Clinical features of patients with common autosomal or sex chromosome aneuploidy.
\\n\\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:{caption:"IntechOpen Maintains",originalUrl:"/media/original/113"}},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"8533",leadTitle:null,fullTitle:"Pesticides - Use and Misuse and Their Impact in the Environment",title:"Pesticides",subtitle:"Use and Misuse and Their Impact in the Environment",reviewType:"peer-reviewed",abstract:'The book, "Pesticides - Use and Misuse and their Impact in the Environment", contains relevant information on diverse pesticides encountered in both anthropogenic and natural environments. This book provides valuable information about the toxicity of several agrochemicals that can negatively influence the health of humans and ecosystems.',isbn:"978-1-83880-047-5",printIsbn:"978-1-83962-647-0",pdfIsbn:"978-1-83880-048-2",doi:"10.5772/intechopen.78909",price:119,priceEur:129,priceUsd:155,slug:"pesticides-use-and-misuse-and-their-impact-in-the-environment",numberOfPages:136,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"420a19fa07c8510eeb08decebed430cc",bookSignature:"Marcelo Larramendy and Sonia Soloneski",publishedDate:"July 17th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/8533.jpg",numberOfDownloads:9282,numberOfWosCitations:4,numberOfCrossrefCitations:38,numberOfCrossrefCitationsByBook:2,numberOfDimensionsCitations:102,numberOfDimensionsCitationsByBook:5,hasAltmetrics:1,numberOfTotalCitations:144,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"August 30th 2018",dateEndSecondStepPublish:"September 20th 2018",dateEndThirdStepPublish:"November 19th 2018",dateEndFourthStepPublish:"February 7th 2019",dateEndFifthStepPublish:"April 8th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"14764",title:"Dr.",name:"Marcelo L.",middleName:null,surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. Larramendy",profilePictureURL:"https://mts.intechopen.com/storage/users/14764/images/system/14764.jpg",biography:"Marcelo L. Larramendy, Ph.D., serves as Professor of Molecular Cell Biology at the School of Natural Sciences and Museum (National University of La Plata, Argentina). Appointed Senior Researcher of the National Scientific and Technological Research Council of Argentina. Former Member of the Executive Committee of the Latin American Association of Environmental Mutagenesis, Teratogenesis and Carcinogenesis. Author of more than 450 contributions, including scientific publications, research communications and conferences worldwide. Recipient of several national and international awards. Prof. Larramendy is a regular Lecturer at the international A. Hollaender Courses organized by the IAEMS and former guest scientist at NIH (USA) and the University of Helsinki, (Finland). He is an expert in Genetic Toxicology and is, or has been, referee for more than 20 international scientific journals. Member of the International Panel of Experts at the International Agency for Research on Cancer (IARC, WHO, Lyon, France) in 2015 for the evaluation of DDT, 2,4-D and Lindane. Presently, Prof. Dr. Larramendy is Head of the Laboratory of Molecular Cytogenetics and Genotoxicology at the UNLP.",institutionString:"National University of La Plata",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"20",institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"14863",title:"Dr.",name:"Sonia",middleName:null,surname:"Soloneski",slug:"sonia-soloneski",fullName:"Sonia Soloneski",profilePictureURL:"https://mts.intechopen.com/storage/users/14863/images/system/14863.jpg",biography:"Sonia Soloneski has a Ph.D. in Natural Sciences and is Assistant Professor of Molecular Cell Biology at the School of Natural Sciences and Museum of La Plata, National University of La Plata, Argentina. She is a member of the National Scientific and Technological Research Council (CONICET) of Argentina in the Genetic Toxicology field, the Latin American Association of Environmental Mutagenesis, Teratogenesis and Carcinogenesis (ALAMCTA), the Argentinean Society of Toxicology (ATA), the Argentinean Society of Biology (SAB) and the Society of Environmental Toxicology and Chemistry (SETAC). She has authored more than 380 contributions in the field, including scientific publications in peer-reviewed journals and research communications. She has served as a review member for more than 30 scientific international journals. She has been a plenary speaker in scientific conferences and a member of scientific committees. She is a specialist in issues related to Genetic Toxicology, Mutagenesis, and Ecotoxicology.",institutionString:"National University of La Plata",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"7",institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"306",title:"Pesticides",slug:"pesticides"}],chapters:[{id:"65801",title:"The Morphophysiological, Histological, and Biochemical Response of Some Nontarget Organisms to the Stress Induced by the Pesticides in the Environment",doi:"10.5772/intechopen.84332",slug:"the-morphophysiological-histological-and-biochemical-response-of-some-nontarget-organisms-to-the-str",totalDownloads:1112,totalCrossrefCites:1,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Ferns, amphibians, and fish are groups of nontarget organisms affected by many types of pesticides that end up in the environment. This chapter aims to approach the following themes: the influence of different pesticides on the spore germination process and on the differentiation of their gametophyte; aspects regarding the impact of some pesticides on breathing in fish (physiology and histopathology at the branchial level), as well as a series of effects at the hematological and biochemical levels; and changes of some hematological, biochemical, and structural parameters in amphibians. Species that are not directly targeted by the action of the pesticide in the environment, ferns can be used in their gametophyte stage, young or mature sporophyte in different biotests to evaluate the risk associated with these substances. The biochemical, hemathological, and histopathological changes recorded in both fish and amphibians can be considered biomarkers of pesticide pollution.",signatures:"Liliana Cristina Soare, Alina Păunescu and Ponepal Cristina Maria",downloadPdfUrl:"/chapter/pdf-download/65801",previewPdfUrl:"/chapter/pdf-preview/65801",authors:[{id:"276263",title:"Associate Prof.",name:"Liliana Cristina",surname:"Soare",slug:"liliana-cristina-soare",fullName:"Liliana Cristina Soare"},{id:"289058",title:"Dr.",name:"Cristina Maria",surname:"Ponepal",slug:"cristina-maria-ponepal",fullName:"Cristina Maria Ponepal"},{id:"289059",title:"Dr.",name:"Alina",surname:"Păunescu",slug:"alina-paunescu",fullName:"Alina Păunescu"}],corrections:null},{id:"66132",title:"Metabolic Impairments Caused by Pesticides in Mammals and Their Interactions with Other Pollutants",doi:"10.5772/intechopen.84966",slug:"metabolic-impairments-caused-by-pesticides-in-mammals-and-their-interactions-with-other-pollutants",totalDownloads:939,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The biological systems are exposed to a complex environment in which the contaminants can interact in a synergistic/antagonistic fashion and for this reason, the study of “chemical cocktails” is of great interest to fully understand the final biological effect. To evaluate the final biological response of a pollutant, it is essential to have an adequate analytical methodology that allows the correct monitoring of environmental systems in order to establish their quality, and, when appropriate, the application of corrective measures. Undoubtedly, massive methods “the omics” are among the most efficient current tools. To this end, transcriptomics, proteomics, metabolomics and chemical speciation can provide very useful information, mainly when they are combined. However, the combination of proteomics with metabolomics has some drawbacks as the temporal space is different (i.e. metabolomics gives information about what happens right now, but it can be related with numerous post-translational modifications happened previously). In this sense, it seems that the combination of genomics with metabolomics is easier. Thus, when metabolomics data are interpreted in combination with genomic, transcriptomic and proteomic results, in the so-called systems biology approach, a holistic knowledge of the organism/process under investigation can be achieved.",signatures:"Gema Rodríguez-Moro, Ana Arias-Borrego, Sara Ramírez-Acosta, Francisco Navarro-Roldán, Nieves Abril-Díaz, Rut Fernández-Torre, Miguel Angel Bello-López, José Luis Gómez-Ariza and Tamara García-Barrera",downloadPdfUrl:"/chapter/pdf-download/66132",previewPdfUrl:"/chapter/pdf-preview/66132",authors:[{id:"34564",title:"Prof.",name:"José Luis",surname:"Gómez-Ariza",slug:"jose-luis-gomez-ariza",fullName:"José Luis Gómez-Ariza"},{id:"39335",title:"Dr.",name:"Miguel-Angel",surname:"Bello-Lopez",slug:"miguel-angel-bello-lopez",fullName:"Miguel-Angel Bello-Lopez"},{id:"39336",title:"Dr.",name:"Rut",surname:"Fernández-Torres",slug:"rut-fernandez-torres",fullName:"Rut Fernández-Torres"},{id:"39337",title:"Dr.",name:"Nieves",surname:"Abril",slug:"nieves-abril",fullName:"Nieves Abril"},{id:"274852",title:"Prof.",name:"Tamara",surname:"García-Barrera",slug:"tamara-garcia-barrera",fullName:"Tamara García-Barrera"},{id:"303409",title:"Dr.",name:"Gema",surname:"Rodríguez-Moro",slug:"gema-rodriguez-moro",fullName:"Gema Rodríguez-Moro"},{id:"303410",title:"Dr.",name:"Ana",surname:"Arias-Borrego",slug:"ana-arias-borrego",fullName:"Ana Arias-Borrego"},{id:"303411",title:"Dr.",name:"Sara",surname:"Ramírez-Acosta",slug:"sara-ramirez-acosta",fullName:"Sara Ramírez-Acosta"},{id:"303412",title:"Dr.",name:"Francisco",surname:"Navarro-Roldán",slug:"francisco-navarro-roldan",fullName:"Francisco Navarro-Roldán"}],corrections:null},{id:"64602",title:"Environmental Risk of Groundwater Pollution by Pesticide Leaching through the Soil Profile",doi:"10.5772/intechopen.82418",slug:"environmental-risk-of-groundwater-pollution-by-pesticide-leaching-through-the-soil-profile",totalDownloads:3095,totalCrossrefCites:25,totalDimensionsCites:69,hasAltmetrics:1,abstract:"Adsorption, degradation, and movement are the key processes conditioning the behavior and fate of pesticides in the soil. Six processes that can move pesticides are leaching, diffusion, volatilization, erosion and run-off, assimilation by microorganisms, and plant uptake. Leaching is the vertical downward displacement of pesticides through the soil profile and the unsaturated zone, and finally to groundwater, which is vulnerable to pollution. Pesticides are frequently leached through the soil by the effect of rain or irrigation water. Pesticide leaching is highest for weakly sorbing and/or persistent compounds, climates with high precipitation and low temperatures, and soils with low organic matter and sandy texture. On the contrary, for pesticides with a low persistence that disappear quickly, the risk of groundwater pollution considerably decreases. Different and varied factors such as physical-chemical properties of the pesticide, a permeability of the soil, texture and organic matter content of the soil, volatilization, crop-root uptake, and method and dose of pesticide application are responsible for the leaching rate of the pesticides. Soils that are high in clays and organic matter will slow the movement of water, attach easily to many pesticides, and generally have a higher diversity and population of soil organisms that can metabolize the pesticides.",signatures:"Gabriel Pérez-Lucas, Nuria Vela, Abderrazak El Aatik and Simón Navarro",downloadPdfUrl:"/chapter/pdf-download/64602",previewPdfUrl:"/chapter/pdf-preview/64602",authors:[{id:"202983",title:"Dr.",name:"Simón",surname:"Navarro",slug:"simon-navarro",fullName:"Simón Navarro"},{id:"202988",title:"Dr.",name:"Nuria",surname:"Vela",slug:"nuria-vela",fullName:"Nuria Vela"},{id:"206059",title:"Dr.",name:"Gabriel",surname:"Pérez-Lucas",slug:"gabriel-perez-lucas",fullName:"Gabriel Pérez-Lucas"},{id:"283154",title:"Mr.",name:"Abderrazak",surname:"El Aatik",slug:"abderrazak-el-aatik",fullName:"Abderrazak El Aatik"}],corrections:null},{id:"65766",title:"Pesticides, Anthropogenic Activities, and the Health of Our Environment Safety",doi:"10.5772/intechopen.84161",slug:"pesticides-anthropogenic-activities-and-the-health-of-our-environment-safety",totalDownloads:1463,totalCrossrefCites:7,totalDimensionsCites:16,hasAltmetrics:1,abstract:"Mankind depends on agricultural products for food consumption. Increasing population (more than 7 billion) requires significant growth in crop yield to meet essential demand. This aim was achieved through the use of pesticides to protect crops from diseases. Pesticides are toxic by design for organisms that can threaten food products. Their mode of action is by targeting systems or enzymes in the pests that may be similar to human system and therefore pose risks to human health and the environment as well. The WHO recommended classifying pesticides according to their toxicity and chemicals according to their chronic health and environmental hazards.",signatures:"Mona Saud AL-Ahmadi",downloadPdfUrl:"/chapter/pdf-download/65766",previewPdfUrl:"/chapter/pdf-preview/65766",authors:[{id:"276726",title:"Ph.D.",name:"Mona",surname:"AL-Ahmadi",slug:"mona-al-ahmadi",fullName:"Mona AL-Ahmadi"}],corrections:null},{id:"65752",title:"Uses and Misuses of Agricultural Pesticides in Africa: Neglected Public Health Threats for Workers and Population",doi:"10.5772/intechopen.84566",slug:"uses-and-misuses-of-agricultural-pesticides-in-africa-neglected-public-health-threats-for-workers-an",totalDownloads:1573,totalCrossrefCites:4,totalDimensionsCites:7,hasAltmetrics:1,abstract:"Pesticides are use in agriculture for their capacity to reduce pest and protect foods. Since their introduction in Africa by colonial masters, the use of these chemicals is constantly growing. Herbicides and insecticides are the two dominant categories. Although they are used in small quantities by farmers who own small exploitation, the frequency of their use, as well as overuses and misuses, constitutes serious factors of exposure and health risks. Farm workers are more vulnerable to occupational effects from pesticide inhalation and skin contacts. Failure to wear protective equipment and observe good agricultural practices explained health symptoms that are frequently experienced: eye and skin irritation, nausea, vomiting, and headache. Population is subject to chronic health effects due to repeated dietary intake of pesticides. Most consumed staple foods on the continent (cereals, vegetables, and fruits) have been found to be contaminated by one or multiple residues of pesticides. The level of residues is often higher than regulatory limits. Organization of surveillance programs to monitor concentration of pesticide residues remains inexistent in most countries, same for toxicovigilance systems to documented poisoning cases. Current data underline the need to carry out pesticide health risk assessment in order to appreciate the threats they pose for public health.",signatures:"Pouokam Guy Bertrand",downloadPdfUrl:"/chapter/pdf-download/65752",previewPdfUrl:"/chapter/pdf-preview/65752",authors:[{id:"276832",title:"Ph.D. Student",name:"Guy Bertrand",surname:"Pouokam",slug:"guy-bertrand-pouokam",fullName:"Guy Bertrand Pouokam"}],corrections:null},{id:"66189",title:"Pesticides, Anthropogenic Activities, History and the Health of Our Environment: Lessons from Africa",doi:"10.5772/intechopen.82600",slug:"pesticides-anthropogenic-activities-history-and-the-health-of-our-environment-lessons-from-africa",totalDownloads:1103,totalCrossrefCites:1,totalDimensionsCites:5,hasAltmetrics:0,abstract:"This chapter describes the historical events related to pesticide use. The description of events focuses on human activities that necessitated the use of chemical agents for pest control to protect crops, and animals including humans in African countries. The description covers the common pests in Africa and the need for pest control using pesticides. History of pesticide use in Africa and the ban of organochlorines are covered. Controversies under discussion in Africa and the current trend of pesticide use in Africa are part of the chapter as well as pesticide import and supply. Hazard and risk of exposure of biological organisms including humans to pesticides due to anthropogenic activities in Africa and pros and cons of pesticide use in Africa are covered.",signatures:"Wilbert Bunini Manyilizu",downloadPdfUrl:"/chapter/pdf-download/66189",previewPdfUrl:"/chapter/pdf-preview/66189",authors:[{id:"274792",title:"Dr.",name:"Bunini",surname:"Manyilizu",slug:"bunini-manyilizu",fullName:"Bunini Manyilizu"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"4637",title:"Toxicity and Hazard of Agrochemicals",subtitle:null,isOpenForSubmission:!1,hash:"6aff74df1ea32df7f1e20e29c8363ff5",slug:"toxicity-and-hazard-of-agrochemicals",bookSignature:"Marcelo L. 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With the discovery in 1956 that the correct chromosome number in humans is 46, the new area of clinical cytogenetic began its rapid growth. Several major chromosomal syndromes with altered numbers of chromosomes were reported, such as Down syndrome (trisomy 21), Turner syndrome (45,X) and Klinefelter syndrome (47,XXY). Since then it has been well established that chromosome abnormalities contribute significantly to genetic disease resulting in reproductive loss, infertility, stillbirths, congenital anomalies, abnormal sexual development, mental retardation and pathogenesis of malignancy [1]. Clinical features of patients with common autosomal or sex chromosome aneuploidy is shown in Table 1.
Trisomy 21 or Down syndrome is one of the best-recognized and most common chromosome disorders caused by the presence of all or part of a third copy of chromosome 21 (Figure 1). It is the single most common genetic cause for mental retardation. The incidence of Down syndrome is approximately 1/800 newborns [2]. The risk for having a child with Down syndrome increases with maternal age. Clinical features include mental and growth retardation, characteristic faces and other abnormalities described in Table 1. Approximately 94% of Down syndrome patients have trisomy 21 resulting from meiotic nondisjunction, the failure of homologous chromosomes or sister chromatids to separate during cell division. The generally exponential increase in the frequency of nondisjunction with increasing maternal age is correlated with a decline in genetic recombination frequency, for example, for chromosomes 21 [3].
XX,+21 female Down syndrome karyotype demonstrating trisomy 21. (Karyotype prepared by Fatma Soylemez)
Aneuploidy is the second major category of chromosome mutations in which chromosome number is abnormal. An aneuploid is an individual organism whose chromosome number differs from the wild type by part of a chromosome set. Double aneuploidy that leads to trisomy of the two different chromosomes occurs due to accidentally meiotic nondisjunction events; both could have a same or different parental origin. The first case of double aneuploidy (48,XXY,+21) was reported in 1959 by Ford et al [4]. Other double aneuploidy that are found frequently are 48,XXX,+21, 48,XXY,+18 and 48,XXX,+18.
In this chapter, we will discuss double aneuploidies in Down syndrome in the light of the published reports. We will also examine possible underlying mechanism involved in the double aneuploidy.
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
Down | \n\t\t\tTrisomy 21 | \n\t\t\tShort, broad hands with single palmar crease, decreased muscle tone, mental retardation, broad head with characteristic features, open mouth with large tongue, up-slanting eyes | \n\t\t
Edwards | \n\t\t\tTrisomy 18 | \n\t\t\tMultiple congenital malformations of many organs, low-set malformed ears, receding mandible, small eyes, mouth and nose with general elfin appearance, severe mental deficiency, congenital heart defects, horseshoe or double kidney, short sternum, posterior heel prominence | \n\t\t
Patau | \n\t\t\tTrisomy 13 | \n\t\t\tSevere mental deficiency, small eyes, cleft lip and/or palate, extra fingers and toes, cardiac anomalies, midline brain anomalies, genitourinary abnormalities | \n\t\t
Turner | \n\t\t\t45,X | \n\t\t\tFemale with retarded sexual development, usually sterile, short stature, webbing of skin in neck region, cardiovascular abnormalities, hearing impairment, normal intelligence | \n\t\t
Klinefelter | \n\t\t\t47,XXY | \n\t\t\tMale, infertile with small testes, may have some breast development, tall, mild mental deficiency, long limbs, at risk for educational problems | \n\t\t
Triple X | \n\t\t\t47,XXX | \n\t\t\tFemale with normal genitalia and fertility, at risk for educational and emotional problems, early menopause | \n\t\t
Clinical features of patients with common autosomal or sex chromosome aneuploidy.
The simultaneous occurrence of two independent chromosomal anomalies in a given individual has been reported for various combinations of aberrations. Such associations most frequently involve aneuploidy of a sex chromosome and trisomy of an autosome, while double autosomal trisomies are less frequent. The reported cases involving autosome and/or sex chromosome aneuploidy, such as double autosomal trisomy are extremely rare in live newborns.
The data of fourteen previously reported cases with double autosomal trisomy, twelve of them mosaics, may be summarized as follows: The distribution of the maternal ages at birth of the patients was striking: six mothers were younger than 21 years, seven mothers were older than 34 years. In those patients with prevalence of one of the two extra chromosomes in their karyotypes, the corresponding trisomy syndrome also predominated clinically. In those cases with an equal proportion of both additional chromosomes there were as many patients with clinical predominance of the one as of the other trisomy syndrome. Survival beyond the second half of the first year of life was seen only in those patients who showed the clinical picture of mongolism.
The trisomy 18 syndrome, also known as Edwards syndrome, is a common chromosomal disorder due to the presence of an extra chromosome 18, either full, mosaic trisomy, or partial trisomy 18q. The condition is the second most common autosomal trisomy syndrome after trisomy 21 [5].
The syndrome pattern comprises a recognizable pattern of major and minor anomalies, an increased risk of neonatal and infant mortality, and significant psychomotor and cognitive disability. The main clinical features represent the clues for the diagnosis in the perinatal period and include prenatal growth deficiency, characteristic craniofacial features, distinctive hand posture, nail hypoplasia, short hallux, short sternum, and major malformations (Table 1).
Most authorities have suggested that the extra chromosome is present because of nondisjunction. In parent of origin analyses the extra chromosome is most often of maternal origin, the result of an error during the segregation of chromosomes in meiosis or post zygotic mitosis. About 50% of the nondisjunction errors in oogenesis occur in meiosis II, unlike other human trisomies where the malsegregation is more frequent in meiosis I. In the minority of cases in which the extra chromosome has a paternal origin, the error is the result of a post zygotic error. The cause of nondisjunction is unknown.
Most reported cases of double aneuploidy of Edwards syndrome are Edwards-Turner, Edwards-XXX, Edwards-Klinefelter and Edwards-XYY. However, double aneuploidy involving Down and Edwards syndromes is very rare occurrence because most of them probably are miscarriages (Table 2). Interestingly, the existence of double autosomal trisomy was reported in a newborn child: Down syndrome-trisomy 18 and Down syndrome and trisomy 13 [6].
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
\n\t\t\t\t | \n\t\t\tEdwards/Down Syndrome | \n\t\t\tHsu et al, 1965 [7] | \n\t\t
\n\t\t\t\t | \n\t\t\tEdwards/Down Syndrome | \n\t\t\tGrosse et al, 1977 [8] | \n\t\t
\n\t\t\t\t | \n\t\t\tEdwards/Down Syndrome | \n\t\t\tCastel et al, 1983 [6] | \n\t\t
\n\t\t\t\t | \n\t\t\tEdwards/Down Syndrome | \n\t\t\tReddy et al, 1997 [9] | \n\t\t
Some examples of double aneuploidy in patients affected with Down and Edwards Syndrome.
Trisomy 13, also called Patau syndrome, is the least common of the major autosomal trisomies with an estimated incidence of 1 in 20 000 live births. Trisomy 13 is associated with advanced maternal age. The extra 13 usually results from a maternal meiotic nondisjunctional error.
Trisomy 13 is a chromosomal condition associated with severe intellectual disability and physical abnormalities in many parts of the body. Individuals with trisomy 13 often have heart defects, brain or spinal cord abnormalities, very small or poorly developed eyes (microphthalmia), extra fingers or toes, an opening in the lip (a cleft lip) with or without an opening in the roof of the mouth (a cleft palate), and weak muscle tone (hypotonia) (Table 1). Owing to severe clinical abnormalities including central nervous system malformations, heart defects, growth retardation and numerous other congenital anomalies, trisomy 13 patients rarely survive the newborn period.
Due to the presence of several life-threatening medical problems, many infants with trisomy 13 die within their first days or weeks of life. Only five percent to 10 percent of children with this condition live past their first year. Like Edwards syndrome many affected pregnancies do not survive to delivery and therefore the incidence in mid pregnancy is higher. Double aneuploidy involving Down and Patau syndromes is very rare occurrence because most of them probably are miscarriages as well as Edwards syndrome (Table 3).
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
\n\t\t\t\t | \n\t\t\tPatau/Down Syndrome | \n\t\t\tCastel et al, 1983 [6] | \n\t\t
\n\t\t\t\t | \n\t\t\tPatau/Down Syndrome mosaic Down Syndrome | \n\t\t\tBarnett et al, 1987 [10] | \n\t\t
\n\t\t\t\t | \n\t\t\tPatau/Down Syndrome | \n\t\t\tReddy et al, 1997 [9] | \n\t\t
\n\t\t\t\t | \n\t\t\tPatau/Down Syndrome | \n\t\t\tJenderny, 2014 [11] | \n\t\t
Some examples of double aneuploidy in patients affected with Down and Patau Syndrome.
Sex chromosome abnormalities have less severe clinical anomalies than those associated with comparable autosomal imbalances. This difference can be attributed to genetic inactivation of all but one X-chromosome in those cases where multiple copies are present, and the relatively low gene content of the Y-chromosome. Sex chromosome aneuploidy is relatively common, with overall frequency of about 1 in 500 live births. Some (XXX, XXY, XYY) are relatively frequent in newborns but rare in spontaneous abortions. Monosomy X (Turner syndrome), in contrast, is one of the most common chromosome abnormalities seen in spontaneous abortions but relatively rare in newborns.
Turner syndrome, a disorder in females characterized by the absence of all or part of a normal second sex chromosome, leads to a constellation of physical findings that often includes congenital lymphedema, short stature, and gonadal dysgenesis (Table 1). Turner’s syndrome occurs in 1 in 2500 to 1 in 3000 live-born girls. Approximately half have monosomy X (45,X), and 5 to 10 percent have a duplication (isochromosome) of the long arm of one X (46,X,i(Xq)). Most of the rest have mosaicism for 45,X, with one or more additional cell lineages.
The clinical features range from a severe phenotypic character with short stature, gonadal dysgenesis and different malformations to an isolated mild reduction in final height or premature ovarian failure. The most visible phenotype is the short stature, which has been reported in up to 98 % of all Turner syndrome patients. Peripheral lymphedema dorsally of the hands and feet may be the initial presenting sign of Turner syndrome and is found in approximately one-third of affected infants. Turner’s syndrome should be suspected in any newborn girl with edema or hypoplastic left heart or coarctation of the aorta, since the frequency of both conditions is increased among children with Turner’s syndrome. In the last decade, the association between aortic dissection and Turner syndrome has been increasingly recognized with several reports of sudden death. In most other patients with Turner’s syndrome, the condition is diagnosed either in adolescence when they fail to enter puberty or in adulthood because of recurrent pregnancy loss.
Most of Turner syndrome cases have mosaicism with Down syndrome. However, double aneuploidy involving Down and Turner syndromes is a rare occurrence (Table 4). The patients reported to have combined Down and Turner syndromes, fundamentally usually different forms of chromosome mosaicism have been noted and all have been mosaic with respect to monosomy X. Townes et al reported the first example of a Turner-Down patient in whom there was no X mosaicism [12].
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
\n\t\t\t\t | \n\t\t\tTurner/Down Syndrome | \n\t\t\tTownes et al, 1975 [12] | \n\t\t
\n\t\t\t\t | \n\t\t\tTurner/Down Syndrome mosaic Down Syndrome | \n\t\t\tMacFaul, 1981 [14] | \n\t\t
\n\t\t\t\t | \n\t\t\tTurner/Down Syndrome | \n\t\t\tRuangdaraganon, 1993 [16] | \n\t\t
\n\t\t\t\t | \n\t\t\tTurner/Down Syndrome | \n\t\t\tJaruratanasirikul et al, 1995 [13] | \n\t\t
\n\t\t\t\t | \n\t\t\tTurner/Down Syndrome mosaic Down Syndrome | \n\t\t\tZaki et al, 2005 [15] | \n\t\t
\n\t\t\t\t | \n\t\t\tTurner/Down Syndrome | \n\t\t\tJenderny, 2014 [11] | \n\t\t
Some examples of double aneuploidy in patients affected with Down and Turner Syndrome
One of the first reports with double aneuploidy (Turner-Down) was reported that the first example of a Turner-Down patient in whom there is no X mosaicism [12]. The case of an 8 month-old female infant with non-mosaic Down-Turner double aneuploidy was reported by Jaruratanasirikul et al [13]. She had Down faces without stigmata of Turner syndrome.
Down\'s/Turner\'s mosaic is a rare chromosomal abnormality, occurring in about 1 in 2 000 000 births. Two babies with Down\'s/Turner\'s mosaic karyotype was reported that 2 babies born with this disorder in each of whom chromosomal analysis of amniotic fluid had mistakenly identified the fetus as a normal male [14]. The infant had the facial appearance of a Down syndrome. She was markedly hypotonic with a low hairline, and had pronounced webbing of the neck. The heart was normal. Karyotype was 46,X+21/47XX+21. The 46,X+21 was present in 12% of the cultured cells. At age 11 months she had the appearance typical of Down syndrome together with some webbing of the neck. Mother was 36 years old. Same investigators reported another patient who had a baby with Down/Turner aneuploidy. Mother was 38 years old. The amniotic fluid karyotype was thought to be 46,XY. A girl weighing 1750 g was delivered at 36 weeks\' gestation by caesarean section performed for intrauterine growth retardation. The infant had the facial appearance of Down\'s syndrome, a large clitoris, puffy hands and feet, and for a few days was cyanosed in air, and had a cardiac murmur. There was a single palmar crease and talipes on the right. She died from bronchopneumonia aged 15 weeks. The karyotype obtained in the neonatal period was 47,XX+21/46,X+21. Zaki and colleagues recently represented a female, mosaic (46,X,+21/47,XX,+21) where monosomy X was detected only by FISH in 15 percentages of cells, nevertheless, stigmata of Turner syndrome was more obvious in this patient [15].
Klinefelter syndrome is a chromosomal condition that affects male physical and cognitive development. Its signs and symptoms vary among affected individuals. The incidence of 48,XXY,+21 in the general population is 0.4 to 0.9 per 10,000 male births. Unlike Turner syndrome, males with Klinefelter syndrome are not usually detected in the newborn period. These individuals are generally normal in appearance before puberty. After puberty they are frequently ascertained in infertility clinics or identified by their small testes, breast enlargement and tall stature. Affected individuals typically have small testes that do not produce as much testosterone as usual. Some affected individuals also have genital differences including undescended testes, the opening of the urethra on the underside of the penis (hypospadias), or an unusually micropenis (Table 1). Significant mental retardation is not part of this syndrome but patients have a higher incidence of educational and emotional problems.
Klinefelter and his colleagues (1942) described a characteristic syndrome in nine male patients who had gynecomastia and a specific form of hypogonadism comprising small testes with hyalinized seminiferous tubules and absent spermatogenesis but with intact Leyding cells. This syndrome is now well established in clinical practice and contributes significantly to infertility in the male.
Most Klinefelter patients have a 47,XXY karyotype (Figure 2). At least 10% have mosaicism involving normal 46,XY cells plus another population of cells with two or more X chromosomes. Mosaic patients have more variable clinical features and occasionally may have relatively normal testicular development. Cytogenetic and molecular data have indicated that 47,XXY is equally likely to result from a maternal or paternal meiotic nondisjunctional error. Maternally derived cases are associated with maternal age. Variants of Klinefelter syndrome include those patients with more than two X-chromosomes, multiple X-chromosome mosaicism and multiple Y-chromosomes. The presence of additional X-chromosomes is associated with increasing severity of clinical abnormalities including mental retardation, sexual development and skeletal anomalies.
XXY Klinefelter syndrome karyotype (Karyotype prepared by Fatma Soylemez).
Trisomy 21 and numerical sex chromosome anomalies are common chromosome disorders. Down syndrome is the most common chromosomal abnormality in humans with an incidence of one in 770 live births. Although it is the most intensively studied human chromosomal abnormality, little is known about its cause and only advanced maternal age is confirmed as a risk factor [17]. On the other hand, Klinefelter syndrome is the most common disorder of sex chromosomes in humans, with prevalence of one in 500 males. The classic form is the most common chromosomal disorder, in which there is one extra X chromosome resulting in the karyotype of 47,XXY [18]. Double aneuploidy was first described in a patient with both Down and Klinefelter (48, XXY,+21) syndromes. This is also the most commonly described double aneuploidy. The karyotype is shown on Figure 3 [19].
The coincidence rate of both Down and Klinefelter syndromes in the same individual is estimated to lie in the range 0.27 to 0.7 × 10-5 [20]. On the other hand, lower values of XXY pattern recorded in older boys and men with Down syndrome suggest that there might be an increased selection against these individuals after birth [21]. Several cases of double aneuploidy of XXY and trisomy 21 have been published since the first report by Ford et al. (Table 5).
Pediatric cardiologists are familiar with screening of babies with Down syndrome for congenital heart defects, expecting in approximately 50% to find a heart defect, typically atrioventricular septal defect. However, in children diagnosed with Klinefelter syndrome, a chronic heart disease has only rarely been reported. Shen et al reported one case of 48,XXY,+21 karyotype with chronic heart disease. The phenotypic characteristics of the 4-month-old child had showed the presence of features typical of mongoloid slant. Also, Doppler echocardiogram detection has been showed atrial septal and ventricular septal defects with patent ductus arteriosus, pulmonary hypertension and mild tricuspid regurgitation [22]. Similarly, a 14-month-old boy was reported with double aneuploidy and a double aortic arch suffered from frequently recurrent severe feeding and respiratory problems [23].
GTG-banded karyotype of the case showing double aneuploidy - 48,XXY,+21. (Karyotype prepared by Fatma Soylemez.)
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
\n\t\t\t\t | \n\t\t\tKlinefelter/Down Syndrome | \n\t\t\tFord et al, 1959 [4] | \n\t\t
\n\t\t\t\t | \n\t\t\tKlinefelter/Down Syndrome | \n\t\t\tHarnden et al, 1960 [33] | \n\t\t
\n\t\t\t\t | \n\t\t\tKlinefelter/Down Syndrome | \n\t\t\tLanman et al, 1960 [34] | \n\t\t
\n\t\t\t\t | \n\t\t\tKlinefelter/Down Syndrome | \n\t\t\tHustinx et al, 1961 [35] | \n\t\t
\n\t\t\t\t | \n\t\t\tKlinefelter/Down Syndrome | \n\t\t\tGelderen and Hustinx, 1961 [36] | \n\t\t
\n\t\t\t\t | \n\t\t\tKlinefelter/Down Syndrome | \n\t\t\tHamerton et al, 1961 [26] | \n\t\t
\n\t\t\t\t | \n\t\t\tKlinefelter/Down Syndrome | \n\t\t\tMilcou and Mainanesco, 1963 [37] | \n\t\t
\n\t\t\t\t | \n\t\t\tKlinefelter/Down Syndrome | \n\t\t\tCourt Brown et al, 1964 [38] | \n\t\t
\n\t\t\t\t | \n\t\t\tKlinefelter/Down Syndrome | \n\t\t\tPfeiffer, 1964 [39] | \n\t\t
\n\t\t\t\t | \n\t\t\tKlinefelter/Down Syndrome | \n\t\t\tTaylor and Moores, 1967 [27] | \n\t\t
\n\t\t\t\t | \n\t\t\tKlinefelter/Down Syndrome-Mosaic | \n\t\t\tYamaguchi et al, 1989 [20] | \n\t\t
\n\t\t\t\t | \n\t\t\tKlinefelter/Down Syndrome | \n\t\t\tAl Awadi et al, 1998 [25] | \n\t\t
\n\t\t\t\t | \n\t\t\tKlinefelter/Down Syndrome | \n\t\t\tIliopoulus et al, 2004 [24] | \n\t\t
\n\t\t\t\t | \n\t\t\tKlinefelter/Down Syndrome | \n\t\t\tCyril et al, 2005 [40] | \n\t\t
\n\t\t\t\t | \n\t\t\tKlinefelter/Down Syndrome | \n\t\t\tGlass et al, 2006 [17] | \n\t\t
\n\t\t\t\t | \n\t\t\tKlinefelter/Down Syndrome | \n\t\t\tAkbas, Soylemez et al, 2008 [19] | \n\t\t
\n\t\t\t\t | \n\t\t\tKlinefelter/Down Syndrome | \n\t\t\tKaraman and Kabalar, 2008 [41] | \n\t\t
\n\t\t\t\t | \n\t\t\tKlinefelter/Down Syndrome | \n\t\t\tBiselli et al, 2009 [42] | \n\t\t
\n\t\t\t\t | \n\t\t\tKlinefelter/Down Syndrome | \n\t\t\tJeanty and Turner, 2009 [43] | \n\t\t
\n\t\t\t\t | \n\t\t\tKlinefelter/Down Syndrome | \n\t\t\tGerretsen et al, 2009 [23] | \n\t\t
\n\t\t\t\t | \n\t\t\tKlinefelter/Down Syndrome | \n\t\t\tShen et al, 2012 [22] | \n\t\t
\n\t\t\t\t | \n\t\t\tKlinefelter/Down Syndrome | \n\t\t\tShu et al, 2013 [24] | \n\t\t
\n\t\t\t\t | \n\t\t\tKlinefelter/Down Syndrome | \n\t\t\tMishra et al, 2014 [44] | \n\t\t
Some examples of double aneuploidy in patients affected with Down and Klinefelter Syndrome.
Facial dysmorphic features of the children with karyotype 48,XXY,+21, reveals signs of Down syndrome. a) [
Shu et al recently presented a neonate with a double aneuploidy associated with congenital heart defect suffered from cyanosis after birth. The patient had typical features of Down syndrome including hypertelorism, slightly lowest ears with protruding pinna (Figure 4). Doppler echocardiography has been indicated complex congenital heart disease with an ostium secundum atrial septal defect, enlarged right ventricle, and mild tricuspid valve regurgitation. Until now, only eight cases of double aneuploidy associated with CHD defect has been reported [24].
This abnormality has also been described in a pair of monozygotic twins [25]. Further, both the sibs of the proband showing 48,XXY,+21 were found to exhibit trisomy 21 in yet another study [26]. Hamerton et al have summarized the data on the frequency of 48,XXY,+21 males and concluded that the expected incidence of double trisomics based on chance association should be about 0.31x10-5 live-born males [27]. In six sex chromatin surveys of the newborn 23.229 live-born males were studied; 47 of these were chromatin positive and two were double trisomics (48,XXY,+21), an incidence of 8.62x10-5 [28]. This was 18 times higher than the indirect estimate for the general population and 30 times higher than the expected frequency based on chance association. These figures suggested that there was a much higher incidence of double trisomics at birth than would be expected by chance; the most satisfactory explanation for the reduced incidence among older groups was that double trisomics had a much higher mortality during the early years of life than the primary trisomics.
The association of Klinefelter Syndrome and Down syndrome in the same siblings has already been referred to and would be expected by chance although this is more difficult to establish. In particular, three of them, trisomy 21, trisomy 18 and trisomy 13 are the most frequently seen autosomal aneuploidies. Other commonly seen gonosomal aneuploidies are Turner syndrome, Klinefelter syndrome and its variants, poly X syndromes and poly Y syndromes. However, neonatal survey data has revealed that the incidence of XXY and trisomy 21 double trisomy at birth is higher than expected from the incidence of either alone [28].
The prenatal mortality rate of Downs-Klinefelter syndrome has not been extensively studied. Mutton et al found that 35% (6 of 17) of double aneuploidy cases that included an additional chromosome 21 died in utero [29]. Kovaleva and Mutton reported 2 miscarriages in 10 cases of prenatally diagnosed 48,XXY,+21, giving a mortality rate of 20%. Compared with either condition alone, the survival rate for the combination of XXY and trisomy 21 appears to be intermediary [30]. Forrester and Merz reported 1 death in utero (3.5%) in 28 cases of Klinefelter syndrome [31]. Bojesen et al reported no intrauterine deaths in 49 fetuses with prenatally diagnosed Klinefelter syndrome [32]. These data excluded terminations of pregnancies. Since the first reported cases of double aneuploidy with 48, XXY,+21 karyotype [20, 28, 33-40], many cases with Down and Klinefelter syndrome in the same individual has been reported in the literature, some of them very new [17,19, 22-26,41-44] (Table 5).
Triple X syndrome, also called trisomy X or 47,XXX, is characterized by the presence of an additional X chromosome in each of a female\'s cells. The frequency of 47,XXX in newborn females is about 1 in 1000 and is associated with maternal age. Most XXX females are clinically normal with normal gonadal function and fertility. Although females with this condition may be taller than average, this chromosomal change typically causes no unusual physical features. Most females with triple X syndrome have normal sexual development and are able to conceive children. However, there is an increased risk for learning disabilities, reduction in performance IQ, menstrual problems and early menopause (Table 1). Triple X syndrome is associated with an increased risk of learning disabilities and delayed development of speech and language skills. Delayed development of motor skills such as sitting and walking, weak muscle tone (hypotonia), and behavioral and emotional difficulties are also possible, but these characteristics vary widely among affected girls and women (Figure 5). Seizures or kidney abnormalities occur in about 10 percent of affected females. Thus, the clinical manifestations are of trisomy 21 alone in many cases reported that Triple X syndrome/Down syndrome double aneuploidy. Trisomy-21 and triple-X in the same individual has been reported earlier [45, 46] and more recently [47-52] and phenotypic features of classical Down syndrome were only seen. However, strabismus, periorbital swelling, scanty eyebrows and microganthia have not been observed in these reports (Table 6).
Phenotype of the child with karyotype 48,XXX,+21 showing characteristic faces with low set ears and short neck. a) [
Sheth et al reported a case of double aneuploidy showing trisomy 21 and triple-X chromosome in a case of Down syndrome born to young non-consanguineous parents. The child presented with strabismus, periorbital swelling, scanty eyebrows and microganthia in addition to Down features. Molecular characterization had shown the maternal origin of double aneuploidy with trisomy 21 at meiosis-II and triple-X at meiosis-I [51].
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
\n\t\t\t\t | \n\t\t\tDouble chromatin positive female with Down Syndrome | \n\t\t\tDay et al, 1963 [45] | \n\t\t
\n\t\t\t\t | \n\t\t\tDouble chromatin positive female with Down Syndrome | \n\t\t\tYunis et al, 1964 [46] | \n\t\t
\n\t\t\t\t | \n\t\t\tTriple X/Down Syndrome | \n\t\t\tPark et al, 1995 [47] | \n\t\t
\n\t\t\t\t | \n\t\t\tTriple X/Down Syndrome | \n\t\t\tDevlin and Morrison, 2004 [48] | \n\t\t
\n\t\t\t\t | \n\t\t\tTriple X/Down Syndrome | \n\t\t\tBalwan et al, 2008 [49] | \n\t\t
\n\t\t\t\t | \n\t\t\tTriple X/Down Syndrome | \n\t\t\tGuzel et al, 2009 [50] | \n\t\t
\n\t\t\t\t | \n\t\t\tTriple X/Down Syndrome | \n\t\t\tSheth et al, 2011 [51] | \n\t\t
\n\t\t\t\t | \n\t\t\tTriple X/Down Syndrome | \n\t\t\tUwineza et al, 2012 [52] | \n\t\t
Some examples of double aneuploidy in patients affected with Down and Triple X Syndrome
47,XYY syndrome is characterized by an extra copy of the Y chromosome in each of a male\'s cells. Approximately 1 in 1000 newborn males have a 47,XYY karyotype. Although most 47,XYY patients are clinically normal, they tend to be taller than normal and have an increased tendency for behavioral and learning problems as children and young adults. Y-chromosome aneuploidy results from paternal meiotic nondisjunction and is not associated with maternal age. Although males with this condition may be taller than average, this chromosomal change typically causes no unusual physical features. Most males with 47,XYY syndrome have normal sexual development and are able to father children. 47,XYY syndrome is associated with an increased risk of learning disabilities and delayed development of speech and language skills. Delayed development of motor skills such as sitting and walking, weak muscle tone (hypotonia), hand tremors or other involuntary movements (motor tics), and behavioral and emotional difficulties are also possible (Table 1). These characteristics vary widely among affected boys and men. A small percentage of males with 47,XYY syndrome are diagnosed with autistic spectrum disorders, which are developmental conditions that affect communication and social interaction.
Most cases of 47,XYY syndrome are not inherited. The chromosomal change usually occurs as a random event during the formation of sperm cells. An error in cell division called nondisjunction can result in sperm cells with an extra copy of the Y chromosome. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have an extra Y chromosome in each of the body\'s cells. The XYY occurs when 24YY spermatozoa are formed due to nondisjunction either at paternal meiosis II or mitosis. Unlike Down syndrome, the XYY is not associated with increased parental age. The only consistent phenotypic feature associated with the XYY syndrome is tall stature, which becomes evident at about 5-6 years of age. These children may have learning difficulties, attention deficits, hyperactivity and increased aggressiveness. However, the behavioral changes appear to be variable and may be modified by the environment in which these children live. Therefore, it is important to recognize the XYY abnormality at the earliest so that these children can be evaluated periodically and given appropriate care and interventions for learning and behavioral needs.
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
\n\t\t\t\t | \n\t\t\t47,XYY/Down Syndrome | \n\t\t\tVerresen et al, 1965 [53] | \n\t\t
\n\t\t\t\t | \n\t\t\t47,XYY/Down Syndrome | \n\t\t\tMigeon, 1965 [54] | \n\t\t
\n\t\t\t\t | \n\t\t\t47,XYY/Down Syndrome | \n\t\t\tUchida et al, 1966 [55] | \n\t\t
\n\t\t\t\t | \n\t\t\t47,XYY/Down Syndrome | \n\t\t\tAl-Aish MS et al, 1971 [56] | \n\t\t
\n\t\t\t\t | \n\t\t\t47,XYY /Down Syndrome mosaic Down Syndrome | \n\t\t\tSchwanitz et al, 1978 [57] | \n\t\t
\n\t\t\t\t | \n\t\t\t47,XYY/Down Syndrome | \n\t\t\tReddy, 1997 [58] | \n\t\t
\n\t\t\t\t | \n\t\t\t47,XYY/Down Syndrome | \n\t\t\tParmar et al, 2002 [59] | \n\t\t
\n\t\t\t\t | \n\t\t\t47,XYY /Down Syndrome | \n\t\t\tKoken et al, 2011 [60] | \n\t\t
\n\t\t\t\t | \n\t\t\t47,XYY/Down Syndrome mosaic Down Syndrome | \n\t\t\tParihar et al, 2013 [61] | \n\t\t
Some examples of double aneuploidy in patients affected with Down and 47,XYY Syndrome
Although etiological predisposing factor for 48,XYY,+21 is not known, there are reported several cases of karyotype with 48,XYY,+21 since 1970’s [53-57] (Table 7). Fewer than 40 cases of Down syndrome with XYY have been reported until date, only one of which has mosaicism for XYY. Reddy observed only 22 cases of double aneuploidy, such as XXY and 21 trisomy among 3024 spontaneous abortuses that the frequency even less than expected if the two aneuploidy events were independent of each other. They also occurred at an older mean maternal age [58]. Koken et al presented the patient had typical features of Down syndrome, however, phenotypic features of XYY was not present (Figure 6). In addition, the patient also had atrial septal defect, multiple trabecular small ventricular septal defect, and moderate degree of pulmonary hypertension [60]. Parihar et al reported a 5-year-old boy with the clinical features of Down syndrome. Cytogenetic analysis has been showed a mosaicism for a double aneuploidy, Down syndrome and XYY. The karyotype was 47, XY,+21(19)/48, XYY,+21(6),ish XYY (DXZ1 × 1, DYZ1 × 2) [61].
Phenotype of the child with karyotype 48,XYY,+21, reveals signs of Down syndrome [60-Koken et al, 2011].
It has been over 50 years since trisomy 21 was identified as the cause of Down’s syndrome, providing the first link between a clinical disorder and a chromosome abnormality. In the intervening half-century, the importance of numerical chromosome abnormalities to human disease pathology has been well-documented. Taken together, these studies established aneuploidy as the leading known cause of congenital birth defects and miscarriage and demonstrated that most aneuploid conceptuses perish in utero.
The occurrence of double aneuploidy i.e. the existence of two chromosomal abnormalities in the same individual is an uncommon phenomenon. Although aneuploidies are common structural chromosomal abnormalities, double aneuploidies involving chromosomes 21 and sex and autosomal chromosomes are very rare. Trisomy 21 and numerical sex chromosome anomalies are common chromosomal disorders, with a birth incidence of 1:700 to 1:2,500 respectively [30]. The chances of two chromosomal anomalies occurring in a single conceptus are a rare event and the reported incidence varies from 0.21% to 2.8% in spontaneous miscarriages subjected to cytogenetic study [50]. In 1959, the first case with autosomal and sex chromosomal anomalies, 48,XXY,+21, was presented by Ford et al [4].
Various double aneuploidy associations are summarized in Tables above. The most frequently reported type of double aneuploidy is the 48,XXY,+21; other types include 48,XYY,+21. In general, the double aneuploidies which involve the sex chromosomes as well as 21-trisomy have phenotypic features representative of both aneuploidy conditions. These usually have the features of both conditions although the more serious condition usually masks the less serious. The presence of an associated sex chromosome abnormality in children with Down syndrome may not be clinically evident until puberty.
The existence of two chromosomal abnormalities in the same individual is relatively a rare phenomenon. Double aneuploidy leading to trisomy and/or monosomy of two different chromosomes arises because of two meiotic nondisjunctional events. Both these aneuploidies could have the same or different parental origin [62]. Double aneuploidy leading to trisomy and / or monosomy of two different chromosomes arises because of two meiotic nondisjunctional events. Both aneuploidies arise as a result of nondisjunction in maternal meiosis II [47] and these results support the hypothesis that a segregation defect at the cellular level may cause nondisjunction involving more than one chromosome. Most reported cases of double aneuploidy are presented in the form of spontaneous abortions. The reported cases involving autosome and/or sex chromosome aneuploidy, such as double autosomal trisomy and autosomal trisomy with sex chromosome monosomy or trisomy, are extremely rare in live newborns. These syndromes include Edwards-Down, Down-Klinefelter, Down-Turner mosaicism, Down-XYY, Patau-Klinefelter, Edwards-Turner mosaicism, Edwards-XXX, Edwards-Klinefelter, and Edwards-XYY. A rare case of double chromosome aneuploidy including Edwards syndrome (trisomy 18) and Klinefelter syndrome was described highlighting the patient’s longer life span. Most cases of double aneuploidies in live births involve the sex chromosomes combined with either trisomy 13, 18 or 21, i.e. XXX/18, XXX/21, XXY/13, XXY/18, XXY/21, XYY/13, XYY/18 and XYY/21.
Double aneuploidies are observed in 0.21-2.8% of the aborted fetuses [63]. For women 35 years and older, the rate of trisomy 21 is increased to 1 per 120 pregnancies when data from 2 sources are combined. The rate of Klinefelter syndrome in pregnancies carried by women 35 years or older is 1 per 787.41 By multiplying the individual frequencies, the expected frequency of 48,XXY,+21 would be 1 per 94,440 pregnancies. Caron et al found 1 case of 48,XXY,+21 in 24,901 amniocentesis performed for advanced maternal age (≥35 years), which is a 3.8-fold increase over the expected rate [64]. The nonrandom aspect of double aneuploidy provides evidence that a hereditary predisposition to nondisjunction exists, with one chromosomal imbalance increasing the risk of another to occur, which suggests that both events arise from the same parent. Nondisjunction in cases of double trisomy has been found to be entirely maternal in origin, entirely paternal in origin, and both maternal and paternal in origin. In such cases in which the additional chromosomes originate from different parents, the two errors may be coincidental and unrelated to a genetically determined nondisjunction. Abnormal separation of chromosomes may occur in older individuals because of dysfunction of structures related to chromosome separation, such as the spindle apparatus and kinetochore. Among 28 reports of 48,XXY,+21, which include 36 cases with known parental ages, Kovaleva and Mutton found that the risk for 48,XXY,+21 was age dependent, with a mean maternal age of 33 years and a mean paternal age of 38 years [30].
Trisomy 21, resulting in Down Syndrome (DS), is the most common autosomal trisomy among live-born infants and is caused mainly by nondisjunction of chromosome 21 within oocytes. Risk factors for nondisjunction depend on the parental origin and type of meiotic error. For errors in the oocyte, increased maternal age and altered patterns of recombination are highly associated with nondisjunction. Studies of normal meiotic events in humans have shown that recombination clusters in regions referred to as hotspots. In addition, GC content, CpG fraction, Poly(A)/Poly(T) fraction and gene density have been found to be significant predictors of the placement of sex-averaged recombination in the human genome. The results from early studies demonstrated that most aneuploidies are due to errors in maternal meiosis and that increasing maternal age is a powerful contributor to the occurrence of aneuploidy. However, studies during the past 10-15 years have also implicated events that occur at the onset of female meiosis in the fetal ovary and during the protracted dictyate arrest. The duration of the division (10 to 50 years and beyond) provides ample opportunity for errors to occur and to accumulate, which is a feature that has been the basis of a number of hypotheses to explain the maternal age effect. Indeed, the emerging picture indicates that aneuploidy is not due to a single causal factor but involves a complex constellation of effects that begins in utero, continues throughout the reproductive lifespan of the woman, is exacerbated by age and is facilitated by the unique features of cell cycle control in the oocyte.
Trisomics and monosomic (aneuploid) embryos account for at least 10% of human pregnancies and, for women nearing the end of their reproductive lifespan, the incidence may exceed 50%. The errors that lead to aneuploidy almost always occur in the oocyte but, despite intensive investigation, the underlying molecular basis has remained elusive. Increased maternal age and altered number and location of recombination events have been found to be associated with maternal meiotic errors involving chromosome 21 [65]. The overwhelming majority of trisomy 21, or Down syndrome, is caused by the failure of chromosomes to separate properly during meiosis, also known as chromosome nondisjunction. As nondisjunction is the leading cause of pregnancy loss, mental retardation and birth defects, it is imperative that we understand the biology underlying this phenomenon. Characteristics of chromosome 21 nondisjunction are typical of many of the other human autosomes. That is, the overwhelming majority is due to errors during oogenesis: at least 90% of cases have chromosome 21 nondisjunction are due to maternal meiotic errors.
Whereas there was no obvious maternal age association with recombination patterns among normally disjoining chromosomes 21, there was a significant one among maternal MI and ‘‘MII’’ errors. One set of observations provides evidence for specific recombination patterns being the proximal cause of nondisjunction, while the others suggest an interaction between specific recombination patterns and maternal age-related risk factors. Specifically, the absence of recombination or the presence of a single recombinant event near the telomere of 21q are associated with maternal meiosis I (MI) errors and these associations appear to be independent of the age of the oocyte (i.e., maternal age at the time of birth of the infant with trisomy 21). Meiosis II (MII) errors appear to be driven by different age and recombination traits: MII errors are associated with the placement of a recombinant event near the centromere of 21q and this association increases with increasing age of the oocyte.
Nondisjunction could be possibly attributed to genetic, environmental or combined factors. Theoretically genes predisposing to increased nondisjunction can be classified in several different ways: a) Gene(s) producing nondisjunction of a specific chromosome (e.g. chromosome 21), b) Gene(s) that can predispose to nondisjunction of different autosome/sex chromosomes in the same individual, or in sibs, due to, parental and/or post zygotic or post systic nondisjunction “double aneuploidy” (such as, 48,XX, or XY,+21; 48,XXY,+21; 46,X,+21). The occurrence of double aneuploidy would not prove the existence of predisposition gene(s). Such outcome resulting from parental mosaicism has been demonstrated in some families with >2 trisomy 21 sibs. Familial double aneuploidy is very rare. However, the occurrence of aneuploidy for different chromosomes is better evidence for genetic predisposition although environmental factors could also be invoked as a possible cause. Amniocentesis and live birth data provide little evidence for a strong double aneuploidy effect although a weak effect cannot be excluded. Studies in abortions are suggestive of genetic mosaicism in double aneuploidy.
In conclusion, since the first description of a case of double aneuploidy with 48, XXY,+21 karyotype, approximately 385 cases with double aneuploidy are reported in the literature. Autosomal double trisomies are observed in spontaneous abortions but are rarely reported in live born infants. Most double aneuploidies are associated with an increased maternal age, abnormal sonogram, and pregnancy loss at a very early gestational age. However, sex chromosome aneuploidy and trisomies involving chromosomes 16, 18, and 21 can survive for longer gestation. The mechanism underlying the origin of double aneuploidy is unclear. It is hypothesized that double aneuploidy results either from two nondisjunctional events in gametogenesis or a single nondisjunctional event in a trisomics zygote. The published literature shows that there is no specific chromosome association in double aneuploidy formation; however, the most frequently involved chromosomes are the sex chromosomes and acrocentric chromosomes.
The theory of asymmetric elasticity introduced in 1909 by the Cosserat brothers [1] gave rise to a variety of Cosserat plate theories. In 1960s, Green and Naghdi specialized their general theory of Cosserat surface to obtain the linear Cosserat plate [2], while independently Eringen proposed a complete theory of plates in the framework of Cosserat elasticity [3]. Numerous plate theories were formulated afterwards; for the review of the latest developments in the area of Cosserat plates we recommend to turn to [4].
\nThe first theory of Cosserat plates based on the Reissner plate theory was developed in [5] and its finite element modeling is provided in [6]. The parametric theory of Cosserat plate, presented by the authors in [7], includes some additional assumptions leading to the introduction of the splitting parameter. This provided the highest level of approximation to the original three-dimensional problem. The theory provides the equilibrium equations and constitutive relations, and the optimal value of the minimization of the elastic energy of the Cosserat plate. The paper [7] also provides the analytical solutions of the presented plate theory and the three-dimensional Cosserat elasticity for simply supported rectangular plate. The comparison of these solutions showed that the precision of the developed Cosserat plate theory is similar to the precision of the classical plate theory developed by Reissner [8, 9].
\nThe numerical modeling of bending of simply supported rectangular plates is given in [10]. We developed the Cosserat plate field equations and a rigorous formula for the optimal value of the splitting parameter. The solution of the Cosserat plate was shown to converge to the Reissner plate as the elastic asymmetric parameters tend to zero. The Cosserat plate theory demonstrates the agreement with the size effect, confirming that the plates of smaller thickness are more rigid than is expected from the Reissner model. The modeling of Cosserat plates with simply supported rectangular holes is also provided. The finite element analysis of the perforated Cosserat plates is given in [11].
\nThe extension of the static model of Cosserat elastic plates to the dynamic problems is presented in [12]. The computations predict a new kind of natural frequencies associated with the material microstructure and were shown to be compatible with the size effect principle reported in [10] for the Cosserat plate bending.
\nThis chapter represents an extension of the paper [12] for different shapes and orientations of micro-elements incorporated into the Cosserat plates. It is based on the generalized variational principle for elastodynamics and includes a non-diagonal rotatory inertia tensor. The numerical computations of the plate free vibrations showed the existence of some additional high frequencies of micro-vibrations depending on the orientation of micro-elements. The comparison with three-dimensional Cosserat elastodynamics shows a high agreement with the exact values of the eigenvalue frequencies.
\nThe Cosserat linear elasticity balance laws are
\nwhere the \n
We will also consider the constitutive equations as in [13]:
\nand the kinematic relations in the form
\nHere \n
The constitutive Eqs. (3)–(4) can be written in the reverse form [5].
\nwhere \n
We will consider the boundary conditions given in [12].
\nand initial conditions
\nwhere \n
The strain stored energy \n
where
\nis non-negative. The relations Eqs. (3)–(4) can be written in the form [12]:
\nThe stress energy is given as
\nwhere
\nand the relations Eqs. (6)–(7) can be written as [12].
\nWe consider the work done by the stresses \n
and
\nHere \n
The stored kinetic energy \n
The kinetic energy \n
where
\nand
\nThe work \n
Keeping in mind that the variation of \n
or
\nand therefore
\nWe modify the HPR principle [14] for the case of Cosserat elastodynamics in the following way: for any set \n
of the functional
\nat \n
\n
Let us consider the variation of the functional \n
Taking into account Eq. (5) we can perform the integration by parts
\nThen keeping in mind that \n
In this section we review our stress, couple stress and kinematic assumptions of the Cosserat plate [7]. We consider the thin plate \n
The set of points \n
In our case we consider the vertical load and pure twisting momentum boundary conditions at the top and bottom of the plate, which can be written in the form:
\nwhere \n
We will also consider the rotatory inertia \n
Let \n
for every \n
Here the plate stress and kinetic energy density by the formulas
\nwhere \n
and
\n\n\n
where \n
The plate characteristics provide the approximation of the components of the three-dimensional tensors \n
where
\nThe pressures \n
and \n
The three-dimensional displacements \n
and the three-dimensional strain and torsion tensors \n
where \n
Then zero variation of the functional
\nis equivalent to the plate bending system of equations (A) and constitutive formulas (B) mixed problems.
\nA. The bending equilibrium system of equations:
\nwhere \n
at the part \n
at the part \n
B. Constitutive formulas in the reverse form:1\n
\nand the optimal value \n
where
\nWe also assume that the initial condition can be presented in the form
\nThe Cosserat plate field equations are obtained by substituting the relations Eqs. (74)–(83) into the system of Eqs. (65)–(70) similar to [10]:
\nwhere
\nThe operators \n
The coefficients \n
For the validation purposes we provide the algorithm and computation results for the three-dimensional Cosserat elastodynamics. We also present the analysis of the numerical results based on the plate theory for the microelements of different shapes and orientations incorporated into the Cosserat plate.
\nIn our computations we consider the plates made of polyurethane foam—a material reported in the literature to behave Cosserat like—and the values of the technical elastic parameters presented in [15]: \n
Let us consider the plate \n
We solve the three-dimensional Cosserat equilibrium Eqs. (1)–(2) accompanied by the constitutive Eqs. (3)–(4) and strain-displacement and torsion-rotation relations Eq. (5) complemented by the following boundary conditions:
\nwhere the initial distribution of the pressure is given as \n
Using the method of separation of variables and taking into account the boundary conditions Eqs. (86)–(87), we express the kinematic variables in the form:
\nwhere the functions \n
If we substitute the expressions Eqs. (91)–(96) into Eqs. (3)–(4) and then into Eqs. (1)–(2), we will obtain the following eigenvalue problem
\nwhere
\nand the differential operators \n
and the coefficients \n
The system of differential Eq. (97) is complemented by the following boundary conditions \n
and the coefficients \n
The idea for the solution of the eigenvalue problem Eq. (97) is based on the following algorithm:
\n\n
We fix certain value of the frequency \n
\n
Mathematically, fixing certain value of \n
\n
We run \n
Large amplitude linear vibrations of the Cosserat body forced to vibrate close to its natural frequency
The comparison of the eigenfrequencies of the Cosserat plate with the eigenfrequencies of the three-dimensional Cosserat elasticity is given in the \nTable 1\n. The rotatory inertia principle moments used are \n
\n | \n\n | \n\n\n | \n\n\n | \n\n\n | \n\n\n | \n
---|---|---|---|---|---|
Plate theory | \n0.310 | \n17.881 | \n501.13 | \n205.62 | \n338.95 | \n
D Cosserat elasticity | \n0.309 | \n17.763 | \n530.82 | \n211.98 | \n317.87 | \n
Comparison of the eigenfrequencies \n
Ball-shaped micro-elements:
We consider a plate \n
and the following hard simply supported boundary conditions [7]:
\nSimilar to [12] we apply the method of separation of variables for the eigenvalue problem Eq. (85) to solve for the kinematic variables \n
where \n
We solve an eigenvalue problem by substituting these expressions into the system of Eq. (85). The obtained nine sequences of positive eigenfrequencies \n
We perform all our numerical simulations for \n
\n | \n\n | \n\n\n | \n\n\n | \n\n\n | \n\n\n | \n\n | \n | \n |
---|---|---|---|---|---|---|---|---|
\n | \n\n\n | \n\n\n | \n\n\n | \n\n\n | \n\n\n | \n\n\n | \n\n\n | \n\n\n | \n
Ball | \n0.001 | \n0.001 | \n0.001 | \n17.88 | \n0.31 | \n501.13 | \n205.62 | \n338.95 | \n
Vertical ellipsoid | \n0.001 | \n0.001 | \n0.0001 | \n17.88 | \n0.31 | \n501.13 | \n650.22 | \n338.95 | \n
Horizontal ellipsoid | \n0.0001 | \n0.001 | \n0.001 | \n17.88 | \n0.31 | \n1363.01 | \n205.62 | \n394.08 | \n
Eigenfrequencies \n
Let \n
The eigenfrequencies for different angles of microrotation of the microelements are given in the \nTable 3\n and the \nFigure 3\n. The rotatory inertia principle moments used are \n
Angle \n | \n\n\n | \n\n\n | \n\n\n | \n\n\n | \n\n\n | \n\n\n | \n\n\n | \n\n\n | \n\n\n | \n
---|---|---|---|---|---|---|---|---|---|
\n\n | \n17.88 | \n17.88 | \n0.31 | \n0.31 | \n650.221 | \n265.37 | \n265.37 | \n450.61 | \n450.61 | \n
\n\n | \n17.88 | \n17.88 | \n0.31 | \n0.31 | \n650.221 | \n255.59 | \n279.40 | \n429.89 | \n469.93 | \n
\n\n | \n17.88 | \n17.88 | \n0.31 | \n0.31 | \n650.221 | \n247.75 | \n295.33 | \n406.70 | \n484.79 | \n
\n\n | \n17.88 | \n17.88 | \n0.31 | \n0.31 | \n650.221 | \n242.57 | \n313.65 | \n382.94 | \n495.14 | \n
\n\n | \n17.88 | \n17.88 | \n0.31 | \n0.31 | \n650.221 | \n239.99 | \n333.10 | \n360.57 | \n500.46 | \n
\n\n | \n17.88 | \n17.88 | \n0.31 | \n0.31 | \n650.221 | \n239.68 | \n338.95 | \n354.35 | \n501.13 | \n
\n\n | \n17.88 | \n17.88 | \n0.31 | \n0.31 | \n650.221 | \n239.99 | \n333.10 | \n360.57 | \n500.46 | \n
\n\n | \n17.88 | \n17.88 | \n0.31 | \n0.31 | \n650.221 | \n242.57 | \n313.65 | \n382.94 | \n495.14 | \n
\n\n | \n17.88 | \n17.88 | \n0.31 | \n0.31 | \n650.221 | \n247.75 | \n295.33 | \n406.70 | \n484.79 | \n
\n\n | \n17.88 | \n17.88 | \n0.31 | \n0.31 | \n650.221 | \n255.59 | \n279.40 | \n429.89 | \n469.93 | \n
\n\n | \n17.88 | \n17.88 | \n0.31 | \n0.31 | \n650.221 | \n265.37 | \n265.37 | \n450.61 | \n450.61 | \n
Eigenfrequencies \n
Micro frequencies
In this chapter, we presented a mathematical model of Cosserat plate vibrations. The dynamic model of the plates has been developed as a dynamic extension of the Reissner plate theory. The equations has been presented in both tensorial and the matrix forms. We also described the validation of the model, which is based on the comparison with the three-dimensional Cosserat elastodynamics exact solutions. Based on the presented results of the computer simulations we were able to detect and classify the additional high resonance frequencies of a plate. We have shown that the frequencies depend on the shape and orientation of microelements (ball-shaped elements, horizontally and vertically stretched ellipsoids) incorporated into the Cosserat plates. We also have been able to identify that micro frequencies associated with the micro rotatory inertia and its transverse variation of the ellipsoid elements have higher micro frequencies than the ball-shaped elements. We also showed the dependence of the eigenfrequencies on the angles of rotation of the horizontal ellipsoid micro-elements. These results can be used to identify the characteristics of the plate micro-elements.
\nWe use the following notation convention:
the values of the Latin subindex \n
the values of the Greek indices \n
the Einstein summation notation is used throughout the chapter
artesian coordinates
\nCosserat thin plate
\nplate thickness
\nLamé parameters
\nCosserat elasticity parameters
\nmaterial density
\nrotatory inertia
\nthe stress tensor
\nthe couple stress tensor
\nstrain tensor
\nbend-twist tensor
\ndisplacement vector
\nmicrorotation vector
\nlinear momentum
\nangular momentum
\nLevi-Civita tensor
\nstrain stored energy
\nstress energy
\nstored kinetic energy
\nwork of inertia forces
\nCosserat plate stress set
\nCosserat plate displacement set
\nCosserat plate strain set
\nsplitting parameter
\npressure
\nnatural frequency of plate vibration
\nangle of microelement orientation
\nbending and twisting moments
\nshear forces
\ntransverse shear forces
\nmicropolar bending moments
\nmicropolar twisting moments
\nmicropolar couple moments
\nrotations of the middle plane around \n
vertical deflections of the middle plate
\nmicrorotations in the middle plate around \n
rate of change of the microrotation
\nIntechOpen - where academia and industry create content with global impact
",metaTitle:"Team",metaDescription:"Advancing discovery in Open Access for the scientists by the scientist",metaKeywords:null,canonicalURL:"page/team",contentRaw:'[{"type":"htmlEditorComponent","content":"Our business values are based on those any scientist applies to their research. We have created a culture of respect and collaboration within a relaxed, friendly and progressive atmosphere, while maintaining academic rigour.
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\\n\\nDr Alex Lazinica
\\n\\nAlex Lazinica is co-founder and Board member of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his Ph.D. in Robotics at the Vienna University of Technology. There, he worked as a robotics 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, co-founded and built the International Journal of Advanced Robotic Systems, the world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career since it proved to be the pathway to the foundation of IntechOpen with its focus on addressing academic researchers’ needs. Alex personifies many of IntechOpen´s key values, including the commitment to developing mutual trust, openness, and a spirit of entrepreneurialism. Today, his focus is on defining the growth and development strategy for the company.
\\n"}]'},components:[{type:"htmlEditorComponent",content:"Our business values are based on those any scientist applies to their research. We have created a culture of respect and collaboration within a relaxed, friendly and progressive atmosphere, while maintaining academic rigour.
\n\nCo-founded by Alex Lazinica and Vedran Kordic: “We are passionate about the advancement of science. As Ph.D. researchers in Vienna, we found it difficult to access the scholarly research we needed. We created IntechOpen with the specific aim of putting the academic needs of the global research community before the business interests of publishers. Our Team is now a global one and includes highly-renowned scientists and publishers, as well as experts in disseminating your research.”
\n\nBut, one thing we have in common is -- we are all scientists at heart!
\n\nSara Uhac, COO
\n\nSara Uhac was appointed Managing Director of IntechOpen at the beginning of 2014. She directs and controls the company’s operations. Sara joined IntechOpen in 2010 as Head of Journal Publishing, a new strategically underdeveloped department at that time. After obtaining a Master's degree in Media Management, she completed her Ph.D. at the University of Lugano, Switzerland. She holds a BA in Financial Market Management from the Bocconi University in Milan, Italy, where she started her career in the American publishing house Condé Nast and further collaborated with the UK-based publishing company Time Out. Sara was awarded a professional degree in Publishing from Yale University (2012). She is a member of the professional branch association of "Publishers, Designers and Graphic Artists" at the Croatian Chamber of Commerce.
\n\nAdrian Assad De Marco
\n\nAdrian Assad De Marco joined the company as a Director in 2017. With his extensive experience in management, acquired while working for regional and global leaders, he took over direction and control of all the company's publishing processes. Adrian holds a degree in Economy and Management from the University of Zagreb, School of Economics, Croatia. A former sportsman, he continually strives to develop his skills through professional courses and specializations such as NLP (Neuro-linguistic programming).
\n\nDr Alex Lazinica
\n\nAlex Lazinica is co-founder and Board member of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his Ph.D. in Robotics at the Vienna University of Technology. There, he worked as a robotics 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, co-founded and built the International Journal of Advanced Robotic Systems, the world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career since it proved to be the pathway to the foundation of IntechOpen with its focus on addressing academic researchers’ needs. Alex personifies many of IntechOpen´s key values, including the commitment to developing mutual trust, openness, and a spirit of entrepreneurialism. Today, his focus is on defining the growth and development strategy for the company.
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In this chapter, the current status of ergonomics in laparoscopy, laparoendoscopic single‐site surgery (LESS), and robot‐assisted surgery will be reviewed. Ergonomic guidelines for laparoscopic surgical practice and methods for ergonomic assessment in surgery will be described. Results will be based on the scientific literature and our experience. Results showed that the surgeon's posture during laparoscopic surgery is mainly affected by the static body postures, the height of the operating table, the design of the surgical instruments, the position of the main screen, and the use of foot pedals. Ergonomics during the laparoscopic surgical practice is related to the level of experience. Better ergonomic conditions entail an improvement in task performance. Laparoscopic instruments with axial handle lead to a more ergonomic posture for the wrist compared to a ring handle. LESS is physically more demanding than conventional and hybrid approaches, requiring greater level of muscular activity in the back and arm muscles, but better wrist position compared with traditional laparoscopy. Physical and cognitive ergonomics with robotic assistance were significantly less challenging when compared to conventional laparoscopic surgery.",book:{id:"5390",slug:"laparoscopic-surgery",title:"Laparoscopic Surgery",fullTitle:"Laparoscopic Surgery"},signatures:"Francisco M. Sánchez-Margallo and Juan A. Sánchez-Margallo",authors:[{id:"14715",title:"Prof.",name:"Francisco M.",middleName:null,surname:"Sánchez-Margallo",slug:"francisco-m.-sanchez-margallo",fullName:"Francisco M. Sánchez-Margallo"},{id:"188738",title:"Dr.",name:"Juan A.",middleName:null,surname:"Sánchez Margallo",slug:"juan-a.-sanchez-margallo",fullName:"Juan A. 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Devices that provide additional and innovative functionalities in comparison with conventional surgical instruments will be considered. Results will be based on studies published in the scientific literature and our experience. These surgical devices will be organized into two main groups, mechanical devices and robotic-driven devices. In general, these instruments intend to simulate the dexterity of movements of a human wrist. Mechanical devices are cheaper and easier to develop, so most of the available handheld instruments fall into this category. The majority of the robotic-driven devices are needle holders with an articulating tip, controlled by an interface implemented on the instrument handle. In general, these handheld devices claim to offer an enhancement of dexterity, precision, and ergonomics.",book:{id:"6360",slug:"new-horizons-in-laparoscopic-surgery",title:"New Horizons in Laparoscopic Surgery",fullTitle:"New Horizons in Laparoscopic Surgery"},signatures:"Francisco M. 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Sánchez Margallo"},{id:"214776",title:"Dr.",name:"Amir",middleName:null,surname:"Szold",slug:"amir-szold",fullName:"Amir Szold"}]},{id:"21003",doi:"10.5772/18033",title:"Risks Associated with Laparoscopic Surgery",slug:"risks-associated-with-laparoscopic-surgery",totalDownloads:16663,totalCrossrefCites:4,totalDimensionsCites:6,abstract:null,book:{id:"1041",slug:"advanced-laparoscopy",title:"Advanced Laparoscopy",fullTitle:"Advanced Laparoscopy"},signatures:"Tülün Öztürk",authors:[{id:"30184",title:"Prof.",name:"Tulun",middleName:null,surname:"Ozturk",slug:"tulun-ozturk",fullName:"Tulun Ozturk"}]},{id:"21013",doi:"10.5772/20516",title:"Port-Site Metastasis Following Laparoscopic Surgery",slug:"port-site-metastasis-following-laparoscopic-surgery",totalDownloads:3950,totalCrossrefCites:1,totalDimensionsCites:5,abstract:null,book:{id:"1041",slug:"advanced-laparoscopy",title:"Advanced Laparoscopy",fullTitle:"Advanced Laparoscopy"},signatures:"Terence C. Chua, Tristan D. Yan, David L. Morris and Paul H. Sugarbaker",authors:[{id:"39316",title:"Dr.",name:"Paul",middleName:null,surname:"Sugarbaker",slug:"paul-sugarbaker",fullName:"Paul Sugarbaker"},{id:"63672",title:"Prof.",name:"David",middleName:"Lawson",surname:"Morris",slug:"david-morris",fullName:"David Morris"},{id:"97099",title:"Dr.",name:"Terence",middleName:null,surname:"Chua",slug:"terence-chua",fullName:"Terence Chua"},{id:"97100",title:"Dr.",name:"Tristan",middleName:null,surname:"Yan",slug:"tristan-yan",fullName:"Tristan Yan"}]},{id:"46621",doi:"10.5772/58533",title:"History of the Inguinal Hernia Repair",slug:"history-of-the-inguinal-hernia-repair",totalDownloads:4910,totalCrossrefCites:3,totalDimensionsCites:4,abstract:null,book:{id:"3818",slug:"inguinal-hernia",title:"Inguinal Hernia",fullTitle:"Inguinal Hernia"},signatures:"Andrzej L. Komorowski",authors:[{id:"169228",title:"Dr.",name:"Andrzej",middleName:null,surname:"Komorowski",slug:"andrzej-komorowski",fullName:"Andrzej Komorowski"}]}],mostDownloadedChaptersLast30Days:[{id:"53643",title:"The Evolution of Minimally Invasive Techniques in Restoration of Colonic Continuity",slug:"the-evolution-of-minimally-invasive-techniques-in-restoration-of-colonic-continuity",totalDownloads:2195,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Restoration of bowel continuity after Hartmann’s procedure is considered technically challenging and is associated with high morbidity and mortality. This is the main reason why restoration of intestinal continuity is often not attempted. Over the past decade, considerable international experience has gained on this topic with new minimally invasive techniques being developed. This review details the evolution of minimally invasive techniques in restoration of colonic continuity after Hartmann’s procedure. A comprehensive search of PubMed and Embase was done. Different restoration modalities were included. Eight studies, from six different countries, in which multiport laparoscopic restoration of continuity was compared to conventional open restoration of bowel continuity, were included. In the total of 254 patients, continuity was restored laparoscopically compared with 255 patients in which continuity was performed in open fashion. Restoration of bowel continuity via trephine access was also reported; three studies including 37 patients were included in this review. Single-port restoration of bowel continuity after Hartmann’s procedure is a natural evolution of multiport laparoscopy and trephine access. Six studies reporting on single-port reversal of Hartmann’s procedure were included with a total of 75 patients. Single-port access in combination with a transanal approach has also been reported; however, data are extremely limited as there is only one study in the published literature. Success of restoration of bowel continuity with less morbidity and mortality has been demonstrated throughout the evolution of the different surgical techniques. In this review advantages of different approaches for restoration of bowel continuity after Hartmann’s procedure are discussed. Furthermore, surgical techniques are described, pictorial guides are added for some techniques, and flowcharts are given for easy use during clinical decision-making.",book:{id:"5390",slug:"laparoscopic-surgery",title:"Laparoscopic Surgery",fullTitle:"Laparoscopic Surgery"},signatures:"Stefan H.E.M. Clermonts, Laurents P.S. 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The major physiologic obstacles to safe laparoscopy include pregnancy, increased intra cranial pressure, abnormalities of cardiac output and gaseous exchange in the lung, chronic liver diseases and coagulation disorders. In a redo surgery there may be problems of laparoscopic port entry.",book:{id:"6360",slug:"new-horizons-in-laparoscopic-surgery",title:"New Horizons in Laparoscopic Surgery",fullTitle:"New Horizons in Laparoscopic Surgery"},signatures:"Nidhi Sharma and Vanusha Selvin",authors:[{id:"220214",title:"Prof.",name:"Nidhi",middleName:null,surname:"Sharma",slug:"nidhi-sharma",fullName:"Nidhi Sharma"},{id:"225521",title:"Dr.",name:"Vanusha",middleName:null,surname:"Selvin",slug:"vanusha-selvin",fullName:"Vanusha Selvin"}]},{id:"56017",title:"Surgical Anatomy of the Groin",slug:"surgical-anatomy-of-the-groin",totalDownloads:2570,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Most surgeons are familiar with the inguinal anatomy from the anterior perspective. With the advent of laparoscopic techniques for inguinal hernia repair, it became important to understand the inguinal anatomy from the preperitoneal view for a posterior approach to the inguinal region. The purpose of this chapter is to describe the anatomic landmarks of the groin region.",book:{id:"5928",slug:"hernia",title:"Hernia",fullTitle:"Hernia"},signatures:"Kamer Tomaoglu",authors:[{id:"201271",title:"M.D.",name:"Kamer",middleName:null,surname:"Tomaoglu",slug:"kamer-tomaoglu",fullName:"Kamer Tomaoglu"}]},{id:"21003",title:"Risks Associated with Laparoscopic Surgery",slug:"risks-associated-with-laparoscopic-surgery",totalDownloads:16663,totalCrossrefCites:4,totalDimensionsCites:6,abstract:null,book:{id:"1041",slug:"advanced-laparoscopy",title:"Advanced Laparoscopy",fullTitle:"Advanced Laparoscopy"},signatures:"Tülün Öztürk",authors:[{id:"30184",title:"Prof.",name:"Tulun",middleName:null,surname:"Ozturk",slug:"tulun-ozturk",fullName:"Tulun Ozturk"}]},{id:"56039",title:"Congenital Diaphragmatic Hernia",slug:"congenital-diaphragmatic-hernia",totalDownloads:2593,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Despite advances in neonatal and surgical care, the management of congenital diaphragmatic hernia (CDH) remains challenging with no definitive standard treatment guidelines. Several centers report mortality rates as low as 20%, but if extracorporeal membrane oxygenation (ECMO) support is required, the mortality rate rises to 50%. The disease severity is related to the degree of pulmonary hypoplasia and pulmonary hypertension that occurs with CDH. Both conditions decrease the infant’s ability to ventilate and oxygenate adequately at delivery. These physiologic conditions that impair gas exchange are the important determinants of morbidity and mortality in CDH infants. Presently, delivery of infants with CDH is recommended close to term gestation. The focus of care includes gentle ventilation, hemodynamic monitoring, and treatment of pulmonary hypertension followed by surgery for the defect. Extracorporeal membrane oxygenation (ECMO) is considered after failure of conventional medical management for infants ≥ 34 weeks’ gestation or with weight >2 kg and no associated major lethal anomalies. This chapter discusses long‐term follow‐up recommendations for survivors, which should involve a multidisciplinary approach, as there are many surgical and nonsurgical consequences to the disease process. Clinical strategies that address these multifaceted aspects of care, from prenatal to long‐term follow‐up, may further reduce the high mortality rate for these infants.",book:{id:"5928",slug:"hernia",title:"Hernia",fullTitle:"Hernia"},signatures:"Joanne Baerg, Arul Thirumoorthi and Rajaie Hazboun",authors:[{id:"178844",title:"Dr.",name:"Joanne",middleName:null,surname:"Baerg",slug:"joanne-baerg",fullName:"Joanne Baerg"},{id:"180308",title:"Dr.",name:"Arul",middleName:null,surname:"Thirumoorthi",slug:"arul-thirumoorthi",fullName:"Arul Thirumoorthi"},{id:"206025",title:"Dr.",name:"Rajaie",middleName:null,surname:"Hazboun",slug:"rajaie-hazboun",fullName:"Rajaie Hazboun"}]}],onlineFirstChaptersFilter:{topicId:"1146",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:18,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:122,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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",coverUrl:"https://cdn.intechopen.com/series/covers/22.jpg",latestPublicationDate:"July 28th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:1,editor:{id:"356540",title:"Prof.",name:"Taufiq",middleName:null,surname:"Choudhry",slug:"taufiq-choudhry",fullName:"Taufiq Choudhry",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000036X2hvQAC/Profile_Picture_2022-03-14T08:58:03.jpg",biography:"Prof. Choudhry holds a BSc degree in Economics from the University of Iowa, as well as a Masters and Ph.D. in Applied Economics from Clemson University, USA. In January 2006, he became a Professor of Finance at the University of Southampton Business School. He was previously a Professor of Finance at the University of Bradford Management School. He has over 80 articles published in international finance and economics journals. His research interests and specialties include financial econometrics, financial economics, international economics and finance, housing markets, financial markets, among others.",institutionString:null,institution:{name:"University of Southampton",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"86",title:"Business and Management",coverUrl:"https://cdn.intechopen.com/series_topics/covers/86.jpg",isOpenForSubmission:!0,editor:{id:"128342",title:"Prof.",name:"Vito",middleName:null,surname:"Bobek",slug:"vito-bobek",fullName:"Vito Bobek",profilePictureURL:"https://mts.intechopen.com/storage/users/128342/images/system/128342.jpg",biography:"Dr. Vito Bobek works as an international management professor at the University of Applied Sciences FH Joanneum, Graz, Austria. He has published more than 400 works in his academic career and visited twenty-two universities worldwide as a visiting professor. 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Dr. Bobek is also a co-founder of the Academy of Regional Management in Slovenia.",institutionString:"Universities of Applied Sciences FH Joanneum, Austria",institution:{name:"Universities of Applied Sciences Joanneum",institutionURL:null,country:{name:"Austria"}}},editorTwo:{id:"293992",title:"Dr.",name:"Tatjana",middleName:null,surname:"Horvat",slug:"tatjana-horvat",fullName:"Tatjana Horvat",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hXb0hQAC/Profile_Picture_1642419002203",biography:"Tatjana Horvat works as a professor for accountant and auditing at the University of Primorska, Slovenia. She is a Certified State Internal Auditor (licensed by Ministry of Finance RS) and Certified Internal Auditor for Business Sector and Certified accountant (licensed by Slovenian Institute of Auditors). At the Ministry of Justice of Slovenia, she is a member of examination boards for court expert candidates and judicial appraisers in the following areas: economy/finance, valuation of companies, banking, and forensic investigation of economic operations/accounting. 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His teaching interests revolve around global economies and markets while his research focuses on topics related to development and growth, global business decisions, and the economics of technical innovation.",institutionString:null,institution:{name:"University of Houston",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},{id:"88",title:"Marketing",coverUrl:"https://cdn.intechopen.com/series_topics/covers/88.jpg",isOpenForSubmission:!0,editor:{id:"203609",title:"Associate Prof.",name:"Hanna",middleName:null,surname:"Gorska-Warsewicz",slug:"hanna-gorska-warsewicz",fullName:"Hanna Gorska-Warsewicz",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSD9pQAG/Profile_Picture_2022-06-14T11:58:32.jpeg",biography:"Hanna Górska-Warsewicz, Ph.D. is Associate Professor at Warsaw University of Life Sciences and Head of Department of Food Market and Consumption Research. She specializes in the subject of brands, brand equity, and brand management in production, service, and trade enterprises. She combines this subject with marketing and marketing management in both theoretical and practical aspects. Prof. Hanna Górska-Warsewicz also analyzes brands in the context of trademarks, legal regulations and the protection of intangible. She is an author or co-author of over 200 publications in this field, including 8 books. 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He has published research in Research Policy, Applied Economics, Review of Economic Philosophy, Strategic Change, International Journal of Logistics, Sustainability, Journal of Environmental Management, Journal of Global Information Management, Journal of Cleaner Production, M@N@GEMENT, and more. He is a member of CEDIMES Institut (France), Academy of International Business (AIB), Strategic Management Society (SMS), Academy of Management (AOM), Administrative Science Association of Canada (ASAC), and Canadian council of small business and entrepreneurship (CCSBE). He is currently the director of the Research Group on Contemporary Asia (GERAC) at Laval University. 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He works as a Senior Clinician at the Veterinary Teaching Hospital of UTAD (HVUTAD) with a role in clinical activity in the area of livestock and equine species as well as to support teaching and research in related areas. He teaches as an Invited Professor in Reproduction Medicine I and II of the Master\\'s in Veterinary Medicine degree at UTAD. Currently, he holds the position of Chairman of the Portuguese Buiatrics Association. He is a member of the Consultive Group on Production Animals of the OMV. He has 19 publications in indexed international journals (ISIS), as well as over 60 publications and oral presentations in both Portuguese and international journals and congresses.",institutionString:"University of Trás-os-Montes and Alto Douro",institution:{name:"University of Trás-os-Montes and Alto Douro",country:{name:"Portugal"}}},{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",country:{name:"Portugal"}}},{id:"283019",title:"Dr.",name:"Oudessa",middleName:null,surname:"Kerro Dego",slug:"oudessa-kerro-dego",fullName:"Oudessa Kerro Dego",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/283019/images/system/283019.png",biography:"Dr. Kerro Dego is a veterinary microbiologist with training in veterinary medicine, microbiology, and anatomic pathology. Dr. Kerro Dego is an assistant professor of dairy health in the department of animal science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. He received his D.V.M. (1997), M.S. (2002), and Ph.D. (2008) degrees in Veterinary Medicine, Animal Pathology and Veterinary Microbiology from College of Veterinary Medicine, Addis Ababa University, Ethiopia; College of Veterinary Medicine, Utrecht University, the Netherlands and Western College of Veterinary Medicine, University of Saskatchewan, Canada respectively. He did his Postdoctoral training in microbial pathogenesis (2009 - 2015) in the Department of Animal Science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. Dr. Kerro Dego’s research focuses on the prevention and control of infectious diseases of farm animals, particularly mastitis, improving dairy food safety, and mitigation of antimicrobial resistance. Dr. Kerro Dego has extensive experience in studying the pathogenesis of bacterial infections, identification of virulence factors, and vaccine development and efficacy testing against major bacterial mastitis pathogens. Dr. Kerro Dego conducted numerous controlled experimental and field vaccine efficacy studies, vaccination, and evaluation of immunological responses in several species of animals, including rodents (mice) and large animals (bovine and ovine).",institutionString:"University of Tennessee at Knoxville",institution:{name:"University of Tennessee at Knoxville",country:{name:"United States of America"}}},{id:"251314",title:"Dr.",name:"Juan Carlos",middleName:null,surname:"Gardón Poggi",slug:"juan-carlos-gardon-poggi",fullName:"Juan Carlos Gardón Poggi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/251314/images/system/251314.jpeg",biography:"Juan Carlos Gardón Poggi received University degree from the Faculty of Agrarian Science in Argentina, in 1983. Also he received Masters Degree and PhD from Córdoba University, Spain. He is currently a Professor at the Catholic University of Valencia San Vicente Mártir, at the Department of Medicine and Animal Surgery. He teaches diverse courses in the field of Animal Reproduction and he is the Director of the Veterinary Farm. He also participates in academic postgraduate activities at the Veterinary Faculty of Murcia University, Spain. His research areas include animal physiology, physiology and biotechnology of reproduction either in males or females, the study of gametes under in vitro conditions and the use of ultrasound as a complement to physiological studies and development of applied biotechnologies. Routinely, he supervises students preparing their doctoral, master thesis or final degree projects.",institutionString:null,institution:{name:"Valencia Catholic University Saint Vincent Martyr",country:{name:"Spain"}}},{id:"309529",title:"Dr.",name:"Albert",middleName:null,surname:"Rizvanov",slug:"albert-rizvanov",fullName:"Albert Rizvanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309529/images/9189_n.jpg",biography:'Albert A. Rizvanov is a Professor and Director of the Center for Precision and Regenerative Medicine at the Institute of Fundamental Medicine and Biology, Kazan Federal University (KFU), Russia. He is the Head of the Center of Excellence “Regenerative Medicine” and Vice-Director of Strategic Academic Unit \\"Translational 7P Medicine\\". Albert completed his Ph.D. at the University of Nevada, Reno, USA and Dr.Sci. at KFU. He is a corresponding member of the Tatarstan Academy of Sciences, Russian Federation. Albert is an author of more than 300 peer-reviewed journal articles and 22 patents. He has supervised 11 Ph.D. and 2 Dr.Sci. dissertations. Albert is the Head of the Dissertation Committee on Biochemistry, Microbiology, and Genetics at KFU.\nORCID https://orcid.org/0000-0002-9427-5739\nWebsite https://kpfu.ru/Albert.Rizvanov?p_lang=2',institutionString:"Kazan Federal University",institution:{name:"Kazan Federal University",country:{name:"Russia"}}},{id:"210551",title:"Dr.",name:"Arbab",middleName:null,surname:"Sikandar",slug:"arbab-sikandar",fullName:"Arbab Sikandar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210551/images/system/210551.jpg",biography:"Dr. Arbab Sikandar, PhD, M. Phil, DVM was born on April 05, 1981. He is currently working at the College of Veterinary & Animal Sciences as an Assistant Professor. He previously worked as a lecturer at the same University. \nHe is a Member/Secretory of Ethics committee (No. CVAS-9377 dated 18-04-18), Member of the QEC committee CVAS, Jhang (Regr/Gen/69/873, dated 26-10-2017), Member, Board of studies of Department of Basic Sciences (No. CVAS. 2851 Dated. 12-04-13, and No. CVAS, 9024 dated 20/11/17), Member of Academic Committee, CVAS, Jhang (No. CVAS/2004, Dated, 25-08-12), Member of the technical committee (No. CVAS/ 4085, dated 20,03, 2010 till 2016).\n\nDr. Arbab Sikandar contributed in five days hands-on-training on Histopathology at the Department of Pathology, UVAS from 12-16 June 2017. He received a Certificate of appreciation for contributions for Popularization of Science and Technology in the Society on 17-11-15. He was the resource person in the lecture series- ‘scientific writing’ at the Department of Anatomy and Histology, UVAS, Lahore on 29th October 2015. He won a full fellowship as a principal candidate for the year 2015 in the field of Agriculture, EICA, Egypt with ref. to the Notification No. 12(11) ACS/Egypt/2014 from 10 July 2015 to 25th September 2015.; he received a grant of Rs. 55000/- as research incentives from Director, Advanced Studies and Research, UVAS, Lahore upon publications of research papers in IF Journals (DR/215, dated 19-5-2014.. He obtained his PhD by winning a HEC Pakistan indigenous Scholarship, ‘Ph.D. fellowship for 5000 scholars – Phase II’ (2av1-147), 17-6/HEC/HRD/IS-II/12, November 15, 2012. \n\nDr. Sikandar is a member of numerous societies: Registered Veterinary Medical Practitioner (life member) and Registered Veterinary Medical Faculty of Pakistan Veterinary Medical Council. The Registration code of PVMC is RVMP/4298 and RVMF/ 0102.; Life member of the University of Veterinary and Animal Sciences, Lahore, Alumni Association with S# 664, dated: 6-4-12. ; Member 'Vets Care Organization Pakistan” with Reference No. VCO-605-149, dated 05-04-06. :Member 'Vet Crescent” (Society of Animal Health and Production), UVAS, Lahore.",institutionString:"University of Veterinary & Animal Science",institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}},{id:"311663",title:"Dr.",name:"Prasanna",middleName:null,surname:"Pal",slug:"prasanna-pal",fullName:"Prasanna Pal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311663/images/13261_n.jpg",biography:null,institutionString:null,institution:{name:"National Dairy Research Institute",country:{name:"India"}}},{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",country:{name:"United Kingdom"}}},{id:"283315",title:"Prof.",name:"Samir",middleName:null,surname:"El-Gendy",slug:"samir-el-gendy",fullName:"Samir El-Gendy",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRduYQAS/Profile_Picture_1606215849748",biography:"Samir El-Gendy is a Professor of anatomy and embryology at the faculty of veterinary medicine, Alexandria University, Egypt. Samir obtained his PhD in veterinary science in 2007 from the faculty of veterinary medicine, Alexandria University and has been a professor since 2017. Samir is an author on 24 articles at Scopus and 12 articles within local journals and 2 books/book chapters. His research focuses on applied anatomy, imaging techniques and computed tomography. Samir worked as a member of different local projects on E-learning and he is a board member of the African Association of Veterinary Anatomists and of anatomy societies and as an associated author at local and international journals. Orcid: https://orcid.org/0000-0002-6180-389X",institutionString:null,institution:{name:"Alexandria University",country:{name:"Egypt"}}},{id:"246149",title:"Dr.",name:"Valentina",middleName:null,surname:"Kubale",slug:"valentina-kubale",fullName:"Valentina Kubale",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246149/images/system/246149.jpg",biography:"Valentina Kubale is Associate Professor of Veterinary Medicine at the Veterinary Faculty, University of Ljubljana, Slovenia. Since graduating from the Veterinary faculty she obtained her PhD in 2007, performed collaboration with the Department of Pharmacology, University of Copenhagen, Denmark. She continued as a post-doctoral fellow at the University of Copenhagen with a Lundbeck foundation fellowship. She is the editor of three books and author/coauthor of 23 articles in peer-reviewed scientific journals, 16 book chapters, and 68 communications at scientific congresses. Since 2008 she has been the Editor Assistant for the Slovenian Veterinary Research journal. She is a member of Slovenian Biochemical Society, The Endocrine Society, European Association of Veterinary Anatomists and Society for Laboratory Animals, where she is board member.",institutionString:"University of Ljubljana",institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"258334",title:"Dr.",name:"Carlos Eduardo",middleName:null,surname:"Fonseca-Alves",slug:"carlos-eduardo-fonseca-alves",fullName:"Carlos Eduardo Fonseca-Alves",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/258334/images/system/258334.jpg",biography:"Dr. Fonseca-Alves earned his DVM from Federal University of Goias – UFG in 2008. He completed an internship in small animal internal medicine at UPIS university in 2011, earned his MSc in 2013 and PhD in 2015 both in Veterinary Medicine at Sao Paulo State University – UNESP. Dr. Fonseca-Alves currently serves as an Assistant Professor at Paulista University – UNIP teaching small animal internal medicine.",institutionString:null,institution:{name:"Universidade Paulista",country:{name:"Brazil"}}},{id:"245306",title:"Dr.",name:"María Luz",middleName:null,surname:"Garcia Pardo",slug:"maria-luz-garcia-pardo",fullName:"María Luz Garcia Pardo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/245306/images/system/245306.png",biography:"María de la Luz García Pardo is an agricultural engineer from Universitat Politècnica de València, Spain. She has a Ph.D. in Animal Genetics. Currently, she is a lecturer at the Agrofood Technology Department of Miguel Hernández University, Spain. Her research is focused on genetics and reproduction in rabbits. The major goal of her research is the genetics of litter size through novel methods such as selection by the environmental sensibility of litter size, with forays into the field of animal welfare by analysing the impact on the susceptibility to diseases and stress of the does. Details of her publications can be found at https://orcid.org/0000-0001-9504-8290.",institutionString:null,institution:{name:"Miguel Hernandez University",country:{name:"Spain"}}},{id:"350704",title:"M.Sc.",name:"Camila",middleName:"Silva Costa",surname:"Ferreira",slug:"camila-ferreira",fullName:"Camila Ferreira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/350704/images/17280_n.jpg",biography:"Graduated in Veterinary Medicine at the Fluminense Federal University, specialist in Equine Reproduction at the Brazilian Veterinary Institute (IBVET) and Master in Clinical Veterinary Medicine and Animal Reproduction at the Fluminense Federal University. She has experience in analyzing zootechnical indices in dairy cattle and organizing events related to Veterinary Medicine through extension grants. I have experience in the field of diagnostic imaging and animal reproduction in veterinary medicine through monitoring and scientific initiation scholarships. I worked at the Equus Central Reproduction Equine located in Santo Antônio de Jesus – BA in the 2016/2017 breeding season. I am currently a doctoral student with a scholarship from CAPES of the Postgraduate Program in Veterinary Medicine (Pathology and Clinical Sciences) at the Federal Rural University of Rio de Janeiro (UFRRJ) with a research project with an emphasis on equine endometritis.",institutionString:null,institution:null},{id:"41319",title:"Prof.",name:"Lung-Kwang",middleName:null,surname:"Pan",slug:"lung-kwang-pan",fullName:"Lung-Kwang Pan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41319/images/84_n.jpg",biography:null,institutionString:null,institution:null},{id:"125292",title:"Dr.",name:"Katy",middleName:null,surname:"Satué Ambrojo",slug:"katy-satue-ambrojo",fullName:"Katy Satué Ambrojo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/125292/images/system/125292.jpeg",biography:"Katy Satué Ambrojo received her Veterinary Medicine degree, Master degree in Equine Technology and doctorate in Veterinary Medicine from the Faculty of Veterinary, CEU-Cardenal Herrera University in Valencia, Spain.Dr. Satué is accredited as a Private University Doctor Professor, Doctor Assistant, and Contracted Doctor by AVAP (Agència Valenciana d'Avaluació i Prospectiva) and currently, as a full professor by ANECA (since January 2022). To date, Katy has taught 22 years in the Department of Animal Medicine and Surgery at the CEU-Cardenal Herrera University in undergraduate courses in Veterinary Medicine (General Pathology, integrated into the Applied Basis of Veterinary Medicine module of the 2nd year, Clinical Equine I of 3rd year, and Equine Clinic II of 4th year). Dr. Satué research activity is in the field of Endocrinology, Hematology, Biochemistry, and Immunology in the Spanish Purebred mare. She has directed 5 Doctoral Theses and 5 Diplomas of Advanced Studies, and participated in 11 research projects as a collaborating researcher. She has written 2 books and 14 book chapters in international publishers related to the area, and 68 scientific publications in international journals. Dr. Satué has attended 63 congresses, participating with 132 communications in international congresses and 19 in national congresses related to the area. Dr. Satué is a scientific reviewer for various prestigious international journals such as Animals, American Journal of Obstetrics and Gynecology, Veterinary Clinical Pathology, Journal of Equine Veterinary Science, Reproduction in Domestic Animals, Research Veterinary Science, Brazilian Journal of Medical and Biological Research, Livestock Production Science and Theriogenology, among others. Since 2014 she has been responsible for the Clinical Analysis Laboratory of the CEU-Cardenal Herrera University Veterinary Clinical Hospital.",institutionString:null,institution:null},{id:"201721",title:"Dr.",name:"Beatrice",middleName:null,surname:"Funiciello",slug:"beatrice-funiciello",fullName:"Beatrice Funiciello",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/201721/images/11089_n.jpg",biography:"Graduated from the University of Milan in 2011, my post-graduate education included CertAVP modules mainly on equines (dermatology and internal medicine) and a few on small animal (dermatology and anaesthesia) at the University of Liverpool. After a general CertAVP (2015) I gained the designated Certificate in Veterinary Dermatology (2017) after taking the synoptic examination and then applied for the RCVS ADvanced Practitioner status. After that, I completed the Postgraduate Diploma in Veterinary Professional Studies at the University of Liverpool (2018). My main area of work is cross-species veterinary dermatology.",institutionString:null,institution:null},{id:"291226",title:"Dr.",name:"Monica",middleName:null,surname:"Cassel",slug:"monica-cassel",fullName:"Monica Cassel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/291226/images/8232_n.jpg",biography:'Degree in Biological Sciences at the Federal University of Mato Grosso with scholarship for Scientific Initiation by FAPEMAT (2008/1) and CNPq (2008/2-2009/2): Project \\"Histological evidence of reproductive activity in lizards of the Manso region, Chapada dos Guimarães, Mato Grosso, Brazil\\". Master\\\'s degree in Ecology and Biodiversity Conservation at Federal University of Mato Grosso with a scholarship by CAPES/REUNI program: Project \\"Reproductive biology of Melanorivulus punctatus\\". PhD\\\'s degree in Science (Cell and Tissue Biology Area) \n at University of Sao Paulo with scholarship granted by FAPESP; Project \\"Development of morphofunctional changes in ovary of Astyanax altiparanae Garutti & Britski, 2000 (Teleostei, Characidae)\\". She has experience in Reproduction of vertebrates and Morphology, with emphasis in Cellular Biology and Histology. She is currently a teacher in the medium / technical level courses at IFMT-Alta Floresta, as well as in the Bachelor\\\'s degree in Animal Science and in the Bachelor\\\'s degree in Business.',institutionString:null,institution:null},{id:"442807",title:"Dr.",name:"Busani",middleName:null,surname:"Moyo",slug:"busani-moyo",fullName:"Busani Moyo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Gwanda State University",country:{name:"Zimbabwe"}}},{id:"439435",title:"Dr.",name:"Feda S.",middleName:null,surname:"Aljaser",slug:"feda-s.-aljaser",fullName:"Feda S. Aljaser",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"423023",title:"Dr.",name:"Yosra",middleName:null,surname:"Soltan",slug:"yosra-soltan",fullName:"Yosra Soltan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Alexandria University",country:{name:"Egypt"}}},{id:"349788",title:"Dr.",name:"Florencia Nery",middleName:null,surname:"Sompie",slug:"florencia-nery-sompie",fullName:"Florencia Nery Sompie",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sam Ratulangi University",country:{name:"Indonesia"}}},{id:"428600",title:"MSc.",name:"Adriana",middleName:null,surname:"García-Alarcón",slug:"adriana-garcia-alarcon",fullName:"Adriana García-Alarcón",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"428599",title:"MSc.",name:"Gabino",middleName:null,surname:"De La Rosa-Cruz",slug:"gabino-de-la-rosa-cruz",fullName:"Gabino De La Rosa-Cruz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"428601",title:"MSc.",name:"Juan Carlos",middleName:null,surname:"Campuzano-Caballero",slug:"juan-carlos-campuzano-caballero",fullName:"Juan Carlos Campuzano-Caballero",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}}]}},subseries:{item:{id:"18",type:"subseries",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11414,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. 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