T1D susceptibility loci identified to date.
\\n\\n
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\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:"267",leadTitle:null,fullTitle:"DNA Replication - Current Advances",title:"DNA Replication",subtitle:"Current Advances",reviewType:"peer-reviewed",abstract:"The study of DNA advanced human knowledge in a way comparable to the major theories in physics, surpassed only by discoveries such as fire or the number zero. However, it also created conceptual shortcuts, beliefs and misunderstandings that obscure the natural phenomena, hindering its better understanding. The deep conviction that no human knowledge is perfect, but only perfectible, should function as a fair safeguard against scientific dogmatism and enable open discussion. With this aim, this book will offer to its readers 30 chapters on current trends in the field of DNA replication. 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He described already >5 molecular processes affecting whole organism morphology and life history traits. This lead to uncover 4 types of cryptic coding systems, which he describes for vertebrate mitochondria. 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Multiplexing (MUX), a method by which multiple analog or digital signals are combined into one signal over a shared medium, increases the capacity of the communication channel by dividing it into several logical channels, one for each message signal or data stream to be transferred. On the receiver side, the reverse process known as de-multiplexing (DEMUX) helps to extract the original channel. This book examines recent advances and novel applications in MUX and DEMUX. It discusses how MUX is applied in free-space optics (FSO) applications and how 5G and 6G signals benefit from MUX, among other topics.",isbn:"978-1-80355-052-7",printIsbn:"978-1-80355-051-0",pdfIsbn:"978-1-80355-053-4",doi:"10.5772/intechopen.95684",price:119,priceEur:129,priceUsd:155,slug:"multiplexing-recent-advances-and-novel-applications",numberOfPages:140,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"f7087bb097e43cc25997790b009fb77a",bookSignature:"Somayeh Mohammady",publishedDate:"July 20th 2022",coverURL:"https://cdn.intechopen.com/books/images_new/10990.jpg",keywords:null,numberOfDownloads:490,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 18th 2021",dateEndSecondStepPublish:"July 16th 2021",dateEndThirdStepPublish:"September 14th 2021",dateEndFourthStepPublish:"December 3rd 2021",dateEndFifthStepPublish:"February 1st 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"a year",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:"Edited by",kuFlag:!1,biosketch:"Dr. Somayeh Mohammady obtained her Ph.D.from University Putra Malaysia and was previously a Research Fellow at CONNECT in Maynooth University. Dr. Mohammady is a member of the Institute of Electrical and Electronics Engineers (IEEE).",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady",profilePictureURL:"https://mts.intechopen.com/storage/users/109280/images/system/109280.jpg",biography:"Somayeh Mohammady holds a bachelor’s degree in Electronic Engineering (Robotics), as well as an MSc and Ph.D. in Electrical and Electronic Engineering from Universiti Putra Malaysia (UPM). She has industrial experience working at Teta, Tabesh Tablou Company, and Symmid Corporation Sdn. Bhd. She also worked as a postdoctoral researcher from 2012 to 2019. Dr. Mohammady is a lecturer at Technological University Dublin (TU Dublin). Her research interests include power amplifier linearization, signals processing for multicarrier signals, and Peak-to-Average Power Ratio (PAPR), also known as Crest Factor Reduction (CFR).",institutionString:"Technological University Dublin",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Technological University Dublin",institutionURL:null,country:{name:"Ireland"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1368",title:"Telecommunication",slug:"information-and-communication-telecommunication"}],chapters:[{id:"81932",title:"Waveguide Amplifier for Extended Reach of WDM/FSO",slug:"waveguide-amplifier-for-extended-reach-of-wdm-fso",totalDownloads:16,totalCrossrefCites:0,authors:[{id:"424338",title:"Associate Prof.",name:"Bentahar",surname:"Attaouia",slug:"bentahar-attaouia",fullName:"Bentahar Attaouia"},{id:"424459",title:"Prof.",name:"Kandouci",surname:"Malika",slug:"kandouci-malika",fullName:"Kandouci Malika"},{id:"424460",title:"Dr.",name:"Ghouali",surname:"Samir",slug:"ghouali-samir",fullName:"Ghouali Samir"},{id:"475618",title:"Dr.",name:"Dinar",surname:"Amina Elbatoul",slug:"dinar-amina-elbatoul",fullName:"Dinar Amina Elbatoul"}]},{id:"82443",title:"Phase Noise in OFDM",slug:"phase-noise-in-ofdm",totalDownloads:6,totalCrossrefCites:0,authors:[{id:"275459",title:"Ms.",name:"Kamayani",surname:"Shrivastav",slug:"kamayani-shrivastav",fullName:"Kamayani Shrivastav"}]},{id:"79832",title:"Multiplexing, Transmission and De-Multiplexing of OAM Modes through Specialty Fibers",slug:"multiplexing-transmission-and-de-multiplexing-of-oam-modes-through-specialty-fibers",totalDownloads:13,totalCrossrefCites:0,authors:[{id:"202732",title:"Dr.",name:"Habib",surname:"Fathallah",slug:"habib-fathallah",fullName:"Habib Fathallah"},{id:"303356",title:"Prof.",name:"Mohsen",surname:"Machhout",slug:"mohsen-machhout",fullName:"Mohsen Machhout"},{id:"354712",title:"Dr.",name:"Alaaeddine",surname:"Rjeb",slug:"alaaeddine-rjeb",fullName:"Alaaeddine Rjeb"}]},{id:"81212",title:"Triple-Hop Hybrid FSO/mmW Based Backhaul Communication System for Wireless Networks Applications of 5G and beyond",slug:"triple-hop-hybrid-fso-mmw-based-backhaul-communication-system-for-wireless-networks-applications-of-",totalDownloads:26,totalCrossrefCites:0,authors:[{id:"227785",title:"Dr.",name:"Bharati",surname:"Bidikar",slug:"bharati-bidikar",fullName:"Bharati Bidikar"},{id:"227794",title:"Prof.",name:"Gottapu",surname:"Sasibhushana Rao",slug:"gottapu-sasibhushana-rao",fullName:"Gottapu Sasibhushana Rao"},{id:"435801",title:"Dr.",name:"Mogadala",surname:"Vinod Kumar",slug:"mogadala-vinod-kumar",fullName:"Mogadala Vinod Kumar"},{id:"448419",title:"Mrs.",name:"Yenneti",surname:"Laxmi Lavanya",slug:"yenneti-laxmi-lavanya",fullName:"Yenneti Laxmi Lavanya"}]},{id:"80194",title:"NOMA Transmission Systems: Overview of SIC Design and New Findings",slug:"noma-transmission-systems-overview-of-sic-design-and-new-findings",totalDownloads:117,totalCrossrefCites:0,authors:[{id:"42898",title:"Prof.",name:"Valeri",surname:"Kontorovich",slug:"valeri-kontorovich",fullName:"Valeri Kontorovich"},{id:"121596",title:"Dr.",name:"Carmen Beatriz",surname:"Rodriguez Estrello",slug:"carmen-beatriz-rodriguez-estrello",fullName:"Carmen Beatriz Rodriguez Estrello"},{id:"214491",title:"Dr.",name:"Fernando",surname:"Ramos-Alarcon",slug:"fernando-ramos-alarcon",fullName:"Fernando Ramos-Alarcon"}]},{id:"79928",title:"Multiplexing Techniques for Applications Based-on 5G Systems",slug:"multiplexing-techniques-for-applications-based-on-5g-systems",totalDownloads:312,totalCrossrefCites:0,authors:[{id:"427589",title:"Associate Prof.",name:"Nguyen",surname:"Huu Trung",slug:"nguyen-huu-trung",fullName:"Nguyen Huu Trung"}]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"278926",firstName:"Ivana",lastName:"Barac",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/278926/images/8058_n.jpg",email:"ivana.b@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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The prevalence of diabetes is increasing worldwide and to date it impacts the lives of approximately 200 million people (Steyn et al., 2009). It is estimated that by 2030, there will be 439 million adults affected by diabetes (International Diabetes Federation/diabetes prevalence: www.idf.org). Type 1 diabetes (T1D) represents approximately 10% of these patients and is most prevalent in populations of European ancestry, where there is ample evidence of increased annual incidence during the past five decades (Onkamo et al., 1999; EURODIAB ACE Study Group, 2000).
T1D is a complex trait that results from the interplay between environmental and genetic factors. Much evidence supports a strong genetic component associated with T1D. The epidemiological data showing differences in geographic prevalence is one clear indicator, with populations of European ancestry having the highest presentation rate. T1D has high concordance among monozygotic twins (33 to 42%) (Redondo et al., 2001) and runs strongly in families with sibling risk being approximately 10 times greater than in the general population (Clayton, 2009); this is in clear contrast to the “less genetic” type 2 diabetes, where the sibling risk ratio is relatively modest at 3.5 (Rich, 1990).
T1D develops at all ages and occurs through the autoimmune destruction of pancreatic β-cells with resulting lack of insulin production. The immune system participates in β-cell destruction through several of its components including natural killer (NK) cells, B lymphocytes, macrophages, dendritic cells (DC), and antigen-presenting cells (APCs). Studies in human and animal models have shown that both innate and adaptive immune responses participate in disease pathogenesis, possibly reflecting the multifactorial nature of this autoimmune disorder.
In this review, we provide an update on genome-wide association studies (GWAS) discoveries to date and discuss the latest associated regions added to the growing repertoire of gene networks predisposing to T1D.
Historically, prior to GWAS, only six loci had been fully established to be associated with T1D. The human leukocyte antigen (HLA) region on chromosome 6p21 was the first known candidate to be strongly associated with T1D in 1970s (Singal & Blajchman, 1973; Nerup et al., 1974; Cudworth & Woodrow, 1975). This cluster of homologous cell-surface proteins is divided into class I (A, B, C) and class II (DP, DQ, RD). The HLA genes encode highly polymorphic proteins, which are essential in self versus non-self immune recognition. The class I molecules are ubiquitously expressed and present intracellular antigen to CD8+ T cells. Class II molecules are expressed mainly on professional APCs: DCs, macrophages, B-lymphocytes and thymus epithelium. Class II molecules are composed of A and B chains, and present antigens to CD4+ T cells, which promote inflammation by secreting cytokines upon recognition of their specific targets. Approximately half of the genetic risk for T1D is conferred by the genomic region harboring the HLA class II genes primarily HLA-DRB1, -DQA1 and -DQB1 genes). In 1984, insulin (INS) gene encoded on chromosome 11p15 was identified as second loci linked with T1D (Bell et al., 1984). In 1996, the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) gene encoded on chromosome 2q33 was recognized as third loci (Nistico et al., 1996). In 2004, a protein tyrosine phosphatase, non-receptor type 22 (PTPN22) gene encoded on chromosome 1p13, was found to be associated with susceptibility to T1D in another case-control study (Bottini et al., 2004). Vella et al., 2005 reported interleukin 2 receptor alpha (IL2RA) gene as fifth T1D loci on chromosome 10p15. In 2006, Smyth et al. identified the interferon-induced with helicase C domain 1 (IFIH1) gene on chromosome 2q24.3 as the sixth gene to be strongly associated with T1D.
The advent of GWAS in the mid-2000s has changed the situation dramatically, increasing the pace and efficiency of discovery for the T1D associated loci, by a factor of ten. The critical platform for this work was laid by the HapMap project (International HapMap Consortium, 2003, 2005). The GWAS approach has been made possible by the development of high-density genotyping arrays. The genome is laid out in discrete linkage disequilibrium (LD) blocks with limited haplotype diversity within each of these blocks. Therefore, a minimal set of single nucleotide polymorphisms (SNPs) can detect almost all common haplotypes present, thus improving genotyping accuracy and reducing cost.
The first full-scale GWAS for T1D were published in 2007 by our group (Hakonarson et al., 2007) and The Wellcome Trust Case-Control Consortium (WTCCC, 2007). We examined a large pediatric cohort of European descent using the Illumina HumanHap 550 BeadChip platform. The design involved 561 cases, 1,143 controls and 467 triads in the discovery stage, followed by a replication effort in 939 nuclear families. In addition to finding the “usual” suspects, including an impressive 392 SNPs capturing the very strong association across the major histocompatibility complex (MHC), we identified significant association with variation at the KIAA0350 gene, which we replicated in an additional cohort. The WTCCC study investigated seven common complex diseases including T1D by genotyping 2,000 cases and 3,000 controls with ~500,000 SNPs using the Affymetrix GeneChip, and reported a number of novel T1D loci, including the KIAA0350 genomic region (WTCCC, 2007). Todd et al., 2007 confirmed these findings, using 4,000 cases, 5,000 controls and 3,000 T1D families as well as association reported in the WTCCC study to the 12q13 region. In a separate effort we fast-tracked 24 SNPs at 23 distinct loci from our original study and established association to the 12q13 region with a combined
In order to get the most from GWAS and to increase the statistical power, several independent research groups carried out meta-analyses using datasets from different investigative groups. Cooper et al., 2008 performed the first meta-analysis by using T1D datasets from the WTCCC, 2007 and the Genetics of Kidneys in Diabetes (GoKind) study (Mueller et al, 2006; Manolio et al., 2007), and confirmed associations for PTPN22, CTLA4, MHC, IL2RA, 12q13, 12q24, CLEC16A and PTPN2. The SNPs with lowest nominal
Barrett et al., 2009 meta-analysis uncovered in excess of 40 loci, including 18 novel regions, plus they confirmed a number of previously reported (Smyth et al., 2008; Fung et al., 2009; Cooper et al., 2009). The study included samples from WTCCC, 20070, the GoKind study (Mueller et al., 2006) and controls and family sets from Type 1 Diabetes Genetics Consortium (T1DGC). The meta-analysis observed association to 1q32.1 (which harbors the immunoregulatory interleukin genes IL10, IL19 and IL20), 9p24.2 contains only Glis family zinc finger protein 3 (GLIS3; first suggested by us in Grant et al., 2009), 12p13.31 which harbors a number of immunoregulatory genes including CD69 and 16p11.2 harboring IL27. These findings were further supported by our
To identify additional genetic loci for T1D susceptibility, we examined associations in the largest meta-analysis to date between the disease and ~2.54 million genotyped and imputed SNPs in a combined cohort of 9,934 cases and 16,956 controls (Bradfield et al., 2011). Targeted follow-up of 53 SNPs in 1,120 affected trios uncovered three new loci associated with T1D that reached genome wide significance. The most significantly associated SNP (rs539514,
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t|
Hakonarson et al., 2007 | \n\t\t\t467 trios, 561 cases, 1,143 controls | \n\t\t\t2,350 individuals in 549 families; 390 trios | \n\t\t\tEuropean ancestry | \n\t\t\tGWAS | \n\t\t\tHLA-DRB1, HLA-DQA2, CLEC16A, INS, PTPN22 | \n\t\t
WTCCC 2007 | \n\t\t\t1,963 cases, 2,938 controls | \n\t\t\tsee Todd et al., 2007 | \n\t\t\tEuropean, British | \n\t\t\tGWAS | \n\t\t\tHLA-DRB1, INS, CTLA4, PTPN22, IL2RA, IFIH1, PPARG, KCNJ11, TCF7L2 | \n\t\t
Todd et al., 2007 | \n\t\t\tsee WTCCC 2007 | \n\t\t\t2997 trios, 4,000 cases, 5,000 controls | \n\t\t\tEuropean British | \n\t\t\tGWAS | \n\t\t\tPHTF1-PTPN22, ERBB3, CLEC16A, C12orf30 | \n\t\t
Hakonarson et al., 2008 | \n\t\t\t467 trios, 561 cases, 1,143 controls | \n\t\t\t549 families, 364 trios | \n\t\t\tEuropean ancestry | \n\t\t\tGWAS | \n\t\t\tSUOX - IKZF4 | \n\t\t
Concannon et al., 2008 | \n\t\t\t2,496 families | \n\t\t\t2,214 trios, 7,721 cases, 9,679 controls | \n\t\t\tEuropean ancestry | \n\t\t\tGWAS | \n\t\t\tINS, IFIH1, CLEC16A, UBASH3A | \n\t\t
Cooper et al., 2008 | \n\t\t\t3,561 cases, 4,646 controls | \n\t\t\t6,225 cases, 6,946 controls, 3,064 trios | \n\t\t\tEuropean ancestry | \n\t\t\tGWAS meta-analysis | \n\t\t\tPTPN22, CTLA4, HLA, IL2RA, ERRB3, C12orf30, CLEC16A, PTPN2 | \n\t\t
Grant et al., 2009 | \n\t\t\t563 cases, 1,146 controls, 483 case-parents trios | \n\t\t\t636 families, 3,303 cases, 4,673 controls | \n\t\t\tEuropean ancestry | \n\t\t\tGWAS | \n\t\t\tEDG7, BACH2, GLIS3, UBASH3A, RASGRP1 | \n\t\t
Awata et al., 2009 | \n\t\t\t735 cases, 621 controls | \n\t\t\t- | \n\t\t\tJapanese | \n\t\t\tTaqMan genotyping | \n\t\t\tERBB3, CLEC16A | \n\t\t
Zoledziewska et al., 2009 | \n\t\t\t1037 cases, 1706 controls | \n\t\t\t- | \n\t\t\tEuropean, Sardinian | \n\t\t\tTaqMan genotyping | \n\t\t\tCLEC16A | \n\t\t
Fung et al., 2009 | \n\t\t\t8010 cases, 9733 controls | \n\t\t\t- | \n\t\t\tEuropean, British | \n\t\t\tTaqMan genotyping | \n\t\t\tSTAT4, STAT3, ERAP1, TNFAIP3, KIF5A/PIP4K2C | \n\t\t
Wu et al., 2009 | \n\t\t\t205 cases, 422 controls | \n\t\t\t- | \n\t\t\tHan Chinese | \n\t\t\tTaqMan genotyping | \n\t\t\tCLEC16A | \n\t\t
Barrett et al., 2009 | \n\t\t\t7,514 cases, 9,045 controls | \n\t\t\t4,267 cases, 4,670 controls, 4,342 trios | \n\t\t\tEuropean | \n\t\t\tGWAS meta-analysis | \n\t\t\tMHC, PTPN22, INS, C10orf59, SH2B3, ERBB3, CLEC16A, CTLA4, PTPN2, IL2RA, IL27, C6orf173, IL2, ORMDL3, GLIS3, CD69, IL10, IFIH1, UBASH3A, COBL, BACH2, CTSH, PRKCQ, C1QTNF6, PGM1 | \n\t\t
Wallace et al., 2010 | \n\t\t\t7,514 cases, 9,045 controls | \n\t\t\t4,840 cases, 2,670 controls, 4,152 trios | \n\t\t\tEuropean ancestry | \n\t\t\tGWAS meta-analysis | \n\t\t\tDLK1, TYK2 | \n\t\t
Wang et al., 2010 | \n\t\t\t989 cases, 6197 controls | \n\t\t\t- | \n\t\t\tEuropean ancestry | \n\t\t\tGWAS | \n\t\t\tPTPN22, IL10, IFIH1, KIAA0746, BACH2, C6orf173, TAGAP, GLIS3, L2R, INS, ERBB3, C14orf181, IL27, PRKD2, HERC2, CLEC16A, IFNG, IL26, | \n\t\t
Reddy et al., 2011 | \n\t\t\t1434 cases, 1864 controls | \n\t\t\t- | \n\t\t\tEuropean ancestry, southeast USA | \n\t\t\tTaqMan genotyping | \n\t\t\tPTPN22, INS, IFIH1, SH2B3, ERBB3, CTLA4, C14orf181, CTSH, CLEC16A, CD69, ITPR3, C6orf173, SKAP2, PRKCQ, RNLS, IL27, SIRPG, CTRB2 | \n\t\t
Bradfield et al., 2011 | \n\t\t\t9,934 cases, 16,956 controls | \n\t\t\t1,120 trios | \n\t\t\tEuropean ancestry | \n\t\t\tGWAS meta-analysis | \n\t\t\tLMO7, EFR3B, 6q27, TNFRSF11B, LOC100128081, FOSL2 | \n\t\t
Asad et al., 2012 | \n\t\t\t424 families, 3078 cases, 1363 controls | \n\t\t\t- | \n\t\t\tEuropean, Scandinavians | \n\t\t\tGenotyping and sequencing | \n\t\t\tHTR1A, RFN180 | \n\t\t
Huang et al., 2012 | \n\t\t\t16,179 individuals | \n\t\t\t- | \n\t\t\tEuropean ancestry | \n\t\t\tGenomes-based imputation | \n\t\t\tCUX2, IL2RA | \n\t\t
T1D susceptibility loci identified to date.
The immune system is well organized and well regulated with a basic function of protecting the host against pathogens. This places the immune system in a vital position between healthy and diseased states of the host. Its protective task is regulated by a complex regulatory mechanism involving a diverse army of cells and molecules of humoral and cellular factors working in concert to protect the body against invaders. The human immune system has two components: innate and adaptive. Innate immunity is comprised of physical, chemical, and microbiological barriers to the entry of antigen, and the elements of immune system (DC, macrophages, mast cells, NK cells, neutrophils, monocytes, complements, cytokines and acute phase proteins), which provide immediate host defense. Adaptive immunity is the hallmark of the immune system of higher animals with T and B cells as the key cellular players that provide more specific life-long immunity.
In T1D this system breaks down: insulin-producing β-cells are subjected to specific attack by the host immune system. To better understand the etiology of T1D, a plethora of research has been done to link the systematic destruction of β-cells and the role of the immune system. Linkage studies in 1970s revealed MHC as the first key contributor to T1D susceptibility. Further linkage analysis and candidate gene association studies revealed additional loci associated with T1D. Starting in 2007, GWAS have increased the number of loci be associated with T1D to almost 60. In Figure 1 we present 59 T1D susceptibility loci as where we have classified them into loci harboring non-immune (14) vs. immune (45) genes. Functional aspects of some genes are discussed below.
Immune and Non-immune T1D genes are depicted in a concept map representing the components of the immune system. The discovery of T1D susceptibility genes started as early as 1974 with just six genes identified by 2006 shown in red. The advent of GWAS led to flurry of novel genes associated with T1D reaching the excess of 40 by 2009 and almost 60 by 2012.
The complex crosstalk between innate and adaptive immune cells has major impact on the pathogenesis and development of T1D as illustrated in Figure 2. The initiation phase (Phase I) of T1D development takes place in the pancreas where conventional dendritic cells (cDCs) capture and process β-cell antigens. Apoptosis (‘natural cell death’) or viral infection can lead to β-cell death. Antiviral responses are mediated by invariant natural killer T (iNKT) cells; crossplay between iNKT and plasmacytoid DCs (pDCs) controls viral replication thus prevents subsequent inflammation, tissue damage, and downregulating T1D pathogenesis. Migration of activated cDCs to the draining lymph node primes pathogenic islet antigen-specific T cells. This activation is promoted by macrophages through IL12 secretion. B cells present β-cell antigen to diabetogenic T cells and secrete autoantibodies in response. The activation of islet antigen-specific T cells can be inhibited by cDCs through engagement of programmed cell death ligand 1 (PDL1). The expansion phase (Phase II): iNKT cells can further promote the recruitment of tolerogenic cDCs and pDCs. These DCs promote expansion of regulatory T (TReg) cells through the production of indoleamine 2,3-dioxygenase (IDO), IL10, transforming growth factor-β (TGFβ) and inducible T cell co-stimulator ligand (ICOSL). Phase III: In the pancreas, β-cell can be killed by diabetogenic T cells and NK cells through the release of interferon-γ (IFNγ), granzymes and perforin, as well as by macrophages through the production of tumour necrosis factor (TNF), IL-1β and nitric oxide (NO). IL12 produced by cDCs sustains the effector functions of activated diabetogenic T cells and NK cells. TReg cells that inhibit diabetogenic T cells and innate immune cells through IL10 and TGFβ can prevent β-cell damage. Tolerogenic pDCs stimulated by iNKT cells could also control diabetogenic T cells through IDO production. Lastly, β-cells can inhibit diabetogenic T cells by expressing PDL1 and escape the cell death.
Pathogenesis model of T1D involves complex interactions between innate and adaptive immune cell types.
The C-type lectin domain family 16, member A (CLEC16A) gene encodes protein with C-type lectin domain structure, which makes it potentially related to the immune response (Robinson et al., 2006). It is established that C-type lectins function both as adhesion and pathogen recognition receptors (PPRs) (Cambi & Figdor, 2003). In addition, CLEC16A is almost exclusively expressed in immune cells including DCs, B-lymphocytes and NK cells. Our 2007 GWAS in a large pediatric cohort of European descent identified CLEC16A as a novel T1D susceptibility gene within a 233-kb linkage disequilibrium block on chromosome 16p13. Three common non-coding variants of the CLEC16A gene (rs2903692, rs725613 and rs17673553) reached genome-wide significance for association with T1D (Hakonarson et al., 2007). Subsequent replication studies in an independent cohort confirmed the association. Importantly, the allele of CLEC16A linked to protection from T1D was also associated with higher levels of CLEC16A expression in NK cells (Hakonarson et al., 2007).
The 2007 WTCCC study independently discovered CLEC16A (formally known as KIAA0350) as a T1D susceptibility locus associated with the non-coding variant rs12708716. This finding was confirmed immediately for T1D in populations of European descent (Todd et al., 2007, Cooper et al., 2008). To date, several SNPs (rs2903692, rs17673553, rs725613, rs12708716, rs12921922, rs12931878) within the CLEC16A gene have been reported to be associated with T1D in several populations: Sardinian (Zoledziewska et al., 2009), Spanish (Martinez et al., 2010), southeast USA (Reddy et al., 2011), Chinese (Wu et al., 2009; Sang et al., 2012), and Japanese (Yamashita et al., 2011). Recently CLEC16A was also associated with adult-onset of autoimmune diabetes (Howson et al., 2011).
Several GWAS in different autoimmune diseases such as multiple sclerosis (MS) (Zuvich, 2011; Nischwitz et al., 2011), Addison’s disease (Skinningsrud et al., 2008), systemic lupus erythematosus (SLE) (Gateva et al., 2009; Zhang et al., 2011), Celiac disease (Dubois et al., 2010), Crohn’s disease (Márquez et al., 2009), selective immunoglobulin A deficiency (Jagielska et al., 2012), alopecia areata (Jagielska et al., 2012), rheumatoid arthritis (Martinez et al., 2010) and primary biliary cirrhosis (Mells et al., 2011; Hirschfield et al., 2012) also demonstrated association of the 16p13 loci with disease risk, implying that the 16p13 region contains a key regulator of the self-reactive immune response.
Recently, Davison et al., 2012 reported intron 19 of the CLEC16A gene behaves as a regulatory sequence, which affects the expression of a neighboring gene dexamethasone-induced (DEXI). While it is clear that intron 19 of CLEC16A is highly enriched for transcription-factor-binding events, more functional studies are needed to advance from GWAS to candidate causal genes and their biological functions.
To find causal variant of CLEC16A gene we sequenced the 16p13 region in 96 T1D patients and found 10 new non-synonymous SNPs resulting in one stop-codon, two splice site mutations, and 7 amino acid changes (unpublished data). The studies are under way to examine if these changes are correlated with CLEC16A expression and if these SPNs are present in control group.
Little is yet proven about CLEC16A functions. Kim et al., 2010 characterized ema as an endosomal membrane protein is required for endosomal trafficking and promotes endosomal maturation. Expression of human orthologue of ema ‘CLEC16A’ rescued the Drosophila mutant demonstrating conserved function of the protein. A recent study by the same group also reported its requirement for the growth of autophagosomes and proposed that the Golgi is a membrane source for autophagosomal growth, and that ema facilitates this process (Kim et al., 2012). Expression of CLEC16A rescued the autophagosome size defect in the ema mutant, suggesting that regulation of autophagosome morphogenesis may be one of the fundamental functions of CLEC16A. Another recent study elucidated the dynamic expression changes and localization of CLEC16A in lipopolysaccharide (LPS) induced neuroinflammatory processes in adult rats. CLEC16A expression was strongly induced in active astrocytes in inflamed cerebral cortex.
In our latest effort to identify additional genetic loci for T1D, we examined associations in the largest meta-analysis to date between T1D and ~2.54 million SNPs in a combined cohort of 9,934 cases and 16,956 controls. Targeted follow-up of 53 SNPs in 1,120 affected trios uncovered three novel loci associated with T1D that reached genome-wide significance (Bradfield et al., 2011).
Nuclear receptor coactivator 1 (NCOA1) protein is a member of the p160/steroid receptor coactivator (SRC) family. The product of this gene binds to a variety of nuclear hormone receptors in a ligand-dependent manner, suggesting that NCOA1 may play a role as a bridging molecule between nuclear hormone receptors and general transcription factors (Onate et al., 1995; Torchia et al., 1997).
C2orf79 is peptidyl-tRNA hydrolase domain containing 1 (PTRHD1) predicted protein with unknown function.
Centromere protein O (CENPO) gene encodes a component of the interphase centromere complex. The protein is localized to the centromere throughout cell division and is required for bipolar spindle assembly, chromosome segregation and checkpoint signaling during mitosis (Okada et al., 2006).
Adenylate cyclase 3 (ADCY3) gene encodes a membrane-associated enzyme. This protein catalyzes the formation of the secondary messenger cyclic adenosine monophosphate (cAMP) and is highly expressed in human placenta, testis, ovary, and colon (Ludwig & Seuwen, 2002). Wong et al., 2000 reported the presence of adenylyl cyclase 2, 3, and 4 in olfactory cilia. ADCY3 mutants failed olfaction-based behavioral tests indicating that ADCY3 and cAMP signaling are critical for olfactory-dependent behavior.
DnaJ/Hsp40 homolog, subfamily C, member 27 (DNAJC27) gene encodes 273 amino acid protein with RAB-like GTPase and DNAJ domains. EST database suggests high expression in nervous system and reproductive organs (Nepomuceno-Silva et al., 2004).
Pro-opiomelanocortin (POMC) gene encodes a polypeptide hormone precursor protein synthesized mainly in corticotroph cells of the anterior pituitary. POMC is essential for normal steroidogenesis and maintenance of adrenal weight. Mutations in this gene have been associated with early onset obesity, adrenal insufficiency, and red hair pigmentation (Krude et al., 1998; Hung et al., 2012).
DNA (cytosine-5)-methyltransferase 3 alpha (DNMT3A) gene encodes a protein that functions as a
Additional fine gene mapping and functional studies are needed to determine causal variants for 2q23 region and their role in T1D.
Plant Homeo Domain (PHD) finger protein 10 (PHF10) encodes a subunit of an ATP-dependent chromatin-remodeling complex that functions in neural precursor cells (Yoo et al., 2009).
Delta-like 1-Drosophila (DLL1) is a human homolog of the Notch Delta ligand and a member of the delta/serrate/jagged family. It plays a role in mediating cell fate decisions during hematopoiesis and cell communication (Santos et al., 2007; Dontje et al., 2006). The protein is expressed in heart, pancreas and brain. Su et al., 2006 reported pancreatic regeneration in chronic pancreatitis requires activation of the notch-signaling pathway.
Family with sequence similarity 120B (FAM120B) gene encodes protein belonging to the constitutive coactivator of peroxisome proliferator-activated receptor gamma (PPARG) family. FAM120B functions in adipogenesis through PPARG activation in a ligand-independent manner (Li et al., 2007).
Proteasome (prosome, macropain) subunit, beta type, 1 (PSMB1) gene encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit (Trachtulec et al., 1997). This gene encodes TBP, the TATA-binding protein a transcription factor that functions at the core of the DNA-binding multiprotein transcription factor IID (TFIID). Binding of TFIID to TBP is the initial transcriptional step of the pre-initiation complex (PIC) and plays a role in the activation of eukaryotic genes transcribed by RNA polymerase II (Keutgens et al., 2010).
Programmed cell death 2 (PDCD2) gene encodes a nuclear protein highly expressed in placenta, heart, pancreas, lung, and liver, and lowly expressed in spleen, lymph nodes, and thymus. Expression of this gene is known to be repressed by B-cell CLL/lymphoma 6 (BCL6); a transcriptional repressor (Agata et al., 1996).
In addition, despite not reaching the genome wide significance, our study observed evidence for association at three additional loci containing the candidate genes LOC100128081, TNFRSF11B and FOSL2 (Bradfield et al., 2011). Of these, it is notable that the tumor necrosis factor receptor superfamily, member 11B (TNFRSF11B) is a strongly associated locus with bone mineral density, also discovered in GWAS, and the locus harboring LOC100128081 has also been reported in the context of a GWAS of SLE. FOS-like antigen 2 (FOSL2) gene encodes a leucine zipper protein that dimerizes with the JUN family proteins and forms the transcription factor complex activator protein 1 (AP-1). The FOS proteins have been implicated as regulators of cell proliferation, differentiation, and transformation (Cohen et al., 1989).
This chapter provides a summary of recent advances in the identification of multiple variants associated with T1D. Genome wide association studies have revolutionized the field of autoimmune mediated disorders. In T1D only six genetic factors were well established before GWAS. GWAS has contributed greatly by expanding the number of established genetic variants to 57 genes. Most of these genes are novel and were not in any investigator’s favorite list. For the first time there is real consensus on the role of specific genetic factors underpinning T1D pathogenesis.
The discoveries of genetic factors involved in the pathogenesis of T1D through GWAS present the first step in a much longer process leading to cure. Genes uncovered using this approach are indeed fundamental to disease biology and will define the key molecular pathways leading to cure of T1D. However, such genome wide scans can lack coverage in certain regions where it is difficult to genotype so it is possible that other loci with reasonable effect sizes remain to be uncovered.
To date most of T1D-associated variants have been discovered utilizing cohorts of European ancestry because the SNP arrays were designed to optimally capture the haplotype diversity in this ethnicity. Novel SNP arrays are needed with the same degree of capture in diverse populations to elucidate the full role of each locus in a worldwide context.
The next challenge is to resolve the specific causal variants and determine how they affect the expression and function of these gene products. The Next-Generation Sequencing (NGS) technology has opened new avenues to elucidate the role of coding and noncoding RNAs in health and disease and would speed up the identification of causative gene variants in T1D.
No doubt, the
This research was financially supported by grant from National Institute of Health (DP3 DK085708-01) and an Institute Development Award to the Center for Applied Genomics from the Children’s Hospital of Philadelphia.
For the first time in the 1970s early work showed that special
These toxins were also called Shiga toxins (Stx) because of their relation to the toxin produced by
Since the beginning of August 1982 specimens obtained from four patients located in the United States of America, who were suffering from an unusual bloody diarrheal illness started suddenly with abdominal pain within 24 hours followed by watery diarrhea, led to identification of
By further examination of stool samples from different cases of this type of diarrheal illness which nowadays designated as “hemorrhagic colitis,” for the first time CDC associated the 1993 large outbreak with undercooked hamburgers served at fast-food chain restaurants in Oregon and Michigan. Hemorrhagic colitis is characterized by severe abdominal pain, grossly bloody diarrhea, and even fever [3].
However, experiences have established a diversity of sources for
As already we know, STEC is a zoonotic pathogen that is responsible for severe outbreaks worldwide. The main virulence factor of STEC is the production of Shiga toxins 1 and 2. There are additional factors like plasmid-encoded enterohemolysin (EhxA), an autoagglutinating adhesin (Saa), a catalase-peroxidase (KatP), an extracellular serine protease (EspP) that can damage the intestinal tissue or even some factors related to the adhesion to bovine colon like intimin which can induce a characteristic histopathological lesion defined as “attaching and effacing” (A/E) [7, 8, 9].
Shiga toxins are encoded by
These toxins that are produced in colon besides causing local damage can travel via bloodstream to its’s target organs such as kidney and play an important role in causing HC and HUS (Figure 1) [11].
The effects of Stx in STEC-HUS caused by enterohemorrhagic
The damaged caused by toxins is because of inhibition of protein synthesis which leads to apoptosis of endothelial cells [12].
Stx-phages are highly mobile genetic elements which can be transferred through horizontal gene transfer to other
The expression of these genes (especially
The whole cluster of other virulence factors is encoded by chromosomal region called the locus of enterocyte effacement (LEE) presents in many STEC strains, which are responsible for the attaching and causing lesions. In a large proportion of STEC, a plasmid encoding several putative virulence factors like hemolysin can also be found [16].
Considerable effort has been done to inhibit or facilitate infection of animals with STEC O157:H7, because of the readily transmission of pathogen strains such as EHEC in the farm environment and animals can even represent as vectors [21, 22].
However, illnesses caused by contaminated meat product still occur. But great effort has recently been placed on developing new strategies to control the widespread of distribution of EHEC serotypes, O157 and even non-O157 in cattle population to maintain their healthy condition and finally to decrease such illnesses in human [23].
Another practice for controlling is, by the use of beneficial bacteria often referred to as probiotics. Probiotics can interfere with pathogenic strains by producing metabolites that are inhibitory to STEC O157:H [24].
Some strains of
O157 STEC can usually be differentiated from most commensal
For isolation this strain, samples are plated onto a selective and differential media, such as sorbitol-MacConkey agar (SMAC), cefixime tellurite-sorbitol MacConkey agar (CT-SMAC), CHROMagar O157, or Rainbow agar. After incubation for 16–24 hours at 37°C, the plate is being examined for possible O157 colonies, which are colorless on SMAC or CT-SMAC and are mauve or pink on CHROMagar O157 [26].
Non-motile flagella-less (H-) sorbitol-fermenting STEC O157 might not grow on CT-SMAC agar because of their susceptibility to tellurite [27].
In the laboratory, culture and biochemical analysis is considered as the “gold standard” for the identification of STEC. Selective media, such as SMAC and CT-SMACK can be used to identified O157:H7 STEC because of the ability to ferment sorbitol within 24 hours [28].
Guidance for public health laboratories on the isolation and characterization of Shiga toxin-producing
Medium | Characteristics | Properties | Morphology |
---|---|---|---|
Cefixime-tellurite sorbitol MacConkey agar (CT-SMAC) | Selective and differential distinguishes O157 from other fecal | Inhibits | O157 STEC appear clear, non-O157 STEC appear pink, and other normal enteric bacteria appear pink |
CHROMagar™ O157 | Selective and differential distinguishes O157 from other fecal | The chromogen mixture consists of artificial substrates | O157 STEC appear mauve, non-O157 STEC appear steel blue or blue green, and other enteric bacteria appear colorless |
Rainbow® agar | Selective and differential distinguishes O157 from other fecal | Tellurite and novobiocin reduce the number of bacteria other than | O157 STEC appear black/gray, non-O157 STEC appear purple or violet, and other enteric bacteria appear pink |
Sorbitol MacConkey agar (SMAC) | Modified MacConkey agar distinguishes O157 from other fecal | Primary carbon source sorbitol supports growth of non-O157 STEC | O157 STEC appear clear, non-O157 STEC appear pink, and other enteric bacteria appear pink |
Guidance for public health laboratories on the isolation and characterization of Shiga toxin-producing
Recently, PCR methods (like real-time PCR and conventional PCR) have been developed to test the samples for the presence of Stx genes [30].
This method is inexpensive and easy to perform. During the protocol multiple primer sets in a single PCR reaction in order to detect different types and subtypes of Stx genes in a certain sample. But we have to keep in mind, the detection of Stx mRNA is not possible because they have not been expressed yet and there’s a possibility of having a false negative test. Also analysts must be aware of the presence of cryptic bacteriophages which are prophages that have become trapped within a bacterial genome [31].
Detection of Shiga-toxin in clinical samples has been approved by the FDA [27].
These kits can detect Shiga-toxin in the enrichment samples, although none of them can distinguish the seven subtypes of Stx2 or the three subtypes of Stx.
In 2015, researchers designed sandwich ELISAs capable of detecting and distinguishing between stx2 subtypes a, c, and d [32].
These antibodies provide a significant way to test the samples as fast as possible, even including samples from beef and pure culture [33].
The most common method used in clinical laboratories when samples suspected to O157:H7 are being tested, is the O-antigen determination which is run by latex agglutination. These latex particles are coated with antibodies against the O157 antigen and when they are mixed with bacterial growth, O157 STEC bacteria will bind to the latex particle to produce visible agglutination which means positive reaction [34].
H7-specific antisera for latex agglutination are available for O157 but unlike the previous method, detection of flagellar antigens may be difficult and usually it is being done for non-O157 outbreaks [34].
STEC infection causes a wide spectrum of illnesses, such as non-bloody diarrhea, hemolytic uremic syndrome (HUS), and hemorrhagic colitis (HC) [35].
Many non-O157:H7 STEC strains may also cause HUS but the majority of diarrhea-associated HUS cases in the US are caused by infection with O157:H7 STEC [36].
STEC are found in the intestines of healthy animals and are easily transmitted to humans by consumption of contaminated food or water, or even through direct contact with infected animals or persons [37].
Undercooked beef especially ground beef plays an important role in many O157:H7 STEC outbreaks, although other foods including unpasteurized juice, raw milk, and raw produces (e.g., lettuce) have been implicated in outbreaks too [38, 39, 40].
For the years 1998 and 1999 data about in implicated vehicles in outbreaks of
Vehicle | 1998 | 1999 | Total |
---|---|---|---|
Ground beef/hamburger | 10 | 9 | 19 |
Roast beef | 0 | 2 | 2 |
Lettuce | 1 | 3 | 4 |
Coleslaw | 2 | 1 | 3 |
Salad | 1 | 1 | 2 |
Milk | 2 | 0 | 2 |
Tacos | 0 | 1 | 1 |
Apple cider | 0 | 1 | 1 |
Game meat | 0 | 1 | 1 |
Cake | 1 | 0 | 1 |
Cheese curd | 1 | 0 | 1 |
Fruit salad | 1 | 0 | 1 |
Macaroni salad | 1 | 0 | 1 |
Multiple | 1 | 0 | 1 |
Unknown | 0 | 2 | 2 |
Total | 21 | 21 | 42 |
CDC officials in several states, and the U.S. Food and Drug Administration (FDA) have collected data to investigate a multistate outbreak of
In December 22, 2020 the FDA and CDC investigated a multistate outbreak of
Outbreaks of
Of the 57
In the United States since 2008, 37 outbreaks of
Information on which month the outbreaks occurred is available for 17 of the 18 outbreaks linked to romaine lettuce in Canada and the United States from 2008 to 2018. The majority of these outbreaks happened during two seasons: eight occurred in the spring (March to June) and eight occurred in the fall (September to December) [46].
A possible theory for the distribution of
In the spring 2018 outbreaks in U.S., trace back investigation identified 36 growing fields on 23 farms in the Yuma, AZ, growing region as potential sources of contaminated lettuce. Growers reported the following common elements: romaine lettuce was grown under conventional agricultural practices; Colorado River water via an open irrigation canal was used to irrigate the romaine lettuce and to dilute agricultural chemicals; and overhead sprinkler irrigation was used during the germination of romaine lettuce followed in most fields by furrow irrigation [48].
In November 5, 2019 to November 16, 2019, CDC and FDA investigated a multistate outbreak of Shiga toxin-producing
As of January 15, 2020, this outbreak appears to be over [49].
In December 2020, CDC, U.S. Food and Drug Administration, and public health regulatory officials reported an outbreak of
Public health investigators used the national PulseNet system to identify illness that may have been included in this outbreak. PulseNet system is the subtyping network of public health and food regulatory agency laboratories conducted by CDC, and with the help of the whole genome sequencing (WGS) method, analyzing the DNA fingerprinting is being done by official investigators. Molecular Investigations showed that people in this outbreak were more likely to share a common source of infection. As of December 16, 2020, a total of 32 people infected with the outbreak strain of
The officials interviewed ill people to determine what they ate, they reported variety of food items. Several ill people also reported eating at the same restaurant with common foods. As of December 18, 2020, this outbreak is over and that ended unknown, before enough information was available for investigators [50].
In November, 2021 CDC and FDA collected data to investigate a multistate outbreak of
Public health investigators are using the PulseNet system and WGS method to identify illnesses that could be part of the outbreak, which showed that bacteria from sick people samples are closely related genetically, that suggests that people in the outbreak got sick from the same food. This outbreak is not over yet and CDC is advising people not to eat, sell or serve Josie’s Organics prepackaged with best by date of October 23, 2021 [51].
On December 11, 2017 the Public Health Agency of Canada (PHAC) announced an outbreak of 21 STEC O157:H7 infections in three provinces linked to romaine lettuce.
This outbreak appears to be over as of January 25, 2018, and 25 people infected with the outbreak strain of STEC O157:H7 were reported [52].
On January 4, 2017 to April 18, 2018
On June 27, 2016 to September 10, 2016, there were 11 reports based on
On October 6, 2015 to November 3, 2015, there were a total of 19 people infected with the outbreak strain of Shiga toxin-producing STEC O157:H7 in Missouri, Colorado, Utah, Virginia, Washington, and Montana, ranged in age from 5 to 84 years, with a median age of 18. Two ill people developed HUS. The epidemiologic evidence collected during this investigation suggested that rotisserie chicken salad made and sold in Costco stores was the likely source of this outbreak. This outbreak seems to be over reported to CDC [55].
On May 19, 2014, a total number of 12 persons were infected with the outbreak strains of Shiga toxin-producing
A total of 33 ill persons infected with the outbreak strain of STEC O157:H7 were reported from Arizona, California, Texas, and Washington, on November 10, 2013. Federal officials indicated that consumption of two ready-to-eat salads, Field Fresh Chopped Salad with Grilled Chicken and Mexicali Salad with Chili Lime Chicken, produced by Glass Onion Catering and sold at Trader Joe’s grocery store locations, was the source of this outbreak of STEC O157:H7 infections and even two ill people developed HUS. This outbreak appears to be over [57].
From October 18, 2012 to November 12, 2012, a total of 33 people infected with the outbreak strain of STEC O157:H7 were reported from Connecticut, Massachusetts, New York, Pennsylvania, and Virginia and two ill persons developed HUS. Epidemiologic investigation conducted by officials in local linked this outbreak to prepackaged leafy greens, produced by State Garden of Chelsea, Massachusetts. Testing conducted by the New York Department Health Wadsworth Center Laboratories isolated the outbreak strain of STEC O157:H7 from four leftover packages of Wegmans brand Organic Spinach and Spring Mix blend collected from four ill person’s homes [58].
As of March 22, 2011, 14 persons infected with the outbreak strain of
From October 16, 2010 through October 27, 2010, 38 persons infected with the outbreak strain of
As of Tuesday, June 30, 2009, 72 persons infected with
As of July 17, 2008, 49 confirmed cases have been linked both epidemiologically and molecular fingerprinting to
On December 14, 2006, 71 persons with illness associated with the Taco Bell restaurant outbreak have been reported to CDC from five states: New Jersey (33 cases), New York (22 cases), Pennsylvania (13 cases), Delaware (2 cases), and South Carolina (1 case). A total of 71 ill persons, 53 were hospitalized and 8 developed HUS. This outbreak has ended [63].
Hemolytic uremic syndrome (HUS) is complication of Shiga-toxin producing
HUS actually develops 1 week or more after diarrhea begins. Due to the use of the immunomagnetic separation (IMS) the isolation of O157:H7 in the stools from patients with HUS has been increased dramatically [65].
You can see the timeframe of the development and evolution of STEC-HUS (Figure 2).
Timeframe of the development and evolution of STEC-HUS. The timeframe and proportion represented are based on median values and are highly variable, depending on strain, epidemiological, and individual patient characteristics [
The pathogenesis is related to the endothelial cell damage caused by Shiga-toxin which is produced in the gastrointestinal tract. These damaged cells become separated from the basement membranes of the glomeruli and in blood vessels to other organs. Clinically HUS from
Year or time period and geographical region | STEC-HUS cases (children) | STEC-HUS cases (adult) |
---|---|---|
1979–1983 Washington and Baltimore | 20 | 0 |
2000–2006 USA (8 states) | 190 | 28 |
1992–2012 Norway | 24 | 1 |
2017 Switzerland | 4 | 3 |
1989–2006 Oklahoma | — | 21 |
2009–2016 Alberta, Canada | 33 | 6 |
2009–2013 England | 66 | 20 |
2009–2017 France | — | 96 |
2014 USA (10 states) | 42 | 0 |
Distribution of children and adults in STEC-HUS cases [67].
HUS primarily affects the kidneys, however it can also lead to sepsis and neurological damages [68]. In (Table 4) there are some information based on Annual HUS incidence per 1,000,000 children in U.S. [69]. All the data based on HUS cases in last 10 years, are given in Section 6.
Year | HUS cases | Incidence |
---|---|---|
2003 | 8 | 5.00 |
2004 | 3 | 1.88 |
2005 | 8 | 5.00 |
2006 | 11 | 6.88 |
2007 | 14 | 8.75 |
2008 | 7 | 4.38 |
2009 | 10 | 6.25 |
2010 | 15 | 9.38 |
2011 | 6 | 3.75 |
2012 | 19 | 11.88 |
Total | 101 | 6.31 |
Annual HUS in U.S. incidence per 1,000,000 children [69].
As
Through decades several outbreaks related to
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\\n\\nThe Author, on his/her own behalf and on behalf of the Co-Authors, will not assert any rights under the Copyright, Designs and Patents Act 1988 to object to derogatory treatment of the Work as a consequence of IntechOpen's changes to the Work arising from the translation of it, corrections and edits for house style, removal of problematic material and other reasonable edits as determined by IntechOpen.
\\n\\nAUTHOR'S DUTIES
\\n\\nWhen distributing or re-publishing the Work, the Author agrees to credit the Monograph/Compacts as the source of first publication, as well as IntechOpen. The Author guarantees that Co-Authors will also credit the Monograph/Compacts as the source of first publication, as well as IntechOpen, when they are distributing or re-publishing the Work.
\\n\\nThe Author agrees to:
\\n\\nThe Author will be held responsible for the payment of the agreed Open Access Publishing Fee before the completion of the project (Monograph/Compacts publication).
\\n\\nAll payments shall be due 30 days from the date of issue of the invoice. The Author or whoever is paying on behalf of the Author and Co-Authors will bear all banking and similar charges incurred.
\\n\\nThe Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Work worldwide for the full term of the above licenses, and shall provide to IntechOpen, at its request, the original copies of such consents for inspection or the photocopies of such consents.
\\n\\nThe Author shall obtain written informed consent for publication from those who might recognize themselves or be identified by others, for example from case reports or photographs.
\\n\\nThe Author shall respect confidentiality during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Author and Co-Authors are confidential and are intended only for the recipients. The contents of any communication may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
\\n\\nAUTHOR'S WARRANTY
\\n\\nThe Author and Co-Authors confirm and warrant that the Work does not and will not breach any applicable law or the rights of any third party and, specifically, that the Work contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy.
\\n\\nThe Author and Co-Authors confirm that: (i) the Work is their original work and is not copied wholly or substantially from any other work or material or any other source; (ii) the Work has not been formally published in any other peer-reviewed journal or in a book or edited collection, and is not under consideration for any such publication; (iii) Authors and any applicable Co-Authors are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) Authors and any applicable Co-Authors have not assigned, and will not during the term of this Publication Agreement purport to assign, any of the rights granted to IntechOpen under this Publication Agreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\\n\\nThe Author and Co-Authors also confirm and warrant that: (i) he/she has the power to enter into this Publication Agreement on his or her own behalf and on behalf of each Co-Author; and (ii) has the necessary rights and/or title in and to the Work to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licences in this Publication Agreement. If the Work was prepared jointly by the Author and Co-Authors, the Author confirms that: (i) all Co-Authors agree to the submission, license and publication of the Work on the terms of this Publication Agreement; and (ii) the Author has the authority to enter into this biding Publication Agreement on behalf of each Co-Author. The Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each Co-Author.
\\n\\nThe Author agrees to indemnify IntechOpen harmless against all liabilities, costs, expenses, damages and losses, as well as all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of, or in connection with, any breach of the agreed confirmations and warranties. This indemnity shall not apply in a situation in which a claim results from IntechOpen's negligence or willful misconduct.
\\n\\nNothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\\n\\nTERMINATION
\\n\\nIntechOpen has the right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Author and/or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Author and/or any Co-Author (being a private individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Author and/or any Co-Author (as a corporate entity) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for, or enters into, any compromise or arrangement with any of its creditors.
\\n\\nIn the event of termination, IntechOpen will notify the Author of the decision in writing.
\\n\\nIntechOpen’s DUTIES AND RIGHTS
\\n\\nUnless prevented from doing so by events beyond its reasonable control, IntechOpen, at its discretion, agrees to publish the Work attributing it to the Author and Co-Authors.
\\n\\nUnless prevented from doing so by events beyond its reasonable control, IntechOpen agrees to provide publishing services which include: managing editing (editorial and publishing process coordination, Author assistance); publishing software technology; language copyediting; typesetting; online publishing; hosting and web management; and abstracting and indexing services.
\\n\\nIntechOpen agrees to offer free online access to readers and use reasonable efforts to promote the Publication to relevant audiences.
\\n\\nIntechOpen is granted the authority to enforce the rights from this Publication Agreement on behalf of the Author and Co-Authors against third parties, for example in cases of plagiarism or copyright infringements. In respect of any such infringement or suspected infringement of the copyright in the Work, IntechOpen shall have absolute discretion in addressing any such infringement that is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\\n\\nIntechOpen has the right to include/use the Author and Co-Authors names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Work and has the right to contact the Author and Co-Authors until the Work is publicly available on any platform owned and/or operated by IntechOpen.
\\n\\nMISCELLANEOUS
\\n\\nFurther Assurance: The Author shall ensure that any relevant third party, including any Co-Author, shall execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\\n\\nThird Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\\n\\nEntire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by, or on behalf of, the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (known as the "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of any fraudulent pre-contract misrepresentation or concealment.
\\n\\nWaiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\\n\\nVariation: No variation of this Publication Agreement shall have effect unless it is in writing and signed by the parties, or their duly authorized representatives.
\\n\\nSeverance: If any provision, or part-provision, of this Publication Agreement is, or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted. Any modification to, or deletion of, a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\\n\\nNo partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Author or any Co-Author, nor authorize any party to make or enter into any commitments for, or on behalf of, any other party.
\\n\\nGoverning law: This Publication Agreement and any dispute or claim, including non-contractual disputes or claims arising out of, or in connection with it, or its subject matter or formation, shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of, or in connection with, this Publication Agreement, including any non-contractual disputes or claims.
\\n\\nPolicy last updated: 2018-09-11
\\n"}]'},components:[{type:"htmlEditorComponent",content:'When submitting a manuscript, the Author is required to accept the Terms and Conditions set out in our Publication Agreement – Monographs/Compacts as follows:
\n\nCORRESPONDING AUTHOR'S GRANT OF RIGHTS
\n\nSubject to the following Article, the Author grants to IntechOpen, during the full term of copyright, and any extensions or renewals of that term, the following:
\n\nThe foregoing licenses shall survive the expiry or termination of this Publication Agreement for any reason.
\n\nThe Author, on his or her own behalf and on behalf of any of the Co-Authors, reserves the following rights in the Work but agrees not to exercise them in such a way as to adversely affect IntechOpen's ability to utilize the full benefit of this Publication Agreement: (i) reprographic rights worldwide, other than those which subsist in the typographical arrangement of the Work as published by IntechOpen; and (ii) public lending rights arising under the Public Lending Right Act 1979, as amended from time to time, and any similar rights arising in any part of the world.
\n\nThe Author, and any Co-Author, confirms that they are, and will remain, a member of any applicable licensing and collecting society and any successor to that body responsible for administering royalties for the reprographic reproduction of copyright works.
\n\nSubject to the license granted above, copyright in the Work and all versions of it created during IntechOpen's editing process, including all published versions, is retained by the Author and any Co-Authors.
\n\nSubject to the license granted above, the Author and Co-Authors retain patent, trademark and other intellectual property rights to the Work.
\n\nAll rights granted to IntechOpen in this Article are assignable, sublicensable or otherwise transferrable to third parties without the specific approval of the Author or Co-Authors.
\n\nThe Author, on his/her own behalf and on behalf of the Co-Authors, will not assert any rights under the Copyright, Designs and Patents Act 1988 to object to derogatory treatment of the Work as a consequence of IntechOpen's changes to the Work arising from the translation of it, corrections and edits for house style, removal of problematic material and other reasonable edits as determined by IntechOpen.
\n\nAUTHOR'S DUTIES
\n\nWhen distributing or re-publishing the Work, the Author agrees to credit the Monograph/Compacts as the source of first publication, as well as IntechOpen. The Author guarantees that Co-Authors will also credit the Monograph/Compacts as the source of first publication, as well as IntechOpen, when they are distributing or re-publishing the Work.
\n\nThe Author agrees to:
\n\nThe Author will be held responsible for the payment of the agreed Open Access Publishing Fee before the completion of the project (Monograph/Compacts publication).
\n\nAll payments shall be due 30 days from the date of issue of the invoice. The Author or whoever is paying on behalf of the Author and Co-Authors will bear all banking and similar charges incurred.
\n\nThe Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Work worldwide for the full term of the above licenses, and shall provide to IntechOpen, at its request, the original copies of such consents for inspection or the photocopies of such consents.
\n\nThe Author shall obtain written informed consent for publication from those who might recognize themselves or be identified by others, for example from case reports or photographs.
\n\nThe Author shall respect confidentiality during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Author and Co-Authors are confidential and are intended only for the recipients. The contents of any communication may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
\n\nAUTHOR'S WARRANTY
\n\nThe Author and Co-Authors confirm and warrant that the Work does not and will not breach any applicable law or the rights of any third party and, specifically, that the Work contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy.
\n\nThe Author and Co-Authors confirm that: (i) the Work is their original work and is not copied wholly or substantially from any other work or material or any other source; (ii) the Work has not been formally published in any other peer-reviewed journal or in a book or edited collection, and is not under consideration for any such publication; (iii) Authors and any applicable Co-Authors are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) Authors and any applicable Co-Authors have not assigned, and will not during the term of this Publication Agreement purport to assign, any of the rights granted to IntechOpen under this Publication Agreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\n\nThe Author and Co-Authors also confirm and warrant that: (i) he/she has the power to enter into this Publication Agreement on his or her own behalf and on behalf of each Co-Author; and (ii) has the necessary rights and/or title in and to the Work to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licences in this Publication Agreement. If the Work was prepared jointly by the Author and Co-Authors, the Author confirms that: (i) all Co-Authors agree to the submission, license and publication of the Work on the terms of this Publication Agreement; and (ii) the Author has the authority to enter into this biding Publication Agreement on behalf of each Co-Author. The Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each Co-Author.
\n\nThe Author agrees to indemnify IntechOpen harmless against all liabilities, costs, expenses, damages and losses, as well as all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of, or in connection with, any breach of the agreed confirmations and warranties. This indemnity shall not apply in a situation in which a claim results from IntechOpen's negligence or willful misconduct.
\n\nNothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\n\nTERMINATION
\n\nIntechOpen has the right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Author and/or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Author and/or any Co-Author (being a private individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Author and/or any Co-Author (as a corporate entity) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for, or enters into, any compromise or arrangement with any of its creditors.
\n\nIn the event of termination, IntechOpen will notify the Author of the decision in writing.
\n\nIntechOpen’s DUTIES AND RIGHTS
\n\nUnless prevented from doing so by events beyond its reasonable control, IntechOpen, at its discretion, agrees to publish the Work attributing it to the Author and Co-Authors.
\n\nUnless prevented from doing so by events beyond its reasonable control, IntechOpen agrees to provide publishing services which include: managing editing (editorial and publishing process coordination, Author assistance); publishing software technology; language copyediting; typesetting; online publishing; hosting and web management; and abstracting and indexing services.
\n\nIntechOpen agrees to offer free online access to readers and use reasonable efforts to promote the Publication to relevant audiences.
\n\nIntechOpen is granted the authority to enforce the rights from this Publication Agreement on behalf of the Author and Co-Authors against third parties, for example in cases of plagiarism or copyright infringements. In respect of any such infringement or suspected infringement of the copyright in the Work, IntechOpen shall have absolute discretion in addressing any such infringement that is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\n\nIntechOpen has the right to include/use the Author and Co-Authors names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Work and has the right to contact the Author and Co-Authors until the Work is publicly available on any platform owned and/or operated by IntechOpen.
\n\nMISCELLANEOUS
\n\nFurther Assurance: The Author shall ensure that any relevant third party, including any Co-Author, shall execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\n\nThird Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\n\nEntire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by, or on behalf of, the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (known as the "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of any fraudulent pre-contract misrepresentation or concealment.
\n\nWaiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\n\nVariation: No variation of this Publication Agreement shall have effect unless it is in writing and signed by the parties, or their duly authorized representatives.
\n\nSeverance: If any provision, or part-provision, of this Publication Agreement is, or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted. Any modification to, or deletion of, a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\n\nNo partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Author or any Co-Author, nor authorize any party to make or enter into any commitments for, or on behalf of, any other party.
\n\nGoverning law: This Publication Agreement and any dispute or claim, including non-contractual disputes or claims arising out of, or in connection with it, or its subject matter or formation, shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of, or in connection with, this Publication Agreement, including any non-contractual disputes or claims.
\n\nPolicy last updated: 2018-09-11
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{},profiles:[{id:"396",title:"Dr.",name:"Vedran",middleName:null,surname:"Kordic",slug:"vedran-kordic",fullName:"Vedran Kordic",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/396/images/7281_n.png",biography:"After obtaining his Master's degree in Mechanical Engineering he continued his education at the Vienna University of Technology where he obtained his PhD degree in 2004. He worked as a researcher at the Automation and Control Institute, Faculty of Electrical Engineering, Vienna University of Technology until 2008. His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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Raja",coverURL:"https://cdn.intechopen.com/books/images_new/11331.jpg",editedByType:"Edited by",publishedDate:"August 17th 2022",editors:[{id:"176044",title:"Dr.",name:"Ramasamy",middleName:null,surname:"Vijayakumar",slug:"ramasamy-vijayakumar",fullName:"Ramasamy Vijayakumar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10820",title:"Data Clustering",subtitle:null,isOpenForSubmission:!1,hash:"086d299ffd05aacd2311c3ca4ebf0d3a",slug:"data-clustering",bookSignature:"Niansheng Tang",coverURL:"https://cdn.intechopen.com/books/images_new/10820.jpg",editedByType:"Edited by",publishedDate:"August 17th 2022",editors:[{id:"221831",title:"Prof.",name:"Niansheng",middleName:null,surname:"Tang",slug:"niansheng-tang",fullName:"Niansheng Tang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited 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Saleh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"302",title:"Pathology",slug:"veterinary-medicine-and-science-pathology",parent:{id:"25",title:"Veterinary Medicine and Science",slug:"veterinary-medicine-and-science"},numberOfBooks:2,numberOfSeries:0,numberOfAuthorsAndEditors:59,numberOfWosCitations:42,numberOfCrossrefCitations:27,numberOfDimensionsCitations:68,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"302",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"10589",title:"Mastitis in Dairy Cattle, Sheep and Goats",subtitle:null,isOpenForSubmission:!1,hash:"10a5864ea0e1e21ee67aa2b55f51f465",slug:"mastitis-in-dairy-cattle-sheep-and-goats",bookSignature:"Oudessa Kerro Dego",coverURL:"https://cdn.intechopen.com/books/images_new/10589.jpg",editedByType:"Edited by",editors:[{id:"283019",title:"Dr.",name:"Oudessa",middleName:null,surname:"Kerro Dego",slug:"oudessa-kerro-dego",fullName:"Oudessa Kerro Dego"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5861",title:"Theriogenology",subtitle:null,isOpenForSubmission:!1,hash:"b5aae519c030c5492d65c181d9c0ea57",slug:"theriogenology",bookSignature:"Rita Payan Carreira",coverURL:"https://cdn.intechopen.com/books/images_new/5861.jpg",editedByType:"Edited by",editors:[{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:2,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"55491",doi:"10.5772/intechopen.69091",title:"Mitigation of the Heat Stress Impact in Livestock Reproduction",slug:"mitigation-of-the-heat-stress-impact-in-livestock-reproduction",totalDownloads:4344,totalCrossrefCites:10,totalDimensionsCites:24,abstract:"Heat stress affects the fertility and reproductive livestock performance by compromising the physiology reproductive tract, through hormonal imbalance, decreased oocyte quality and poor semen quality, and decreased embryo development and survival. Heat stress decreases the secretion of luteinizing hormone and estradiol resulting in reduced length and intensity of estrus expression, increased incidence of anoestrus and silent heat in farm animals. Oocytes exposed to thermal stress lose its competence for fertilization and development into the blastocyst stage, which results in decreased fertility because of the production of poor quality oocytes and embryos. Furthermore, low progesterone secretion limits the endometrial functions, and subsequently embryo development. In addition, the increased secretion of endometrial prostaglandin F2 alpha during heat stress threatens the maintenance of pregnancy. In general, the percentage of conception rate was found to be reduced by 4.6% for each unit increase in temperature humidity index (THI) above 70, and heat stress during pregnancy further slows down the growth of the foetus and results in lower birth weight. In tropical and subtropical regions, during hot days, the testicular temperature may increase and impair both the spermatogenic cycle and semen quality, which culminates in decreased bull fertility. The effects of heat stress on livestock can be minimized via adapting suitable scientific strategies comprising physical modifications of the environment, nutritional management and genetic development of breeds that are less sensitive to heat stress. In addition, the summer infertility may be countered through advanced reproductive technologies involving hormonal treatments, timed artificial insemination and embryo transfer, which may enhance the chances for establishing pregnancy in farm animals.",book:{id:"5861",slug:"theriogenology",title:"Theriogenology",fullTitle:"Theriogenology"},signatures:"Govindan Krishnan, Madiajagan Bagath, Prathap Pragna,\nMallenahally Kusha Vidya, Joy Aleena, Payyanakkal Ravindranathan\nArchana, Veerasamy Sejian and Raghavendra Bhatta",authors:[{id:"89780",title:"Dr.",name:"Veerasamy",middleName:null,surname:"Sejian",slug:"veerasamy-sejian",fullName:"Veerasamy Sejian"},{id:"177210",title:"Dr.",name:"Raghavendra",middleName:null,surname:"Bhatta",slug:"raghavendra-bhatta",fullName:"Raghavendra Bhatta"},{id:"177220",title:"Dr.",name:"M",middleName:null,surname:"Bagath",slug:"m-bagath",fullName:"M Bagath"},{id:"201967",title:"Dr.",name:"Govindan",middleName:null,surname:"Krishnan",slug:"govindan-krishnan",fullName:"Govindan Krishnan"},{id:"201968",title:"Ms.",name:"Archana",middleName:null,surname:"Pr",slug:"archana-pr",fullName:"Archana Pr"},{id:"201969",title:"Ms.",name:"Pragna",middleName:null,surname:"Prathap",slug:"pragna-prathap",fullName:"Pragna Prathap"},{id:"201970",title:"Ms.",name:"Aleena",middleName:null,surname:"Joy",slug:"aleena-joy",fullName:"Aleena Joy"},{id:"201971",title:"Dr.",name:"Vidya",middleName:null,surname:"Mk",slug:"vidya-mk",fullName:"Vidya Mk"}]},{id:"55006",doi:"10.5772/intechopen.68650",title:"Immunocastration as Alternative to Surgical Castration in Pigs",slug:"immunocastration-as-alternative-to-surgical-castration-in-pigs",totalDownloads:1931,totalCrossrefCites:11,totalDimensionsCites:22,abstract:"Surgical castration of piglets is a routine practice in pig production used to prevent the incidence of boar taint of pig meat, which may develop in entire male pigs as they reach puberty. This practice is being presently questioned in the European Union, and there is a strong initiative to end it. The initiative is presently voluntary; however, key stakeholders of European pig production sector have signed a declaration, and the actions undertaken by them already affect the business. Before such new concepts in pig production can be implemented, alternative solutions are needed, one of them being immunocastration. The present chapter will thus focus on the presentation of immunocastration as one of the promising alternatives to surgical castration. Theoretical and practical aspects of immunocastration in pig production will be described, and the advantages and disadvantages of this alternative will be summarised. Physiological principles of immunocastration and impacts on metabolism, growth performance, body composition and meat quality will be described and aspects of public acceptability reviewed.",book:{id:"5861",slug:"theriogenology",title:"Theriogenology",fullTitle:"Theriogenology"},signatures:"Marjeta Čandek-Potokar, Martin Škrlep and Galia Zamaratskaia",authors:[{id:"23161",title:"Dr.",name:"Marjeta",middleName:null,surname:"Čandek-Potokar",slug:"marjeta-candek-potokar",fullName:"Marjeta Čandek-Potokar"},{id:"198220",title:"Dr.",name:"Martin",middleName:null,surname:"Škrlep",slug:"martin-skrlep",fullName:"Martin Škrlep"},{id:"198221",title:"Prof.",name:"Galia",middleName:null,surname:"Zamaratskaia",slug:"galia-zamaratskaia",fullName:"Galia Zamaratskaia"}]},{id:"55696",doi:"10.5772/intechopen.69444",title:"Estrus Cycle Monitoring in Wild Mammals: Challenges and Perspectives",slug:"estrus-cycle-monitoring-in-wild-mammals-challenges-and-perspectives",totalDownloads:1888,totalCrossrefCites:0,totalDimensionsCites:6,abstract:"The knowledge of reproductive physiology is of paramount importance to guide reproductive management and to make possible future application of assisted reproduction techniques (ARTs) aiming ex situ conservation of wild mammals. Nevertheless, information on the basic reproductive aspects of wild mammals remain scarce, and appropriate management practices have not yet been developed for all the species. This chapter discusses the methods most currently used for reproductive monitoring in wild females. Additionally, the difficulties regarding their use in different species and the possibilities of these procedures in captivity or in free-living mammals are addressed.",book:{id:"5861",slug:"theriogenology",title:"Theriogenology",fullTitle:"Theriogenology"},signatures:"Alexandre R. Silva, Nei Moreira, Alexsandra F. Pereira, Gislayne C.X.\nPeixoto, Keilla M. Maia, Lívia B. Campos and Alana A. Borges",authors:[{id:"90066",title:"Dr.",name:"Alexandre",middleName:"Rodrigues",surname:"Silva",slug:"alexandre-silva",fullName:"Alexandre Silva"},{id:"177090",title:"Dr.",name:"Alexsandra Fernandes",middleName:null,surname:"Pereira",slug:"alexsandra-fernandes-pereira",fullName:"Alexsandra Fernandes Pereira"},{id:"177093",title:"MSc.",name:"Gislayne Christianne Xavier",middleName:null,surname:"Peixoto",slug:"gislayne-christianne-xavier-peixoto",fullName:"Gislayne Christianne Xavier Peixoto"},{id:"198314",title:"Prof.",name:"Nei",middleName:null,surname:"Moreira",slug:"nei-moreira",fullName:"Nei Moreira"},{id:"198315",title:"MSc.",name:"Keilla Moreira",middleName:null,surname:"Maia",slug:"keilla-moreira-maia",fullName:"Keilla Moreira Maia"},{id:"198316",title:"MSc.",name:"Lívia Batista",middleName:null,surname:"Campos",slug:"livia-batista-campos",fullName:"Lívia Batista Campos"},{id:"198317",title:"MSc.",name:"Alana Azevedo",middleName:null,surname:"Borges",slug:"alana-azevedo-borges",fullName:"Alana Azevedo Borges"}]},{id:"56522",doi:"10.5772/intechopen.69549",title:"Role of Melatonin in Reproductive Seasonality in Buffaloes",slug:"role-of-melatonin-in-reproductive-seasonality-in-buffaloes",totalDownloads:1772,totalCrossrefCites:2,totalDimensionsCites:5,abstract:"Buffaloes are characterized by seasonal reproductive activity. Anestrus buffalo heifers and lactating buffaloes were used to study the effect of melatonin treatment on the resumption of ovarian activity during out-of-breeding season. Buffaloes of treated group were injected or implanted with melatonin (18 mg melatonin/50 kg body weight). Using CIDR-eCG protocol preceded with melatonin successfully achieved estrus behavior and induced conception rate during out-of-breeding season. Furthermore, the reproductive performance of buffaloes during out-of-breeding season was clearly improved by melatonin implantation in conjunction with CIDR-eCG protocol due to the luteotrophic effect of melatonin expressed as increasing diameter of CL (corpus luteum) and progesterone concentration. This improvement resulted in greater values of conception rate, in melatonin implanted compared to not implanted buffaloes. Melatonin implantation in anestrus buffalo heifers increased the diameter of largest follicles and melatonin concentration but progesterone and luteinizing hormone (LH) concentrations were decreased. In addition, melatonin implantation in anestrus lactating buffaloes increased the SOD (superoxide dismutase) enzyme activity. Sustained release of exogenous melatonin significantly protects against oxidative stress while increasing beneficial total antioxidant capacity (TAC) concentration in summer-stressed anestrus buffaloes. Melatonin implantation in conjunction with CIDR-eCG protocol successfully improved some blood metabolites, in anestrus buffalo heifers during out-of-breeding season under tropical conditions.",book:{id:"5861",slug:"theriogenology",title:"Theriogenology",fullTitle:"Theriogenology"},signatures:"Tamer Awad Ramadan",authors:[{id:"197651",title:"Dr.",name:"Tamer",middleName:"Awad",surname:"Ramadan",slug:"tamer-ramadan",fullName:"Tamer Ramadan"}]},{id:"54974",doi:"10.5772/intechopen.68651",title:"Markers for Sperm Freezability and Relevance of Transcriptome Studies in Semen Cryopreservation: A Review",slug:"markers-for-sperm-freezability-and-relevance-of-transcriptome-studies-in-semen-cryopreservation-a-re",totalDownloads:1618,totalCrossrefCites:0,totalDimensionsCites:4,abstract:"Advances in sperm assessment techniques have offered new perspectives to improve the technology of semen cryopreservation. This review addresses some recent achievements in the proteomics of seminal plasma and spermatozoa and exemplifies its importance as markers for sperm fertility following cryopreservation. Recent advances in transcriptome studies on sperm RNA-Seq data have generated new information aimed to unravel the physiological roles of RNAs in the sperm-egg fertilization processes and their associations with male fertility. The relevance of the sperm freezability markers and the potential associations of RNA-profiling sequences with the sperm biological functions have been discussed.",book:{id:"5861",slug:"theriogenology",title:"Theriogenology",fullTitle:"Theriogenology"},signatures:"Leyland Fraser",authors:[{id:"199650",title:"Dr.",name:"Leyland",middleName:null,surname:"Fraser",slug:"leyland-fraser",fullName:"Leyland Fraser"}]}],mostDownloadedChaptersLast30Days:[{id:"79344",title:"Epidemiology of Bovine Mastitis and Its Diagnosis, Prevention, and Control",slug:"epidemiology-of-bovine-mastitis-and-its-diagnosis-prevention-and-control",totalDownloads:312,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Mastitis is an inflammation of mammary glands that is prevalent in dairy bovines. It causes a significant proportion of economic losses to the dairy farmers in India. Cattle and buffalo farming contribute significantly to the economy of the state. Various infectious agents such as bacteria, fungi, and algae may cause mastitis. Hence, it is essential to understand the etiological agents and predisposing factors that lead to mastitis in susceptible bovine populations in Madhya Pradesh state so that appropriate prevention and control strategies can be implemented. In this chapter, epidemiology, diagnosis, prevention, and control measures of mastitis in general and in India, the state of Madhya Pradesh, in particular, will be presented.",book:{id:"10589",slug:"mastitis-in-dairy-cattle-sheep-and-goats",title:"Mastitis in Dairy Cattle, Sheep and Goats",fullTitle:"Mastitis in Dairy Cattle, Sheep and Goats"},signatures:"S.D. Audarya, D. Chhabra, R. Sharda, R. Gangil, R. Sikrodia, J. Jogi and N. Shrivastava",authors:[{id:"291434",title:"Dr.",name:"N.",middleName:null,surname:"Shrivastav",slug:"n.-shrivastav",fullName:"N. Shrivastav"},{id:"317236",title:"Dr.",name:"S.D.",middleName:null,surname:"Audarya",slug:"s.d.-audarya",fullName:"S.D. Audarya"},{id:"344698",title:"Dr.",name:"D.",middleName:null,surname:"Chhabra",slug:"d.-chhabra",fullName:"D. Chhabra"},{id:"344699",title:"Dr.",name:"R.",middleName:null,surname:"Sharda",slug:"r.-sharda",fullName:"R. Sharda"},{id:"344700",title:"Dr.",name:"R.",middleName:null,surname:"Gangil",slug:"r.-gangil",fullName:"R. Gangil"},{id:"344702",title:"Dr.",name:"R.",middleName:null,surname:"Sikrodia",slug:"r.-sikrodia",fullName:"R. Sikrodia"},{id:"344703",title:"Dr.",name:"J.",middleName:null,surname:"Jogi",slug:"j.-jogi",fullName:"J. Jogi"}]},{id:"55696",title:"Estrus Cycle Monitoring in Wild Mammals: Challenges and Perspectives",slug:"estrus-cycle-monitoring-in-wild-mammals-challenges-and-perspectives",totalDownloads:1886,totalCrossrefCites:0,totalDimensionsCites:6,abstract:"The knowledge of reproductive physiology is of paramount importance to guide reproductive management and to make possible future application of assisted reproduction techniques (ARTs) aiming ex situ conservation of wild mammals. Nevertheless, information on the basic reproductive aspects of wild mammals remain scarce, and appropriate management practices have not yet been developed for all the species. This chapter discusses the methods most currently used for reproductive monitoring in wild females. Additionally, the difficulties regarding their use in different species and the possibilities of these procedures in captivity or in free-living mammals are addressed.",book:{id:"5861",slug:"theriogenology",title:"Theriogenology",fullTitle:"Theriogenology"},signatures:"Alexandre R. Silva, Nei Moreira, Alexsandra F. Pereira, Gislayne C.X.\nPeixoto, Keilla M. Maia, Lívia B. Campos and Alana A. Borges",authors:[{id:"90066",title:"Dr.",name:"Alexandre",middleName:"Rodrigues",surname:"Silva",slug:"alexandre-silva",fullName:"Alexandre Silva"},{id:"177090",title:"Dr.",name:"Alexsandra Fernandes",middleName:null,surname:"Pereira",slug:"alexsandra-fernandes-pereira",fullName:"Alexsandra Fernandes Pereira"},{id:"177093",title:"MSc.",name:"Gislayne Christianne Xavier",middleName:null,surname:"Peixoto",slug:"gislayne-christianne-xavier-peixoto",fullName:"Gislayne Christianne Xavier Peixoto"},{id:"198314",title:"Prof.",name:"Nei",middleName:null,surname:"Moreira",slug:"nei-moreira",fullName:"Nei Moreira"},{id:"198315",title:"MSc.",name:"Keilla Moreira",middleName:null,surname:"Maia",slug:"keilla-moreira-maia",fullName:"Keilla Moreira Maia"},{id:"198316",title:"MSc.",name:"Lívia Batista",middleName:null,surname:"Campos",slug:"livia-batista-campos",fullName:"Lívia Batista Campos"},{id:"198317",title:"MSc.",name:"Alana Azevedo",middleName:null,surname:"Borges",slug:"alana-azevedo-borges",fullName:"Alana Azevedo Borges"}]},{id:"76529",title:"Mastitis in Small Ruminants",slug:"mastitis-in-small-ruminants",totalDownloads:226,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Bacterial mastitis in small ruminants is a complex disease, with massive economic loss in dairy sheep/goat industry due to poor productivity. The current mastitis prevention strategy relies on culling of infected ewes or does and or the use of antimicrobial agents to eliminate the bacterial infection. This has a potential risk for developing antibiotic resistant bacteria, posing human health risk from consumption of raw sheep or goat dairy products. Existing experimental and licensed vaccines on the market are ineffective against reducing the risk of mastitis in herds or flocks. Raising the needs for development of improved vaccines against mastitis for use in sheep and goats. This review examines, current understanding of the pathological processes and immunological responses against bacterial mastitis, using S. aureus as an example. By highlighting the protective defense mechanism induced in the udder against S. aureus mastitis. Based on evidence from published studies on pathological process and protective immune response mechanism, the need for improved vaccines for prevention of mastitis in small ruminant is highlighted and the development of a vaccine capable of enhancing immune response mechanism, that reduce the establishment of intramammary infection through induction of local IgA, IgG2 and Th17 immune responses is proposed.",book:{id:"10589",slug:"mastitis-in-dairy-cattle-sheep-and-goats",title:"Mastitis in Dairy Cattle, Sheep and Goats",fullTitle:"Mastitis in Dairy Cattle, Sheep and Goats"},signatures:"Christine T. Mwenge Kahinda",authors:[{id:"335924",title:"Dr.",name:"Christine T.",middleName:"Christine",surname:"Mwenge Kahinda",slug:"christine-t.-mwenge-kahinda",fullName:"Christine T. Mwenge Kahinda"}]},{id:"55491",title:"Mitigation of the Heat Stress Impact in Livestock Reproduction",slug:"mitigation-of-the-heat-stress-impact-in-livestock-reproduction",totalDownloads:4337,totalCrossrefCites:10,totalDimensionsCites:24,abstract:"Heat stress affects the fertility and reproductive livestock performance by compromising the physiology reproductive tract, through hormonal imbalance, decreased oocyte quality and poor semen quality, and decreased embryo development and survival. Heat stress decreases the secretion of luteinizing hormone and estradiol resulting in reduced length and intensity of estrus expression, increased incidence of anoestrus and silent heat in farm animals. Oocytes exposed to thermal stress lose its competence for fertilization and development into the blastocyst stage, which results in decreased fertility because of the production of poor quality oocytes and embryos. Furthermore, low progesterone secretion limits the endometrial functions, and subsequently embryo development. In addition, the increased secretion of endometrial prostaglandin F2 alpha during heat stress threatens the maintenance of pregnancy. In general, the percentage of conception rate was found to be reduced by 4.6% for each unit increase in temperature humidity index (THI) above 70, and heat stress during pregnancy further slows down the growth of the foetus and results in lower birth weight. In tropical and subtropical regions, during hot days, the testicular temperature may increase and impair both the spermatogenic cycle and semen quality, which culminates in decreased bull fertility. The effects of heat stress on livestock can be minimized via adapting suitable scientific strategies comprising physical modifications of the environment, nutritional management and genetic development of breeds that are less sensitive to heat stress. In addition, the summer infertility may be countered through advanced reproductive technologies involving hormonal treatments, timed artificial insemination and embryo transfer, which may enhance the chances for establishing pregnancy in farm animals.",book:{id:"5861",slug:"theriogenology",title:"Theriogenology",fullTitle:"Theriogenology"},signatures:"Govindan Krishnan, Madiajagan Bagath, Prathap Pragna,\nMallenahally Kusha Vidya, Joy Aleena, Payyanakkal Ravindranathan\nArchana, Veerasamy Sejian and Raghavendra Bhatta",authors:[{id:"89780",title:"Dr.",name:"Veerasamy",middleName:null,surname:"Sejian",slug:"veerasamy-sejian",fullName:"Veerasamy Sejian"},{id:"177210",title:"Dr.",name:"Raghavendra",middleName:null,surname:"Bhatta",slug:"raghavendra-bhatta",fullName:"Raghavendra Bhatta"},{id:"177220",title:"Dr.",name:"M",middleName:null,surname:"Bagath",slug:"m-bagath",fullName:"M Bagath"},{id:"201967",title:"Dr.",name:"Govindan",middleName:null,surname:"Krishnan",slug:"govindan-krishnan",fullName:"Govindan Krishnan"},{id:"201968",title:"Ms.",name:"Archana",middleName:null,surname:"Pr",slug:"archana-pr",fullName:"Archana Pr"},{id:"201969",title:"Ms.",name:"Pragna",middleName:null,surname:"Prathap",slug:"pragna-prathap",fullName:"Pragna Prathap"},{id:"201970",title:"Ms.",name:"Aleena",middleName:null,surname:"Joy",slug:"aleena-joy",fullName:"Aleena Joy"},{id:"201971",title:"Dr.",name:"Vidya",middleName:null,surname:"Mk",slug:"vidya-mk",fullName:"Vidya Mk"}]},{id:"79839",title:"Antimicrobial Usage for the Management of Mastitis in the USA: Impacts on Antimicrobial Resistance and Potential Alternative Approaches",slug:"antimicrobial-usage-for-the-management-of-mastitis-in-the-usa-impacts-on-antimicrobial-resistance-an",totalDownloads:176,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Mastitis is the most frequently diagnosed disease of dairy cattle responsible for the reduction in milk quantity and quality and major economic losses. Dairy farmers use antibiotics for the prevention and treatment of mastitis. Frequent antimicrobial usage (AMU) undeniably increased antimicrobial resistance (AMR) in bacteria from dairy farms. Antimicrobial-resistant bacteria (ARB) from dairy farms can spread to humans directly through contact with carrier animals or indirectly through the consumption of raw milk or undercooked meat from culled dairy cows. Indirect spread from dairy farms to humans can also be through dairy manure fertilized vegetables or run-off waters from dairy farms to the environment. The most frequently used antibiotics in dairy farms are medically important and high-priority classes of antibiotics. As a result, dairy farms are considered one of the potential reservoirs of ARB and antimicrobial resistance genes (ARGs). To mitigate the rise of ARB in dairy farms, reducing AMU by adopting one or more of alternative disease control methods such as good herd health management, selective dry-cow therapy, probiotics, and others is critically important. This chapter is a concise review of the effects of antimicrobials usage to control mastitis in dairy cattle farms and its potential impact on human health.",book:{id:"10589",slug:"mastitis-in-dairy-cattle-sheep-and-goats",title:"Mastitis in Dairy Cattle, Sheep and Goats",fullTitle:"Mastitis in Dairy Cattle, Sheep and Goats"},signatures:"Benti D. Gelalcha, Getahun E. Agga and Oudessa Kerro Dego",authors:[{id:"283019",title:"Dr.",name:"Oudessa",middleName:null,surname:"Kerro Dego",slug:"oudessa-kerro-dego",fullName:"Oudessa Kerro Dego"},{id:"332974",title:"Ph.D. Student",name:"Benti D.",middleName:"Deresa",surname:"Gelalcha",slug:"benti-d.-gelalcha",fullName:"Benti D. 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He previously worked as a post-doctoral fellow at the Ben-Gurion University of Negev, Israel; University of the Free State, South Africa; and Central University of Technology Bloemfontein, South Africa. He obtained his Ph.D. in Organic Chemistry from Nagaoka University of Technology, Japan. He has published more than seventy-four journal articles and attended several national and international conferences as speaker and chair. Dr. Kendrekar has received many international awards. He has several funded projects, namely, anti-malaria drug development, MRSA, and SARS-CoV-2 activity of curcumin and its formulations. He has filed four patents in collaboration with the University of Central Lancashire and Mayo Clinic Infectious Diseases. His present research includes organic synthesis, drug discovery and development, biochemistry, nanoscience, and nanotechnology.",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null},{id:"428125",title:"Dr.",name:"Vinayak",middleName:null,surname:"Adimule",slug:"vinayak-adimule",fullName:"Vinayak Adimule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428125/images/system/428125.jpg",biography:"Dr. Vinayak Adimule, MSc, Ph.D., is a professor and dean of R&D, Angadi Institute of Technology and Management, India. He has 15 years of research experience as a senior research scientist and associate research scientist in R&D organizations. He has published more than fifty research articles as well as several book chapters. He has two Indian patents and two international patents to his credit. Dr. Adimule has attended, chaired, and presented papers at national and international conferences. He is a guest editor for Topics in Catalysis and other journals. He is also an editorial board member, life member, and associate member for many international societies and research institutions. His research interests include nanoelectronics, material chemistry, artificial intelligence, sensors and actuators, bio-nanomaterials, and medicinal chemistry.",institutionString:"Angadi Institute of Technology and Management",institution:null},{id:"284317",title:"Prof.",name:"Kantharaju",middleName:null,surname:"Kamanna",slug:"kantharaju-kamanna",fullName:"Kantharaju Kamanna",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284317/images/21050_n.jpg",biography:"Prof. K. Kantharaju has received Bachelor of science (PCM), master of science (Organic Chemistry) and Doctor of Philosophy in Chemistry from Bangalore University. He worked as a Executive Research & Development @ Cadila Pharmaceuticals Ltd, Ahmedabad. He received DBT-postdoc fellow @ Molecular Biophysics Unit, Indian Institute of Science, Bangalore under the supervision of Prof. P. Balaram, later he moved to NIH-postdoc researcher at Drexel University College of Medicine, Philadelphia, USA, after his return from postdoc joined NITK-Surthakal as a Adhoc faculty at department of chemistry. Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. 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He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a scientist and Principal Investigator at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering the lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via artificial intelligence-based analyses of exosomal Raman signatures. Dr. Paul also works on spatial multiplex immunofluorescence-based tissue mapping to understand the immune repertoire in lung cancer. Dr. Paul has published in more than sixty-five peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award and the 2022 AAISCR-R Vijayalaxmi Award for Innovative Cancer Research. He is a senior member of the Institute of Electrical and Electronics Engineers (IEEE) and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null}]}},subseries:{item:{id:"1",type:"subseries",title:"Oral Health",keywords:"Oral Health, Dental Care, Diagnosis, Diagnostic Imaging, Early Diagnosis, Oral Cancer, Conservative Treatment, Epidemiology, Comprehensive Dental Care, Complementary Therapies, Holistic Health",scope:"\r\n\tThis topic aims to provide a comprehensive overview of the latest trends in Oral Health based on recent scientific evidence. 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Her qualifications are: a specialist in Dental Imaging and Radiology, Master in Dentistry (Periodontics) from the University of São Paulo (FORP-USP, Ribeirão Preto, SP), and Doctor (Ph.D.) in Dentistry (Stomatology Clinic) from Hospital São Lucas of the Pontifical Catholic University of Rio Grande do Sul (HSL-PUCRS, Porto Alegre, RS). She held a postdoctoral internship at the Federal University from Jequitinhonha and Mucuri Valleys (UFVJM, Diamantina, MG). She is currently a member of the Brazilian Society for Dental Research (SBPqO) and the Brazilian Society of Stomatology and Pathology (SOBEP). 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