Commonly used ZIKV strains.
\\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!
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 179 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 252 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!
\n'}],latestNews:[{slug:"stanford-university-identifies-top-2-scientists-over-1-000-are-intechopen-authors-and-editors-20210122",title:"Stanford University Identifies Top 2% Scientists, Over 1,000 are IntechOpen Authors and Editors"},{slug:"intechopen-authors-included-in-the-highly-cited-researchers-list-for-2020-20210121",title:"IntechOpen Authors Included in the Highly Cited Researchers List for 2020"},{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"},{slug:"oiv-awards-recognizes-intechopen-s-editors-20201127",title:"OIV Awards Recognizes IntechOpen's Editors"},{slug:"intechopen-joins-crossref-s-initiative-for-open-abstracts-i4oa-to-boost-the-discovery-of-research-20201005",title:"IntechOpen joins Crossref's Initiative for Open Abstracts (I4OA) to Boost the Discovery of Research"},{slug:"intechopen-hits-milestone-5-000-open-access-books-published-20200908",title:"IntechOpen hits milestone: 5,000 Open Access books published!"},{slug:"intechopen-books-hosted-on-the-mathworks-book-program-20200819",title:"IntechOpen Books Hosted on the MathWorks Book Program"}]},book:{item:{type:"book",id:"2519",leadTitle:null,fullTitle:"Applications of Calorimetry in a Wide Context - Differential Scanning Calorimetry, Isothermal Titration Calorimetry and Microcalorimetry",title:"Applications of Calorimetry in a Wide Context",subtitle:"Differential Scanning Calorimetry, Isothermal Titration Calorimetry and Microcalorimetry",reviewType:"peer-reviewed",abstract:"Calorimetry, as a technique for thermal analysis, has a wide range of applications which are not only limited to studying the thermal characterisation (e.g. melting temperature, denaturation temperature and enthalpy change) of small and large drug molecules, but are also extended to characterisation of fuel, metals and oils. Differential Scanning Calorimetry is used to study the thermal behaviours of drug molecules and excipients by measuring the differential heat flow needed to maintain the temperature difference between the sample and reference cells equal to zero upon heating at a controlled programmed rate. Microcalorimetry is used to study the thermal transition and folding of biological macromolecules in dilute solutions. Microcalorimetry is applied in formulation and stabilisation of therapeutic proteins. This book presents research from all over the world on the applications of calorimetry on both solid and liquid states of materials.",isbn:null,printIsbn:"978-953-51-0947-1",pdfIsbn:"978-953-51-6295-7",doi:"10.5772/2898",price:139,priceEur:155,priceUsd:179,slug:"applications-of-calorimetry-in-a-wide-context-differential-scanning-calorimetry-isothermal-titration-calorimetry-and-microcalorimetry",numberOfPages:486,isOpenForSubmission:!1,isInWos:1,hash:"8f344832659ae99060d03528c11b0eb0",bookSignature:"Amal Ali Elkordy",publishedDate:"January 23rd 2013",coverURL:"https://cdn.intechopen.com/books/images_new/2519.jpg",numberOfDownloads:71017,numberOfWosCitations:140,numberOfCrossrefCitations:29,numberOfDimensionsCitations:141,hasAltmetrics:0,numberOfTotalCitations:310,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"December 5th 2011",dateEndSecondStepPublish:"January 9th 2012",dateEndThirdStepPublish:"April 14th 2012",dateEndFourthStepPublish:"July 13th 2012",dateEndFifthStepPublish:"August 12th 2012",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,editors:[{id:"136133",title:"Dr.",name:"Amal Ali",middleName:null,surname:"Elkordy",slug:"amal-ali-elkordy",fullName:"Amal Ali Elkordy",profilePictureURL:"https://mts.intechopen.com/storage/users/136133/images/3736_n.jpg",biography:"Dr. Amal Ali Elkordy is a Senior Lecturer in Pharmaceutics in the Department of Pharmacy, Health and Well-being, Faculty of Applied Sciences, University of Sunderland, UK. Her area of research interest is the stabilisation of protein formulations (using spray drying and crystallisation technology) and their delivery via oral and pulmonary routes. Her work in this field has been recognised by the award of two prizes at the British Pharmaceutical Conference in 2002 and in 2004. Her more recent work is concerned with the enhancement of poorly water soluble drugs and gene therapeutics (awarded national recognition from the College of Mental Health Pharmacists, 2010). Dr. Elkordy has many publications in peer-review journals and she was invited speaker in a number of conferences.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"University of Sunderland",institutionURL:null,country:{name:"United Kingdom"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"699",title:"Analytical Chemistry",slug:"engineering-chemical-engineering-analytical-chemistry"}],chapters:[{id:"42247",title:"Application of Differential Scanning Calorimetry to the Characterization of Biopolymers",doi:"10.5772/53822",slug:"application-of-differential-scanning-calorimetry-to-the-characterization-of-biopolymers",totalDownloads:8304,totalCrossrefCites:1,totalDimensionsCites:35,signatures:"Adriana Gregorova",downloadPdfUrl:"/chapter/pdf-download/42247",previewPdfUrl:"/chapter/pdf-preview/42247",authors:[{id:"142120",title:"Dr",name:"Adriana",surname:"Gregorova",slug:"adriana-gregorova",fullName:"Adriana Gregorova"}],corrections:null},{id:"42255",title:"Thermal Stability of the Nanostructured Powder Mixtures Prepared by Mechanical Alloying",doi:"10.5772/54151",slug:"thermal-stability-of-the-nanostructured-powder-mixtures-prepared-by-mechanical-alloying",totalDownloads:2540,totalCrossrefCites:0,totalDimensionsCites:7,signatures:"Safia Alleg, Saida Souilah and Joan Joseph Suñol",downloadPdfUrl:"/chapter/pdf-download/42255",previewPdfUrl:"/chapter/pdf-preview/42255",authors:[{id:"139038",title:"Prof.",name:"Safia",surname:"Alleg",slug:"safia-alleg",fullName:"Safia Alleg"},{id:"167407",title:"Dr.",name:"Saida",surname:"Souilah",slug:"saida-souilah",fullName:"Saida Souilah"},{id:"167408",title:"Prof.",name:"Joan Josep",surname:"Sunol",slug:"joan-josep-sunol",fullName:"Joan Josep Sunol"}],corrections:null},{id:"42259",title:"Studies on Growth, Crystal Structure and Characterization of Novel Organic Nicotinium Trifluoroacetate Single Crystals",doi:"10.5772/53795",slug:"studies-on-growth-crystal-structure-and-characterization-of-novel-organic-nicotinium-trifluoroacetat",totalDownloads:3365,totalCrossrefCites:0,totalDimensionsCites:2,signatures:"P.V. Dhanaraj and N.P. Rajesh",downloadPdfUrl:"/chapter/pdf-download/42259",previewPdfUrl:"/chapter/pdf-preview/42259",authors:[{id:"73822",title:"Dr.",name:"Narayana Perumal",surname:"Rajesh",slug:"narayana-perumal-rajesh",fullName:"Narayana Perumal Rajesh"}],corrections:null},{id:"42254",title:"Isothermal Titration Calorimetry: Thermodynamic Analysis of the Binding Thermograms of Molecular Recognition Events by Using Equilibrium Models",doi:"10.5772/53311",slug:"isothermal-titration-calorimetry-thermodynamic-analysis-of-the-binding-thermograms-of-molecular-reco",totalDownloads:5930,totalCrossrefCites:5,totalDimensionsCites:14,signatures:"Jose C. Martinez, Javier Murciano-Calles, Eva S. Cobos,\nManuel Iglesias-Bexiga, Irene Luque and Javier Ruiz-Sanz",downloadPdfUrl:"/chapter/pdf-download/42254",previewPdfUrl:"/chapter/pdf-preview/42254",authors:[{id:"139651",title:"Dr.",name:"Jose",surname:"Martinez",slug:"jose-martinez",fullName:"Jose Martinez"},{id:"140286",title:"Dr.",name:"Eva S",surname:"Cobos",slug:"eva-s-cobos",fullName:"Eva S Cobos"},{id:"140287",title:"Dr.",name:"Irene",surname:"Luque",slug:"irene-luque",fullName:"Irene Luque"},{id:"140288",title:"Dr.",name:"Manuel",surname:"Iglesias-Bexiga",slug:"manuel-iglesias-bexiga",fullName:"Manuel Iglesias-Bexiga"},{id:"140289",title:"Dr.",name:"Javier",surname:"Murciano-Calles",slug:"javier-murciano-calles",fullName:"Javier Murciano-Calles"},{id:"140290",title:"Dr.",name:"Javier",surname:"Ruiz-Sanz",slug:"javier-ruiz-sanz",fullName:"Javier Ruiz-Sanz"}],corrections:null},{id:"42253",title:"Applications of Calorimetric Techniques in the Formation of Protein-Polyelectrolytes Complexes",doi:"10.5772/54260",slug:"applications-of-calorimetric-techniques-in-the-formation-of-protein-polyelectrolytes-complexes",totalDownloads:2551,totalCrossrefCites:1,totalDimensionsCites:4,signatures:"Diana Romanini, Mauricio Javier Braia and María Cecilia Porfiri",downloadPdfUrl:"/chapter/pdf-download/42253",previewPdfUrl:"/chapter/pdf-preview/42253",authors:[{id:"141993",title:"Dr.",name:"Diana",surname:"Romanini",slug:"diana-romanini",fullName:"Diana Romanini"},{id:"143343",title:"Mr.",name:"Mauricio",surname:"Braia",slug:"mauricio-braia",fullName:"Mauricio Braia"},{id:"143344",title:"Ms.",name:"María",surname:"Porfiri",slug:"maria-porfiri",fullName:"María Porfiri"}],corrections:null},{id:"42249",title:"Insights into the Relative DNA Binding Affinity and Preferred Binding Mode of Homologous Compounds Using Isothermal Titration Calorimetry (ITC)",doi:"10.5772/54061",slug:"insights-into-the-relative-dna-binding-affinity-and-preferred-binding-mode-of-homologous-compounds-u",totalDownloads:2248,totalCrossrefCites:1,totalDimensionsCites:2,signatures:"Ruel E. McKnight",downloadPdfUrl:"/chapter/pdf-download/42249",previewPdfUrl:"/chapter/pdf-preview/42249",authors:[{id:"141997",title:"Dr.",name:"Ruel",surname:"McKnight",slug:"ruel-mcknight",fullName:"Ruel McKnight"}],corrections:null},{id:"42250",title:"Thermodynamic Signatures of Macromolecular Complexes ‒ Insights on the Stability and Interactions of Nucleoplasmin, a Nuclear Chaperone",doi:"10.5772/54062",slug:"thermodynamic-signatures-of-macromolecular-complexes-insights-on-the-stability-and-interactions-of-n",totalDownloads:2102,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Stefka G. Taneva, Sonia Bañuelos and María A. Urbaneja",downloadPdfUrl:"/chapter/pdf-download/42250",previewPdfUrl:"/chapter/pdf-preview/42250",authors:[{id:"141733",title:"Prof.",name:"Stefka",surname:"Taneva",slug:"stefka-taneva",fullName:"Stefka Taneva"}],corrections:null},{id:"42260",title:"Determination of Folding Reversibility of Lysozyme Crystals Using Microcalorimetry",doi:"10.5772/51131",slug:"determination-of-folding-reversibility-of-lysozyme-crystals-using-microcalorimetry",totalDownloads:1978,totalCrossrefCites:0,totalDimensionsCites:1,signatures:"Amal A. Elkordy, Robert T. Forbes and Brian W. Barry",downloadPdfUrl:"/chapter/pdf-download/42260",previewPdfUrl:"/chapter/pdf-preview/42260",authors:[{id:"136133",title:"Dr.",name:"Amal Ali",surname:"Elkordy",slug:"amal-ali-elkordy",fullName:"Amal Ali Elkordy"}],corrections:null},{id:"42266",title:"Calorimetric Study of Inulin as Cryo- and Lyoprotector of Bovine Plasma Proteins",doi:"10.5772/54462",slug:"calorimetric-study-of-inulin-as-cryo-and-lyoprotector-of-bovine-plasma-proteins",totalDownloads:2849,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Laura T. Rodriguez Furlán, Javier Lecot, Antonio Pérez Padilla, Mercedes E. Campderrós and Noemi E. Zaritzky",downloadPdfUrl:"/chapter/pdf-download/42266",previewPdfUrl:"/chapter/pdf-preview/42266",authors:[{id:"146768",title:"PhD.",name:"Mercedes",surname:"Campderros",slug:"mercedes-campderros",fullName:"Mercedes Campderros"},{id:"148674",title:"MSc.",name:"Laura",surname:"Rodriguez Furlán",slug:"laura-rodriguez-furlan",fullName:"Laura Rodriguez Furlán"},{id:"148676",title:"BSc.",name:"Javier",surname:"Lecot",slug:"javier-lecot",fullName:"Javier Lecot"},{id:"148677",title:"Dr.",name:"Antonio",surname:"Pérez Padilla",slug:"antonio-perez-padilla",fullName:"Antonio Pérez Padilla"},{id:"148678",title:"Dr.",name:"Noemi",surname:"Zaritzky",slug:"noemi-zaritzky",fullName:"Noemi Zaritzky"}],corrections:null},{id:"42256",title:"Silver Particulate Films on Compatible Softened Polymer Composites",doi:"10.5772/54502",slug:"silver-particulate-films-on-compatible-softened-polymer-composites",totalDownloads:2125,totalCrossrefCites:0,totalDimensionsCites:1,signatures:"Pratima Parashar",downloadPdfUrl:"/chapter/pdf-download/42256",previewPdfUrl:"/chapter/pdf-preview/42256",authors:[{id:"142089",title:"Dr.",name:"Pratima",surname:"Parashar Pandey",slug:"pratima-parashar-pandey",fullName:"Pratima Parashar Pandey"}],corrections:null},{id:"42257",title:"Liquid-Solid Phase Equilibria of Paraffinic Systems by DSC Measurements",doi:"10.5772/54575",slug:"liquid-solid-phase-equilibria-of-paraffinic-systems-by-dsc-measurements",totalDownloads:4484,totalCrossrefCites:2,totalDimensionsCites:6,signatures:"Luis Alberto Alcazar-Vara and Eduardo Buenrostro-Gonzalez",downloadPdfUrl:"/chapter/pdf-download/42257",previewPdfUrl:"/chapter/pdf-preview/42257",authors:[{id:"149836",title:"Dr.",name:"Eduardo",surname:"Buenrostro-Gonzalez",slug:"eduardo-buenrostro-gonzalez",fullName:"Eduardo Buenrostro-Gonzalez"},{id:"149837",title:"Dr.",name:"Luis A.",surname:"Alcazar-Vara",slug:"luis-a.-alcazar-vara",fullName:"Luis A. Alcazar-Vara"}],corrections:null},{id:"42248",title:"Thermal Analysis of Phase Transitions and Crystallization in Polymeric Fibers",doi:"10.5772/54063",slug:"thermal-analysis-of-phase-transitions-and-crystallization-in-polymeric-fibers",totalDownloads:4853,totalCrossrefCites:4,totalDimensionsCites:10,signatures:"W. Steinmann, S. Walter, M. Beckers, G. Seide and T. Gries",downloadPdfUrl:"/chapter/pdf-download/42248",previewPdfUrl:"/chapter/pdf-preview/42248",authors:[{id:"141006",title:"Mr.",name:"Wilhelm",surname:"Steinmann",slug:"wilhelm-steinmann",fullName:"Wilhelm Steinmann"},{id:"142699",title:"Mr.",name:"Markus",surname:"Beckers",slug:"markus-beckers",fullName:"Markus Beckers"}],corrections:null},{id:"42269",title:"Energy Expenditure Measured by Indirect Calorimetry in Obesity",doi:"10.5772/55605",slug:"energy-expenditure-measured-by-indirect-calorimetry-in-obesity",totalDownloads:4942,totalCrossrefCites:2,totalDimensionsCites:4,signatures:"Eliane Lopes Rosado, Vanessa Chaia Kaippert and Roberta Santiago de Brito",downloadPdfUrl:"/chapter/pdf-download/42269",previewPdfUrl:"/chapter/pdf-preview/42269",authors:[{id:"150535",title:"Dr.",name:"Eliane",surname:"Rosado",slug:"eliane-rosado",fullName:"Eliane Rosado"}],corrections:null},{id:"42252",title:"Thermal Decomposition Kinetics of Aged Solid Propellant Based on Ammonium Perchlorate – AP/HTPB Binder",doi:"10.5772/52109",slug:"thermal-decomposition-kinetics-of-aged-solid-propellant-based-on-ammonium-perchlorate-ap-htpb-binder",totalDownloads:3944,totalCrossrefCites:2,totalDimensionsCites:9,signatures:"R. F. B. Gonçalves, J. A. F. F. Rocco and K. Iha",downloadPdfUrl:"/chapter/pdf-download/42252",previewPdfUrl:"/chapter/pdf-preview/42252",authors:[{id:"140146",title:"Dr.",name:"Rene",surname:"Gonçalves",slug:"rene-goncalves",fullName:"Rene Gonçalves"},{id:"141917",title:"Dr.",name:"José Atílio",surname:"Fritz Fidel Rocco",slug:"jose-atilio-fritz-fidel-rocco",fullName:"José Atílio Fritz Fidel Rocco"},{id:"142049",title:"Dr.",name:"Koshun",surname:"Iha",slug:"koshun-iha",fullName:"Koshun Iha"}],corrections:null},{id:"42258",title:"Numerical Solutions for Structural Relaxation of Amorphous Alloys Studied by Activation Energy Spectrum Model",doi:"10.5772/53723",slug:"numerical-solutions-for-structural-relaxation-of-amorphous-alloys-studied-by-activation-energy-spect",totalDownloads:1715,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Kazu-masa Yamada",downloadPdfUrl:"/chapter/pdf-download/42258",previewPdfUrl:"/chapter/pdf-preview/42258",authors:[{id:"140988",title:"Dr.",name:"Kazu-Masa",surname:"Yamada",slug:"kazu-masa-yamada",fullName:"Kazu-Masa Yamada"}],corrections:null},{id:"42251",title:"Thermal Analysis of Sulfur and Selenium Compounds with Multiple Applications, Including Anticancer Drugs",doi:"10.5772/53048",slug:"thermal-analysis-of-sulfur-and-selenium-compounds-with-multiple-applications-including-anticancer-dr",totalDownloads:2038,totalCrossrefCites:1,totalDimensionsCites:3,signatures:"Daniel Plano, Juan Antonio Palop and Carmen Sanmartín",downloadPdfUrl:"/chapter/pdf-download/42251",previewPdfUrl:"/chapter/pdf-preview/42251",authors:[{id:"67542",title:"Prof.",name:"Carmen",surname:"Sanmartín",slug:"carmen-sanmartin",fullName:"Carmen Sanmartín"},{id:"67557",title:"Prof.",name:"Juan Antonio",surname:"Palop",slug:"juan-antonio-palop",fullName:"Juan Antonio Palop"},{id:"69223",title:"Dr.",name:"Daniel",surname:"Plano",slug:"daniel-plano",fullName:"Daniel Plano"}],corrections:null},{id:"42265",title:"Calorimetric Determination of Heat Capacity, Entropy and Enthalpy of Mixed Oxides in the System CaO–SrO–Bi2O3–Nb2O5–Ta2O5",doi:"10.5772/54064",slug:"calorimetric-determination-of-heat-capacity-entropy-and-enthalpy-of-mixed-oxides-in-the-system-cao-s",totalDownloads:2917,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Jindřich Leitner, David Sedmidubský,\nKvětoslav Růžička and Pavel Svoboda",downloadPdfUrl:"/chapter/pdf-download/42265",previewPdfUrl:"/chapter/pdf-preview/42265",authors:[{id:"140149",title:"Prof.",name:"Jindrich",surname:"Leitner",slug:"jindrich-leitner",fullName:"Jindrich Leitner"},{id:"167242",title:"Prof.",name:"David",surname:"Sedmidubský",slug:"david-sedmidubsky",fullName:"David Sedmidubský"},{id:"167243",title:"Prof.",name:"Květoslav",surname:"Růžička",slug:"kvetoslav-ruzicka",fullName:"Květoslav Růžička"},{id:"167244",title:"Prof.",name:"Pavel",surname:"Svoboda",slug:"pavel-svoboda",fullName:"Pavel Svoboda"}],corrections:null},{id:"42261",title:"Differential Scanning Calorimetry Studies of Phospholipid Membranes: The Interdigitated Gel Phase",doi:"10.5772/51882",slug:"differential-scanning-calorimetry-studies-of-phospholipid-membranes-the-interdigitated-gel-phase",totalDownloads:4197,totalCrossrefCites:3,totalDimensionsCites:25,signatures:"Eric A. Smith and Phoebe K. Dea",downloadPdfUrl:"/chapter/pdf-download/42261",previewPdfUrl:"/chapter/pdf-preview/42261",authors:[{id:"139501",title:"Prof.",name:"Phoebe",surname:"Dea",slug:"phoebe-dea",fullName:"Phoebe Dea"},{id:"141802",title:"Mr.",name:"Eric",surname:"Smith",slug:"eric-smith",fullName:"Eric Smith"}],corrections:null},{id:"42267",title:"Oxidative Stability of Fats and Oils Measured by Differential Scanning Calorimetry for Food and Industrial Applications",doi:"10.5772/54486",slug:"oxidative-stability-of-fats-and-oils-measured-by-differential-scanning-calorimetry-for-food-and-indu",totalDownloads:7949,totalCrossrefCites:7,totalDimensionsCites:18,signatures:"M.D.A. Saldaña and S.I. Martínez-Monteagudo",downloadPdfUrl:"/chapter/pdf-download/42267",previewPdfUrl:"/chapter/pdf-preview/42267",authors:[{id:"150352",title:"Prof.",name:"Marleny D A",surname:"Saldana",slug:"marleny-d-a-saldana",fullName:"Marleny D A Saldana"},{id:"150353",title:"Ph.D.",name:"Sergio I.",surname:"Martínez-Monteagudo",slug:"sergio-i.-martinez-monteagudo",fullName:"Sergio I. Martínez-Monteagudo"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},relatedBooks:[{type:"book",id:"51",title:"Desalination",subtitle:"Trends and Technologies",isOpenForSubmission:!1,hash:null,slug:"desalination-trends-and-technologies",bookSignature:"Michael Schorr",coverURL:"https://cdn.intechopen.com/books/images_new/51.jpg",editedByType:"Edited by",editors:[{id:"16436",title:"Dr.",name:"Michael",surname:"Schorr",slug:"michael-schorr",fullName:"Michael Schorr"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1981",title:"Distillation",subtitle:"Advances from Modeling to Applications",isOpenForSubmission:!1,hash:"a4aa04e09e4d644e7e47345f69eb6a7b",slug:"distillation-advances-from-modeling-to-applications",bookSignature:"Sina Zereshki",coverURL:"https://cdn.intechopen.com/books/images_new/1981.jpg",editedByType:"Edited by",editors:[{id:"112622",title:"Dr.",name:"Sina",surname:"Zereshki",slug:"sina-zereshki",fullName:"Sina Zereshki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"854",title:"Micromachining Techniques for Fabrication of Micro and Nano Structures",subtitle:null,isOpenForSubmission:!1,hash:"8087b869b2e754a00b9f69835b14f51e",slug:"micromachining-techniques-for-fabrication-of-micro-and-nano-structures",bookSignature:"Mojtaba Kahrizi",coverURL:"https://cdn.intechopen.com/books/images_new/854.jpg",editedByType:"Edited by",editors:[{id:"113045",title:"Dr.",name:"Mojtaba",surname:"Kahrizi",slug:"mojtaba-kahrizi",fullName:"Mojtaba Kahrizi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3616",title:"New Developments in Liquid Crystals",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"new-developments-in-liquid-crystals",bookSignature:"Georgiy V Tkachenko",coverURL:"https://cdn.intechopen.com/books/images_new/3616.jpg",editedByType:"Edited by",editors:[{id:"2659",title:"Mr.",name:"Georgiy",surname:"Tkachenko",slug:"georgiy-tkachenko",fullName:"Georgiy Tkachenko"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3487",title:"Column Chromatography",subtitle:null,isOpenForSubmission:!1,hash:"b521796f3859c30413e7fe048c47c996",slug:"column-chromatography",bookSignature:"Dean F. Martin and Barbara B. Martin",coverURL:"https://cdn.intechopen.com/books/images_new/3487.jpg",editedByType:"Edited by",editors:[{id:"161611",title:"Dr.",name:"Dean",surname:"Martin",slug:"dean-martin",fullName:"Dean Martin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6770",title:"Laboratory Unit Operations and Experimental Methods in Chemical Engineering",subtitle:null,isOpenForSubmission:!1,hash:"a139364b1ca4b347f2321a0430079830",slug:"laboratory-unit-operations-and-experimental-methods-in-chemical-engineering",bookSignature:"Omar M. Basha and Badie I. Morsi",coverURL:"https://cdn.intechopen.com/books/images_new/6770.jpg",editedByType:"Edited by",editors:[{id:"174770",title:"Dr.",name:"Omar M.",surname:"Basha",slug:"omar-m.-basha",fullName:"Omar M. Basha"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5452",title:"Distillation",subtitle:"Innovative Applications and Modeling",isOpenForSubmission:!1,hash:"ec5881c323f1825291a733ddb8356285",slug:"distillation-innovative-applications-and-modeling",bookSignature:"Marisa Fernandes Mendes",coverURL:"https://cdn.intechopen.com/books/images_new/5452.jpg",editedByType:"Edited by",editors:[{id:"35803",title:"Dr.",name:"Marisa",surname:"Mendes",slug:"marisa-mendes",fullName:"Marisa Mendes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],ofsBooks:[]},correction:{item:{id:"66063",slug:"corrigendum-to-introductory-chapter-historical-perspective-and-brief-overview-of-insulin",title:"Corrigendum to: Introductory Chapter: Historical Perspective and Brief Overview of Insulin",doi:null,correctionPDFUrl:"https://cdn.intechopen.com/pdfs/66063.pdf",downloadPdfUrl:"/chapter/pdf-download/66063",previewPdfUrl:"/chapter/pdf-preview/66063",totalDownloads:null,totalCrossrefCites:null,bibtexUrl:"/chapter/bibtex/66063",risUrl:"/chapter/ris/66063",chapter:{id:"63640",slug:"introductory-chapter-historical-perspective-and-brief-overview-of-insulin",signatures:"Gaffar Sarwar Zaman",dateSubmitted:"June 29th 2018",dateReviewed:"August 28th 2018",datePrePublished:"November 5th 2018",datePublished:"February 6th 2019",book:{id:"6675",title:"Ultimate Guide to Insulin",subtitle:null,fullTitle:"Ultimate Guide to Insulin",slug:"ultimate-guide-to-insulin",publishedDate:"February 6th 2019",bookSignature:"Gaffar Zaman",coverURL:"https://cdn.intechopen.com/books/images_new/6675.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"203015",title:"Dr.",name:"Gaffar Sarwar",middleName:"Sarwar",surname:"Zaman",slug:"gaffar-sarwar-zaman",fullName:"Gaffar Sarwar Zaman"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"203015",title:"Dr.",name:"Gaffar Sarwar",middleName:"Sarwar",surname:"Zaman",fullName:"Gaffar Sarwar Zaman",slug:"gaffar-sarwar-zaman",email:"gffrzaman@gmail.com",position:null,institution:{name:"King Khalid University",institutionURL:null,country:{name:"Saudi Arabia"}}}]}},chapter:{id:"63640",slug:"introductory-chapter-historical-perspective-and-brief-overview-of-insulin",signatures:"Gaffar Sarwar Zaman",dateSubmitted:"June 29th 2018",dateReviewed:"August 28th 2018",datePrePublished:"November 5th 2018",datePublished:"February 6th 2019",book:{id:"6675",title:"Ultimate Guide to Insulin",subtitle:null,fullTitle:"Ultimate Guide to Insulin",slug:"ultimate-guide-to-insulin",publishedDate:"February 6th 2019",bookSignature:"Gaffar Zaman",coverURL:"https://cdn.intechopen.com/books/images_new/6675.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"203015",title:"Dr.",name:"Gaffar Sarwar",middleName:"Sarwar",surname:"Zaman",slug:"gaffar-sarwar-zaman",fullName:"Gaffar Sarwar Zaman"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"203015",title:"Dr.",name:"Gaffar Sarwar",middleName:"Sarwar",surname:"Zaman",fullName:"Gaffar Sarwar Zaman",slug:"gaffar-sarwar-zaman",email:"gffrzaman@gmail.com",position:null,institution:{name:"King Khalid University",institutionURL:null,country:{name:"Saudi Arabia"}}}]},book:{id:"6675",title:"Ultimate Guide to Insulin",subtitle:null,fullTitle:"Ultimate Guide to Insulin",slug:"ultimate-guide-to-insulin",publishedDate:"February 6th 2019",bookSignature:"Gaffar Zaman",coverURL:"https://cdn.intechopen.com/books/images_new/6675.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"203015",title:"Dr.",name:"Gaffar Sarwar",middleName:"Sarwar",surname:"Zaman",slug:"gaffar-sarwar-zaman",fullName:"Gaffar Sarwar Zaman"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"10918",leadTitle:null,title:"Digital Economy",subtitle:null,reviewType:"peer-reviewed",abstract:"This book will be a self-contained collection of scholarly papers targeting an audience of practicing researchers, academics, PhD students and other scientists. The contents of the book will be written by multiple authors and edited by experts in the field.",isbn:null,printIsbn:null,pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,hash:"dbdfd9caf5c4b0038ff4446c7bc6a681",bookSignature:"",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10918.jpg",keywords:null,numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 25th 2020",dateEndSecondStepPublish:"December 16th 2020",dateEndThirdStepPublish:"February 14th 2021",dateEndFourthStepPublish:"May 5th 2021",dateEndFifthStepPublish:"July 4th 2021",remainingDaysToSecondStep:"2 months",secondStepPassed:!0,currentStepOfPublishingProcess:1,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"7",title:"Business, Management and Economics",slug:"business-management-and-economics"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:null},relatedBooks:[{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3621",title:"Silver Nanoparticles",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"silver-nanoparticles",bookSignature:"David Pozo Perez",coverURL:"https://cdn.intechopen.com/books/images_new/3621.jpg",editedByType:"Edited by",editors:[{id:"6667",title:"Dr.",name:"David",surname:"Pozo",slug:"david-pozo",fullName:"David Pozo"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"19824",title:"Sarcopenia, Sarcopenic Obesity and Insulin Resistance",doi:"10.5772/22008",slug:"sarcopenia-sarcopenic-obesity-and-insulin-resistance",body:'The number of people greater than 65 years old will increase from 35.9 million in 2003 (12.4%) to 71.5 million (20%) by the year 2030. Current estimates in the United States demonstrate that this population is numbered at 39.6million, representing 12.6% of the population, or one in every eight Americans. Women tend to outnumber men and their life expectancy is undoubtedly longer. These numbers reflect predominantly the influx of baby boomers into this age group (Spillman and Lubitz 2000).
Since the early part of 1900, the elderly age group has nearly tripled from 4.1% in 1900 to 12.9% in 2009, and the number of individuals has increased over thirteen times (from 3.1 to 39.6 million). The ‘old old’, persons aged >80 are one of the fastest growing segments of the population (A Profile of Older Americans 2010). In addition, life expectancy in the elderly has been increasing in the past few decades and continues to do so (Lubitz et al. 2003). For instance, those reaching the age of 65 years, had a mean life expectancy of 19.9 and 17.2 years, respectively, for females and males. Framed alternatively, life expectancy at birth in 2007 was 77.9 years, approximately 30 years longer than a child born in 1900. Compounded with a reduced death rate due to medical advances, patients are living longer than they previously were, much of this due to improved survival from cardiovascular and cerebrovascular diseases (Ford et al. 2007). Figure #1 demonstrates data on the aging population in the United States, and Figure #2 demonstrates estimates from worldwide figures.
In a report published by the Organisation for Economic Co-operation and Development (OECD) in 2007, these trends observed in the United States are paralleled elsewhere. In certain countries, specifically Italy and Japan, one out of every five people is aged 65+ (Trends in Severe Disability Among Elderly People: Assessing the Evidence in 12 OECD Countries and the Future Implications 2007). As in the United States, Table #1 illustrates the proportion of people that will be 85+, which is the fastest growing segment of the population. Understandably these are worrisome trends as these individuals are, from a public health standpoint, the ones with the most number of chronic conditions, disabilities and greatest long-term care needs. It is believed that unless there are significant improvements in functional awareness and improvement, this group poses the largest burden on existing healthcare resources.
Projected Elderly Population of the United States: 2000-2050, Data obtained from the US Census Bureau from the year 2000. www.census.gov
Population in OECD Countries of Elderly >65 years old. Proportion of People >65 years old in a sample of Organisation for Economic Co-operation and Development (OECD) countries from 1960 to projects at 2050. Lafortune, G. and G. Balestat (2007), "Trends in Severe Disability Among Elderly People: Assessing the Evidence in 12 OECD Countries and the Future Implications", OECD Health Working Papers, No. 26, http://dx.doi.org/10.1787/217072070078
Proportion of Patients Aged >85 years in OECD Countries. All numbers in the table above are percentages Lafortune, G. and G. Balestat (2007), "Trends in Severe Disability Among Elderly People: Assessing the Evidence in 12 OECD Countries and the Future Implications", OECD Health Working Papers, No. 26, http://dx.doi.org/10.1787/217072070078
As patients age, health needs escalate, resulting in disproportionate consumption of health care resources (Lakdawalla, Goldman, and Shang 2005). According to a 1995 US Bureau of Census publication, approximately 80% of >65 year olds will have a minimum of one chronic medical illness, with many suffering multiple. A number of elderly subjects report a type of disability, including hearing impairment, visual impairment, cognitive impairment, self-care troubles, or needing higher level of care. A number of studies have demonstrated the impact of aging on disability. An early study by Vita et al (Vita et al. 1998) studied 1,741 university alumni, first surveyed in 1962 (mean age 43 years) and then annually in 1986. Cumulative disability was determined using a health-assessment questionnaire. Those with high health risks at baseline had earlier onset of disability and had a lower follow-up disability index. The onset of disability was postponed by more than 5 years in the low-risk subject group than those with high risk behaviors. Predictors of subsequent disability included smoking, body mass index and exercise patterns in midlife and late-adulthood. These authors concluded that although disability is inevitable, the time frame was compressed into fewer years at the end of life.
In one study the number of geriatric conditions was related to dependency in activities of daily living (Cigolle et al. 2007). These authors used data from the Health and Retirement study survey administered in 2000 on subjects >65 years (n=11,093) residing either in the community or in nursing homes, and assessed the number of geriatric syndromes and dependency of activities of daily living (ADL)s. Of those >65 years, ~49.9% had at least one geriatric syndrome, prevalence rates that were as common as heart disease and diabetes. After adjusting for demographic characteristics and chronic diseases, the risk ratio for dependence on ADLs were 2.1 [95%CI: 1.9-2.4] for one geriatric condition, 3.6 [3.1-4.1] for two conditions, and 6.6 [5.6-7.6] for greater than 3 conditions. This important study highlights the similar prevalences of geriatric conditions to chronic diseases in elderly adults and their strong association to disability. As the authors note, these are often overlooked in the care of older adults. One’s reported disability increases with age. In a study by the Administration on Aging in the United States, approximately 56% of persons >80years reported a severe disability and 29% reported the need for some type of assistance (A Profile of Older Americans 2010). This is of course impairs one self-reported health status and may lead to institutionalization.
As one ages, there are changes in body composition. As patients age, there is a reduction in lean mass and a progressive increase in fat mass. This normally occurs after the age of 20-30 years and can be extensive, involving up to 40% of a population (Baumgartner et al. 1995; Flynn et al. 1989; Gallagher et al. 1997; Muller et al. 1996). As is demonstrated in Figure #3, maximal fat free mass (muscle mass) is usually reached at about 20 years of age and fat mass peaks at the ages between 60 and 70 years (Baumgartner et al. 1995; Gallagher et al. 1997). Particularly after the age of 70 years, there is a redistribution of body fat and fat free mass, with reductions in peripheral skeletal muscle (Beaufrere and Morio 2000), increases in intramuscular and intrahepatic fat, both of which are associated with insulin resistance (Cree et al. 2004).
Muscle Mass Changes with Aging.Peak muscle mass occurs between the ages of 20 and 30 years, and naturally declines as one ages.
Declining function parallels the concept of sarcopenia. Sarcopenia comes from the Greek word, “Sarcos” meaning flesh, and ‘penia’ meaning lack of. This age-related decline in lean body mass can affect ambulation, mobility, and functional independence (Morley et al. 2001). An analogy often used is the age-related decline in bone mass, where, once it reaches a critical level, one’s risk of fracture is increased. Sarcopenia can be conceptualized on the spectrum of frailty and disability and has been shown to be increasingly prevalent with age. More recently, the concept of declining strength has been incorporated into the definition, although, a widely accepted definition of sarcopenia has yet to be established (Cruz-Jentoft et al. 2010)). Sarcopenia indeed can be considered a geriatric syndrome. These are common, complex and costly entities of impaired health in elderly individuals which involve multiple systems, have a myriad of interactions, and have varied phenotypes. Falls, urinary incontinence and delirium are but some examples of such. Sarcopenia has also been associated with malnutrition and diminished physical function, both of which are associated with geriatric functional decline and mortality. The loss of muscle mass during the aging process is important clinically as it reduces strength and exercise capacity, both which are needed to perform one’s activity of daily living. It is hypothesized that subjects reach a given threshold at which impairment in function occurs. Absolute loss of muscle mass leads to reduced muscle function and hence physical performance measures are increasingly being used in the definition and identification of sarcopenia. There are a number of definitions outlined in the literature making standardization, particularly in clinical practice, rather difficult (Baumgartner et al. 1998; Bouchard, Dionne, and Brochu 2009;\n\t\t\t\tDavison et al. 2002; Zoico et al. 2004). Prevalence rates can vary dramatically and is the subject of current investigation. This syndrome has a number of risk factors, a number that are modifiable over the course of one’s life span, but can have profound impact on one’s overall state of health and quality of life.
The trajectory of one’s muscle loss can be altered by physical exercise and/or the environment. Muscle mass develops up to the age of 20 and 30 years, and is relatively maintained throughout adult life. As one ages, muscle mass decreases and one reaches a threshold whereby low muscle mass will inevitably lead to disability and future complications (Sayer et al. 2008).
Assessing sarcopenia has been a challenge in the research literature. There are a number of definitions that have been proposed, yet they have been developed on different populations and ethnicities, factors which are known to affect body composition. Additionally, muscle quality and strength have yet to be incorporated into such definitions. Recently, there was a European consensus on the definition and diagnosis on Sarcopenia (Cruz-Jentoft et al. 2011). This taskforce suggested the use of both low muscle mass and low muscle function (strength or performance) for the diagnosis of sarcopenia. The rationale for using these criteria include that muscle mass and muscle strength are not directly correlated to each other (Goodpaster et al. 2006; Janssen et al. 2004). DEXA scanning is unique in that it not only allows ascertainment of muscle mass but can be used concurrently to assess bone density as well. Bioelectrical impedance on the other hand is inexpensive, and easily reproducible with prediction equations available to calculate various measures of body composition (Chumlea et al. 2002) and has been considered as a portable alternative to DEXA. Body water can affect these results, though, and elders’ changes in body composition, both in health and disease, may affect such estimates. Unfortunately, the relative availability and cost of DEXA in particular can be prohibitively expensive, not portable, and would be impractical to use for routine use in an office setting (Chien, Kuo, and Wu 2010). Other measures, including grip strength, knee strength, or gait speed have been proposed but no studies have validated such measures.
Figure #4 (Cruz-Jentoft et al. 2011) illustrates the proposed mechanisms of sarcopenia. These vary over one’s lifespan and are impacted by each other, with interactions that are poorly understood.
Along with the rise in the number of elderly patients, the number of patients diagnosed with overweight and obesity are increasing. Obesity is defined by the World Health Organization (WHO) as a body mass index (BMI) greater than or equal to over 30kg/m2, calculated as the body weight in kilograms divided by the height in meters squared (Quetelet 1871). Little attention has been given to the obese elder, largely due to a paucity of studies including elderly (>65 years old) patients. Yet, current estimates, specifically in the United States population, indicate that the prevalence of obesity continues to rise, and exceeds 35% of the general population, a trend that is also observed in elderly subjects. The prevalence of obesity has increased almost three-fold from 1960-2008, and continues to rise at a frightening rate (Flegal et al. 2011). Latest estimates illustrate by using body mass index as a surrogate for obesity estimates, that 33.6% of women and 37.1% of males are classified as having obesity over the age of 60years (Flegal et al. 2010). These numbers are remarkably higher than estimates in 1999 whereby 31.8% of males were obese, yet prevalence estimates seem to be similar in females. However, trends demonstrate rises in prevalence rates, in particular subjects with morbid obesity (BMI >40kg/m2). Figure #5 illustrates these trends.
Mechanisms of Sarcopenia. The Sarcopenia taskforce did conclude the importance of identifying such mechanisms to better understand the underlying pathophysiology, and to allow the identifications of interventions these targets.
Obesity is associated with an increased number of medical conditions and complications, and is a recognized independent cardiovascular risk factor. Obesity is associated with an increased risk of both physical and cognitive disability (Beydoun, Beydoun, and Wang 2008; Jensen 2005). Houston et al used data from the Health, Aging and Body Composition Study in looking the association between overweight and/or obesity in young, middle, and late adulthood and its cumulative effect on incident mobility limitation in 2,845 community dwelling US adults (Houston et al. 2009). The authors identified mobility limitations as difficulty walking ¼ mile or climbing 10 steps over a 7-year of follow-up. Men and women who were overweight or obese at all three time points had increased risk of mobility limitations compared to normal weights (HR 1.61 [1.25-2.06], and 2.85 [2.15-3.78]. There appeared to be a graded response (P<0.001) on risk of mobility limitations on the cumulative effect of obesity in men and women. Earlier onset of obesity in life contributed to increased mobility limitations of old age (Houston et al. 2009). This is also observed in Figure #6.\n\t\t\t
Obesity in the United States, 1960-2008.Trends in the obesity epidemic in the United States in both males and females over the age of 60 years. In males, the trajectory of multiple epidemiological surveys is that of an increase. In females, there was an initial drop, but subsequent, yet steady increase
Mobility Limitations and Body Size, Caption: Hazard ratios and 95% confidence intervals for incident mobility limitation among Men (A) and women (B) by history of overweight or obesity (BMI >25kg/m2), the Health, Aging and Body Composition Study, 7 years of followup. Models were adjusted for age, race, field center, education, smoking status, alcohol consumption, and physical activity at study baseline. (Houston et al. 2009)
A recent study using NHANES data demonstrated a J or U-shaped association between overweight/obesity and years of life lost, with the study authors concluding that obesity appears to decrease life expectancy (Figure #7) (Flegal et al. 2005). In addition, recent meta-analyses using body mass index as a surrogate for obesity have demonstrated that regardless of age, mortality is increased in patients with a BMI <22kg/m2 and those who are morbidly obese (BMI>35kg/m2) [Figure #8] (Whitlock et al. 2009). Continued debate in the literature with regard to associations of mortality with BMIs between 25 and 35 continue and will not be reviewed here. Obesity has also been demonstrated to be associated with disability, lower quality of life, and increased resource utilization, particularly in elderly subjects (Guralnik, Fried, and Salive 1996). Obesity is associated with nursing home admissions and increasing one’s risk to be homebound (Jensen et al. 2006; Valiyeva et al. 2006; Zizza et al. 2002). These issues all create a worrisome public health concern in that, in one study, 9% of all total excess healthcare costs may be attributable to overweight or obesity (Finkelstein, Fiebelkorn, and Wang 2003).
Relative Risks of Mortality by Body Mass Index Category by Epidemiological Survey Data, Caption: BMI indicates body mass index, measured as weight in kilograms divided by the square of height in meters. The reference category with relative risk 1.0 is BMI 18 to <25. Error bars indicate 95% confidence intervals. Copryight © American medical Association, JAMA 2005;293:1861-1867, All Rights Reserved. (Flegal et al. 2005)
All-cause mortality vs. Body Mass Index.These studies demonatrate J-shaped curves in all age groups, in the range 15-50kg/m2 by age at risks (excluding the first 5 years of followup) (Whitlock et al. 2009)
Often times, we consider sarcopenia in the context of weight loss and cachexia; but sarcopenia can occur with obesity. The impact of obesity on sarcopenia continues to be a subject of investigation and emerging as a public health problem. In subjects who gain weight, there is proportionally an increase in fat mass as compared to lean mass. As described above, both entities lead to disability and the synergistic effects lead to worsening disability. These subjects can also be considered ‘fat frail’ who suffer from increased weakness from sarcopenia and the requirement to carry additional weight from obesity (Launer et al. 1994).
Common inflammatory pathways have linked sarcopenia and obesity yet the interplay between these two entities is poorly understood. One author hypothesized that both sarcopenia and obesity are similar behaviorally and biologically (Roubenoff 2000). One of the most trophic effects on muscle is physical activity, which normally falls as people age. Concurrently, there is a positive energy balance and weight gain, predominantly fat in nature. Additionally, this loss of fat-free mass (muscle) lowers the amount of tissues that can respond to insulin targeting, thereby promoting insulin resistance, metabolic syndrome and obesity (Reaven 1988). Muscle and fat are both metabolically active, the latter producing TNF-a, IL-6 and adipokines all of which have a direct catabolic effect on the former, and promote insulin resistance. Leptin and low adiponectin concentrations have been found to negatively impact muscle mass and lead to a decline in muscle quality (Hamrick et al. 2010). On a biological level, macrophages in adipocytes or in adipose tissue, produce such proinflammatory cytokines (Fantuzzi 2005) which can upregulate the inflammatory response. Cesari et al. evaluated the relationship between body-composition measures and inflammatory markers, using data from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors study (Cesari et al. 2005). These authors demonstrated the positive association of CRP and IL-6 with BMI (p=0.03 and p<0.001) and total fat mass (<0.001 and <0.001), and inverse association with fat-adjusted appendicular lean mass (p<0.002 and p=0.02). Using data from the INChianti study, global and central obesity directly affect inflammation, negatively affects muscle strength and can contribute to the development and progression of sarcopenic obesity (Schrager et al. 2007).
This cycle continues until the development of disability and medical illnesses. Furthermore, compounding the decline in neuronal and hormonal signals that occur with aging, malnutrition, and loss of a-motor units and changes in gene expression, further increase the risk of this entity in occurring (Doherty et al. 1993; Marcell 2003; Morley et al. 2001). This pro-inflammatory state leads to a perpetuating cycle of reduced muscle strength among obese subjects inevitably further contributing to functional decline. The aging process also itself leads to elevated IL-6 levels, TNF-α and CRP as well. While a number of chronic medical conditions prevalent in elders, including cancer, COPD and heart failure are associated with elevated pro-inflammatory levels and can lead to loss of muscle mass, the process of age-related sarcopenia is a natural phenomenon and differs from such.
Baumgartner et al. defined sarcopenic obesity as a muscle mass index less than two standard deviations below the sex-specific reference for a young healthy population (Baumgartner 2000). Alternative definitions have been used by other authors (Bouchard, Dionne, and Brochu 2009;\n\t\t\t\tDavison et al. 2002;\n\t\t\t\tZoico et al. 2004), yet a harmonious definition has yet to be solidified at this time. More recently, the incorporation of muscle quality into these definitions has been proposed (Cruz-Jentoft et al. 2010). The debate is outside the scope of this chapter.
A number of studies have outlined the differences between those with and without sarcopenia or obesity. In one of the pivotal studies, 52 subjects matched obese elderly, non-obese frail, and non-obese, non-frail were evaluated on objective measures of functional status and health-related quality of life and differences in body composition (Villareal et al. 2004). They discovered that obese and non-obese frail groups had lower and similar scores in physical function, functional status and impairments in strength and walking speed. They concluded that physical frailty in obese elders was associated with lower fat free mass (lean mass), poor muscle quality and worsening quality of life.
One of the more pivotal studies by Baumgartner’s group demonstrated the combined effect of obesity and muscle mass or strength on physical functioning or disability (Baumgartner 2000). Baumgartner’s group examined the impact of sarcopenic obesity and incident instrumental ADL disability in the New Mexico elder health survey and New Mexico aging process study (Baumgartner et al. ). This study ascertained ADLs in patients longitudinally and assigned points (0-2) depending on whether someone could not perform an instrumental activities of daily living, could do it with difficulty, or could do it independently. Their primary outcome was time to a drop in ADL, defined as a drop in 2 points. As can be seen in the Figure #9 below, only those with sarcopenic obesity had a markedly shorter time to drop in ADLs. The other three groups were no different from each other (sarcopenic non-obese, obese non-sarcopenic, and non-obese non-sarcopenic).
Incident Disabilty over Time. SO – sarcopenic obesity; S – sarcopenia; O – obesity; NS – non-sarcopenic; NO – non-obese
The data demonstrate that subjects with Sarcopenic Obesity have worsened disability, than subjects with sarcopenia alone, obesity alone, or neither sarcopenia nor obesity(Baumgartner et al. 2004).
Other cross-sectional studies have demonstrated conflicting results based on NHANES III (Davison et al. 2002) and a sample of elder females in Verona (Zoico et al. 2004). Davison’s study looked at 1,526 females and 1,391 males who were 70 years and older. These authors observed that women in the highest quintile for percent body fat were twice as likely to report functional limitations than in the other comparison groups, and weaker but similar relationships were observed in men. Low muscle mass and sarcopenia with obesity, in this study were not associated with additional limitations. In Zoico’s cross-sectional study of 167 females, aged 67-78, those in the highest quintile of body fat demonstrated a significantly higher prevalence of functional limitation, but 40% of sarcopenic elderly women and 50% of elderly women with high body fat and normal muscle mass were functionally limited (Figure #10). Functional limitation increased in those with a higher degree of sarcopenia. They demonstrated that isometric leg strength was significantly lower in subjects with sarcopenia and sarcopenic obesity. These two studies used the same categorization to define these entities. It was felt that using muscle mass instead of a functional measure such as strength as an indicator of sarcopenia may have explained the lack of results.
Self-Reported Functional Limitations
There were no differences between subjects in this cohort on self-reported functional limitations with regard to body composition measures (Zoico et al. 2004).
There are other studies that have demonstrated the relationship between sarcopenic obesity and higher degrees of functional limitations. Stenholm et al (Stenholm et al. 2008) examined the association between different obesity indicators and walking limitations in examining the role of C-reactive protein and handgrip strength. This cross-sectional study of a Finnish population looked at subjects >55 years, and demonstrated that the highest two quartiles of body fat percent and C-reactive protein and the lowest two quartiles of handgrip strength were significantly associated with greater risk of walking limitations after adjusting for chronic diseases and other pertinent co-variates. The prevalence of walking limitations were higher in persons who had high fat and low handgrip (61%) than in those with low fat and high handgrip (7%). Their results are better observed in the figure below:
Walking Limitations, C-reactive Protein and Handgrip Strength.Age- and sex-adjusted prevalence of walking limitations according to body fat percentage levels according to C-reactive protein (CRP) and handgrip strength. Low, medium and high levels of body fat percentage, CRP and handgrip strength were defined by recoding quartiles of each variable in to three categories by combining quartiles II and III. Numbers inside the bars indicate the number of subjects in each category (Stenholm et al. 2008).
Finally, Cesari’s group (Cesari et al. 2009), using the InCHIANTI study, analyzed data from 934 participants aged 65 years and older with at least 6 years of follow-up. In unadjusted analyzes, muscle density (HR 0.78 [0.69-0.88]), muscle area (HR 0.75 [0.66-0.86]) and fat area (HR 0.82 [0.73-0.92) were associated with mortality. However, adjusting for confounders, these associations were no longer significant. Walking speed was associated with mortality risk (HR 0.73 [0.60-0.88]). The relationship with mortality, though, has been examined by other others. Rantanen (Rantanen et al. 2000). Those who were overweight in the lowest grip strength tertile had 1.4 times higher mortality risk compared to normal weight persons in the highest grip strength. Muscle strength has been previously examined as a predictor of mortality (Gale et al. 2007; Newman et al. 2006; Rantanen et al. 2003) and that of obesity has been fully described previously.
There are hormonal changes linking age-related decline in muscle strength and mass, which include insulin, growth hormone, and catecholamines as a few examples. On a cellular level, animal studies have demonstrated a relationship between obesity-related insulin resistance and insulin receptor signaling pathway. A low grade inflammation often is present in most obese patients which is a result of chronic activation of the innate immune system, leading to insulin resistance, impaired fasting glucose and diabetes. The involvement of cytokines and inflammation in obesity in relation to glucose metabolism continues to be controversial. Both IL-6 and TNF- alter insulin sensitivity by impacting given steps in the insulin signaling pathway. In animal models, resistin induces insulin resistance, but whether this occurs in humans is unclear. Subjects with obesity-related insulin resistance, type 2 diabetes and coronary heart disease have low levels of adiponectin. This hormone is known to inhibit liver gluconeogenesis and can promote fatty acid oxidation in skeletal muscle. These cytokines also are known to impact NF-kB and JNK systems (Zamboni et al. 2007).
With aging, muscle can be infiltrated with fat, and this may eventually perpetuate insulin resistance. In a large study of 2,964 elderly subjects with a mean age of 73.6 years, despite similar amounts of subcutaneous thigh fat, intermuscular fat was higher in subjects with type 2 diabetes and impaired glucose tolerance than in subjects with normal glucose tolerance (p<0.001) (Goodpaster et al. 2003). As expected higher rates of intermuscular fat and visceral abdominal fat were associated with higher fasting insulin levels. This study concluded that elderly men and women with normal body weight may be at risk for metabolic abnormalities, including type 2 diabetes if they possess an inordinate amount of muscle fat or visceral abdominal fat. A smaller study by the same group elucidated whether thigh fat was a determinant of insulin resistance. They compared a small number of subjects and confirmed that muscle composition reflected increased fat content was associated with insulin resistance (Goodpaster, Thaete, and Kelley 2000).
Furthermore, insulin is well known to be an anabolic hormone which may have a pleiotrophic effect on muscle tissue and protein metabolism. Lower protein synthesis and higher insulin levels occur in elderly subjects compared to younger subjects after food intake. Previous studies have shown that subjects with insulin resistance can negatively predict muscle strength, often seen in elderly subjects with diabetes. The correlation between insulin resistance and muscle strength is quite poor and accelerates the loss of leg muscle strength and quality. In a pilot study examining this relationship examined the homeostasis model assessment (HOMA-IR) in type 2 diabetes, demonstrated that knee extension, adjusted for body weight was significantly correlated with HOMA-IR in both sexes and that this relationship persisted as an independent determinant in a stepwise regression model (Nomura et al. 2007). In another study, the degree of insulin resistance was evaluated using HOMA-IR and muscle strength using handgrip strength. BMI-adjusted handgrip strength correlated positively with physical activity, muscle area, and muscle density (Abbatecola et al. 2005). Physical activity has a positive effect on muscle mass and quality specifically with resistance training (Goodpaster and Brown 2005). This latter activity is also known to improve insulin sensitivity and glycemic control.
Possible Mechanisms linking Ageing, Obesity, Sarcopenia and Insulin resistance (Zamboni et al. 2008)
Additional contributors to sarcopenia include insulin-like growth factor-1 (IGF-1) and growth hormone (GH), both of which decline with age. Growth hormone is associated with low fat mass, increased lean body mass and ideal metabolic profile, while IGF-1 can increase protein synthesis in existing muscles. One study partially described the relationship of the hypothalamic pituitary axis in subjects with sarcopenia and sarcopenic obesity. Using DEXA, they ascertained 45 subjects with varying degrees of adiposity and lean mass and measured pituitary function (Waters et al. 2008). They demonstrated that appendicular skeletal muscle mass was independently and negatively correlated with leptin in all groups, even after adjusting for body fat, and that subjects with sarcopenic obesity had lowered and blunted GH responses. Low levels of this anabolic hormone has been proposed to be positively associated with low muscle strength (Ceda et al. 2005). Using data from the Longitudinal Ageing Study Amsterdam (LASA), among subjects aged 65-88 years, serum testosterone levels were positively associated with muscle strength and physical performance (Schaap et al. 2005). With respect to IGF-1 levels, physiologically one would expect that the age-associated decline in IGF-1 levels would be associated with poorer muscle strength and mobility. Data from 617 women from Women’s Health and Aging Study were examined and demonstrated a positive association between IGF-1 levels and knee extensor strength (p=0.004) and walking speed (P<0.001). A decline in IGF-1 levels was associated with difficulty self-reported mobility tasks. It is hypothesized that the aging muscle loses the capability of secreting GH and the responsiveness to IGF-1 is also likely attenuated. Evidence suggests that exercise can reverse the latter. These may be molecular targets in the future to promote muscle building and prevent sarcopenia.
Diabetes is associated with an increased incidence of many geriatric syndromes. Many studies have demonstrated the impact of diabetes on functional impairment, including inability to ambulate and perform instrumental ADLs (Volpato et al. 2002; Gregg et al. 2002). Diabetes itself, on a microvascular level can lead to functional impairment, but notably, complications of diabetes have also been implicated. Diabetes has been implicated in fall risk (Volpato et al. 2005), fractures (Schwartz et al. 2001), urinary incontinence (Ebbesen et al. 2007) and depression (Anderson et al. 2001).
There are a number of similarities between diabetes and sarcopenia. It is known that persons with diabetes have an accelerated aging process leading to disability and frailty. Diabetes is known to lead to each of the components of the operationalized definition of frailty and insulin resistance appears to be a core factor in this pathophysiology (Morley 2008). In the Health, Aging and Body Composition study, type 2 diabetes was associated with lower skeletal muscle strength and quality, as well as excessive skeletal muscle mass loss (Park et al. 2006; Park et al. 2009). Loss of muscle mass has also been associated with type 2 diabetes in elderly subjects. Low grip strength as a surrogate for sarcopenia is associated with features of metabolic syndrome as well, post-prandial glucose levels and HOMA index/ insulin-resistance. It is believed that hyperglycemia directly impairs skeletal muscle contractility and force (Sayer et al. 2005) ; whether this is due to excessive toxicity of sugar alcohols on muscles remains elusive at this time. Other hypotheses include the accumulation of lipids which may affect insulin signaling (Janssen and Ross 2005; Furler et al. 2001; Shulman 2000), impaired rate of synthesis of muscular proteins, seen in both ageing and insulin resistance (Nair 2005; Rasmussen et al. 2006). Diabetics are at high risk for sarcopenia as there is a 1.5-2.0 fold increased rate of skeletal muscle mass and strength loss (Park et al. 2007). There are a number of similarities between metabolic syndrome and insulin resistance and one study by Sayer examined the relationship between these entities and sarcopenia (Sayer et al. 2007). Their findings suggested that impaired grip strength was associated, not only with individual constructs of the metabolic syndrome but also the composite definition itself. Although the authors acknowledge that further investigation is required to understand the underlying mechanisms, the potential for using grip strength and interventions tested thereof to improve muscle strength, could also potentially improve insulin resistance. The following figure (Figure #13) demonstrates some of the potentiating cellular mechanisms observed in diabetes.
There are a number of emerging studies observing the relationship between sarcopenia, obesity, sarcopenic obesity and diabetes. The Korean Sarcopenic Obesity Study examined the prevalence of sarcopenia in Korean subjects with and without type 2 diabetes (Kim et al. 2000). The study included 810 subjects, of which 414 had diabetes and 396 were controls, and demonstrated that the prevalence of sarcopenia was 15.7% and 6.9% in subjects with and without diabetes. Skeletal muscle index (muscle mass adjusted for height squared), as a measure of sarcopenia, was significantly lower in patients with diabetes compared to subjects without diabetes. In their multiple logistic regression model, type 2 diabetes was independently associated with sarcopenia (OR 3.06 [1.42-6.6.62)] than subjects without diabetes after adjusting for age, sex, BMI, smoking, alcohol consumption, physical activity, medications, blood pressure and lipid profiles. Quite interestingly, though, the prevalence of type 2 diabetes was highest in Mexican Americans using NHANES III data with the lowest prevalence of obesity and sarcopenia, while Whites had the highest prevalence of sarcopenic obesity (Castaneda and Janssen 2005). This study challenges whether there indeed is a relationship between sarcopenia and obesity. Whether ethnicities need to be accounted for due to differences in body composition is a matter of further investigation.
Biochemical Changes in Muscle in Diabetes, ↓, decreased, ↑ increased; KT, active human protein kinase (protein kinase-B); FOXO, forkhead protein; MURF, muscle ring finger protein; P13K, phosphatidyl inositol-3-kinase (Morley 2008).
In other population, specifically, dialysis subjects, diabetes is thought to be a risk factor for losing lean mass (Pupim et al. 2005). Muscle mass, particularly in dialysis patients, are known to decline continuously and hence this study suggested that controlling a risk factor for incipient sarcopenia (diabetes), would reduce this declining process. Many of the changes suggested, in one editorial, were due to systemic inflammatory cytokines previously described, often which are implicated in diabetes and insulin resistance (Kaysen 2005). This was echoed in another small study looking at changes in inflammatory cytokines implicated in losing lean mass (Pedersen et al. 2003).
Subjects with diabetes are at higher risk of developing peripheral neuropathy, which leads to a decrease in one’s motor end plates. This entity is important in maintaining muscle homeostasis and coordination of muscle contraction, therefore their loss can perpetuate and accelerate age-related decline in muscle mass. Diabetics also have impaired levels of growth hormone and pro-inflammatory cytokines. Additionally, the microvascular damage from hypoxia not only affects nerves, renal glomeruli and optic nerves, but also can lead to muscle hypoxia. Macrovascularly, atherosclerosis can lead to diminished peripheral blood flow to leg muscles leading to impaired strength. Other cellular entities are implicated, as well as other endocrine changes as illustrated in the figure below. Undoubtedly there is a relationship between the underlying pathophysiology of sarcopenia, insulin resistance and diabetes.
A number of studies are increasingly confirming the relationship between sarcopenia and reduced functional activities and disability. Sarcopenia and obesity are often thought as a preludes to frailty, known to adversely predict hospitalizations, morbidity, institutionalization and mortality (Figure #14). Reduced physical activity and a sedentary lifestyle are important risk factors for developing sarcopenia, which subsequently leads to physical disability and reduced physical performance (Figure #15). More importantly, those with elevated fat mass with sarcopenia are at even high risk. The relationship between sarcopenia, sarcopenic obesity and insulin resistance requires further investigation. The clinical implications are not insignificance in that globally, sedentary lifestyles are becoming the norm and the potential implications on utilization are not significant.
Possible Consequence of sarcopenic obesity in the Elderly (Zamboni et al. 2008)
Body Composition Changes Leading to Sarcopenic Obesity (Jarosz and Bellar 2009)
ADL – Activities of Daily Living
BMI – body mass index
BIA – bioelectrical impedance analysis;
DEXA – Dual Energy X-Ray Absorptiometry
HOMA – homeostatic model assessment
HOMA-IR – homeostasis model of assessment – insulin resistance
OECD – Organisation of Economic Cooperation and Development
US – United States
TNF- – tumor necrosis factor α
IL-6 – interleukine 6
GH – growth hormone
NK-kB - nuclear factor-kappa B
JNK - Jun N-terminal kinases
IGF-1 - insuline-like growth factor 1
Zika virus (ZIKV) is a single-stranded, positive-sense virus of the genus Flavivirus of the family Flaviviridae that was discovered in the Ziika forest of Uganda in 1947 [1]. The virus was isolated during a surveillance campaign to attempt to identify yellow fever virus in the region. Sentinel rhesus macaques were placed in cages in the canopy layer of the trees and monitored daily for spikes in temperature. One of the rhesus macaques became febrile and was bled to isolate the causative agent of the fever. Serum from clarified blood caused illness when injected intra-cranially in white mice and the brain homogenates from these animals contained the first isolate of ZIKV, MR766. It is noteworthy that this strain, which is used in many contemporaneous studies, was passaged over 100 times in mice to increase its virulence in rodents. A second strain, ZIKV 758, was made from another rhesus macaque injected with homogenates of Aedes africanus mosquitoes collected in that same area. These data demonstrate that ZIKV caused febrile disease in NHPs and could be isolated from mosquitoes, solidifying it as an arbovirus [1]. In the years since, many additional isolates have been made and the ones discussed in this review are listed in Table 1.
\nStrain | \nYear Isolation | \nLineage | \nLocation | \nNotes | \n
---|---|---|---|---|
MR766 | \n1947 | \nAfrican | \nZiika forest, Uganda | \nContemporaneously available strains are heavily passaged in mice, altering their virulence | \n
PRVABC59 | \n2015 | \nAsian (American) | \nPuerto Rico | \nIsolated from human serum during the American outbreak | \n
FSS13025 | \n2010 | \nAsian | \nFrench Polynesia | \nCommon isolate used collected prior to the American outbreak. Human isolate | \n
IBH30656 | \n1968 | \nAfrican | \nNigeria | \nIsolated from human blood sample | \n
H/PF/2013 | \n2013 | \nAsian | \nFrench Polynesia | \nHuman isolate | \n
BeH815744 | \n2015 | \nAsian (American) | \nBrazil | \nHuman isolate | \n
Commonly used ZIKV strains.
Prior to the major outbreaks in the 2000s, ZIKV had not been detected in the Americas and reported human cases of ZIKV-caused disease were scarce worldwide. Seroprevalence studies in Asia and Africa revealed human populations were exposed to the virus but disease was rarely reported, likely due to a high percentage of asymptomatic infection or because the signs and symptoms were indistinguishable from other known diseases [2]. Data collected during recent outbreaks in Yap Island and across the Americas revealed ZIKV is usually asymptomatic, with symptomatic cases being characterized by flu-like symptoms including self-limiting fever, headache, rash, and myalgia [3].
\nWorldwide outbreaks in Gabon, Micronesia and French Polynesia expanded the virus’ known range and susceptible population, allowing prospective epidemiological studies. ZIKV likely arrived in the Americas in 2014, and in 2015 it quickly spread, starting its largest outbreaks to date [4, 5]. The large number of infected patients and heightened medical and scientific response allowed rare outcomes and transmission routes to be noticed. It was possible to identify that ZIKV causes congenital malformations [6]. Prior to this, cases of miscarriage, microcephaly and other congenital malformations, such as microcephaly or damage to brain and eye tissues, had been identified and were retrospectively observed to be correlated with infection [7, 8]. Infected travelers returning home initiated small traveler-associated transmission cycles, some of which were between sexual partners. Sexual transmission was proposed by Foy and colleagues, who described a probable case of ZIKV sexual transmission of a scientist that visited Senegal in 2008 [9]. Many more cases of sexual transmission were reported after the outbreaks in the Americas, confirming that sexual transmission played a role in the spread of ZIKV, although the full impact of sexual transmission may be underappreciated since it occurs concomitantly with the more efficient transmission by mosquito vectors [10, 11, 12, 13].
\nZIKV or viral RNA was found to persist in human semen, vaginal secretions and blood [14, 15]. Acquiring samples to study viral persistence in these tissues is difficult because ZIKV infection is frequently asymptomatic and identification of ZIKV-positive samples has to be done by serology or molecular biology, since other viruses that cause similar signs and symptoms are present in the same regions as ZIKV. In Brazil, for example, there are several other flaviviruses and alphaviruses in circulation which produce clinical pictures that cannot be readily differentiated from the signs and symptoms associated with ZIKV. Therefore, molecular and serological tools are critical for the identification and classification of such samples [16]. In many locations, this requires a concerted collaborative effort between hospitals and laboratories, and many samples may need to be shipped before determining which patients came in contact with ZIKV. Additionally, sample collection is made difficult because once symptoms have rescinded, sample collections can no longer be made by hospitals and people may be opposed to having samples collected from them when they are no longer in need of medical care. In spite of these obstacles, several studies were able to assess ZIKV persistence in human samples. In semen, ZIKV RNA was detected for up to 6 months and ZIKV infectious particles could be isolated up to 1 month after primary infection [17]. Vaginal secretions were also found to be positive for RNA for up to 6 months after onset of symptoms [18]. These observations suggest sexual transmission could potentially happen even long after resolution of primary infection. Caution must be taken when trying to directly interpret the consequences of persistent viral RNA since this does not directly imply infectious viral particles. Regardless, transmission is possible, as demonstrated by a woman infecting her partner 44 days after onset of symptoms [13]. Although sexual transmission has most often been reported from males to females, there have been reports of suspected male-to-female [19], male-to-male [20] and female-to-male [21] transmissions. The actual rate of sexual transmission remains unknown.
\nOur current knowledge of the potential for sexual transmission among members of the Flavivirus genus is scarce but it appears that ZIKV is unique among this genus since most members are transmitted between hematophagous arthropods and vertebrate hosts. Although there is limited evidence that other flaviviruses could be sexually transmitted and persist in semen, the currently available body of data does not support this mode of transmission as significant for the spread of these viruses. West Nile virus (WNV) was proposed to have been possibly sexually transmitted in a clinical study of a woman who developed meningo-encephalitis by WNV 2 weeks after intercourse with an infected individual [22]. Other medically important flaviviruses, dengue virus (DENV) [23] and yellow fever virus (YFV) [24], have both been detected in human semen. DENV RNA was detected in a man returning from Thailand to Italy at 37 days post onset of symptoms, when virus RNA was not detectable in the serum or urine anymore [23]. Detection of DENV RNA in the seminal fluid is nevertheless not commonly reported, and another study that performed PCR in the semen of five man with acute DENV infection failed to detect any viral RNA [25]. YFV RNA was detected in urine and semen, but not in the serum, and the virus was isolated from urine on day 21 post onset the symptoms [24]. Another flavivirus, Japanese encephalitis virus (JEV), can be naturally found in porcine semen [26]. JEV was isolated from aborted fetus and semen of pigs which were naturally infected in China from 2004 to 2009 [27]. This raises the question of whether JEV also has the potential to reside in human testes and semen. Experimental approaches have also been used to determine the potential of flaviviruses to be sexually transmitted. Spondweni virus, a close relative to ZIKV, was detected in semen of mice lacking types I and III interferon (AG129) that were inoculated subcutaneously, although this was a rare occurrence when compared to ZIKV-infected AG129 mice [28]. Despite these clinical and experimental reports, the extent of the contribution of sexual transmission to the spread and maintenance of ZIKV in the human population remains unknown.
\nExamples of sexual transmission may be more common in the family Flaviviridae than in the genus Flavivirus, as exemplified by bovine viral diarrhea virus (pestivirus, BVDV) in cattle and hepatitis C virus (hepacivirus, HCV) in humans. Both of these infections can cause persistent infections in their hosts under certain conditions and can be sexually transmitted. For BVDV, persistent infection was found in the testes, and bulls persistently shed viral particles in the seminal fluid which allows for sexual transmission [29, 30, 31]. For HCV, sexual transmission has been well-documented [32, 33, 34, 35]; however, transmission is relatively inefficient [36] and increases with the number of partners, among human immunodeficient virus-positive (HIV+) individuals or among men who have sex with other men [37, 38]. Although there are similarities between ZIKV and these two viruses, caution must be exercised when drawing comparisons, especially when looking for viral determinants of persistence since there are multiple and substantial genomic differences between flaviviruses, pestiviruses and hepaciviruses.
\nThe fact that ZIKV was shown to be sexually transmitted raised many questions, as many aspects of this mode of transmission are poorly understood for these viruses. Namely, the importance of sexual transmission for ZIKV in different regions of the world, the role of cells of the reproductive tract involved in ZIKV persistence and transmission, mutations in the virus which favor successful sexual transmission, interactions of ZIKV with the immune system in the reproductive tract and molecular interactions between ZIKV and host cells allowing for sexual transmission to take place, are all critical points of study. Although abundant data on human disease was generated during the recent outbreaks, animal experiments are an important tool to answer these questions because they allow controlled and rationally designed experiments which could ultimately lead to the development of new vaccines, therapeutics and prophylactic measures. This review will focus on what is currently known for ZIKV infection in the male reproductive tract.
\nUpon discovery of ZIKV, animal experiments were first conducted by Dick [39]. They found that white mice younger than 2 weeks were susceptible to ZIKV infections via intraperitoneal route, whereas mice older than 2 weeks were only susceptible to intracerebral inoculations [39]. Non-human primates inoculated subcutaneously developed neutralizing antibodies against ZIKV and only one animal presented a slight elevation in temperature [39, 40]. Several decades after this initial study, several other model species were used as animal models for ZIKV, but efforts were mostly focused on mice [41, 42, 43] and non-human primates (NHPs) [44, 45, 46, 47], with most studies being conducted after the outbreak in the Americas in 2015–2016. The experimental design and analyses should carefully consider the anatomical and physiological differences from the species used to humans as well as confounding factors such as different viral strains and inoculation titer and route.
\nMouse models of sexual transmission for ZIKV initially utilized either interferon receptor deficient mice lacking type I (A129) [41] and or type I and II (AG129) interferon receptors [42]. Other models included interferon responsive mouse strains for which a transient knock-down of interferon response was induced by exogenous treatment with antibody against murine type I interferon receptor of wild-type mice or Rag1−/− mice (lacking both B and T lymphocytes) [48]. Several of these models have demonstrated sexual transmission from needle-inoculated male mice to naive female mice following mating. These studies, coupled with the use of surrogate breeding females from which uteri were gavaged, allowed direct assessment of virus and viral RNA shedding efficiency over time. AG129 males infected with ZIKV strain PRVABC59 were shown to shed infectious virus from 7 to 21 days post infection (dpi). Vasectomized males also were shown to shed virus; however, the magnitude was shown to be significantly lower compared to non-vasectomized males [42]. This finding was consistent with a previous study reporting ZIKV RNA shedding in symptomatic men infected with ZIKV in which vasectomized men shed significantly lower levels of ZIKV RNA [17].
\nThe necessity for the use of mice lacking the ability to respond to interferon is due to the inherent resistance of murine STAT2 from being inhibited by ZIKV NS5 [49]. In contrast, human STAT2 has been demonstrated to be highly susceptible to antagonism by ZIKV NS5 [50]. As such, the subsequent development of humanized STAT2 mice have proven useful as a fully interferon responsive model for which ZIKV can replicate and induce pathogenic responses [51].
\nA number of different models have been developed in order to directly assess sexual transmission Sexual transmission has been modeled via direct intravaginal inoculation. In one model, AG129 male mice euthanized and caudal epididymal lumen (containing sperm) was collected. This suspension was used to inoculate female AG129 mice. In this study, the antioxidant ebselen was used to alleviate testicular pathology caused by ZIKV. Although intravaginally inoculated female AG129 mice with sperm from male mice treated with ebselen demonstrated reduced mortality, sexual transmission was not prevented, as female organs (ovary/fallopian tubes, spleen and brain) were infected [52]. Other studies have used homogenized accessory gland fluid and epididymal lumen fluid from Ifnar1−/− male mice subcutaneously inoculated with PRVABC59 to intravaginally inoculated female AG129 mice. In this study, females became viremic and succumbed to infection. Furthermore, progesterone pre-treatment of female mice before intravaginal inoculation was shown to increase mortality of females [53]. IFNAR1−/− male mice inoculated subcutaneously with PRVABC59 and then at 14 dpi or 35 dpi, prostatic and seminal vesicular homogenates and epididymal flushes were collected. Female AG129 mice inoculated intravaginally with this insemination fluid failed to become viremic [54].
\nIntravaginal inoculation of di-estrus timed AG129 mice or LysMCre+IFNARfl/fl mice (lacking IFNAR in myeloid cells) was shown to result in viremia and virus replication in peripheral organs and in the vaginal tissues measured by viral assay by RT-PCR through 10 dpi [55]. In an alternative study, immunocompetent C57BL/6 N female mice intravaginally inoculated with PRVABC59 showed a slight increase in viral RNA in the lower female reproductive tract (LFRT) from dpi 1 to 2 and mRNA expression of type I and III IFNs, IRF3/7, RIG-I, and MDA-5 was comparable to uninfected controls, suggesting that a dampened antiviral immune response occurs in the LFRT in response to infection with ZIKV. When mice were treated with an enhancer of RIG-1 signaling, the increase in ZIKV RNA in LFRT was not observed [56]. After intravaginal inoculation during the diestrus phase, ZIKV was shown to replicate in vaginal mucosa of wild type (WT) C57BL/6 and Ifnar1−/− mice. Fetuses from pregnant WT C57BL/6 mice developed intrauterine growth restriction and fetal brains were infected following intravaginal ZIKV inoculation. Fetuses from pregnant IFNAR1−/− mice developed severe intrauterine growth restriction and fetal death was observed. The pregnant females were found to develop viremia. These data are suggestive of an ascending infection from the vaginal tissues to the uterus for fetal involvement [57].
\nIn addition to sexual transmission models that have utilized intravaginal exposure to model sexual transmission potential, several studies have addressed transmission dynamics through direct coitus models. AG129 males were found to sexually transmit to naïve AG129 females in 50% of all matings as measured by subsequent viremias in mated females. This initial study demonstrated in utero infection after sexual transmission [42]. A subsequent study compared sexual transmission with subcutaneous and intravaginal routes on female disease presentation, tropism and fetal infection. Sexual transmission of ZIKV to naïve female AG129 mice increased morbidity and mortality in these females as compared to female mice subcutaneously or intravaginally inoculated. Fetuses from females infected via sexual transmission had higher ZIKV titers compared to fetuses from pregnant females infected subcutaneously or intravaginally [58].
\nThe majority of ZIKV detected in the seminal fluid of infected AG129 mice during the peak timing of sexual transmission (10–12 dpi) was from the supernatant fraction, suggesting cell-free ZIKV may be largely responsible for sexual transmission. In this study, the testes and epididymides were determined to be infected concurrently and epididymal epithelial cells were identified as the predominant cell population infected in epididymides and shown to contain replicating ZIKV by in situ hybridization. In the testes, interstitial leukocytes and peritubular myoid cells were found to be infected initially, followed by extensive infection of all layers of the seminiferous tubule epithelium [59]. Similar results were also shown in IFNAR1−/− mice for which epithelial components of epididymides were identified to be infected and that testes and epididymides could be infected concurrently [60]. In another experiment with immune competent C57BL/6 mice treated with anti-IFNAR1 blocking antibody and subcutaneously inoculated with Asian and African genotype ZIKVs, sexual transmission potential was observed for all viruses with infectious virus identified in the epididymides from all groups even when infectious virus was absent from the testes and seminal vesicles. Infection of the epididymides was demonstrated to be critical for establishing sexual transmission potential, as infectious virus and viral RNA was detected in the epididymides and in semen days before infectious virus was detected in the seminal vesicles or testes [61].
\nTissue restricted ZIKVs generated through the incorporation of microRNA target sequences within recombinant ZIKVs were utilized to assess the importance of different cell populations for sexual transmission potential. Testes-restricted ZIKVs could still infect the epididymides, demonstrating a hematogenous/lymphogenous route of infection. Epididymides-restricted ZIKV had high titers in epididymides by plaque assay, but immunohistochemical analysis confirmed epididymides-restricted ZIKV did not replicate in the epididymal epithelium, suggesting that ZIKV is transported from testes to epididymides via excurrent ducts in a cell-free form or transported in sloughed spermatids/infected luminal leukocytes, and ZIKV can infect the epididymides via hematogenous/lymphogenous route of infection [62].
\nTropism and persistence of ZIKV in the male reproductive tract may be the key factor responsible for the presence of the virus in semen even long after initial infection. A model of the male mouse reproductive tract is shown in Figure 1A. Based on in vivo studies, ZIKV is thought to infect the testes, an immunologically privileged site, via a hematogenous route [62] and by infecting the Sertoli cells (SC, Figure 1B), an important cell population responsible for the formation of the blood-testes barrier, as shown using AG129 mouse models [63, 64]. SC are critical for spermatogenesis, since they nourish germ cells and help them mature. Tight junctions formed by adjacent SC are functional components of the blood-testes barrier (Figure 1C), which prevents molecules from passing between the blood and the lumen of a seminiferous tubule. From the testes, ZIKV can then reach the epididymides by the excurrent testicular route either by infecting germ cells or as free virus particles [62]. ZIKV can also infect the epididymides directly from the hematogenous route [62] (Figure 1), and infection of epididymides was observed to happen concurrently with testes infection, indicating that epididymal infection could happen directly and through the testes, or independently of the testes. Infection of germ cells in the testes is not a requirement for sexual transmission as there are reported cases of ZIKV sexual transmission from vasectomized men [65] and in experiments with vasectomized AG129s [42]. Instead, AG129 mouse models indicate that infection of epididymal epithelial cells may the major factor leading to shedding of virus particles in the semen, with these cells being the predominant source of cell-free ZIKV in the seminal fluid [66].
\nThe male reproductive tract. (A) Overall representation of the male reproductive tract. (B) Seminiferous tubules. (C) Seminiferous tubules in detail.
Intracellular viral persistence is likely an important component for long-term sexual transmission. Although the cells that act as reservoirs of ZIKV in testes and the reproductive tract are unknown, possible reservoirs in the host are SC [67, 68] germ cells [69], Leydig cells [70] and epididymal epithelial cells [59, 62] which have been shown to support persistent infections of ZIKV (Figure 1). When primary SCs persistently infected with two strains of ZIKV (PRVABC59 or MR766) were monitored for a period of 6 weeks, it was found that 15% of the cells were still positive for both strains of ZIKV [67]. In this same study, Leydig cells were not observed to support persistence [67]. The mechanisms underlying persistence of ZIKV in testes are likely multifactorial and represent a complex phenomenon involving interactions between viral and host factors that needs to be studied in depth. The interactions that occur between ZIKV and host factors that are required for long-term infection of the testes/epididymides are poorly understood and viral persistence likely requires a balance between efficient viral replication and damage caused to host cells. The AXL receptor tyrosine kinase, which was previously shown to be required for entry of ZIKV and other flaviviruses into certain cell types, has been shown to be required for ZIKV entry in SCs [71], but may also be involved in negatively regulating SCs innate immune response [72]. ZIKV infection of SCs results in gene expression changes, with upregulation of antiviral pathways, dysregulation of junction and growth pathways [67, 73]. Although the immune system of the reproductive tract in females is able to eventually clear ZIKV, largely due to interferon signaling [74, 75], such as the type III interferon lambda [76], the microenvironment of the male testes is an immune-privileged site that lacks adequate response for clearance [77].
\nMosquito-vectored flaviviruses that can result in persistent infections are usually associated with an accumulation of adaptive mutations, suggesting that viral genetics may also play an important role for establishing persistence. Examples of mutations in viruses causing persistence were shown with ZIKV, WNV [78, 79, 80], JEV [81], YFV [24, 82], and DENV [23]. These mutations happen in different viral proteins and appear to affect various viral functions, but in general attenuate the virus to cause less cytopathic effects, which is likely important for persistence. Identifying the mutations and cellular components that allow flaviviruses to cause long-term infections may elucidate mechanisms by which ZIKV is able to remain stable in seminal fluid long after infection. Although functional mutations in ZIKV may have been found in the male reproductive tract and ejaculates of mice [83], these were do not appear to be specific to these tissues as they were also found after passaging in Vero cells [83], and no mutation has been identified to be required for persistence and/or sexual transmission. Continuing research efforts using animal models are paramount to understand the mechanisms of ZIKV persistence, sexual transmission, reservoirs and interactions with cellular targets.
\nNHP models are also frequently used to study ZIKV since their biology more closely relates to a human than does mouse biology. Several non-human primates were shown to be susceptible to ZIKV and used to study pathogenesis and infection of the reproductive tract, including cynomolgus macaques (Macaca fascicularis), rhesus macaques (Macaca mulatta), pigtail macaques (Macaca nemestrina) and olive baboon (Papio anubis), as well as neotropical non-human primates of the Callithrix, Saimiri and Aotus genera [46, 84]. These species presented viremia and variable degrees of clinical signs following ZIKV infection. Although many studies were conducted looking at ZIKV pathogenesis and the effects of infection on reproductive tissues, studies directly testing sexual transmission are lacking due to technical and logistical difficulties. Instead, vaginal or rectal inoculations have been used to simulate a sexual transmission. These and other insights into sexual transmission of non-human primates can also shed light on whether this type of transmission play a role in maintenance of ZIKV in nature, since primates are putative ZIKV reservoirs.
\nBecause NHPs are evolutionarily close to humans, it is not surprising that these animals and their reproductive tract are anatomically and physiologically more similar to humans than other models such as mice; thus, NHPs are often considered to be one of the most relevant animal models [85, 86]. Unlike mice, immunocompetent NHPs are more suitable to study ZIKV infections, although the extent to which disease is mimicked is difficult to assess and varies with NHP species. Most NHP models were similar to humans in that most infections were asymptomatic, with clinical signs observed in some individuals [87, 88]. Considering that many human infections are asymptomatic, it is currently unclear if the clinical signs displayed by NHPs are a good model for disease rate and severity in humans. In a study using four cynomolgus macaques one individual was shown to present reduced body temperature [87]. Studying ZIKV pathogenesis in NHPs is important to understand disease progression, clinical signs, negative effects to the reproductive tract and outcomes of pregnancy. These data also inform the design of sexual transmission studies as far as titers, timepoints and strain used for infection, tissues that are important for disease and persistence so sexual transmission can take place. It is worth noting that these experimental infections are performed using virus in a needle while most [89] natural infections occur by a mosquito bite; mosquito saliva has immunomodulatory properties that have been shown to enhance disease in other flaviviral infection [90, 91, 92] and could be another confounding factor in these studies.
\nCynomolgus macaques were shown to be suitable as models for ZIKV pathogenesis and sexual transmission [87, 88, 93]. Infection with 5 log10 of plaque forming units (PFU) of ZIKV from various geographical origins resulted in viremia which peaked at 2-4 dpi at 4-7 log10 ZIKV genome copies/ml [87, 88]. The outbreak strain PRVABC59 was more virulent than the Asian FSS13025 and the African IBH30656 ZIKV, with the animals infected with the PRVABC59 strain being viremic for extended periods of time. Bodily fluids checked did not include seminal fluid, and shedding of virus in the urine and saliva was not observed with either the FSS13025 [87] or IBH30656 strains. ZIKV FSS13025 was detected in testes [88], consistent with murine infections with this strain [41]. On the other hand, ZIKV PRVABC59 was detected in urine, saliva and testes [88]. The fact that virus was found in testes suggests this species of NHP could model virus persistence in testes well and may also be a positive feature of this model for sexual transmission in general. The cynomolgus macaque model has also been shown to likely support sexual transmission, as macaques inoculated with 7 log10 PFU of virus intravaginally and intrarectally became viremic 50% and 100% of the time, respectively [93]. To understand the implications of these findings would be important to know the ranges of ZIKV titers in the semen. Although it is not clear what the viral titers are in most human semen samples, studies detected up to 9 log10 RNA copies/ml of virus in semen of patients [17, 89].
\nAs with cynomolgus macaques, infection of olive baboons with different strains of ZIKV did not result in overt clinical signs. Following subcutaneous inoculation of a French Polynesian ZIKV (H/PF/2013), the baboons presented viremia that peaked at 3 and 4 dpi [45]. Around 40 days post infection, tissues were collected and virus was found in lymph nodes and epididymides, suggesting these are the places where the virus can persist even after viral clearance from the blood [45]. This suggests the testes were likely infected at some point and that the epididymides may also play a role in virus persistence [45]. Olive baboons were also used to model ZIKV infection during pregnancy. Infection of 4 log10 of ZIKV H/PF/2013 resulted in vertical transmission in 3 out of 4 pregnant NHPs [94]. Unlike the non-pregnant animals, all dams presented rash and conjunctivitis [94]. Fetal death and defects in the frontal cortex of the fetus were observed [94].
\nThe rhesus macaque is perhaps the most utilized NHP model to study ZIKV infection. Many studies of ZIKV were done using this species, including pathogenesis analyses in pregnant and non-pregnant animals, immunological and serological studies, and testing of anti-ZIKV vaccines or drugs [44, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106]. A study in which ZIKV was inoculated intravaginally in rhesus macaques to mimic sexual transmission found ZIKV RNA in the reproductive tract of all 6 animals infected, thus raising the question of whether fetal disease could be more pronounced after sexual transmission when compared to vectored transmission [103]. This study lacked subcutaneous inoculation controls and further studies need to be conducted to confirm these findings. Another study comparing the intravaginal and subcutaneous routes using ZIKV PRVABC59 found peak viremia at 5–8 dpi that were variable in titer (3–7.5 log10 PFUs). Although the types of tissue found to be positive differed between subcutaneous and intravaginal inoculated animals, there was no obvious preference for reproductive tract tissues in the intravaginal route [107]. The data showed that intravaginal infection resulted in less CD11Chi myeloid cells, reduced expression of programmed cell death protein 1 (PD-1) in natural killer cells (NK) and more Ki67+ CD8+ central memory cells, indicating the route of infection may play a role in shaping the immune response [107].
\nPersistent ZIKV in reproductive tissues may play a role in sexual transmission long after primary infection. After intravenous inoculation of 5 log10 of a Brazilian ZIKV (BeH815744) in female rhesus macaques, ZIKV RNA was detected in multiple tissues of the NHPs, including reproductive tissues 14 dpi [108]. Lymphoid tissues had the highest detectable amount of viral RNA, suggesting these organs, which span many parts of the body, may act as possible viral reservoir [108].
\nSeveral other animal models have been used to study ZIKV but most are not focused on sexual transmission. These models include guinea pigs [109, 110, 111], hamsters [112], bats [113], chick embryos, piglets [114, 115] and boars [116]. Porcine fetuses were shown to present mild to severe neuropathology upon ZIKV infection [114, 115]. Boar semen was inoculated with ZIKV, but it was concluded that ZIKV does not appear to cause cell damage and cannot replicate efficiently or persist in the semen of this species [116]. With respect to the neotropical chiropteran model, viral RNA was found in different tissues of fruit bats 28 dpi, suggesting ZIKV can infect bats which may serve as virus reservoirs. Bats did not show any signs of disease [113]. Stat-2 knockout hamsters infected with ZIKV have shown presence on infected cells with morphology of SCs and spermatogonia, suggesting this could be a suitable model to study persistence of the virus in testes [112]. The guinea pig models report conflicting results. One study with ZIKV challenge mid-gestation showed no evidence of infection [109]; however, Kumar et al. show guinea pigs inoculated subcutaneously with PRVABC59 had viremia and presented signs such as fever, hunched posture and detectable viral RNA in the blood [110]. Deng et al. showed that intranasally-infected guinea pigs have virus in the sera, saliva and tears [111].
\nZIKV has emerged explosively since 2007, causing an epidemic in the Americas in 2015/16 and become a matter of global health importance. Although data from epidemiologic analyses and case studies helped shed light on the diseases caused by ZIKV, animal models will be important to substantiate and extend these findings under controlled experimental settings. Animal models can be—and have already proven to be—useful as a tool to understand ZIKV transmission and ZIKV-caused illnesses. Animal models do not fully recapitulate diseases as seen in humans; therefore, it is critical to consider the advantages and drawbacks of each model when designing and executing the experiments as well as interpreting the data. Models to study sexual transmission are currently scarce and need further development. Challenges include scarcity of good models to study ZIKV sexual transmission, low number of animals used and the requirement to improve reproducibility of the findings from animal models, which is caused by differences in experimental conditions and the number of animals used. As in certain cases increasing the number of animals used is not possible due to it being prohibitively expensive or posing ethical issues, future experiments assessing sexual transmission of ZIKV should focus on optimizing experimental design and analysis, when possible standardizing experimental conditions so they can be compared between studies.
\nWe thank Drs. Sasha Azar and Nikos Vasilakis for their critical reading of the chapter and helpful discussions.
\nWe have no conflicts of interest to declare.
Customer Satisfaction is of paramount importance at IntechOpen and we take all complaints very seriously. Our Authors, their institutions, and other purchasers, if dissatisfied with the service provided, or the product purchased, can file a written complaint to IntechOpen, 5 Princes Gate Court, London, SW7 2QJ, UK or via the following e-mail address: info@intechopen.com.
',metaTitle:"Customer Complaints",metaDescription:"Our authors, their institutions and other purchasers, if unsatisfied with the service provided or the product purchased, can file a written complaint at IN TECH d.o.o offices at Janeza Trdine 9, 51000 Rijeka, Croatia, or via the following e-mail address: info@intechopen.com.",metaKeywords:null,canonicalURL:null,contentRaw:'[{"type":"htmlEditorComponent","content":"Receipt of complaints will be acknowledged in writing and Intech Limited will respond fully to concerns within 15 business days.
\\n\\nCustomers have the right to terminate the contract without giving any reason (written notice of termination). The deadline for said termination is fourteen (14) days from the date of receipt of goods. Returns are at the expense of the Customer and must be made within the fourteen (14) days from the date of the written notice of termination. Intech Limited will process refunds to the Customer without undue delay.
\\n\\nIn the event that the Publisher ships damaged or misbound copies of products, or duplicate or incorrect copies of the products are received by the Customer, the Publisher will accept returns at the Publisher's expense, provided notice of such damaged or incorrect shipment is given to the Publisher within fourteen (14) working days from the date of receipt.
\\n\\nPublishing errors, including but not limited to typographical errors, having no significant effect on the editorial content or design characteristics of the products, cannot be considered a reason for rejecting payment or, as the case may be, modifying the agreed price.
\\n\\nAt the Publisher's request, the customer should provide evidence of the damaged or incorrect shipment. The Publisher will refund or ship the ordered products without delays.
\\n"}]'},components:[{type:"htmlEditorComponent",content:"Receipt of complaints will be acknowledged in writing and Intech Limited will respond fully to concerns within 15 business days.
\n\nCustomers have the right to terminate the contract without giving any reason (written notice of termination). The deadline for said termination is fourteen (14) days from the date of receipt of goods. Returns are at the expense of the Customer and must be made within the fourteen (14) days from the date of the written notice of termination. Intech Limited will process refunds to the Customer without undue delay.
\n\nIn the event that the Publisher ships damaged or misbound copies of products, or duplicate or incorrect copies of the products are received by the Customer, the Publisher will accept returns at the Publisher's expense, provided notice of such damaged or incorrect shipment is given to the Publisher within fourteen (14) working days from the date of receipt.
\n\nPublishing errors, including but not limited to typographical errors, having no significant effect on the editorial content or design characteristics of the products, cannot be considered a reason for rejecting payment or, as the case may be, modifying the agreed price.
\n\nAt the Publisher's request, the customer should provide evidence of the damaged or incorrect shipment. The Publisher will refund or ship the ordered products without delays.
\n"}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. His current research interests include the areas of mobile communication systems and channel modeling in addition to atmospheric optical communications, adaptive optics and statistics",institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5766},{group:"region",caption:"Middle and South America",value:2,count:5227},{group:"region",caption:"Africa",value:3,count:1717},{group:"region",caption:"Asia",value:4,count:10367},{group:"region",caption:"Australia and Oceania",value:5,count:897},{group:"region",caption:"Europe",value:6,count:15789}],offset:12,limit:12,total:118188},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{topicId:"24"},books:[{type:"book",id:"10764",title:"Antenna Systems",subtitle:null,isOpenForSubmission:!0,hash:"2fbf1c7a5d92723f08198fc9b526a8ad",slug:null,bookSignature:"Prof. Hussain Al-Rizzo and Dr. Said Abushamleh",coverURL:"https://cdn.intechopen.com/books/images_new/10764.jpg",editedByType:null,editors:[{id:"153384",title:"Prof.",name:"Hussain",surname:"Al-Rizzo",slug:"hussain-al-rizzo",fullName:"Hussain Al-Rizzo"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10964",title:"Wearable Technologies",subtitle:null,isOpenForSubmission:!0,hash:"0981ee7867892cc6e0a4edd65b792ac9",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10964.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:14},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:3},{group:"topic",caption:"Business, Management and Economics",value:7,count:1},{group:"topic",caption:"Chemistry",value:8,count:7},{group:"topic",caption:"Computer and Information Science",value:9,count:6},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:7},{group:"topic",caption:"Engineering",value:11,count:15},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:3},{group:"topic",caption:"Materials Science",value:14,count:5},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:24},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:2},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:4},{group:"topic",caption:"Social Sciences",value:23,count:2},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:1}],offset:12,limit:12,total:2},popularBooks:{featuredBooks:[{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9027",title:"Human Blood Group Systems and Haemoglobinopathies",subtitle:null,isOpenForSubmission:!1,hash:"d00d8e40b11cfb2547d1122866531c7e",slug:"human-blood-group-systems-and-haemoglobinopathies",bookSignature:"Osaro Erhabor and Anjana Munshi",coverURL:"https://cdn.intechopen.com/books/images_new/9027.jpg",editors:[{id:"35140",title:null,name:"Osaro",middleName:null,surname:"Erhabor",slug:"osaro-erhabor",fullName:"Osaro Erhabor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7841",title:"New Insights Into Metabolic Syndrome",subtitle:null,isOpenForSubmission:!1,hash:"ef5accfac9772b9e2c9eff884f085510",slug:"new-insights-into-metabolic-syndrome",bookSignature:"Akikazu Takada",coverURL:"https://cdn.intechopen.com/books/images_new/7841.jpg",editors:[{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8558",title:"Aerodynamics",subtitle:null,isOpenForSubmission:!1,hash:"db7263fc198dfb539073ba0260a7f1aa",slug:"aerodynamics",bookSignature:"Mofid Gorji-Bandpy and Aly-Mousaad Aly",coverURL:"https://cdn.intechopen.com/books/images_new/8558.jpg",editors:[{id:"35542",title:"Prof.",name:"Mofid",middleName:null,surname:"Gorji-Bandpy",slug:"mofid-gorji-bandpy",fullName:"Mofid Gorji-Bandpy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9668",title:"Chemistry and Biochemistry of Winemaking, Wine Stabilization and Aging",subtitle:null,isOpenForSubmission:!1,hash:"c5484276a314628acf21ec1bdc3a86b9",slug:"chemistry-and-biochemistry-of-winemaking-wine-stabilization-and-aging",bookSignature:"Fernanda Cosme, Fernando M. Nunes and Luís Filipe-Ribeiro",coverURL:"https://cdn.intechopen.com/books/images_new/9668.jpg",editors:[{id:"186819",title:"Prof.",name:"Fernanda",middleName:null,surname:"Cosme",slug:"fernanda-cosme",fullName:"Fernanda Cosme"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7847",title:"Medical Toxicology",subtitle:null,isOpenForSubmission:!1,hash:"db9b65bea093de17a0855a1b27046247",slug:"medical-toxicology",bookSignature:"Pınar Erkekoglu and Tomohisa Ogawa",coverURL:"https://cdn.intechopen.com/books/images_new/7847.jpg",editors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoglu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8620",title:"Mining Techniques",subtitle:"Past, Present and Future",isOpenForSubmission:!1,hash:"b65658f81d14e9e57e49377869d3a575",slug:"mining-techniques-past-present-and-future",bookSignature:"Abhay Soni",coverURL:"https://cdn.intechopen.com/books/images_new/8620.jpg",editors:[{id:"271093",title:"Dr.",name:"Abhay",middleName:null,surname:"Soni",slug:"abhay-soni",fullName:"Abhay Soni"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9660",title:"Inland Waters",subtitle:"Dynamics and Ecology",isOpenForSubmission:!1,hash:"975c26819ceb11a926793bc2adc62bd6",slug:"inland-waters-dynamics-and-ecology",bookSignature:"Adam Devlin, Jiayi Pan and Mohammad Manjur Shah",coverURL:"https://cdn.intechopen.com/books/images_new/9660.jpg",editors:[{id:"280757",title:"Dr.",name:"Adam",middleName:"Thomas",surname:"Devlin",slug:"adam-devlin",fullName:"Adam Devlin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9122",title:"Cosmetic Surgery",subtitle:null,isOpenForSubmission:!1,hash:"207026ca4a4125e17038e770d00ee152",slug:"cosmetic-surgery",bookSignature:"Yueh-Bih Tang",coverURL:"https://cdn.intechopen.com/books/images_new/9122.jpg",editors:[{id:"202122",title:"Prof.",name:"Yueh-Bih",middleName:null,surname:"Tang",slug:"yueh-bih-tang",fullName:"Yueh-Bih Tang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9043",title:"Parenting",subtitle:"Studies by an Ecocultural and Transactional Perspective",isOpenForSubmission:!1,hash:"6d21066c7438e459e4c6fb13217a5c8c",slug:"parenting-studies-by-an-ecocultural-and-transactional-perspective",bookSignature:"Loredana Benedetto and Massimo Ingrassia",coverURL:"https://cdn.intechopen.com/books/images_new/9043.jpg",editors:[{id:"193200",title:"Prof.",name:"Loredana",middleName:null,surname:"Benedetto",slug:"loredana-benedetto",fullName:"Loredana Benedetto"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9731",title:"Oxidoreductase",subtitle:null,isOpenForSubmission:!1,hash:"852e6f862c85fc3adecdbaf822e64e6e",slug:"oxidoreductase",bookSignature:"Mahmoud Ahmed Mansour",coverURL:"https://cdn.intechopen.com/books/images_new/9731.jpg",editors:[{id:"224662",title:"Prof.",name:"Mahmoud Ahmed",middleName:null,surname:"Mansour",slug:"mahmoud-ahmed-mansour",fullName:"Mahmoud Ahmed Mansour"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5229},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9644",title:"Glaciers and the Polar Environment",subtitle:null,isOpenForSubmission:!1,hash:"e8cfdc161794e3753ced54e6ff30873b",slug:"glaciers-and-the-polar-environment",bookSignature:"Masaki Kanao, Danilo Godone and Niccolò Dematteis",coverURL:"https://cdn.intechopen.com/books/images_new/9644.jpg",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9671",title:"Macrophages",subtitle:null,isOpenForSubmission:!1,hash:"03b00fdc5f24b71d1ecdfd75076bfde6",slug:"macrophages",bookSignature:"Hridayesh Prakash",coverURL:"https://cdn.intechopen.com/books/images_new/9671.jpg",editors:[{id:"287184",title:"Dr.",name:"Hridayesh",middleName:null,surname:"Prakash",slug:"hridayesh-prakash",fullName:"Hridayesh Prakash"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9313",title:"Clay Science and Technology",subtitle:null,isOpenForSubmission:!1,hash:"6fa7e70396ff10620e032bb6cfa6fb72",slug:"clay-science-and-technology",bookSignature:"Gustavo Morari Do Nascimento",coverURL:"https://cdn.intechopen.com/books/images_new/9313.jpg",editors:[{id:"7153",title:"Prof.",name:"Gustavo",middleName:null,surname:"Morari Do Nascimento",slug:"gustavo-morari-do-nascimento",fullName:"Gustavo Morari Do Nascimento"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9888",title:"Nuclear Power Plants",subtitle:"The Processes from the Cradle to the Grave",isOpenForSubmission:!1,hash:"c2c8773e586f62155ab8221ebb72a849",slug:"nuclear-power-plants-the-processes-from-the-cradle-to-the-grave",bookSignature:"Nasser Awwad",coverURL:"https://cdn.intechopen.com/books/images_new/9888.jpg",editors:[{id:"145209",title:"Prof.",name:"Nasser",middleName:"S",surname:"Awwad",slug:"nasser-awwad",fullName:"Nasser Awwad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9027",title:"Human Blood Group Systems and Haemoglobinopathies",subtitle:null,isOpenForSubmission:!1,hash:"d00d8e40b11cfb2547d1122866531c7e",slug:"human-blood-group-systems-and-haemoglobinopathies",bookSignature:"Osaro Erhabor and Anjana Munshi",coverURL:"https://cdn.intechopen.com/books/images_new/9027.jpg",editors:[{id:"35140",title:null,name:"Osaro",middleName:null,surname:"Erhabor",slug:"osaro-erhabor",fullName:"Osaro Erhabor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10432",title:"Casting Processes and Modelling of Metallic Materials",subtitle:null,isOpenForSubmission:!1,hash:"2c5c9df938666bf5d1797727db203a6d",slug:"casting-processes-and-modelling-of-metallic-materials",bookSignature:"Zakaria Abdallah and Nada Aldoumani",coverURL:"https://cdn.intechopen.com/books/images_new/10432.jpg",editors:[{id:"201670",title:"Dr.",name:"Zak",middleName:null,surname:"Abdallah",slug:"zak-abdallah",fullName:"Zak Abdallah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7841",title:"New Insights Into Metabolic Syndrome",subtitle:null,isOpenForSubmission:!1,hash:"ef5accfac9772b9e2c9eff884f085510",slug:"new-insights-into-metabolic-syndrome",bookSignature:"Akikazu Takada",coverURL:"https://cdn.intechopen.com/books/images_new/7841.jpg",editors:[{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"9550",title:"Entrepreneurship",subtitle:"Contemporary Issues",isOpenForSubmission:!1,hash:"9b4ac1ee5b743abf6f88495452b1e5e7",slug:"entrepreneurship-contemporary-issues",bookSignature:"Mladen Turuk",coverURL:"https://cdn.intechopen.com/books/images_new/9550.jpg",editedByType:"Edited by",editors:[{id:"319755",title:"Prof.",name:"Mladen",middleName:null,surname:"Turuk",slug:"mladen-turuk",fullName:"Mladen Turuk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editedByType:"Edited by",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9313",title:"Clay Science and Technology",subtitle:null,isOpenForSubmission:!1,hash:"6fa7e70396ff10620e032bb6cfa6fb72",slug:"clay-science-and-technology",bookSignature:"Gustavo Morari Do Nascimento",coverURL:"https://cdn.intechopen.com/books/images_new/9313.jpg",editedByType:"Edited by",editors:[{id:"7153",title:"Prof.",name:"Gustavo",middleName:null,surname:"Morari Do Nascimento",slug:"gustavo-morari-do-nascimento",fullName:"Gustavo Morari Do Nascimento"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9888",title:"Nuclear Power Plants",subtitle:"The Processes from the Cradle to the Grave",isOpenForSubmission:!1,hash:"c2c8773e586f62155ab8221ebb72a849",slug:"nuclear-power-plants-the-processes-from-the-cradle-to-the-grave",bookSignature:"Nasser Awwad",coverURL:"https://cdn.intechopen.com/books/images_new/9888.jpg",editedByType:"Edited by",editors:[{id:"145209",title:"Prof.",name:"Nasser",middleName:"S",surname:"Awwad",slug:"nasser-awwad",fullName:"Nasser Awwad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8098",title:"Resources of Water",subtitle:null,isOpenForSubmission:!1,hash:"d251652996624d932ef7b8ed62cf7cfc",slug:"resources-of-water",bookSignature:"Prathna Thanjavur Chandrasekaran, Muhammad Salik Javaid, Aftab Sadiq",coverURL:"https://cdn.intechopen.com/books/images_new/8098.jpg",editedByType:"Edited by",editors:[{id:"167917",title:"Dr.",name:"Prathna",middleName:null,surname:"Thanjavur Chandrasekaran",slug:"prathna-thanjavur-chandrasekaran",fullName:"Prathna Thanjavur Chandrasekaran"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9644",title:"Glaciers and the Polar Environment",subtitle:null,isOpenForSubmission:!1,hash:"e8cfdc161794e3753ced54e6ff30873b",slug:"glaciers-and-the-polar-environment",bookSignature:"Masaki Kanao, Danilo Godone and Niccolò Dematteis",coverURL:"https://cdn.intechopen.com/books/images_new/9644.jpg",editedByType:"Edited by",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10432",title:"Casting Processes and Modelling of Metallic Materials",subtitle:null,isOpenForSubmission:!1,hash:"2c5c9df938666bf5d1797727db203a6d",slug:"casting-processes-and-modelling-of-metallic-materials",bookSignature:"Zakaria Abdallah and Nada Aldoumani",coverURL:"https://cdn.intechopen.com/books/images_new/10432.jpg",editedByType:"Edited by",editors:[{id:"201670",title:"Dr.",name:"Zak",middleName:null,surname:"Abdallah",slug:"zak-abdallah",fullName:"Zak Abdallah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9671",title:"Macrophages",subtitle:null,isOpenForSubmission:!1,hash:"03b00fdc5f24b71d1ecdfd75076bfde6",slug:"macrophages",bookSignature:"Hridayesh Prakash",coverURL:"https://cdn.intechopen.com/books/images_new/9671.jpg",editedByType:"Edited by",editors:[{id:"287184",title:"Dr.",name:"Hridayesh",middleName:null,surname:"Prakash",slug:"hridayesh-prakash",fullName:"Hridayesh Prakash"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8415",title:"Extremophilic Microbes and Metabolites",subtitle:"Diversity, Bioprospecting and Biotechnological Applications",isOpenForSubmission:!1,hash:"93e0321bc93b89ff73730157738f8f97",slug:"extremophilic-microbes-and-metabolites-diversity-bioprospecting-and-biotechnological-applications",bookSignature:"Afef Najjari, Ameur Cherif, Haïtham Sghaier and Hadda Imene Ouzari",coverURL:"https://cdn.intechopen.com/books/images_new/8415.jpg",editedByType:"Edited by",editors:[{id:"196823",title:"Dr.",name:"Afef",middleName:null,surname:"Najjari",slug:"afef-najjari",fullName:"Afef Najjari"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9731",title:"Oxidoreductase",subtitle:null,isOpenForSubmission:!1,hash:"852e6f862c85fc3adecdbaf822e64e6e",slug:"oxidoreductase",bookSignature:"Mahmoud Ahmed Mansour",coverURL:"https://cdn.intechopen.com/books/images_new/9731.jpg",editedByType:"Edited by",editors:[{id:"224662",title:"Prof.",name:"Mahmoud Ahmed",middleName:null,surname:"Mansour",slug:"mahmoud-ahmed-mansour",fullName:"Mahmoud Ahmed Mansour"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"409",title:"Bacteriology",slug:"biochemistry-genetics-and-molecular-biology-microbiology-bacteriology",parent:{title:"Microbiology",slug:"biochemistry-genetics-and-molecular-biology-microbiology"},numberOfBooks:17,numberOfAuthorsAndEditors:386,numberOfWosCitations:572,numberOfCrossrefCitations:316,numberOfDimensionsCitations:761,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"biochemistry-genetics-and-molecular-biology-microbiology-bacteriology",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"8133",title:"Pathogenic Bacteria",subtitle:null,isOpenForSubmission:!1,hash:"b26e69f94525a38ead8ac88e3c68631a",slug:"pathogenic-bacteria",bookSignature:"Sahra Kırmusaoğlu and Sonia Bhonchal Bhardwaj",coverURL:"https://cdn.intechopen.com/books/images_new/8133.jpg",editedByType:"Edited by",editors:[{id:"179460",title:"Dr.",name:"Sahra",middleName:null,surname:"Kırmusaoğlu",slug:"sahra-kirmusaoglu",fullName:"Sahra Kırmusaoğlu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8032",title:"Staphylococcus and Streptococcus",subtitle:null,isOpenForSubmission:!1,hash:"b9ddbf132ac8ea9d2a7613836e5a27ca",slug:"staphylococcus-and-streptococcus",bookSignature:"Sahra Kırmusaoğlu",coverURL:"https://cdn.intechopen.com/books/images_new/8032.jpg",editedByType:"Edited by",editors:[{id:"179460",title:"Dr.",name:"Sahra",middleName:null,surname:"Kırmusaoğlu",slug:"sahra-kirmusaoglu",fullName:"Sahra Kırmusaoğlu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7240",title:"Growing and Handling of Bacterial Cultures",subtitle:null,isOpenForSubmission:!1,hash:"a76c3ef7718c0b72d0128817cdcbe6e3",slug:"growing-and-handling-of-bacterial-cultures",bookSignature:"Madhusmita Mishra",coverURL:"https://cdn.intechopen.com/books/images_new/7240.jpg",editedByType:"Edited by",editors:[{id:"204267",title:"Dr.",name:"Madhusmita",middleName:null,surname:"Mishra",slug:"madhusmita-mishra",fullName:"Madhusmita Mishra"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8038",title:"Pseudomonas Aeruginosa",subtitle:"An Armory Within",isOpenForSubmission:!1,hash:"308d6be5ffbb4b2caa0a7c4146a7737d",slug:"pseudomonas-aeruginosa-an-armory-within",bookSignature:"Dinesh Sriramulu",coverURL:"https://cdn.intechopen.com/books/images_new/8038.jpg",editedByType:"Edited by",editors:[{id:"91317",title:"Dr.",name:"Dinesh",middleName:null,surname:"Sriramulu",slug:"dinesh-sriramulu",fullName:"Dinesh Sriramulu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6965",title:"Helicobacter Pylori",subtitle:"New Approaches of an Old Human Microorganism",isOpenForSubmission:!1,hash:"acf3954c4d9d440038f3074fb81d7411",slug:"helicobacter-pylori-new-approaches-of-an-old-human-microorganism",bookSignature:"Bruna Maria Roesler",coverURL:"https://cdn.intechopen.com/books/images_new/6965.jpg",editedByType:"Edited by",editors:[{id:"54995",title:"Dr.",name:"Bruna Maria",middleName:null,surname:"Roesler",slug:"bruna-maria-roesler",fullName:"Bruna Maria Roesler"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6970",title:"The Universe of Escherichia coli",subtitle:null,isOpenForSubmission:!1,hash:"92027ca0bca1f8ae2971739a4ae6af84",slug:"the-universe-of-escherichia-coli",bookSignature:"Marjanca Starčič Erjavec",coverURL:"https://cdn.intechopen.com/books/images_new/6970.jpg",editedByType:"Edited by",editors:[{id:"58980",title:"Dr.",name:"Marjanca",middleName:null,surname:"Starčič Erjavec",slug:"marjanca-starcic-erjavec",fullName:"Marjanca Starčič Erjavec"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6580",title:"Staphylococcus Aureus",subtitle:null,isOpenForSubmission:!1,hash:"2e820aab20964b63f185451d9a7b73f8",slug:"-i-staphylococcus-aureus-i-",bookSignature:"Hassan Hemeg, Hani Ozbak and Farhat Afrin",coverURL:"https://cdn.intechopen.com/books/images_new/6580.jpg",editedByType:"Edited by",editors:[{id:"187330",title:"Dr.",name:"Hassan",middleName:null,surname:"Hemeg",slug:"hassan-hemeg",fullName:"Hassan Hemeg"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6685",title:"Basic Biology and Applications of Actinobacteria",subtitle:null,isOpenForSubmission:!1,hash:"301e66d4a6b29d4326c39ff2922ec420",slug:"basic-biology-and-applications-of-actinobacteria",bookSignature:"Shymaa Enany",coverURL:"https://cdn.intechopen.com/books/images_new/6685.jpg",editedByType:"Edited by",editors:[{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",slug:"shymaa-enany",fullName:"Shymaa Enany"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6764",title:"Cyanobacteria",subtitle:null,isOpenForSubmission:!1,hash:"87c7d8f86f7c1185aa4dd47c6492951a",slug:"cyanobacteria",bookSignature:"Archana Tiwari",coverURL:"https://cdn.intechopen.com/books/images_new/6764.jpg",editedByType:"Edited by",editors:[{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6354",title:"Salmonella",subtitle:"A Re-emerging Pathogen",isOpenForSubmission:!1,hash:"e18481d5470f967439dde815fcd52b57",slug:"salmonella-a-re-emerging-pathogen",bookSignature:"Maria Teresa Mascellino",coverURL:"https://cdn.intechopen.com/books/images_new/6354.jpg",editedByType:"Edited by",editors:[{id:"156556",title:"Prof.",name:"Maria Teresa",middleName:null,surname:"Mascellino",slug:"maria-teresa-mascellino",fullName:"Maria Teresa Mascellino"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6425",title:"Probiotics",subtitle:"Current Knowledge and Future Prospects",isOpenForSubmission:!1,hash:"129bd046ff0fb4db6584e5afeebe98fa",slug:"probiotics-current-knowledge-and-future-prospects",bookSignature:"Shymaa Enany",coverURL:"https://cdn.intechopen.com/books/images_new/6425.jpg",editedByType:"Edited by",editors:[{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",slug:"shymaa-enany",fullName:"Shymaa Enany"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6148",title:"Bacterial Pathogenesis and Antibacterial Control",subtitle:null,isOpenForSubmission:!1,hash:"92128a5094670f6b0c9321640f60d3a3",slug:"bacterial-pathogenesis-and-antibacterial-control",bookSignature:"Sahra",coverURL:"https://cdn.intechopen.com/books/images_new/6148.jpg",editedByType:"Edited by",editors:[{id:"179460",title:"Dr.",name:"Sahra",middleName:null,surname:"Kırmusaoğlu",slug:"sahra-kirmusaoglu",fullName:"Sahra Kırmusaoğlu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:17,mostCitedChapters:[{id:"42319",doi:"10.5772/50364",title:"Lactic Acid Bacteria in Hydrogen-Producing Consortia: On Purpose or by Coincidence?",slug:"lactic-acid-bacteria-in-hydrogen-producing-consortia-on-purpose-or-by-coincidence-",totalDownloads:3133,totalCrossrefCites:19,totalDimensionsCites:66,book:{slug:"lactic-acid-bacteria-r-d-for-food-health-and-livestock-purposes",title:"Lactic Acid Bacteria",fullTitle:"Lactic Acid Bacteria - R & D for Food, Health and Livestock Purposes"},signatures:"Anna Sikora, Mieczysław Błaszczyk, Marcin Jurkowski and Urszula Zielenkiewicz",authors:[{id:"143688",title:"Dr.",name:"Urszula",middleName:null,surname:"Zielenkiewicz",slug:"urszula-zielenkiewicz",fullName:"Urszula Zielenkiewicz"},{id:"146985",title:"Dr.",name:"Anna",middleName:null,surname:"Sikora",slug:"anna-sikora",fullName:"Anna Sikora"},{id:"162424",title:"Prof.",name:"Mieczysław",middleName:null,surname:"Błaszczyk",slug:"mieczyslaw-blaszczyk",fullName:"Mieczysław Błaszczyk"},{id:"162425",title:"Mr.",name:"Marcin",middleName:null,surname:"Jurkowski",slug:"marcin-jurkowski",fullName:"Marcin Jurkowski"}]},{id:"49873",doi:"10.5772/62329",title:"An Introduction to Actinobacteria",slug:"an-introduction-to-actinobacteria",totalDownloads:6221,totalCrossrefCites:12,totalDimensionsCites:53,book:{slug:"actinobacteria-basics-and-biotechnological-applications",title:"Actinobacteria",fullTitle:"Actinobacteria - Basics and Biotechnological Applications"},signatures:"Ranjani Anandan, Dhanasekaran Dharumadurai and Gopinath\nPonnusamy Manogaran",authors:[{id:"48914",title:"Dr.",name:"Dharumadurai",middleName:null,surname:"Dhanasekaran",slug:"dharumadurai-dhanasekaran",fullName:"Dharumadurai Dhanasekaran"}]},{id:"42322",doi:"10.5772/51282",title:"The Current Status and Future Expectations in Industrial Production of Lactic Acid by Lactic Acid Bacteria",slug:"the-current-status-and-future-expectations-in-industrial-production-of-lactic-acid-by-lactic-acid-ba",totalDownloads:8384,totalCrossrefCites:16,totalDimensionsCites:38,book:{slug:"lactic-acid-bacteria-r-d-for-food-health-and-livestock-purposes",title:"Lactic Acid Bacteria",fullTitle:"Lactic Acid Bacteria - R & D for Food, Health and Livestock Purposes"},signatures:"Sanna Taskila and Heikki Ojamo",authors:[{id:"139705",title:"Dr.",name:null,middleName:null,surname:"Taskila",slug:"taskila",fullName:"Taskila"},{id:"142916",title:"Prof.",name:"Heikki",middleName:null,surname:"Ojamo",slug:"heikki-ojamo",fullName:"Heikki Ojamo"}]}],mostDownloadedChaptersLast30Days:[{id:"55303",title:"Classification of Anti‐Bacterial Agents and Their Functions",slug:"classification-of-anti-bacterial-agents-and-their-functions",totalDownloads:7445,totalCrossrefCites:5,totalDimensionsCites:8,book:{slug:"antibacterial-agents",title:"Antibacterial Agents",fullTitle:"Antibacterial Agents"},signatures:"Hamid Ullah and Saqib Ali",authors:[{id:"201024",title:"Dr.",name:"Hamid",middleName:null,surname:"Ullah",slug:"hamid-ullah",fullName:"Hamid Ullah"},{id:"202624",title:"Dr.",name:"Saqib",middleName:null,surname:"Ali",slug:"saqib-ali",fullName:"Saqib Ali"}]},{id:"49873",title:"An Introduction to Actinobacteria",slug:"an-introduction-to-actinobacteria",totalDownloads:6219,totalCrossrefCites:12,totalDimensionsCites:53,book:{slug:"actinobacteria-basics-and-biotechnological-applications",title:"Actinobacteria",fullTitle:"Actinobacteria - Basics and Biotechnological Applications"},signatures:"Ranjani Anandan, Dhanasekaran Dharumadurai and Gopinath\nPonnusamy Manogaran",authors:[{id:"48914",title:"Dr.",name:"Dharumadurai",middleName:null,surname:"Dhanasekaran",slug:"dharumadurai-dhanasekaran",fullName:"Dharumadurai Dhanasekaran"}]},{id:"49285",title:"Morphological Identification of Actinobacteria",slug:"morphological-identification-of-actinobacteria",totalDownloads:7412,totalCrossrefCites:12,totalDimensionsCites:27,book:{slug:"actinobacteria-basics-and-biotechnological-applications",title:"Actinobacteria",fullTitle:"Actinobacteria - Basics and Biotechnological Applications"},signatures:"Qinyuan Li, Xiu Chen, Yi Jiang and Chenglin Jiang",authors:[{id:"175852",title:"Dr.",name:"Chen",middleName:null,surname:"Jiang",slug:"chen-jiang",fullName:"Chen Jiang"}]},{id:"59952",title:"Probiotics and Its Relationship with the Cardiovascular System",slug:"probiotics-and-its-relationship-with-the-cardiovascular-system",totalDownloads:1333,totalCrossrefCites:2,totalDimensionsCites:3,book:{slug:"probiotics-current-knowledge-and-future-prospects",title:"Probiotics",fullTitle:"Probiotics - Current Knowledge and Future Prospects"},signatures:"Suresh Antony and Marlina Ponce de Leon",authors:[{id:"45333",title:"Dr.",name:"Suresh",middleName:"Jude",surname:"Antony",slug:"suresh-antony",fullName:"Suresh Antony"}]},{id:"49207",title:"Isolation and Cultivation Methods of Actinobacteria",slug:"isolation-and-cultivation-methods-of-actinobacteria",totalDownloads:4401,totalCrossrefCites:6,totalDimensionsCites:19,book:{slug:"actinobacteria-basics-and-biotechnological-applications",title:"Actinobacteria",fullTitle:"Actinobacteria - Basics and Biotechnological Applications"},signatures:"Yi Jiang, Qinyuan Li, Xiu Chen and Chenglin Jiang",authors:[{id:"175852",title:"Dr.",name:"Chen",middleName:null,surname:"Jiang",slug:"chen-jiang",fullName:"Chen Jiang"}]},{id:"59058",title:"Antibacterial Activity of Metallic Nanoparticles",slug:"antibacterial-activity-of-metallic-nanoparticles",totalDownloads:1396,totalCrossrefCites:5,totalDimensionsCites:8,book:{slug:"bacterial-pathogenesis-and-antibacterial-control",title:"Bacterial Pathogenesis and Antibacterial Control",fullTitle:"Bacterial Pathogenesis and Antibacterial Control"},signatures:"Shamaila Shahzadi, Nosheen Zafar and Rehana Sharif",authors:[{id:"26975",title:"Prof.",name:"Rehana",middleName:null,surname:"Sharif",slug:"rehana-sharif",fullName:"Rehana Sharif"},{id:"209851",title:"Dr.",name:"Shahzadi",middleName:null,surname:"Shamaila",slug:"shahzadi-shamaila",fullName:"Shahzadi Shamaila"},{id:"210177",title:"Dr.",name:"Nosheen",middleName:null,surname:"Zafar",slug:"nosheen-zafar",fullName:"Nosheen Zafar"}]},{id:"49330",title:"Production of Antibacterial Compounds from Actinomycetes",slug:"production-of-antibacterial-compounds-from-actinomycetes",totalDownloads:3295,totalCrossrefCites:1,totalDimensionsCites:2,book:{slug:"actinobacteria-basics-and-biotechnological-applications",title:"Actinobacteria",fullTitle:"Actinobacteria - Basics and Biotechnological Applications"},signatures:"Letizia Lo Grasso, Delia Chillura Martino and Rosa Alduina",authors:[{id:"175972",title:"Associate Prof.",name:"Rosa",middleName:null,surname:"Alduina",slug:"rosa-alduina",fullName:"Rosa Alduina"},{id:"176031",title:"Dr.",name:"Letizia",middleName:null,surname:"Lo Grasso",slug:"letizia-lo-grasso",fullName:"Letizia Lo Grasso"},{id:"177429",title:"Prof.",name:"Delia",middleName:null,surname:"Chillura Martino",slug:"delia-chillura-martino",fullName:"Delia Chillura Martino"}]},{id:"54862",title:"Current Approaches for Exploration of Nanoparticles as Antibacterial Agents",slug:"current-approaches-for-exploration-of-nanoparticles-as-antibacterial-agents",totalDownloads:2659,totalCrossrefCites:10,totalDimensionsCites:15,book:{slug:"antibacterial-agents",title:"Antibacterial Agents",fullTitle:"Antibacterial Agents"},signatures:"Didem Şen Karaman, Suvi Manner, Adyary Fallarero and Jessica M.\nRosenholm",authors:[{id:"199962",title:"Ph.D.",name:"Didem",middleName:null,surname:"Sen Karaman",slug:"didem-sen-karaman",fullName:"Didem Sen Karaman"},{id:"200393",title:"Dr.",name:"Suvi",middleName:null,surname:"Manner",slug:"suvi-manner",fullName:"Suvi Manner"},{id:"200398",title:"Prof.",name:"Adyary",middleName:null,surname:"Fallarero",slug:"adyary-fallarero",fullName:"Adyary Fallarero"},{id:"200400",title:"Prof.",name:"Jessica",middleName:"M.",surname:"Rosenholm",slug:"jessica-rosenholm",fullName:"Jessica Rosenholm"}]},{id:"49273",title:"Cultural, Physiological, and Biochemical Identification of Actinobacteria",slug:"cultural-physiological-and-biochemical-identification-of-actinobacteria",totalDownloads:3552,totalCrossrefCites:5,totalDimensionsCites:5,book:{slug:"actinobacteria-basics-and-biotechnological-applications",title:"Actinobacteria",fullTitle:"Actinobacteria - Basics and Biotechnological Applications"},signatures:"Qinyuan Li, Xiu Chen, Yi Jiang and Chenglin Jiang",authors:[{id:"175852",title:"Dr.",name:"Chen",middleName:null,surname:"Jiang",slug:"chen-jiang",fullName:"Chen Jiang"}]},{id:"69255",title:"The War between Bacteria and Bacteriophages",slug:"the-war-between-bacteria-and-bacteriophages",totalDownloads:817,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"growing-and-handling-of-bacterial-cultures",title:"Growing and Handling of Bacterial Cultures",fullTitle:"Growing and Handling of Bacterial Cultures"},signatures:"Beata Orzechowska and Manal Mohammed",authors:null}],onlineFirstChaptersFilter:{topicSlug:"biochemistry-genetics-and-molecular-biology-microbiology-bacteriology",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"10176",title:"Microgrids and Local Energy Systems",subtitle:null,isOpenForSubmission:!0,hash:"c32b4a5351a88f263074b0d0ca813a9c",slug:null,bookSignature:"Prof. Nick Jenkins",coverURL:"https://cdn.intechopen.com/books/images_new/10176.jpg",editedByType:null,editors:[{id:"55219",title:"Prof.",name:"Nick",middleName:null,surname:"Jenkins",slug:"nick-jenkins",fullName:"Nick Jenkins"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:1},route:{name:"profile.detail",path:"/profiles/240573/trung-dung-do",hash:"",query:{},params:{id:"240573",slug:"trung-dung-do"},fullPath:"/profiles/240573/trung-dung-do",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()