Clinical training
All clinical staff must undertake regular training for the identification and management of serious disease conditions or potential emergencies or signs and symptoms of potentially life-threatening conditions, circulatory failure, severe hypertension or major hemorrhage, pyrexia >38°C, tachycardia >100 bpm, breathlessness. The local clinicians may be excellent at the management of severely ill women but must also accept written, documented, and audited courses. There should be a well-trained team of doctors for recording and charting investigations performed, obtaining quick results, ensuring that abnormal results are followed up promptly and have resulted in a better outcome.
Identifying and managing very sick women with critical illness before, during or after hysterectomy
In very acute situations, a team approach can be very healthful. The management of patients with an acute severe illness with circulatory failure, arterial hypertension, and major hemorrhage requires a team approach and help from the anesthetic and critical care services. There are some healthcare professionals who failed to manage crisis situations outside their immediate area of expertise; therefore, it is crucial to recognize their limitations and to know when and whom to call for another opinion once the patient was admitted to the hospital.
Coagulation factors, hematocrit, serum calcium, glucose, and electrolytes could be assessed every 120 minutes or after 10 U of transfusion; these lab tests are very helpful for the diagnosis of postoperative bleeding.
RCOG guidelines of the responsibilities of the consultant on call should be followed.
Bilateral hypogastric artery ligation can reduce blood loss to a minimum during hysterectomy [9].
Hypotensive anesthesia is also a safe and effective technique in reducing the circulation to the operative field [9].
Serious incident and women death reporting
Health professionals, senior or junior, must recognize an act on the signs and symptoms of potentially life-threatening conditions.
The evaluation of such a report must include clinicians from relevant disciplines (including anesthetics) who were not involved with the deaths. This report is recommended to be a requirement in the future.
The identification and act on women’s death should be reviewed as a serious incident and disseminated to all health professionals, junior or senior. Women’s deaths are generally underreported because of incorrect classification of cause.
Fatal hemorrhage can result from laceration of the external iliac vein or the hypogastric vein where they join together which are at risk of injury when the surgeon dissects between the distal common iliac artery, the psoas muscle, and the area of lumbosacral nerve trunks [9]. These vessels cannot be clamped and ligated with clips or sutures [9].
Dissection around the aorta and vena cava done with inadequate exposure performed in order to remove lymph nodes around them can result in serious hemorrhage. Bleeding usually can be avoided by placing a finger over the laceration and a vascular needle is used to close the laceration from side to side. The same technique may be used for common and external iliac veins [9].
Also, bleeding can occur by dissecting pararectal space and presacral space as well as obturator fossa [9].
Pathology
Patient death autopsy must be improved and require more expertise.
In Romania, the number of women death after hysterectomy (death rate) is very small and many of the autopsies reviewed were considered adequate. When an autopsy is needed, the body can be taken to another area for more expert examination. Despite evaluation by many examiners in the different specialties, the final diagnosis could not be resolved because of inadequate clinical data, poor autopsy quality, or the unmanageable nature of some death.
The lack of routine observation in the postoperative period or a failure to appreciate blood loss or recognition of abnormal vital signs such as oxygen saturation and respiratory rate can lead to death after hysterectomy. The patient should be evaluated before hysterectomy for risk factors and the medical conditions of the women should be diagnosed by a careful history and lab tests in order to decrease the possibility of hemorrhage.
The risks of blood transfusion, the transmission of HIV or hepatitis B should be discussed before surgical procedure.
The peace of surgical intervention should be governed by good exposure of the tissue, accuracy of dissection, and clamping or suturing the vessels in a precise manner. The skills and experiences of the surgeon without wasting time with unnecessary hesitation or indecision will reduce the risk of uncontrolled hemorrhage after a hysterectomy.
The surgeon should control the life-threatening hemorrhage by judgment, knowledge, and technical skills. The patient’s medical history for vital signs, blood loss volume, and levels of coagulation factors will determine how quickly blood transfusion is initiated. Careful postoperative clinical evaluation of the patient by the surgeon and surgical team with abdominal or pelvic ultrasound or CT scanning will help to prevent or minimize significant blood loss after hysterectomy and localize the site of bleeding.
No funding was received for this chapter.
The Internet has irrevocably changed the dynamics of scholarly communication and publishing. Consequently, we find it necessary to indicate, unambiguously, our definition of what we consider to be a published scientific work.
",metaTitle:"Prior Publication Policy",metaDescription:"Prior Publication Policy",metaKeywords:null,canonicalURL:"/page/prior-publication-policy",contentRaw:'[{"type":"htmlEditorComponent","content":"A significant number of working papers, early drafts, and similar work in progress are openly shared online between members of the scientific community. It has become common to announce one’s own research on a personal website or a blog to gather comments and suggestions from other researchers. Such works and online postings are, indeed, published in the sense that they are made publicly available. However, this does not mean that if submitted for publication by IntechOpen they are not original works. We differentiate between reviewed and non-reviewed works when determining whether a work is original and has been published in a scholarly sense or not.
\\n\\nThe significance of Peer Review cannot be overstated when it comes to defining, in our terms, what constitutes a published scientific work. Peer Review is widely considered to be the cornerstone of modern publishing processes and the key value-adding contribution to a scholarly manuscript that a publisher can make.
\\n\\nOther than the issue of originality, research misconduct is another major issue that all publishers have to address. IntechOpen’s Retraction & Correction Policy and various publication ethics guidelines identify both redundant publication and (self)plagiarism to fall within the definition of research misconduct, thus constituting grounds for rejection or the issue of a Retraction if the work has already been published.
\\n\\nIn order to facilitate the tracking of a manuscript’s publishing history and its development from its earliest draft to the manuscript submitted, we encourage Authors to disclose any instances of a manuscript’s prior publication, whether it be through a conference presentation, a newspaper article, a working paper publicly available in a repository or a blog post.
\\n\\nA note to the Academic Editor containing detailed information about a submitted manuscript’s previous public availability is the preferred means of reporting prior publication. This helps us determine if there are any earlier versions of a manuscript that should be disclosed to our readers or if any of those earlier versions should be cited and listed in a manuscript’s references.
\\n\\nSome basic information about the editorial treatment of different varieties of prior publication is laid out below:
\\n\\n1. CONFERENCE PAPERS & PRESENTATIONS
\\n\\nGiven that conference papers and presentations generally pass through some sort of peer or editorial review, we consider them to be published in the accepted scholarly sense, particularly if they are published as a part of conference proceedings.
\\n\\nAll submitted manuscripts originating from a previously published conference paper must contain at least 50% of new original content to be accepted for review and considered for publication.
\\n\\nAuthors are required to report any links their manuscript might have with their earlier conference papers and presentations in a note to the Academic Editor, as well as in the manuscript itself. Additionally, Authors should obtain any necessary permissions from the publisher of their conference paper if copyright transfer occurred during the publishing process. Failure to do so may prevent Us from publishing an otherwise worthy work.
\\n\\n2. NEWSPAPER & MAGAZINE ARTICLES
\\n\\nNewspaper and magazine articles usually do not pass through any extensive peer or editorial review and we do not consider them to be published in the scholarly sense. Articles appearing in newspapers and magazines rarely possess the depth and structure characteristic of scholarly articles.
\\n\\nSubmitted manuscripts stemming from a previous newspaper or magazine article will be accepted for review and considered for publication. However, Authors are strongly advised to report any such publication in an accompanying note to the External Editor.
\\n\\nAs with the conference papers and presentations, Authors should obtain any necessary permissions from the newspaper or magazine that published the work, and indicate that they have done so in a note to the External Editor.
\\n\\n3. GREY LITERATURE
\\n\\nWhite papers, working papers, technical reports and all other forms of papers which fall within the scope of the ‘Luxembourg definition’ of grey literature do not pass through any extensive peer or editorial review and we do not consider them to be published in the scholarly sense.
\\n\\nAlthough such papers are regularly made publicly available via personal websites and institutional repositories, their general purpose is to gather comments and feedback from Authors’ colleagues in order to further improve a manuscript intended for future publication.
\\n\\nWhen submitting their work, Authors are required to disclose the existence of any publicly available earlier drafts in a note to the Academic Editor. In cases where earlier drafts of the submitted version of the manuscript are publicly available, any overlap between the versions will generally not be considered an instance of self-plagiarism.
\\n\\n4. SOCIAL MEDIA, BLOG & MESSAGE BOARD POSTINGS
\\n\\nWe feel that social media, blogs and message boards are generally used with the same intention as grey literature, to formulate ideas for a manuscript and gather early feedback from like-minded researchers in order to improve a particular piece of work before submitting it for publication. Therefore, we do not consider such internet postings to be publication in the scholarly sense.
\\n\\nNevertheless, Authors are encouraged to disclose the existence of any internet postings in which they outline and describe their research or posted passages of their manuscripts in a note to the Academic Editor. Please note that we will not strictly enforce this request in the same way that we would instructions we consider to be part of our conditions of acceptance for publication. We understand that it may be difficult to keep track of all one’s internet postings in which the researcher´s current work might be mentioned.
\\n\\nIn cases where there is any overlap between the Author´s submitted manuscript and related internet postings, we will generally not consider it to be an instance of self-plagiarism. This also holds true for any co-Author as well.
\\n\\nFor more information on this policy please contact permissions@intechopen.com.
\\n\\nPolicy last updated: 2017-03-20
\\n"}]'},components:[{type:"htmlEditorComponent",content:'A significant number of working papers, early drafts, and similar work in progress are openly shared online between members of the scientific community. It has become common to announce one’s own research on a personal website or a blog to gather comments and suggestions from other researchers. Such works and online postings are, indeed, published in the sense that they are made publicly available. However, this does not mean that if submitted for publication by IntechOpen they are not original works. We differentiate between reviewed and non-reviewed works when determining whether a work is original and has been published in a scholarly sense or not.
\n\nThe significance of Peer Review cannot be overstated when it comes to defining, in our terms, what constitutes a published scientific work. Peer Review is widely considered to be the cornerstone of modern publishing processes and the key value-adding contribution to a scholarly manuscript that a publisher can make.
\n\nOther than the issue of originality, research misconduct is another major issue that all publishers have to address. IntechOpen’s Retraction & Correction Policy and various publication ethics guidelines identify both redundant publication and (self)plagiarism to fall within the definition of research misconduct, thus constituting grounds for rejection or the issue of a Retraction if the work has already been published.
\n\nIn order to facilitate the tracking of a manuscript’s publishing history and its development from its earliest draft to the manuscript submitted, we encourage Authors to disclose any instances of a manuscript’s prior publication, whether it be through a conference presentation, a newspaper article, a working paper publicly available in a repository or a blog post.
\n\nA note to the Academic Editor containing detailed information about a submitted manuscript’s previous public availability is the preferred means of reporting prior publication. This helps us determine if there are any earlier versions of a manuscript that should be disclosed to our readers or if any of those earlier versions should be cited and listed in a manuscript’s references.
\n\nSome basic information about the editorial treatment of different varieties of prior publication is laid out below:
\n\n1. CONFERENCE PAPERS & PRESENTATIONS
\n\nGiven that conference papers and presentations generally pass through some sort of peer or editorial review, we consider them to be published in the accepted scholarly sense, particularly if they are published as a part of conference proceedings.
\n\nAll submitted manuscripts originating from a previously published conference paper must contain at least 50% of new original content to be accepted for review and considered for publication.
\n\nAuthors are required to report any links their manuscript might have with their earlier conference papers and presentations in a note to the Academic Editor, as well as in the manuscript itself. Additionally, Authors should obtain any necessary permissions from the publisher of their conference paper if copyright transfer occurred during the publishing process. Failure to do so may prevent Us from publishing an otherwise worthy work.
\n\n2. NEWSPAPER & MAGAZINE ARTICLES
\n\nNewspaper and magazine articles usually do not pass through any extensive peer or editorial review and we do not consider them to be published in the scholarly sense. Articles appearing in newspapers and magazines rarely possess the depth and structure characteristic of scholarly articles.
\n\nSubmitted manuscripts stemming from a previous newspaper or magazine article will be accepted for review and considered for publication. However, Authors are strongly advised to report any such publication in an accompanying note to the External Editor.
\n\nAs with the conference papers and presentations, Authors should obtain any necessary permissions from the newspaper or magazine that published the work, and indicate that they have done so in a note to the External Editor.
\n\n3. GREY LITERATURE
\n\nWhite papers, working papers, technical reports and all other forms of papers which fall within the scope of the ‘Luxembourg definition’ of grey literature do not pass through any extensive peer or editorial review and we do not consider them to be published in the scholarly sense.
\n\nAlthough such papers are regularly made publicly available via personal websites and institutional repositories, their general purpose is to gather comments and feedback from Authors’ colleagues in order to further improve a manuscript intended for future publication.
\n\nWhen submitting their work, Authors are required to disclose the existence of any publicly available earlier drafts in a note to the Academic Editor. In cases where earlier drafts of the submitted version of the manuscript are publicly available, any overlap between the versions will generally not be considered an instance of self-plagiarism.
\n\n4. SOCIAL MEDIA, BLOG & MESSAGE BOARD POSTINGS
\n\nWe feel that social media, blogs and message boards are generally used with the same intention as grey literature, to formulate ideas for a manuscript and gather early feedback from like-minded researchers in order to improve a particular piece of work before submitting it for publication. Therefore, we do not consider such internet postings to be publication in the scholarly sense.
\n\nNevertheless, Authors are encouraged to disclose the existence of any internet postings in which they outline and describe their research or posted passages of their manuscripts in a note to the Academic Editor. Please note that we will not strictly enforce this request in the same way that we would instructions we consider to be part of our conditions of acceptance for publication. We understand that it may be difficult to keep track of all one’s internet postings in which the researcher´s current work might be mentioned.
\n\nIn cases where there is any overlap between the Author´s submitted manuscript and related internet postings, we will generally not consider it to be an instance of self-plagiarism. This also holds true for any co-Author as well.
\n\nFor more information on this policy please contact permissions@intechopen.com.
\n\nPolicy last updated: 2017-03-20
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The importance of antioxidant mechanisms is to understand the biological meaning of antioxidants, their possible uses, their production by organic synthesis or biotechnological methods, or for the standardization of the determination of antioxidant activity. In general, antioxidant molecules can react either by multiple mechanisms or by a predominant mechanism. The chemical structure of the antioxidant substance allows understanding of the antioxidant reaction mechanism. This chapter reviews the in vitro antioxidant reaction mechanisms of organic compounds polyphenols, carotenoids, and vitamins C against free radicals (FR) and prooxidant compounds under diverse conditions, as well as the most commonly used methods to evaluate the antioxidant activity of these compounds according to the mechanism involved in the reaction with free radicals and the methods of in vitro antioxidant evaluation that are used frequently depending on the reaction mechanism of the antioxidant.",book:{id:"8008",slug:"antioxidants",title:"Antioxidants",fullTitle:"Antioxidants"},signatures:"Norma Francenia Santos-Sánchez, Raúl Salas-Coronado, Claudia Villanueva-Cañongo and Beatriz Hernández-Carlos",authors:[{id:"143354",title:"Dr.",name:"Raúl",middleName:null,surname:"Salas-Coronado",slug:"raul-salas-coronado",fullName:"Raúl Salas-Coronado"},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez"},{id:"193718",title:"Dr.",name:"Beatriz",middleName:null,surname:"Hernández-Carlos",slug:"beatriz-hernandez-carlos",fullName:"Beatriz Hernández-Carlos"},{id:"278133",title:"Dr.",name:"Claudia",middleName:null,surname:"Villanueva-Cañongo",slug:"claudia-villanueva-canongo",fullName:"Claudia Villanueva-Cañongo"}]},{id:"67588",title:"Preformulation Studies: An Integral Part of Formulation Design",slug:"preformulation-studies-an-integral-part-of-formulation-design",totalDownloads:4059,totalCrossrefCites:2,totalDimensionsCites:5,abstract:"When a promising new chemical entity is synthesized, it needs transformation to appropriate formulation in order to show a better and desirable action at appropriate site. 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The highlighted chapter is framed with a vision to provide an in-depth knowledge about pharmaceutical formulation development.",book:{id:"8331",slug:"pharmaceutical-formulation-design-recent-practices",title:"Pharmaceutical Formulation Design",fullTitle:"Pharmaceutical Formulation Design - Recent Practices"},signatures:"Pinak Patel",authors:null},{id:"37165",title:"Modern Medicine and Pharmaceutics",slug:"modern-medicine-and-pharmaceutics",totalDownloads:4471,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"1519",slug:"promising-pharmaceuticals",title:"Promising Pharmaceuticals",fullTitle:"Promising Pharmaceuticals"},signatures:"Purusotam Basnet",authors:[{id:"98426",title:"Prof.",name:"Purusotam",middleName:null,surname:"Basnet",slug:"purusotam-basnet",fullName:"Purusotam Basnet"}]},{id:"37170",title:"Good Manufacturing Practices (GMP) for Medicinal Products",slug:"good-manufacturing-practices-gmp-for-medicinal-products",totalDownloads:32651,totalCrossrefCites:1,totalDimensionsCites:1,abstract:null,book:{id:"1519",slug:"promising-pharmaceuticals",title:"Promising Pharmaceuticals",fullTitle:"Promising Pharmaceuticals"},signatures:"Jaya Bir Karmacharya",authors:[{id:"155087",title:"Mr.",name:"Jaya",middleName:"Bir",surname:"Karmacharya",slug:"jaya-karmacharya",fullName:"Jaya Karmacharya"}]},{id:"66222",title:"Bioavailability and Bioequivalence Studies",slug:"bioavailability-and-bioequivalence-studies",totalDownloads:3351,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"In vivo bioavailability studies are performed for new drug to establish essential pharmacokinetic parameters including rate of absorption, extent of absorption, rates of excretion and metabolism and elimination half-life after a single and multiple dose administration. These essential pharmacokinetic parameters are useful in establishing dosage regimens. Bioequivalence used to assess the expected in vivo biological equivalence of two proprietary preparations of drug products. If two drugs are bioequivalent, it means that they are expected to be same for all intents and purposes. In determining bioequivalence between two drugs such as a reference drug or brand and potential to be test drug or marketed generic drug. Pharmacokinetic studies are conducted whereby each of the drugs is administered in a cross over study to healthy volunteer’s subjects. Plasma is obtained at regular intervals and assayed for parent drug or metabolite concentration to compare the two drugs. For comparison purpose of two formulations, the plasma concentration data are used to assess key pharmacokinetic parameters. If 90% confidence interval for the ratio of the geometric least square means of peak plasma concentration, area under curve of test and reference drugs are within 80–125%, then bioequivalence will be established.",book:{id:"8331",slug:"pharmaceutical-formulation-design-recent-practices",title:"Pharmaceutical Formulation Design",fullTitle:"Pharmaceutical Formulation Design - Recent Practices"},signatures:"Divvela Hema Nagadurga",authors:null}],onlineFirstChaptersFilter:{topicId:"217",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}},{id:"441116",title:"Dr.",name:"Jovanka M.",middleName:null,surname:"Voyich",slug:"jovanka-m.-voyich",fullName:"Jovanka M. Voyich",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Montana State University",country:{name:"United States of America"}}},{id:"330412",title:"Dr.",name:"Muhammad",middleName:null,surname:"Farhab",slug:"muhammad-farhab",fullName:"Muhammad Farhab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"349495",title:"Dr.",name:"Muhammad",middleName:null,surname:"Ijaz",slug:"muhammad-ijaz",fullName:"Muhammad Ijaz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}}]}},subseries:{item:{id:"20",type:"subseries",title:"Animal Nutrition",keywords:"Sustainable Animal Diets, Carbon Footprint, Meta Analyses",scope:"An essential part of animal production is nutrition. Animals need to receive a properly balanced diet. One of the new challenges we are now faced with is sustainable animal diets (STAND) that involve the 3 P’s (People, Planet, and Profitability). We must develop animal feed that does not compete with human food, use antibiotics, and explore new growth promoters options, such as plant extracts or compounds that promote feed efficiency (e.g., monensin, oils, enzymes, probiotics). These new feed options must also be environmentally friendly, reducing the Carbon footprint, CH4, N, and P emissions to the environment, with an adequate formulation of nutrients.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11416,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. 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