Effect of CsA on plasma lipid parameters in humans
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"6307",leadTitle:null,fullTitle:"Congenital Anomalies - From the Embryo to the Neonate",title:"Congenital Anomalies",subtitle:"From the Embryo to the Neonate",reviewType:"peer-reviewed",abstract:"Nowadays, nobody can imagine practicing obstetrics without using obstetrical ultrasound. Working in the prenatal diagnosis field requires dedication, patience, skills, experience, caution, and empathy. The concept of this book was guided by the desire to provide some help to the ultrasound operators. On a daily basis, they are confronted with the challenging task of ruling out or suspecting/confirming the diagnosis of fetal anomalies, either structural or chromosomal. The chapters of this book contain objective and exhaustive updated reviews of the pertinent literature, so that the reader would have a wide reference basis on each subject. Yet, many authors scan the fetus themselves or are directly involved with managing pregnancies with structural malformations or chromosomal anomalies. They kindly shared their personal experience and lessons learned over the years. This book is beneficial for all the professionals working in the prenatal diagnosis.",isbn:"978-1-78923-115-1",printIsbn:"978-1-78923-114-4",pdfIsbn:"978-1-83881-391-8",doi:"10.5772/intechopen.69423",price:159,priceEur:175,priceUsd:205,slug:"congenital-anomalies-from-the-embryo-to-the-neonate",numberOfPages:544,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"235b2f3a6f890667d7d2c0a6a79b3aec",bookSignature:"Stefania Tudorache",publishedDate:"May 2nd 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6307.jpg",numberOfDownloads:37777,numberOfWosCitations:6,numberOfCrossrefCitations:11,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:22,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:39,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 31st 2017",dateEndSecondStepPublish:"June 21st 2017",dateEndThirdStepPublish:"September 17th 2017",dateEndFourthStepPublish:"December 16th 2017",dateEndFifthStepPublish:"February 14th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"209081",title:"Dr.",name:"Stefania",middleName:null,surname:"Tudorache",slug:"stefania-tudorache",fullName:"Stefania Tudorache",profilePictureURL:"https://mts.intechopen.com/storage/users/209081/images/5462_n.jpg",biography:"Stefania Tudorache, PhD, MD, MPH, is a university senior lecturer at the Department Mother and Child, University of Medicine and Pharmacy of Craiova. She has a degree from the University of Medicine and Pharmacy in Craiova, Romania, in 1994. In 2002 she joined the university\\'s faculty as a research fellow following with a position as a lecturer and is currently the head of the Prenatal Diagnostic Unit. Her training has been mainly in the field of maternal-fetal medicine, prenatal diagnosis. She has authored articles in ultrasound, including original investigations, published in peer-review journals. She is the author of several books and book chapters and co-authored many more.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1065",title:"Embryology",slug:"obstetrics-and-gynecology-embryology"}],chapters:[{id:"57858",title:"Congenital Fetal Anomalies and the Role of Prenatal Ultrasound",doi:"10.5772/intechopen.71907",slug:"congenital-fetal-anomalies-and-the-role-of-prenatal-ultrasound",totalDownloads:1811,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The ultrasound is the most widely used diagnostic tool in obstetrics nowadays, in particular in the detection of developmental disorders. However, it is important to know which are those disorders that can be detected prenatally with great certainty, and which ones can be detected only partially or not at all prior to giving birth. Pregnant women have high expectations, that any abnormalities should be fully recognizable and detected early during pregnancy, and this often leads to damages lawsuits. Thus, the right information is essential, so the doctors providing information also must have up to date knowledge about the effectiveness of ultrasound diagnostics. Prenatal diagnostics also entails enormous medical professional responsibility, since the consequences of an accidental inaccurate diagnosis can have significant consequences for both the fetus and the family. Thus, it is important to determine that how early and in what proportion the ultrasound protocol of the current Hungarian pregnancy care system is able to detect the individual disorder groups.",signatures:"Fanni Rebeka Erős and Artúr Beke",downloadPdfUrl:"/chapter/pdf-download/57858",previewPdfUrl:"/chapter/pdf-preview/57858",authors:[{id:"211641",title:"Dr.",name:"Artúr",surname:"Beke",slug:"artur-beke",fullName:"Artúr Beke"},{id:"211676",title:"Dr.",name:"Fanni Rebeka",surname:"Erős",slug:"fanni-rebeka-eros",fullName:"Fanni Rebeka Erős"}],corrections:null},{id:"58674",title:"Congenital Anomalies in Human Embryos",doi:"10.5772/intechopen.72628",slug:"congenital-anomalies-in-human-embryos",totalDownloads:1503,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Morphogenesis mainly occurs during embryonic stage, and congenital anomalies also occur at that time. The Kyoto Collection, one of the largest collections of human embryos, including a lot of those with congenital anomalies, is significantly helpful for analyzing embryonic growth. From the collection, normal and abnormal embryos have been selectively presented in this chapter. Recently developed imaging technology enabled three-dimensional (3D) imaging of embryos and fetuses in high resolution. The devices available for embryonic and fetal imaging and the results obtained therefrom are introduced in this chapter. In addition, new strategies for diagnosing congenital anomalies, such as autopsy imaging and genetic analyses, are discussed.",signatures:"Shiori Nakano, Haruyuki Makishima and Shigehito Yamada",downloadPdfUrl:"/chapter/pdf-download/58674",previewPdfUrl:"/chapter/pdf-preview/58674",authors:[{id:"49486",title:"Prof.",name:"Shigehito",surname:"Yamada",slug:"shigehito-yamada",fullName:"Shigehito Yamada"},{id:"210777",title:"Dr.",name:"Haruyuki",surname:"Makishima",slug:"haruyuki-makishima",fullName:"Haruyuki Makishima"}],corrections:null},{id:"60546",title:"Fetal Central Nervous System Abnormalities",doi:"10.5772/intechopen.76208",slug:"fetal-central-nervous-system-abnormalities",totalDownloads:2107,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Central nervous system (CNS) is one of the most frequent sites for prenatal diagnosed congenital abnormalities (10 per 1000 live births, much higher than the heart—eight per 1000, kidneys—four per 1000, and other fetal systems). Due to the evolving pattern, ultrasound screening for fetal brain malformations is usually performed at 19–22 weeks’ gestation, but severe congenital anomalies can be diagnosed much earlier. This chapter is a short review, structured in eight subchapters: the first one is dedicated to the normal ultrasound aspect of different CNS segments, and the following ones are to detect pathology in prenatal life. We used many ultrasound images and tried to correlate the prenatal findings with the ones obtained postpartum/postabortum for each case, by means of pathology/imaging techniques.",signatures:"Andreea Ceausescu, Andreea Docea, Marina Dinu, Stefan\nDegeratu, Dominic Iliescu and Monica Cara",downloadPdfUrl:"/chapter/pdf-download/60546",previewPdfUrl:"/chapter/pdf-preview/60546",authors:[{id:"212459",title:"Dr.",name:"Dominic",surname:"Iliescu",slug:"dominic-iliescu",fullName:"Dominic Iliescu"},{id:"244664",title:"Dr.",name:"Andreea",surname:"Ceausescu",slug:"andreea-ceausescu",fullName:"Andreea Ceausescu"},{id:"247842",title:"Dr.",name:"Andreea",surname:"Docea",slug:"andreea-docea",fullName:"Andreea Docea"},{id:"247843",title:"Dr.",name:"Marina",surname:"Dinu",slug:"marina-dinu",fullName:"Marina Dinu"},{id:"247844",title:"Dr.",name:"Stefan",surname:"Degeratu",slug:"stefan-degeratu",fullName:"Stefan Degeratu"},{id:"247846",title:"Dr.",name:"Monica",surname:"Cara",slug:"monica-cara",fullName:"Monica Cara"}],corrections:null},{id:"58229",title:"Correlations between Ultrasound and Pathology in Fetal Ventricular System Anomalies",doi:"10.5772/intechopen.71934",slug:"correlations-between-ultrasound-and-pathology-in-fetal-ventricular-system-anomalies",totalDownloads:1100,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"A total of 113 cases of fetal hydrocephalus with a lethal outcome (FHLO) from the Embryo-Fetopathologic Clinic at the Center for Maternity and Neonatology, Tunis, Tunisia and Obstetrics and Gynecology Clinic at St. George EAD University Hospital, Plovdiv, Bulgaria were studied, 86 of which had syndrome malformations: neural tube defects (NTDs)—29.2%, chromosomal abnormalities—23.9%, skeletal dysplasias—9.8%, VACTERL association—5.3%, Dandy-Walker malformation—3.4%, Other—14.2%. Risk factors for FHLO are miscarriages (odds ratio (OR): 19.500; confidence interval (CI): 4.020-94.594), stillbirths (OR: 10.897; CI: 1.169-10.564) and previous birth of a malformative child (OR = 5.385; CI: 1.385–18.896). FHLO is significantly associated with a maternal age over 40 years and third degree consanguinity of the fetus (OR = 18.500; CI: 1.146–298.547). The trisomies in our study were 27 (23.9%) and are significantly associated with an age above 38 years and FHLO (OR = 13.689; CI: 3.952–52.122). In medical abortion, stillbirth, or neonatal death, a fetopathological study enriches our knowledge of malformations, complements and completes the ultrasound examination, modifies genetic counseling, and determines the medical behavior in subsequent pregnancies. Also, associated risk factors and fetopathological changes in FHLO must be studied to increase the ultrasound prenatal diagnosis success.",signatures:"Tanya Kitova, Borislav Kitov, Denis Milkov and Aida Masmoudi",downloadPdfUrl:"/chapter/pdf-download/58229",previewPdfUrl:"/chapter/pdf-preview/58229",authors:[{id:"211907",title:"Associate Prof.",name:"Tanya",surname:"Kitova",slug:"tanya-kitova",fullName:"Tanya Kitova"},{id:"212795",title:"Prof.",name:"Borislav",surname:"Kitov",slug:"borislav-kitov",fullName:"Borislav Kitov"},{id:"212798",title:"Prof.",name:"Aida",surname:"Masmoudi",slug:"aida-masmoudi",fullName:"Aida Masmoudi"},{id:"221779",title:"Dr.",name:"Denis",surname:"Milkov",slug:"denis-milkov",fullName:"Denis Milkov"}],corrections:null},{id:"58770",title:"Congenital Abnormalities of the Fetal Face",doi:"10.5772/intechopen.73072",slug:"congenital-abnormalities-of-the-fetal-face",totalDownloads:2245,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Even at the early stages of gestation, the fetal face can be examined. There have been observations of the normal anatomy, such as orbits and the forehead, starting with the 12th week of gestation. However, nowadays, ultrasound equipment still cannot distinguish the soft tissues of the face, which are too thin. Yet, after the age of 14 weeks, we can easily examine the forehead, orbits, nose, lips, and ears. Recently, three-dimensional ultrasound (3D) images of the fetus can also be obtained. However, two-dimensional (2D) ultrasonographic (US) images are more easily, rapidly, efficiently, and accurately obtained. At the first stage of embryogenesis, the main part in the development of the fetal face is taken by the genetic factors. Later, the influence of the environment becomes more important. It is known that the outcome of chromosomal aberrations and of teratogenic factors is the facial malformation. Therefore, examining the facial dimorphism may get us useful hints in revealing chromosomal or genetic abnormalities. This chapter focuses on the fetal face anomalies more frequently found while performing the prenatal diagnosis. It is divided into anomalies of the orbits, nose, lip, palate, and mandible.",signatures:"Maria Șorop-Florea, Roxana-Cristina Dragușin, Ciprian Laurențiu\nPătru, Lucian George Zorilă, Cristian Marinaș, Virgiliu-Bogdan\nȘorop, Cristian Neamțu, Alina Veduța, Dominic Gabriel Iliescu and\nNicolae Cernea",downloadPdfUrl:"/chapter/pdf-download/58770",previewPdfUrl:"/chapter/pdf-preview/58770",authors:[{id:"212459",title:"Dr.",name:"Dominic",surname:"Iliescu",slug:"dominic-iliescu",fullName:"Dominic Iliescu"},{id:"212490",title:"Dr.",name:"Dragusin",surname:"Roxana",slug:"dragusin-roxana",fullName:"Dragusin Roxana"},{id:"212493",title:"Dr.",name:"Pătru",surname:"Ciprian",slug:"patru-ciprian",fullName:"Pătru Ciprian"},{id:"212494",title:"Dr.",name:"Șorop-Florea",surname:"Maria",slug:"sorop-florea-maria",fullName:"Șorop-Florea Maria"},{id:"222056",title:"Dr.",name:"Cristian",surname:"Marinaș",slug:"cristian-marinas",fullName:"Cristian Marinaș"},{id:"222057",title:"Dr.",name:"Lucian George",surname:"Zorila",slug:"lucian-george-zorila",fullName:"Lucian George Zorila"},{id:"222058",title:"Dr.",name:"Bogdan Virgiliu",surname:"Sorop",slug:"bogdan-virgiliu-sorop",fullName:"Bogdan Virgiliu Sorop"},{id:"222526",title:"Dr.",name:"Cristian",surname:"Neamțu",slug:"cristian-neamtu",fullName:"Cristian Neamțu"},{id:"222699",title:"Prof.",name:"Nicolae",surname:"Cernea",slug:"nicolae-cernea",fullName:"Nicolae Cernea"}],corrections:null},{id:"60148",title:"Congenital Abnormalities of the Fetal Heart",doi:"10.5772/intechopen.74077",slug:"congenital-abnormalities-of-the-fetal-heart",totalDownloads:1643,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Congenital heart defects (CHDs) are the most frequent congenital malformations, the costliest hospital admissions for structural defects and the leading cause of infant general and malformations related mortality. Fetal echocardiography represents a skilled ultrasound examination, because of the complexity, physiological and structural particularities of the fetal heart. The efficiency of the cardiac scan is reported with great variation, depending on the scanning protocol, examiner experience and equipment quality but CHDs remains among the most frequently missed congenital abnormalities.",signatures:"Dominic Gabriel Iliescu, Ștefania Tudorache, Dragos Nemescu,\nMonica Mihaela Cirstoiu, Simona Vlădăreanu, Claudiu Marginean,\nIuliana Ceausu, Daniel Muresan, Marius Calomfirescu Vicea, Mona\nElena Zvanca, Cezara Muresan, Laura Monica Cara, Ciprian\nLaurentiu Patru, Roxana Cristina Drăgușin and Maria Sorop-Florea",downloadPdfUrl:"/chapter/pdf-download/60148",previewPdfUrl:"/chapter/pdf-preview/60148",authors:[{id:"212459",title:"Dr.",name:"Dominic",surname:"Iliescu",slug:"dominic-iliescu",fullName:"Dominic Iliescu"},{id:"31905",title:"Dr.",name:"Dragos",surname:"Nemescu",slug:"dragos-nemescu",fullName:"Dragos Nemescu"},{id:"215135",title:"Prof.",name:"Iuliana",surname:"Ceausu",slug:"iuliana-ceausu",fullName:"Iuliana Ceausu"},{id:"215279",title:"Prof.",name:"Claudiu",surname:"Marginean",slug:"claudiu-marginean",fullName:"Claudiu Marginean"},{id:"215280",title:"Prof.",name:"Mona",surname:"Zvanca",slug:"mona-zvanca",fullName:"Mona Zvanca"},{id:"215281",title:"Prof.",name:"Alina",surname:"Veduta",slug:"alina-veduta",fullName:"Alina Veduta"}],corrections:null},{id:"59077",title:"Neonatal Ebstein’s Anomaly",doi:"10.5772/intechopen.72891",slug:"neonatal-ebstein-s-anomaly",totalDownloads:1207,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Ebstein’s anomaly is a congenital heart disease that results from failure of delamination of the tricuspid valve with resulting apical displacement of the septal and posterior leaflets of the tricuspid valve. Age at presentation can vary greatly but neonatal presentation is associated with extraordinary high mortality rates. Comprehensive multispecialty care is required starting at the time of fetal diagnosis. Fetal echocardiography is vital in monitoring progression of the disease in utero. Fetal echocardiogram can evaluate for complications such as arrhythmias, pericardial effusion, or fetal hydrops. Post-natal evaluation should include evaluation of functional pulmonary atresia or circular shunt. Despite advances in surgical technique for Ebstein’s anomaly, mortality for it remains high with early surgical intervention. Aggressive medical management should be used to support patients with Ebstein’s anomaly during the neonatal period. Surgical procedures for neonatal Ebstein’s vary widely from systemic to pulmonary shunts with or without tricuspid valve closure to tricuspid valve repair.",signatures:"Umar Boston, Ken-Michael Bayle, TK Susheel Kumar and\nChristopher Knott-Craig",downloadPdfUrl:"/chapter/pdf-download/59077",previewPdfUrl:"/chapter/pdf-preview/59077",authors:[{id:"214499",title:"Dr.",name:"Umar",surname:"Boston",slug:"umar-boston",fullName:"Umar Boston"},{id:"214816",title:"Dr.",name:"Ken-Michael",surname:"Bayle",slug:"ken-michael-bayle",fullName:"Ken-Michael Bayle"},{id:"225210",title:"Dr.",name:"Christopher",surname:"Knott-Craig",slug:"christopher-knott-craig",fullName:"Christopher Knott-Craig"},{id:"225937",title:"Dr.",name:"Tk Susheel",surname:"Kumar",slug:"tk-susheel-kumar",fullName:"Tk Susheel Kumar"}],corrections:null},{id:"58140",title:"Thoracic Anomalies",doi:"10.5772/intechopen.71959",slug:"thoracic-anomalies",totalDownloads:1111,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The antenatal and postnatal prognosis for fetuses with chest noncardiac anomalies varies widely, depending of the type of lesion present. An important issue is to establish an accurate prenatal diagnosis, which allows an appropriate counseling of the couple, fetal karyotyping and eventually in utero fetal therapy, if possible. Also, another important feature is preparation for delivery in a tertiary center or an appropriate perinatal institution, able to provide care to the immediate neonatal consequences in such cases. The ultrasound exam is not only crucial in the diagnosis of such lesions, but also important in the serial antenatal follow up, some of them being progressive, and having the potential to lead to compromise of cardiac function and eventually to fetal death. Thus, the sonographer has an important role in the management of such difficult cases. Currently, perinatal centers provide multidisciplinary teams, with maternal fetal specialists, neonatologists, pediatric surgeons, all involved in counseling parents about the outcome and the management options for a fetus with a diagnosis of thoracic anomalies. Although the precise prenatal diagnosis is often possible, this does not necessarily ensure improvement of the postnatal outcome, due to associated pulmonary hypoplasia.",signatures:"Cringu Ionescu",downloadPdfUrl:"/chapter/pdf-download/58140",previewPdfUrl:"/chapter/pdf-preview/58140",authors:[{id:"215200",title:"Prof.",name:"Cringu Antoniu",surname:"Ionescu",slug:"cringu-antoniu-ionescu",fullName:"Cringu Antoniu Ionescu"}],corrections:null},{id:"59588",title:"Congenital Diaphragmatic Hernia",doi:"10.5772/intechopen.74500",slug:"congenital-diaphragmatic-hernia",totalDownloads:1423,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Over the past 20 years, prenatal detection of congenital diaphragmatic hernia (CDH) has improved worldwide, reaching up to 60% in Europe. Pulmonary hypoplasia and persistent pulmonary hypertension are the two main determinants of neonatal mortality and morbidity, so new tools have been focused on their evaluation. Fetal surgery for severe cases requires proper evaluation of the prognosis of fetuses with CDH. It is very important to identify reliable prenatal prognostic factors that can be used worldwide for several reasons: patient counseling is more accurate; the results of pre- and postnatal treatments will be comparable across different institutions; fetuses eligible for fetal surgery will be selected correctly; and a woman expecting a child with a very poor prognosis can prepare herself for the postnatal demise of her baby or, in some countries, opt for termination of pregnancy.",signatures:"Adrian Claudiu Ratiu",downloadPdfUrl:"/chapter/pdf-download/59588",previewPdfUrl:"/chapter/pdf-preview/59588",authors:[{id:"215004",title:"Dr.",name:"Adrian",surname:"Ratiu",slug:"adrian-ratiu",fullName:"Adrian Ratiu"}],corrections:null},{id:"58163",title:"Fetal Abdominal Wall Defects",doi:"10.5772/intechopen.71936",slug:"fetal-abdominal-wall-defects",totalDownloads:3387,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Abdominal wall defects (AWDs) represent a group of congenital anomalies that can be diagnosed early during pregnancy even at the time of the first trimester assessment, with direct impact on pre- and postnatal fetal prognosis and management decisions. The most frequent anomalies in this group are gastroschisis and omphalocele. The key method available, that allows the detection of any deviation from the physiologic midgut herniation, is the ultrasound (US) assessment. A precise algorithmic scan approach is imposed not only for an accurate detection of any abdominal wall defect, but also for a proper location of the defect and of the spatial relation to the umbilical cord insertion, fundamentally important in differentiating among various malformations. Other structural or chromosomal anomalies should be excluded. Suitable multidisciplinary counseling should be considered. Unfortunately, in utero surgery, in these cases, has not been yet successful. Postnatal early interventions are usually required in specialized pediatric centers.",signatures:"Roxana Cristina Drăgușin, Maria Șorop-Florea, Ciprian Laurențiu\nPătru, Lucian Zorilă, Cristian Marinaș, Nicolae Cernea, Cristian\nNeamțu and Dominic Gabriel Iliescu",downloadPdfUrl:"/chapter/pdf-download/58163",previewPdfUrl:"/chapter/pdf-preview/58163",authors:[{id:"212459",title:"Dr.",name:"Dominic",surname:"Iliescu",slug:"dominic-iliescu",fullName:"Dominic Iliescu"},{id:"212490",title:"Dr.",name:"Dragusin",surname:"Roxana",slug:"dragusin-roxana",fullName:"Dragusin Roxana"},{id:"212493",title:"Dr.",name:"Pătru",surname:"Ciprian",slug:"patru-ciprian",fullName:"Pătru Ciprian"},{id:"212494",title:"Dr.",name:"Șorop-Florea",surname:"Maria",slug:"sorop-florea-maria",fullName:"Șorop-Florea Maria"},{id:"222056",title:"Dr.",name:"Cristian",surname:"Marinaș",slug:"cristian-marinas",fullName:"Cristian Marinaș"},{id:"222057",title:"Dr.",name:"Lucian George",surname:"Zorila",slug:"lucian-george-zorila",fullName:"Lucian George Zorila"},{id:"222058",title:"Dr.",name:"Bogdan Virgiliu",surname:"Sorop",slug:"bogdan-virgiliu-sorop",fullName:"Bogdan Virgiliu Sorop"},{id:"222526",title:"Dr.",name:"Cristian",surname:"Neamțu",slug:"cristian-neamtu",fullName:"Cristian Neamțu"},{id:"214960",title:"Prof.",name:"Nicolae",surname:"Cernea",slug:"nicolae-cernea",fullName:"Nicolae Cernea"}],corrections:null},{id:"59525",title:"Gastroschisis: Prenatal Diagnosis and Outcome",doi:"10.5772/intechopen.74270",slug:"gastroschisis-prenatal-diagnosis-and-outcome",totalDownloads:1142,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The purpose of this retrospective cohort study was to investigate and identify prenatal predictors of perinatal outcomes of gastroschisis. Antenatal data included extra-abdominal bowel dilatation (EABD) and intra-abdominal bowel dilatation (IABD). Perinatal data included gestational age, sex, and birth weight. Surgical data included presence of intestinal atresia, necrosis, perforation, strictures, and method of closure. Outcome data included duration of mechanical ventilation and total parenteral nutrition, pseudoobstruction, sepsis, reoperations, length of hospital stay, and mortality rates. Results were analyzed in 65 patients. EABD was documented in 55 patients with no significant difference between simple and complex gastroschisis group. In 27 patients (in 32% of simple and 73% of complex cases), IABD persisted until the last ultrasound scan. Simple gastroschisis group had a shorter hospital stay, shorter ventilation support duration, less bowel pseudoobstruction, less need for reoperation, and received less parenteral nutrition. The most frequent extraintestinal complication was sepsis. The only factor that has been shown to predict poorer outcomes of gastroschisis is the presence of complex gastroschisis. Current available evidence suggests that antenatal bowel dilatation is not associated with increased risk of adverse perinatal outcome in infants with gastroschisis. Also, the absence of bowel dilatation cannot fully exclude complex patients.",signatures:"Vesna Milojković Marinović, Blagoje Grujić, Aleksandra Stojanović,\nDalibor Sabbagh and Petar Rašić",downloadPdfUrl:"/chapter/pdf-download/59525",previewPdfUrl:"/chapter/pdf-preview/59525",authors:[{id:"210778",title:"Ph.D.",name:"Vesna",surname:"Milojković Marinović",slug:"vesna-milojkovic-marinovic",fullName:"Vesna Milojković Marinović"},{id:"223427",title:"Dr.",name:"Blagoje",surname:"Grujić",slug:"blagoje-grujic",fullName:"Blagoje Grujić"},{id:"237503",title:"Dr.",name:"Aleksandra",surname:"Stojanović",slug:"aleksandra-stojanovic",fullName:"Aleksandra Stojanović"},{id:"237504",title:"Dr.",name:"Dalibor",surname:"Sabbagh",slug:"dalibor-sabbagh",fullName:"Dalibor Sabbagh"},{id:"237505",title:"Dr.",name:"Petar",surname:"Rašić",slug:"petar-rasic",fullName:"Petar Rašić"}],corrections:null},{id:"58219",title:"Congenital Abdominal Anomalies",doi:"10.5772/intechopen.72170",slug:"congenital-abdominal-anomalies",totalDownloads:1404,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Introduction: Abdominal anomalies that appear during intrauterine life are complex due to many organs that are affected. In cases, the ultrasound appearance is a cystic image with different content and the differential diagnosis is often difficult. Body—research methods: the organs affected by abdominal congenital anomalies involve the gastrointestinal tract (stomach, duodenum, small bowel or colon, and gall bladder), the kidney and urinary tract, the peritoneal cavity (ascites), suprarenal glands, and tumors of the reproductive system (especially the ovaries). In order to identify the affected structures, it is mandatory to know the normal aspect of the abdominal content at different gestational ages. The diagnosis may be very difficult, but its accuracy is important, considering the need of further counseling the couple. In minor conditions, without chromosomal anomalies or associations, the outcome is usually good, and there are even possibilities of in utero treatment. In severe conditions, with poor outcome, the couple can choose to terminate the pregnancy, after counseling is provided. Conclusion: abdominal congenital anomalies are common findings in ultrasound screenings for anomalies in all the trimesters of pregnancy and their recognition is important for subsequent management.",signatures:"Ples Liana and Anca Lesnic",downloadPdfUrl:"/chapter/pdf-download/58219",previewPdfUrl:"/chapter/pdf-preview/58219",authors:[{id:"212333",title:"Associate Prof.",name:"Liana",surname:"Ples",slug:"liana-ples",fullName:"Liana Ples"}],corrections:null},{id:"57831",title:"Renal Anomalies",doi:"10.5772/intechopen.71925",slug:"renal-anomalies",totalDownloads:1229,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter is dedicated to the main renal anomalies detectable by ultrasound. Anomalies of the lower urinary tract will be addressed in a separate chapter. The anomalies presented are renal agenesis, renal development variants, autosomal recessive polycystic kidney disease, multicystic dysplastic kidney disease, autosomal dominant polycystic kidney disease, obstructive cystic dysplasia, pelvis dilatation, renal tumors, and nonchromosomal syndromes associated with renal anomalies. All chapters are structured similar into definition, incidence, pathology, ultrasound findings, differential diagnosis, and clinical facts.",signatures:"Alexandru Cristian Comanescu, Florentina Tanase, Maria Cristina\nComanescu, Razvan Cosmin Pana, Madalina Barbu and Nicolae\nCernea",downloadPdfUrl:"/chapter/pdf-download/57831",previewPdfUrl:"/chapter/pdf-preview/57831",authors:[{id:"214960",title:"Prof.",name:"Nicolae",surname:"Cernea",slug:"nicolae-cernea",fullName:"Nicolae Cernea"},{id:"214946",title:"Dr.",name:"Alexandru",surname:"Comanescu",slug:"alexandru-comanescu",fullName:"Alexandru Comanescu"},{id:"214956",title:"Dr.",name:"Florentina",surname:"Tanase",slug:"florentina-tanase",fullName:"Florentina Tanase"},{id:"214957",title:"Dr.",name:"Maria Cristina",surname:"Comanescu",slug:"maria-cristina-comanescu",fullName:"Maria Cristina Comanescu"},{id:"220288",title:"Dr.",name:"Razvan Cosmin",surname:"Pana",slug:"razvan-cosmin-pana",fullName:"Razvan Cosmin Pana"},{id:"224296",title:"Dr.",name:"Madalina",surname:"Barbu",slug:"madalina-barbu",fullName:"Madalina Barbu"}],corrections:null},{id:"59202",title:"Congenital Anomalies of Urinary Tract and Anomalies of Fetal Genitalia",doi:"10.5772/intechopen.73641",slug:"congenital-anomalies-of-urinary-tract-and-anomalies-of-fetal-genitalia",totalDownloads:1827,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Congenital anomalies of the kidney, urinary tract and genitalia anomalies are among the most frequent types of congenital malformations. Many can be diagnosed by means of ultrasound examination during pregnancy. Some will be discovered after birth. Kidney and urinary malformations represent 20% of all birth defects, appearing in 3–7 cases at 1000 live births. Environmental factors (maternal diabetes or intrauterine exposure to angiotensin-converting enzyme inhibitors) and genetic factors (inherited types of diseases) seem to be among causes that lead to the disturbance of normal nephrogenesis and generate anomalies of the reno-urinary tract. It is very important to diagnose and differentiate between the abnormalities incompatible with life and those that are asymptomatic in the newborn. The former requires interruption of pregnancy, whereas the latter could lead to saving the renal function if diagnosed antenatally. In many cases, the congenital anomalies of the urinary and genital tract may remain asymptomatic for a long time, even up until adulthood, and can be at times the only manifestation of a complex systemic disease. Some can manifest in more than one member in the family. This is the reason why the accurate genetic characterization is needed; it can help give not only the patient but also her family the appropriate genetic counseling, and also, in some cases, the management may prevent severe complications.",signatures:"Sidonia Maria Sandulescu, Ramona Mircea Vicol, Adela Serban,\nAndreea Veliscu Carp and Vaduva Cristian",downloadPdfUrl:"/chapter/pdf-download/59202",previewPdfUrl:"/chapter/pdf-preview/59202",authors:[{id:"194540",title:"Dr.",name:"Sidonia Maria",surname:"Sandulescu",slug:"sidonia-maria-sandulescu",fullName:"Sidonia Maria Sandulescu"},{id:"214964",title:"Dr.",name:"Andreea",surname:"Veliscu Carp",slug:"andreea-veliscu-carp",fullName:"Andreea Veliscu Carp"},{id:"214965",title:"Dr.",name:"Ramona",surname:"Mircea Vicol",slug:"ramona-mircea-vicol",fullName:"Ramona Mircea Vicol"},{id:"214967",title:"Dr.",name:"Adela",surname:"Serban",slug:"adela-serban",fullName:"Adela Serban"},{id:"232987",title:"Dr.",name:"Cristian",surname:"Vaduva",slug:"cristian-vaduva",fullName:"Cristian Vaduva"}],corrections:null},{id:"60751",title:"The Antenatal Detection of Fetal Limb Anomalies",doi:"10.5772/intechopen.76108",slug:"the-antenatal-detection-of-fetal-limb-anomalies",totalDownloads:1606,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The etiology of fetal limb abnormalities is very complex, involving different risk factors: chromosomal abnormalities, gene disorders, intrauterine factors, maternal diseases, or exposure to different risk factors. The prevalence of fetal limb anomalies is reported to be approximately 6 in 10,000 live births, and the impairments of the upper limbs seem to present a higher incidence in comparison to the inferior limbs, more often are affected unilaterally and on the right side in comparison to the left side, some being isolate or may associate other anomalies, as a part of an underlying syndrome. According to the current guidelines, the assessment of the fetal limbs should be performed in the late first and early second trimester. Three-dimensional ultrasound provides a better understanding of the fetal anomaly for the parents and helps a better counseling, and it is used to confirm the anomalies detected by the conventional ultrasound. In cases of treatable anomalies, a multidisciplinary approach involving an obstetrician, geneticist, neonatologist, pediatrician, and pediatric orthopedic surgeon is essential to improve the postnatal outcome. Ultrasound examination and genetic counseling for the parents has an important benefit since some conditions present a genetic inheritance, and the recurrence rate in further pregnancies is very high.",signatures:"Iuliana Ceausu, Dominic Iliescu, Cristian Poalelungi, Cristian Posea,\nNicolae Bacalbasa, Dragos Dobritoiu and Liana Ples",downloadPdfUrl:"/chapter/pdf-download/60751",previewPdfUrl:"/chapter/pdf-preview/60751",authors:[{id:"212459",title:"Dr.",name:"Dominic",surname:"Iliescu",slug:"dominic-iliescu",fullName:"Dominic Iliescu"},{id:"215135",title:"Prof.",name:"Iuliana",surname:"Ceausu",slug:"iuliana-ceausu",fullName:"Iuliana Ceausu"}],corrections:null},{id:"60402",title:"Abnormalities of the Placenta",doi:"10.5772/intechopen.75985",slug:"abnormalities-of-the-placenta",totalDownloads:3352,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The placenta is considered an important organ that evolves with the implantation of the blastocyst throughout the pregnancy. The placenta has an essential role in functions such as nutrition, excretion, and immunologic and endocrine function. The normal placenta is a round- or oval-shaped organ that attaches to the uterine wall and has roughly 22 cm in diameter and a thickness of about 2–2.5 cm and weighs about one sixth of the fetal birth weight. Thus, a normal development of the placenta is important for an uneventful embryonic and fetal development. Consequently, the placenta abnormalities can range from structural anomalies, to function disorders, to site of implantation abnormalities.",signatures:"Roxana Cristina Drăgușin, Maria Șorop-Florea, Ciprian Laurențiu\nPătru, Lucian Zorilă, Cristian Marinaș, Bogdan Virgiliu Șorop, Răzvan\nCăpitănescu and Dominic Gabriel Iliescu",downloadPdfUrl:"/chapter/pdf-download/60402",previewPdfUrl:"/chapter/pdf-preview/60402",authors:[{id:"212459",title:"Dr.",name:"Dominic",surname:"Iliescu",slug:"dominic-iliescu",fullName:"Dominic Iliescu"},{id:"212490",title:"Dr.",name:"Dragusin",surname:"Roxana",slug:"dragusin-roxana",fullName:"Dragusin Roxana"},{id:"212493",title:"Dr.",name:"Pătru",surname:"Ciprian",slug:"patru-ciprian",fullName:"Pătru Ciprian"},{id:"212494",title:"Dr.",name:"Șorop-Florea",surname:"Maria",slug:"sorop-florea-maria",fullName:"Șorop-Florea Maria"},{id:"222056",title:"Dr.",name:"Cristian",surname:"Marinaș",slug:"cristian-marinas",fullName:"Cristian Marinaș"},{id:"222057",title:"Dr.",name:"Lucian George",surname:"Zorila",slug:"lucian-george-zorila",fullName:"Lucian George Zorila"},{id:"222058",title:"Dr.",name:"Bogdan Virgiliu",surname:"Sorop",slug:"bogdan-virgiliu-sorop",fullName:"Bogdan Virgiliu Sorop"},{id:"246816",title:"Dr.",name:"Capitanescu",surname:"Razvan",slug:"capitanescu-razvan",fullName:"Capitanescu Razvan"}],corrections:null},{id:"58537",title:"Abnormalities of the Umbilical Cord",doi:"10.5772/intechopen.72666",slug:"abnormalities-of-the-umbilical-cord",totalDownloads:1988,totalCrossrefCites:2,totalDimensionsCites:4,hasAltmetrics:1,abstract:"Abnormalities of the umbilical cord, related to morphology, placental insertion, number of vessels and primary tumors, can influence the perinatal outcome and may be associated with other fetal anomalies and aneuploidies. The chapter investigates the most important congenital anomalies of this structure. Single umbilical artery appears to be associated with ventricular septal defects and conotruncal anomalies, hydronephrosis, dysplastic kidneys, esophageal atresia, spina bifida, holoprosencephaly, diaphragmatic hernia, and cystic hygromas. Velamentous insertion of the cord can be associated with trisomy 21, spina bifida, ventricular septal defects, and esophageal atresia. A hypoplastic umbilical artery has an artery-to-artery diameter difference of more than 50%; described anomalies include trisomy 21, polyhydramnios, congenital heart disease, and fetal growth restriction. Pseudocysts are more common than true cysts, and they are strongly associated with chromosomal defects and other congenital anomalies, especially omphalocele, hydrops, and trisomy 18. Other benign masses are teratomas, angiomyxomas, and patent urachus. Alterations in morphology and ultrastructure of the umbilical cord should extend the investigation, since there are associations with chromosomal anomalies.",signatures:"Sidonia Catalina Vrabie, Liliana Novac, Maria Magdalena Manolea,\nLorena Anda Dijmarescu, Marius Novac and Mirela Anisoara Siminel",downloadPdfUrl:"/chapter/pdf-download/58537",previewPdfUrl:"/chapter/pdf-preview/58537",authors:[{id:"98280",title:"Prof.",name:"Liliana",surname:"Novac",slug:"liliana-novac",fullName:"Liliana Novac"},{id:"214796",title:"Dr.",name:"Vrabie",surname:"Sidonia",slug:"vrabie-sidonia",fullName:"Vrabie Sidonia"},{id:"215033",title:"Dr.",name:"Dijmarescu",surname:"Lorena Anda",slug:"dijmarescu-lorena-anda",fullName:"Dijmarescu Lorena Anda"},{id:"215034",title:"Dr.",name:"Manolea",surname:"Maria Magdalena",slug:"manolea-maria-magdalena",fullName:"Manolea Maria Magdalena"},{id:"215036",title:"Dr.",name:"Siminel",surname:"Mirela",slug:"siminel-mirela",fullName:"Siminel Mirela"},{id:"215041",title:"Prof.",name:"Marius",surname:"Novac",slug:"marius-novac",fullName:"Marius Novac"}],corrections:null},{id:"59104",title:"Prenatal Biochemical and Ultrasound Markers in Chromosomal Anomalies",doi:"10.5772/intechopen.73604",slug:"prenatal-biochemical-and-ultrasound-markers-in-chromosomal-anomalies",totalDownloads:1303,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The unbalanced chromosomal anomalies generate an abnormal pattern of development and usually determine miscarriage. The most frequent prenatal chromosomal anomalies are X monosomy, trisomies of chromosomes 21, 18, 13, 16, 8, triploidy and tetraploidy. Identification of chromosomal anomalies can be done by prenatal screening and diagnosis. Prenatal screening is biochemical, sonographic or molecular (detection of fetal DNA in maternal blood). Biochemical screening can be done in the first or second trimester. First-trimester screening is based on the detection in maternal serum of beta-hCG (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A). Biochemical screening in the second trimester requires the detection of alpha-fetoprotein (aFP) hGC, unconjugated estriol (μE) and inhibin A. The sonographic examination can be used in the first or second trimesters. In the first trimester, an ultrasound can identify soft markers like nuchal translucency, nasal bone and ductus venous flow. In the second trimester the sonographic examination can identify congenital anomalies or different soft markers. Prenatal chromosomal diagnosis requires an invasive procedure to obtain embryonic or fetal material. Such procedures are represented by chorionic villus sampling amniocentesis or cordocentesis. The fetal cells are used for cell cultures (in cytogenetic methods) or for molecular analyses (FISH, QF-PCR, MLPA, array-CGH).",signatures:"Eusebiu Vlad Gorduza, Demetra Gabriela Socolov and Răzvan\nVladimir Socolov",downloadPdfUrl:"/chapter/pdf-download/59104",previewPdfUrl:"/chapter/pdf-preview/59104",authors:[{id:"86372",title:"Dr.",name:"Demetra",surname:"Socolov",slug:"demetra-socolov",fullName:"Demetra Socolov"},{id:"212385",title:"Prof.",name:"Gorduza",surname:"Eusebiu Vlad",slug:"gorduza-eusebiu-vlad",fullName:"Gorduza Eusebiu Vlad"},{id:"212386",title:"Prof.",name:"Socolov",surname:"Razvan",slug:"socolov-razvan",fullName:"Socolov Razvan"}],corrections:null},{id:"58838",title:"Genomic Testing for Prenatal Clinical Evaluation of Congenital Anomalies",doi:"10.5772/intechopen.73247",slug:"genomic-testing-for-prenatal-clinical-evaluation-of-congenital-anomalies",totalDownloads:1133,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Congenital anomalies occur in about 2–3% of liveborn and 20% of stillborn infants. They constitute a serious public health and epidemiological problem. The etiology of congenital anomalies is complex; they can result from genetic factors, environmental factors, or a combination of both. It is estimated that genetic factors represent an important cause of congenital anomalies and may be due to different genetic mechanisms: aneuploidies, deletions and duplications of DNA segments, and single gene disorders. Due to the genetic complexity, the targeted prenatal genetic diagnostics of congenital anomalies is usually problematic and challenging. In recent years new diagnostic algorithms for prenatal genetic testing are being developed with the advent of new genomic technologies, like molecular karyotyping and next-generation sequencing. These technologies offer testing options that exceed conventional karyotyping and targeted molecular genetic testing with better diagnostic yield. In this chapter, an overview of the conventional genetic diagnostic approach and the use of new genomic technologies in the diagnostic algorithm of prenatally detected congenital anomalies are discussed.",signatures:"Gorazd Rudolf, Luca Lovrečić, Aleš Maver, Marija Volk and Borut\nPeterlin",downloadPdfUrl:"/chapter/pdf-download/58838",previewPdfUrl:"/chapter/pdf-preview/58838",authors:[{id:"49809",title:"Prof.",name:"Borut",surname:"Peterlin",slug:"borut-peterlin",fullName:"Borut Peterlin"},{id:"61599",title:"Prof.",name:"Ales",surname:"Maver",slug:"ales-maver",fullName:"Ales Maver"},{id:"75615",title:"Dr.",name:"Luca",surname:"Lovrecic",slug:"luca-lovrecic",fullName:"Luca Lovrecic"},{id:"212411",title:"M.Sc.",name:"Gorazd",surname:"Rudolf",slug:"gorazd-rudolf",fullName:"Gorazd Rudolf"},{id:"212417",title:"Mrs.",name:"Marija",surname:"Volk",slug:"marija-volk",fullName:"Marija Volk"}],corrections:null},{id:"58355",title:"Congenital Heart Disease: Genetic Aspect and Prenatal and Postnatal Counseling",doi:"10.5772/intechopen.72486",slug:"congenital-heart-disease-genetic-aspect-and-prenatal-and-postnatal-counseling",totalDownloads:1135,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Cardiac malformation present at birth is an important component of pediatric cardiovascular disease. The etiology of congenital heart disease is multifaceted including environmental, genetic and stochastic factors. With the advancement of cardiac diagnostic and therapeutic techniques in the past decade, with relatively low morbidity and mortality, has led to more and more children with congenital heart disease living to adulthood. Therefore the role of prenatal and postnatal genetic counseling becomes even more paramount as there is a higher likelihood of these patients living to adulthood and having families of their own. Prenatal counseling allows for the expectant parents to understand the full ramifications of continuing the pregnancy and possible events after birth. It is a multidisciplinary approach to help parents reach an informed decision on how to best to proceed with the pregnancy. After the birth of the child with congenital heart defects, the course is significantly dependent on the type of cardiac lesion. Postnatally, if the lesion is amenable to surgery, therapeutics intervention is offered. The postnatal counseling session includes the possibility of performing advanced genetic testing to help determine the hereditary potential of the cardiac defect in future offspring.",signatures:"Amal Zubani, Irfan Asra and Amjad Kouatli",downloadPdfUrl:"/chapter/pdf-download/58355",previewPdfUrl:"/chapter/pdf-preview/58355",authors:[{id:"214843",title:"M.D.",name:"Amal",surname:"Zubani",slug:"amal-zubani",fullName:"Amal Zubani"},{id:"214860",title:"Dr.",name:"Irfan",surname:"Asra",slug:"irfan-asra",fullName:"Irfan Asra"},{id:"214886",title:"Dr.",name:"Amjad",surname:"Al-Kouatli",slug:"amjad-al-kouatli",fullName:"Amjad Al-Kouatli"}],corrections:null},{id:"59635",title:"Prenatal Genetic Counseling in Congenital Anomalies",doi:"10.5772/intechopen.74394",slug:"prenatal-genetic-counseling-in-congenital-anomalies",totalDownloads:1275,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The impact of genetic variability on embryogenesis and fetus development established medical genetics as essential for the prevention of congenital anomalies, early detection and appropriate management. Advances in ultrasonography equipment and technique allow early detection of many congenital malformations. In addition, genetic testing can be performed in a prenatal setting on a variety of biological samples obtained by invasive and noninvasive procedures: chorionic villus sampling, amniocentesis, cordocentesis, or maternal blood collection (i.e., cell free fetal DNA). In the past, only a small percentage of congenital anomalies had a readily identifiable etiology; genetic diagnostic procedures can provide at least some of the answers for the remaining unsolved cases. Undoubtedly, the need for appropriate case management and counseling justifies the importance of uncovering the underlying genetic cause of birth defects. In this chapter, we will focus on genetic counseling in congenital anomalies, including isolated congenital anomalies and preimplantation genetic diagnosis. Genetic counseling provides information and support, assisting parents in making informed decisions. Through this process, parents learn about the risk of having a newborn with a congenital malformation and the nature of the disorder and its natural history, are advised on available testing for that particular case, and discuss options for risk management and family planning.",signatures:"Mihaela Amelia Dobrescu, Florin Burada, Mihai Gabriel Cucu, Anca\nLelia Riza, Gratiela Chelu, Razvan Mihail Plesea, Adela Cucu, Alina\nLiliana Cimpoeru and Mihai Ioana",downloadPdfUrl:"/chapter/pdf-download/59635",previewPdfUrl:"/chapter/pdf-preview/59635",authors:[{id:"215055",title:"Dr.",name:"Mihaela Amelia",surname:"Dobrescu",slug:"mihaela-amelia-dobrescu",fullName:"Mihaela Amelia Dobrescu"},{id:"215064",title:"Dr.",name:"Florin",surname:"Burada",slug:"florin-burada",fullName:"Florin Burada"},{id:"215069",title:"Dr.",name:"Mihai Gabriel",surname:"Cucu",slug:"mihai-gabriel-cucu",fullName:"Mihai Gabriel Cucu"},{id:"215086",title:"Dr.",name:"Gratiela",surname:"Chelu",slug:"gratiela-chelu",fullName:"Gratiela Chelu"},{id:"215090",title:"Dr.",name:"Mihai",surname:"Ioana",slug:"mihai-ioana",fullName:"Mihai Ioana"},{id:"227476",title:"Dr.",name:"Alina",surname:"Cimpoeru",slug:"alina-cimpoeru",fullName:"Alina Cimpoeru"},{id:"227482",title:"Dr.",name:"Anca Lelia",surname:"Riza",slug:"anca-lelia-riza",fullName:"Anca Lelia Riza"},{id:"227483",title:"Dr.",name:"Razvan Mihail",surname:"Plesea",slug:"razvan-mihail-plesea",fullName:"Razvan Mihail Plesea"}],corrections:null},{id:"58185",title:"Management of Pregnancy and Delivery in Prenatally Diagnosed Congenital Anomalies",doi:"10.5772/intechopen.71802",slug:"management-of-pregnancy-and-delivery-in-prenatally-diagnosed-congenital-anomalies",totalDownloads:1416,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Prenatal diagnosis of congenital anomalies provides valuable information and allows proper management of pregnancy and delivery. The common congenital anomalies are cardiovascular anomalies, congenital anomalies of the central nervous system, fetal thoracic anomalies, abdominal wall defects, kidney and urinary tract defects, and esophageal, gastrointestinal, and anorectal abnormalities. Different defects require particular assessment, evaluation and care. Pregnancy management mainly includes detection of the malformations, genetic assessment, ultrasound follow-ups and evaluation of fetal well-being as well as performing various invasive or non-invasive procedures. Managing delivery is also highly important and fetal anomaly specific. The main aspects of delivery management discussed in this chapter are delivery place, timing, route and delivery room care.",signatures:"Diana Ramasauskaite",downloadPdfUrl:"/chapter/pdf-download/58185",previewPdfUrl:"/chapter/pdf-preview/58185",authors:[{id:"211837",title:"Prof.",name:"Diana",surname:"Ramašauskaitė",slug:"diana-ramasauskaite",fullName:"Diana Ramašauskaitė"}],corrections:null},{id:"58402",title:"The Neonate with Minor Dysmorphisms",doi:"10.5772/intechopen.71902",slug:"the-neonate-with-minor-dysmorphisms",totalDownloads:1430,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Congenital anomalies are present in at least 10% of all neonatal intensive care unit admissions, of whom many have an underlying genetic condition. About 50–60% of human congenital anomalies are of unknown etiology, and approximately one- third are caused by genetic factors. A smaller percentage of birth defects are the result of chromosomal aberrations and gene mutations. Around 1 in 40 or 2.5% of all newborns have a malformation at birth. This may be an isolated malformation or may occur together with other malformations and/or dysmorphic features as part of a malformation syndrome. Around 4000 malformation syndromes have now been delineated. Many are associated with medical problems and making a specific syndrome diagnosis can influence immediate medical management. However, the infant with dysmorphism often does not have a major malformation, and may simply have an appearance that is unusual compared with the general population and of unaffected close relatives. The chapter intends to provide semnificative data concerning the approach and management of a dysmorphic neonate, mainly when there are minor anomalies and will offer all those relevant data and try to establish a protocol guide for the approach of the dimorphic neonate.",signatures:"Simona Vlădăreanu, Mihaela Boț, Costin Berceanu, Claudia\nMehedințu and Simona Popescu",downloadPdfUrl:"/chapter/pdf-download/58402",previewPdfUrl:"/chapter/pdf-preview/58402",authors:[{id:"215126",title:"Prof.",name:"Simona",surname:"Vladareanu",slug:"simona-vladareanu",fullName:"Simona Vladareanu"},{id:"222031",title:"Dr.",name:"Mihaela",surname:"Bot",slug:"mihaela-bot",fullName:"Mihaela Bot"},{id:"222033",title:"Prof.",name:"Costin",surname:"Berceanu",slug:"costin-berceanu",fullName:"Costin Berceanu"},{id:"222049",title:"Prof.",name:"Claudia",surname:"Mehedintu",slug:"claudia-mehedintu",fullName:"Claudia Mehedintu"},{id:"222050",title:"Dr.",name:"Simona",surname:"Popescu",slug:"simona-popescu",fullName:"Simona Popescu"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"702",title:"Recent Advances in Research on the Human Placenta",subtitle:null,isOpenForSubmission:!1,hash:"2ec960f95ad477086c54b65993d58c49",slug:"recent-advances-in-research-on-the-human-placenta",bookSignature:"Jing Zheng",coverURL:"https://cdn.intechopen.com/books/images_new/702.jpg",editedByType:"Edited by",editors:[{id:"89898",title:"Dr.",name:"Jing",surname:"Zheng",slug:"jing-zheng",fullName:"Jing Zheng"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"700",title:"The Human Embryo",subtitle:null,isOpenForSubmission:!1,hash:"86474f84fc2e891369f79e859bd84d44",slug:"the-human-embryo",bookSignature:"Shigehito Yamada and Tetsuya Takakuwa",coverURL:"https://cdn.intechopen.com/books/images_new/700.jpg",editedByType:"Edited by",editors:[{id:"114031",title:"Dr.",name:"Shigehito",surname:"Yamada",slug:"shigehito-yamada",fullName:"Shigehito Yamada"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2586",title:"Skeletal Muscle",subtitle:"From Myogenesis to Clinical Relations",isOpenForSubmission:!1,hash:"39cac55a7eca71b41c2a28933c1e2d4d",slug:"skeletal-muscle-from-myogenesis-to-clinical-relations",bookSignature:"Julianna Cseri",coverURL:"https://cdn.intechopen.com/books/images_new/2586.jpg",editedByType:"Edited by",editors:[{id:"135579",title:"Dr.",name:"Julianna",surname:"Cseri",slug:"julianna-cseri",fullName:"Julianna Cseri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7175",title:"Placenta",subtitle:null,isOpenForSubmission:!1,hash:"447d49d62164c5437461f3b0aae7a67f",slug:"placenta",bookSignature:"Ahmed R. 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We wish to have automatic devices/gadgets/instruments with no or minimal intervention from humans in their daily operation. Then only, these devices can qualify to call it is smart instruments. To fulfill this, one of the major requirements is to come up with highly sensitive, long-lasting, low-cost smart sensors. On the other hand, the healthcare industry demands low-cost, Lab-on-chip type biosensors for simple and rapid detection of various biomolecules or biogases. A sensor is an analytical device that detects the change in the environment and responds to some output in terms of a measurable analog resistance/voltage/current converted into a human-readable display or transmitted for further processing. In the last two decades, a significant amount of research has been devoted to the development of various types of gas sensors using different nanomaterials in the electronic and healthcare industry.
\r\n\r\n\tThis book aims to provide the reader (research scholars, scientists, and engineers working in the field of sensors) an overview of the recent advances made in the development of various gas sensors for the electronic and healthcare industries for the betterment of the human lifestyle. Also, this book will intend to address existing challenges and a few future directions of research for easy integration and cost-effective fast sensing of such
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Cyclosporin A (CsA) is an immunosuppressant drug widely used in organ transplant recipients and patients with auto-immune disorders. Long-term treatment with CsA is associated with hyperlipidemia and an increased risk of atherosclerosis. The mechanisms by which cyclosporin A causes hyperlipidemia are unclear. Cell and animal studies have pointed to various mechanisms that may mediate CsA-induced hyperlipidemia. In this review we will give an overview of CsA-induced hyperlipidemia, with a focus on the data available that might explain the underlying mechanism(s) and describe the available treatment regimes used to treat hyperlipidemia induced by immunosuppressant drugs.
Hyperlipidemia is observed in about 60% of kidney, liver, cardiac and bone marrow transplants after treatment with CsA (for review see [1,2]. There are multiple factors potentially contributing to hyperlipidemia in these patients, such as post-transplantation obesity, multiple drug therapy and diabetes. The concurrent use of steroids in particular, makes it hard to establish a direct contribution of CsA to dyslipidemia in humans, as corticosteroids are known to exacerbate hyperlipidemia in transplant recipients [3,4].
Studies investigating plasma lipids after CsA monotherapy are limited [4,5,6,7,8,9] and only a few studies have directly compared the combination of CsA therapy with low dose prednisolone with other immune suppressing strategies in combination with low dose steroids [10,11]. In general, these studies indicate that CsA treatment can independently lead to elevated plasma triglyceride and cholesterol levels in humans and that these effects are reversible upon cessation of immunosuppression therapy (Table 1). Animal studies (reviewed in [12]), where the effect of CsA can be studied in a more controlled background, indicate that CsA directly raises plasma lipid levels in rats, mice, guinea pigs and rabbits, and have proven that animals are valuable models to study mechanismsof CsA-induced hyperlipidemia.
Monotherapy | Amyotrophic lateral sclerosis | 36 | 2 mnths | TC (21%) LDL-C (31%) apoB (12%) TG = HDL = | [5] |
Monotherapy | Autologous bone marrow transplants | 13 | 32 days | TC (26%) LDL-C HDL-C TG = VLDL-C = | [13] |
Monotherapy | Renal transplants | 59 | 3-6 and 12 mnths | TC = LDL-C = apoB TG HDL-C apoA-I | [8] |
Monotherapy | Renal transplants | 58 | "/>1 yr | TC LDL-C apoB TG VLDL-C = HDL-C HDL2-C = HDL3-C | [14] |
Monotherapy and CsA/pred | Bone marrow transplants | 180 | 100 days | TC LDL-C apoB TG VLDL-trig VLDL-C = HDL HDL2 HDL3 = apoA-I | [4] |
Monotherapy | Psoriasis | 15 | 3 mnths | TC (22%) LDL-C (35%) TG = VLDL-C = HDL-C = | [9] |
ALG/aza/cortv CsA/ALG/aza/cort | Renal transplants | 702 | 52 wks | TC (20%) LDL-C TG HDL-C = | [7] |
Aza/pred v CsA v CsA/pred | Renal transplants | 9 | 3 mnths | TC LDL-C (45%) TG = VLDL-C = HDL-C = | [6] |
Aza/pred v CsA/pred | Renal transplants | 20 | 7.7 yrs | TC LDL-C apoB TG VLDL-C HDL-C | [10] |
Effect of CsA on plasma lipid parameters in humans
Triglyceride-containing VLDL particles are produced in the liver via lipidation of apolipoprotein B (apoB) by microsomal triglyceride transfer protein (MTP), generating triglyceride-poor (VLDL2) as well as triglyceride-rich VLDL (VLDL1) particles, both of which can be secreted [15]. In plasma, VLDL is converted to intermediate-density lipoprotein (IDL) by lipoprotein lipase (LPL). IDL can be further hydrolyzed by lipases to low density lipoprotein (LDL). CsA increases plasma VLDL levels in transplant recipients and a concomitant increase in plasma apoB levels is observed [4,10,11]. It is unclear whether both plasma VLDL1 and VLDL2 levels are elevated. In contrast to LDL levels, plasma triglyceride and VLDL levels appear to increase only after long-term treatment with CsA (Table 1 and [8])
Hypertriglyceridemia in transplant patients is associated with increased plasma apolipoprotein CIII (apoCIII) levels [16,17,18] and decreased lipase activity (see below). As apoCIII inhibits LPL and hepatic lipase (HL) as well as uptake of triglyceride lipoprotein in liver, the increase of apoCIII may be an important contributor to hypertriglyceridemia found in transplant patients.
Plasma LDL levels appear to be consistently elevated by CsA [4,5,6,7,9,10,13,14] even in patients where plasma VLDL levels are not altered [5,6,9,13]. A correlation between CsA levels and plasma LDL-C has been described in some studies [19], but was not observed in others [5,20]. Regulation of plasma LDL levels is complex, depending on hepatic VLDL production, subsequent lipolysis of VLDL, clearance of LDL via the LDL receptor (LDLr) in the liver and conversion into bile. CsA may affect LDL metabolism at several levels (section 3.2).
Total plasma HDL levels are inversely correlated with the risk of cardiovascular disease [21]. HDL particles are however heterogeneous in size and composition, and occur as HDL2a, HDL2b, HDL3a, HDL3b and HDL3c which are progressively smaller in diameter and contain higher protein to lipid ratios. The precise contribution of various HDL subclasses to cardiovascular disease is currently unclear [21,22]. Plasma HDL cholesterol levels are determined by production of nascent HDL particles in the liver and intestine,by plasma transfer reactions of lipids between HDL and lipolysed triglyceride lipoproteins such as VLDL or chylomicrons,hepatic uptake of HDL lipids via the scavenger receptor class B1 (SRB1) HDL receptor in the liver, and renal clearance of small, lipid-poor apoA-I particles. Nascent HDL particles are formed by lipidation of apolipoprotein A-I (apoA-I) via the ATP-binding cassette transporter-1 (ABCA1) located in cellular membranes, although ABCA1-independent pathways of apoA-I lipidation also exist [23]. The formed lipid-poor HDL particles acquire more lipid after interaction with ABCG1 and mature by the subsequent esterification of cholesterol by lecithin-acyl transferase (LCAT). Further remodeling occurs by phospholipid transfer protein (PLTP) generating HDL2. HDL2 can be converted into HDL3 by hydrolysis via lipases and by transfer of cholesteryl esters to triglyceride-containing lipoproteins with the reciprocal exchange for triglycerides, which is mediated by cholesteryl ester transfer protein (CETP).
Immunosuppressive therapy has been reported to increase, decrease or leave HDL levels unaffected [5,10,11,24]. Parallel changes in plasma apoA-I levels are usually observed. Increased HDL levels are observed in most transplant patients, but this is most likely related to the concomitant treatment with steroids, which are known to increase plasma HDL [3]. CsA may affect particular subclasses of HDL more than others. Independently of steroids, plasma HDL levels, especially the HDL3 subpopulation, were found to inversely relate to plasma CsA levels [19].In a study of bone marrow transplant recipients CsA decreased total plasma HDL, and in particular HDL2 [4]. In rats, a similar decrease in plasma HDL and HDL2 levels was observed after CsA treatment [25]. A recent study performed in pediatric renal transplant recipients showed that although total plasma HDL levels were not changed with CsA treatment, the relative proportion of HDL2b decreased while the relative proportion of HDL3a, HDL3b and HDL3c increased [26]. This is important as decreased HLD2b with increased HDL3b is associated with an atherogenic lipoprotein phenotype characterized by increased triglycerides and small dense LDL [27]. This result also emphases that simple monitoring of total HDL cholesterol may be insufficient to understand the consequences of CsA on HDL biology.
Lipoprotein (a) [Lp(a)] is a LDL-like lipoprotein consisting of LDL with one molecule of apoB covalently linked to a molecule of apolipoprotein (a). Plasma Lp(a) levels, and especially certain genetic Lp(a) variants, are independently associated with an increased risk for CVD [28,29]. Elevated Lp(a) plasma levels have been observed in renal transplant studies [14,30] this was however, not observed by others [31]. Although some studies suggested normalization of elevated Lp(a) levels after successful transplantation due to improved kidney function [31,32], CsA treatment has been indicated to independently increase Lp(a) levels in renal transplant recipients [8,14,33]. The mechanisms by which CsA affect plasma Lp(a) levels are unexplored, but may involve similar mechanisms to that of elevation of plasma LDL levels. As the LDLr does not play a major role in the clearance of Lp(a), the mechanism however, is unlikely mediated via effects of CsA on the LDLr (see section 3.2.1).
Elevated plasma triglyceride levels are associated with the formation of triglyceride rich LDL particles that are more atherogenic [34]. A high prevalence of smaller denser LDL particles is observed in transplant recipients [35] and appears to be associated with CsA therapy [26,36]. Inhibition of lipoprotein lipase (LPL) activity is associated with the formation of small dense LDL subclasses. As apoCIII inhibits lipase activity, increased plasma apoCIII levels observed with CsA-treatment may explain inhibited lipase activity and subsequent increase in small dense LDL particles [17]. In addition decreased lipase activity could contribute to decreased HDL2 subclassesobserved, while effects on CETP by CsA may help explain increases in HDL3 subfractions (see section 2.3 and 3.1.2).
In whole blood CsA is primarily transported bound to lipoproteins (33%) and erythrocytes (58%)and whole blood CsA levels correlate with lipoprotein levels [37,38].
Concerns have been raised about changes to the bioavailabilty and activity of CsA resulting from its binding to lipoproteins, especially as decreased CsA activity and increased toxicity have been observed in patients with hyperlipidemia [42,44]. CsA levels are higher in hyperlipidemic patients due to decreased clearance which was reversed after lipid-lowering with fibrates (reviewed in [37]).
As the effects of CsA in humans are confounded by many factors such as other medication, obesity, insulin resistance and nutritional status, cell and animal studies are useful to elucidate the mechanism(s) of CsA-induced hyperlipidemia. Figure 1 depicts the reported CsA-effects on VLDL, LDL and HDL metabolism.
CsA decreased apoB translocation over the endoplasmic reticulum (ER) membrane in the human liver cell line HepG2 [47]. It was suggested that this was due to a reduction in the efficiency of lipid transfer by inhibition of MTP, however whether MTP activity is inhibited by CsA was not investigated. These findings are in line with the report from Kaptein et al. [48], which showed that CsA inhibits VLDL and apoB secretion from HepG2 cells, by post-translational mechanisms. In contrast, in mice, CsA increased the rate of hepatic VLDL secretion
Inhibition of lipolysis by CsA could contribute to increased plasma VLDL and reduced HDL concentrations. Various studies have investigated lipase activity in patients, but results may be confounded by co-treatment with steroids. HL activity was increased in cardiac transplant patients and correlated with CsA dose while lipoprotein lipase (LPL) activity was decreased in these patients [51]. Others have shown decreased HL as well as LPL activity in kidney transplant recipients [52]. More directly, Tory et al [53] showed suppression of LPL activity in plasma from normolipidemic subjects treated with CsA, while in rats, CsA dose- and time-dependent decreased plasma LPL activity [24]. In addition, LPL abundance in skeletal muscle and adipose tissue was decreased in rats [50]. These latter studies suggested CsA can inhibit LPL activity independently of steroids. Although the precise mechanism of CsA-inhibited LPL activity is unknown, it helps to explain increased triglyceride levels observed after CsA treatment.
Some studies show reduced cholesteryl ester transfer protein (CETP) activity in transplant recipients [54]. In contrast, CsA directly added to human plasma
We have recently reviewed this literature in detail [55]. There appear to be conflicting conclusions arising from
CsA effects on plasma HDL and HDL subclasses may be mediated by effects on the synthesis and/or formation of HDL as well as by effecting remodeling of HDL through changes inlipase and/or CETP activity (see 3.1.2)
Direct effects of CsA on the expression of ABCA1 and apoA-I have also been reported and may contribute to the changes in HDL formation. The target of immunosuppression by CsA, Nuclear Factor of activated T-cells, cytoplasmic 2 (NFATc2), was found to bind the mouse ABCA1 promoter and mediate CsA-inhibition of ABCA1 expression by inflammatory stimuli [63]. In addition CsA has been found to inhibit apoA-I gene expression in human HepG2 cells and rats [64]. A recent proteomic study in HepG2 cells showed that CsA decreased secretion levels of apoA-I suggesting that the transcriptional effects of CsA on apoA-I expression may lead to decreased amounts of secreted apoA-I [65].
As mentioned above (section 3.1.2), CsA directly suppresses LPL activity and increases CETP activity in human plasma and animals (section 3.1.2). LPL activity is strongly associated with plasma HDL2 concentrations [66], and decreased LPL levels in CsA treatment may therefore contribute to decreased HDL2 levels [4,25]. On the other hand, increased CETP activity will generate triglyceride-rich HDL, which is converted to smaller HDL3 particles by HL [66].
In liver, cholesterol is converted to bile acids by 7-hydroxylase (CYP7) or 27-hydroxylase (CYP27A1) [67]. In healthy humans, CYP7α is considered the predominantly pathway while CYP27A1 accounts for 10% of bile acid synthesis and subsequent formation of chenodeoxycholate. However inhibition of Cyp7α can increase the contribution of the CYP27A1 pathway [68].
Mechanisms of CsA-mediated hyperlipidemia. Figure only displays pathways that are reported to be affected by CsA. 1) Inhibition of VLDL formation via inhibition of MTP, 2) Increased and decreased secretion of VLDL particles have been reported, 3) Decreased lipolysis of VLDL due to increased apoCIII and subsequent inhibition of LPL, 4) hypertriglyceridemia by increased CETP activity, 5) Increased LDL due to decreased LDLr expression as well as activity, 6) Increased liver FC content leading to decreased LDLr levels, 7) Increased and decreased levels of HMG-CoAr affecting cholesterol synthesis, 8/9) Inhibition of bile acid conversion via CYP27A1 or CYP7α leading to increased liver FC levels, however in most studies Cyp7 is not affected by CsA. NB: decreased CYP27A1 activity can increase HMG-CoAr levels via negative feedback, 10) Decreased flow of bile salts, cholesterol and phospholipids into bile, 11) Decreased expressionand secretion of apoA-I, 12) Inhibition of ABCA1 expression, 13) inhibition of apoA-I lipidation via inhibition of ABCA1 activity 14) Stimulation of HL and CETP leads to increased formation of HDL2 to HDL3, however decreased HL activity has also been reported. VLDL, very low density lipoprotein; IDL, intermediate density lipoprotein; LDL, low density lipoprotein; HDL, high density lipoprotein; AI, apolipoprotein A-I, B, apolipoprotein B; CIII, apolipoprotein CIII; MTP, microsomal triglyceride transfer protein; LPL, lipoprotein lipase; HL, hepatic lipase; CETP, cholesteryl ester transfer protein; ABCA1, ATP-binding cassette transporter-1; SRB1, scavenger receptor class B1; LDLr, LDLreceptor; VLDLr, VLDLreceptor; PL, phospholipid; FC, free cholesterol; HMG-CoAr, 3-hydroxy-3-methyl-glutaryl-CoA reductase; CYP7, 7-hydroxylase; CYP27A1, 27-hydroxylase; MRD, multidrug resistance protein; BSEP, bile salt export protein.
The effects of CsA on CYP27A1 may relate to effects of CsA on cholesterol metabolism. 27-hydroxycholesterol is a potent negative feedback regulator of HMG-CoA reductase [74] and decreased CYP27A1 activity may therefore explain increased HMG-CoA reductase mRNA and cholesterol levels [57]. Although important in macrophages, it should be noted however that it is not clear whether such a feedback loop exists in liver cells [75]. Increased cholesterol synthesis could subsequently lead to downregulation of LDLr levels as observed in some CsA studies, also contributing to increased plasma cholesterol levels (see section 3.2.1).
Besides effects on bile acid synthesis CsA may affect bile flow. CsA treatment is associated with increased plasma bile acid concentrations and cholestasis in humans as well as in animal models [9,52,76]. Studies in rat indicate that bile flow and the secretion of bile salts, proteins and lipids into the bile are dose-dependently inhibited by CsA [52,76,77]. Interestingly, the changes in serum levels of bile acids are consistent with CsA-mediated inhibition of hepatocellular uptake of individual bile acids [78,79]. The inhibitory effect was greater for phosholipid secretion than that for cholesterol [80] and in some studies no inhibition of cholesterol excretion was observed [81], suggesting differential effects on transport mechanisms. Transport pumps involved in bile synthesis and secretion belong to the family of the ATP-binding cassette transporters which include, multidrug resistance proteins (MDR) and P-glycoprotein, and most of which are effectively inhibited by CsA [79,82]. Interestingly, comparison of the bile salt export pump (BSEP) activity from different species, showed that CsA inhibits bile salt transport with species and bile salt specific variation [83]. Rat BSEP was for example more effectively inhibited than mouse BSEP. Biliary cholesterol secretion is mediated via ABCG5 and ABCG8 [84]. Although both members of the ATP-binding cassette family, it has not been investigated whether CsA inhibits ABCG5/8 activity. As phospholipids are transported via MDR3, it is likely that differences in efficacy of CsA between inhibition of MRD3 and ABCG5/8 exist. It is clear that CsA can affect bile flow and secretion in cultured cells and animal models. It should be noted however, that in humans no inhibitory effect of CsA on secretion of bile acids and lipids or on bile composition after liver transplantation was observed [85]. Others have shown that although cholate synthesis was reduced by CsA, compensatory increased intestinal absorption counteracted this decrease [86]. It remains therefore unclear to what extent inhibition of bile flow and secretion by CsA are contributing to hypercholesteremia
Hyperlipidemia is associated with significant morbidity and mortality rates in transplant recipients [87]. Many strategies have been investigated to target dyslipidemia in transplant patients. A number of excellent comprehensive reviews have been published on the clinical management of hyperlipidemia and its risks (eg [88,89]). We will therefore restrict our comments to a very brief summary of this area.
Statins inhibit HMG-CoA reductase, the rate limiting enzyme in the cholesterol synthesis pathway and are world-wide the drug of choice to lower plasma LDL-C levels. Various statins have been tested in transplant patients and all show significant lowering of plasma cholesterol, LDL-C and apoB levels with some indicating improved survival rates (for review see [88,89,90]). A randomized trial, investigating the safety and efficacy of statins in renal transplant patients, the Assessment of LEscol in Renal Transplantation (ALERT) study, showed that fluvastatin effectively lowered LDL-C by 32% and reduced cardiac death and non-fatal myocardial infarction incidence significantly [91]. Importantly, statins may provide beneficial effects other then their lipid-lowering properties [92]. Wissing et al [93] reported improved flow mediated brachial artery vasodilatation by atorvastatin in kidney transplant patients and significant reductions in acute rejections have been observed in cardiac transplant patients [94].
Rhabdomyolysis, one of the few serious side effects of statins, is more common with high dose statin treatment. The risk is elevated in patients with renal disease and in patients taking drugs affecting statin metabolism, especaily in those taking CsA [88,89]. All statins have the potential to interact with CsA, as CsA substantially increases plasma levels of all statins. Although this is most notable for those metabolized via the Cyp3A4 pathway, statins not metabolized via the Cyp3A4 pathway [95] such as pravastatin and fluvastatin are also affected [95], suggesting that the interaction of CsA and statins may involve other mechanisms such as inhibition of drug transporters. Simvastatin poses the highest risk of myopathy, and particular care must be taken with higher doses of this agent, with recommendations that doses of 10mg/d are not exceeded in transplant patients [89]. Because statin therapy has been associated with mortality benefit after transplantation, correction of hyperlipidemia using lower doses of statins is mandatory after transplantation. Therefore careful clinical monitoring of patients as well as measurement of creatine kinase levels to detect muscle injury is advised, and the use of statins that are not metabolized via CYP3A4, such as fluvastatin or pravastatinmay be preferential [95].
Fibrates lower plasma triglyceride levels via activation of the Peroxisome Proliferator Activated Receptor alpha (PPARα) and may be useful in transplant patients with elevated plasma triglycerides especially in combination with statin treatment to lower plasma cholesterol levels. Gemfibrozil was found to significantly lower plasma triglyceride levels in heart transplant patients and increase long term survival [96,97]. Fenofibrate is less well studied in transplant patients and may be associated with increased nephrotoxicity [88,98]. Care must be taken administering fibrates with CsA, particularly in combination with statins as drug-drug interactions exist via CYP3A4 as well as the hepatic uptake transporter the organic anion transporting polypeptide 1B1 (OAT1B1).
Inhibition of intestinal cholesterol absorption to lower high plasma cholesterol levels may be used when statins or fibrates are ineffective or are not tolerated. Ezetimibe proved to be an effective drug lowering plasma LDL-C levels significantly by blocking cholesterol absorption in the small intestine [99]. To that point though, various studies showed effective LDL-C lowering in liver, cardiac and renal transplant recipients [99]. Although, drug-drug interaction between CsA and ezetimibe were suggested (See [88]), CsA levels in studied transplant patients were not affected by combined ezetimibe use (reviewed in [99]). Co-administration of ezetimibe with (low-dose) statins has been found to effectively reduce high plasma cholesterol levels in transplant recipients and may be useful in patients that resistant to high-dose statin or where target plasma lipid levels can not be achieved by statin therapy alone [100,101].
CsA-induced hyperlipidemia is well established and remains a significant clinical issue. CsA potentially affects many aspects of lipid and lipoprotein metabolism and the precise underlying mechanism(s) causing dyslipidemia are still unclear. Further mechanistic studies may lead to the generation immunosuppressants that do not cause hyperlipidemia or may help to develop strategies to effectively target CsA-induced hyperlipidemia.
The purpose of this work was to show the real and potential health risks of the European bison, which have or can influence the general condition of the population and affect the restitution effects of this endangered by extinction species. From the species history, through the old, however recently increasingly re-emerging, threats until the new challenges for the species conservation, we have tried to present the most complete picture of the veterinary aspect of the species protection. Not without significance is also the manner in which these tasks are implemented, i.e., active species protection, not always accepted, but effective, which is best evidenced by the continuous increase in the number of the world’s European bison population. Today, when the number of the species exceeded 7000 individuals, it is not of key importance to protect individual European bison at all costs but to improve the welfare of the whole population, e.g., by minimizing the risk of infectious diseases by eliminating sick animals. Health threats can be removed or minimized through implemented prophylaxis and monitoring of pathological conditions in individual populations. Moreover, the exchange of experience and cooperation between breeders at national and international levels is extremely important. Another important aspect is the sanitary control of the animals in movement, especially of the greatest health threats such as tuberculosis and bluetongue disease and conducting quarantine for the introduced animals. One should also not underestimate the potential health hazards that can be assessed by postmortem diagnostics of fallen and selectively eliminated animals followed by discriminatory laboratory testing. The future of the European bison depends on the wise care of the herd managers and veterinary medicine specialists based on the best scientific and practical knowledge.
\nThe European bison (
European bison population distribution in Poland, 2018 (graphic design by J. Tomana).
One of the dangers, often underestimated by ignorance or financial incentives, is the commercial breeding of American bison (
Despite that the species was just starting to be re-established, European bison were put under epidemic pressure and exposed to many pathogens endemic to domestic ruminants in Poland at the beginning of the twentieth century. After the Second World War, the European bison population in Poland systematically increased, except for several incidents associated with the occurrence of infectious diseases (Figure 2). Konrad Wróblewski [14], a vet and researcher, gave the first detailed descriptions of the health problems in European bison in Białowieża at the turn of the nineteenth and twentieth centuries. At that time, the causes of morbidity and pathological changes were not yet fully understood due to the lack of knowledge and research tools. Dr. Wróblewski observed pleuropneumonia caused by
Dynamics of the European bison number in Poland (bars) and Białowieża Forest (curve) between 1947 and 2017 (European Bison Pedigree Book). The cases of diseases which caused significant declines in the population size and dates of their detection are marked.
In 1980s, due to the occurrence of Q fever in domestic animals in northeastern Poland, several dozen free-ranging European bison from Borecka Forest were examined for the presence of specific antibodies [20]. The high seroprevalence (76%) to
The first signs of another important disease in the male European bison, referred to as necrotic posthitis or balanoposthitis (called also pizzle rot), the causes of which still remain unsolved, were observed in Białowieża in 1980 remain unsolved, were observed in Białowieża in 1980 (Figure 3) [22].
One of the most devastating bacterial diseases, which remains a current problem in Polish European bison populations, is tuberculosis. The disease was diagnosed in the free-living European bison population in the Bieszczady mountains in the 1990s [28, 29, 30, 31], European bison are very susceptible to mycobacterial infections, and since no vaccination programs or treatment could have been introduced, the only method of disease control and prevention from spreading was the elimination of infected European bison [28, 29, 31, 32, 33, 34]. The eradication resulted in a significant depopulation observed in decrease of the numbers of European bison (Figure 2). Tuberculosis affecting European bison in Poland is caused by
Male
Free-ranging European bison create herds consisting of cows, their offspring, and youth; solitary bulls live outside of the herd and, however, approach or join in the mixed groups during rutting season and winter (for feeding), while young bulls often create small male groups [37]. Since European bison move over considerable distances during the day (especially the bulls), in order to monitor the distribution of these animals and study their use of space and different ecosystems, telemetric transmitters are being placed on selected individuals. Through such transmitters, we can track the daily rhythm of European bison and the use of various habitats for feeding and resting, divided into seasons and various periods relevant to the behavior of animals (the calving season, mating season) [1]. Such transmitters can use a radio signal emission (the oldest way, currently replaced by GPS); it requires the involvement of a person with a radio receiver together with an antenna to track the animal and record their location. Another way is to connect the transmitter to the server via cellular telephony; coordinates from the GPS system are collected, converted, and transferred to the operator’s server, processed and plotted on the map; however, it requires the animal remains within the GSM network, and the reading may be analyzed by the inspector only after some time. The most modern, but also significantly more expensive, way is placing satellite emitters on the European bison, which allows tracking these animals in different conditions (also outside the GSM network) and the ability to record the location of the “marked” animal systematically regardless of the environment in which it is located. By monitoring European bison for a longer period of time, maps can be created for the use of both males and females of different ecosystems, determine the range of existence of individual herds, and determine, for example, the nutritional preferences of these animals. The telemetric coordinates of European bison location are applied to maps and visualized showing land usage of individuals/herds in relation to season, differences in distribution, and behavior of females and males [38]. Same as European bison counting, setting up telemetry transmitters is usually performed during winter concentration at feeding places. For this purpose, the individual is pharmacologically immobilized (Figure 4) [7], and the belt with the telemetry transmitter is adjusted to its neck. This is important because a too tight collar may cause difficulties in swallowing and regurgitation, while too loosely attached collar may cause injuries (entrapment of the limb, foreign bodies such as branches). For an adult European bison, a telemetry transmitter that weighs approx. 2 kg may be compared to a watch on a human wrist. Additionally, during the pharmacological immobilization of European bison, samples are collected for veterinary, genetic, and toxicological tests, which is a part of the health monitoring described in paragraph 3.
\nChemical immobilization of free-living European bison (photo: J. Klej).
When considering the problems of infectious and invasive diseases, three aspects (the so-called epidemiological triangle: animal-environment-pathogen) should be considered. The epizootic and epidemiological situation is a resultant of the interactions between the natural environment of the free-living animals, other wild reservoir species and farm animals at the wildlife-lifestock interface. An important environmental component will also be access to competent vectors of a given microorganism. In the case of environmental impact, it is also necessary to take into account people who are susceptible to zoonoses, can themselves be a source of infections, or can be a mechanical vector of infectious and invasive agents transmitted to animals, becoming endemic in sylvatic environment [39]. Those aspects meet in the One Health approach, which include wildlife as a key component of the ecosystem [9, 32, 40, 41]. Therefore, in the case of an epizootic, surveillance should be carried out in both domestic and non-domestic populations, both free-living and captive, and the potential role of humans (animal care takers, breeders, vets) as vectors should be taken into account. Climate, environment, socioeconomical changes create alterations also in the distribution of infectious diseases and remind us that animals and humans, environment, and pathogens are the elements of the same ecosystem. In the last 20 years, the population size of European bison in Białowieża Forest and in the whole country increased more than twice (Figure 2). It generated an increasing epidemiological pressure connected to higher animal density, a need for expanding the habitat, and what further increases the frequency of contacts between wildlife, farm animals, and humans. The evident environmental changes may provoke also emergence and re-emergence of new pathogens, change the seasonality of wild species, and induce stress and therefore the immunosuppression leading to increased susceptibility to diseases.
\nSince the European bison population was on the verge of extinction at the beginning of the twentieth century, each individual was extremely valuable; therefore one of the main aspects of European bison restitution still remains veterinary health protection, especially in terms of the threat of infectious and invasive disease occurrence. The role of European bison veterinarians and keepers include the supervision, health monitoring, understanding disease characteristics, identification of disease risks, provision of information for control, prevention or treatment, and evaluation of the effectiveness of control and its adjustment. One of the effective tools to control the disease is selective elimination of diseased animals and limiting the population size to reduce its density [32]. The selection is made by a panel of experts in the field; however, it should be remembered that the approach presented here is based on veterinary health protection sometimes argued by epidemiologists [42]. In the case of protected species such European bison, enforcement of the veterinary regulations to protect the species by a sacrifice of few diseased individuals, which are reservoirs of the pathogens putting on risk the whole population, becomes often inconvenient decision against some environmentalist protests.
\nEuropean bison monitoring in Poland consists of four elements: (1) passive surveillance, (2) active (targeted) monitoring, (3) sanitary control of transported animals, and (4) habitat monitoring (Figure 5) [43]. The first approach is based on one of the most suitable ways of health control, the postmortem examination as an element of mortality and morbidity investigations and sampling of the material for laboratory testing [6, 23, 44].
\nThe four main elements of the European bison health monitoring scheme in Poland.
The most recent study involved the analysis of necropsy findings of over 230 fallen or selectively culled European bison from Białowieża Forest between 2008 and 2013 [6]. Changes in the male reproductive tract such as posthitis and balanoposthitis remained the most common pathological changes observed in European bison bulls; however, it should be kept in mind that those changes are the main reason for bull elimination (Figure 6). Moreover, the decrease in the proportion of males with prepuce and penis lesions of the whole Białowieża male population in regard to the last century was significant [1, 44].
\nPercentage of European bison with individual pathological changes and parasitic invasions observed at postmortem examinations performed between 2008 and 2013 in Białowieża Forest [
The next most common problem included pneumonia (45% necropsied animals) and pulmonary emphysema (33%) [6], which were also reported in earlier studies [44]. Respiratory problems were associated with
Another large serosurvey has revealed the possible involvement of some respiratory viruses in the pathogenesis of the frequent changes observed in the lungs or in the upper respiratory tract such as bovine adenovirus type 3 (BAdV-3), bovine parainfluenza type 3 (PIV-3), and bovine respiratory syncytial virus (BRSV) [46]. The high seroprevalences observed especially for BAdV-3 (60%) and PIV-3 (34%) were surprising, also because they have not been studied too intensively before [47]. Interestingly, the association between BAdV-3 and PIV-3 infections and health status of European bison were demonstrated, with significantly lowest seroprevalences in the apparently healthy animals. Whether the high BAdV-3 and PIV-3 infection rates were due to the circulation inside the European bison population or it is connected to the transmission of those viruses from domestic ruminants remains unsolved. However, higher infection rates in the free-living European bison suggested that it might have been associated with a spillover from farm animals. The European bison kept in the enclosures were possibly protected from a direct contact with domestic species, not sharing grazing areas as observed in Białowieża [48, 49]. The studies on the characterization of the viral strains in European bison, what may explain the transmission source, are ongoing.
\nMoreover, other endemic in ruminants infectious agents were considered as potential threats to European bison. Those included pestiviruses with bovine viral diarrhea virus type 1 (BVDV-1) and alpha- and gammaherpesviruses (bovine herpesvirus type 1—BoHV-1, BoHV-4, and BoHV-6), endemic in Polish cattle herds [46]. While in farm animals those viruses are responsible for economic losses, they may prevent the reproduction of an endangered species and make the restitution program fail. However, very low seroprevalence to those viruses suggests certain resistance or only accidental exposure of European bison and hence little importance for European bison at present [15, 25, 46, 47]. On the other hand, low seroprevalence means that most European bison are naïve and fully susceptible to infections with BVDV-1 and BoHV-1, BoHV-4, and BoHV-6. The involvement of herpesviruses in the etiology of balanoposthitis was also disclosed [22].
\nOther respiratory agents, which could affect the clinical picture observed frequently postmortem in European bison such as
Further studies are concerned with pathogens, which may be depopulating through their influence on European bison reproduction, reducing already fragile number of the species under restitution. Low seroprevalences of
Bovine leukemia virus (BLV) and
Finally, it is worth mentioning European bison susceptibility to malignant catarrhal fever virus (MCFV) infection, which is comparable to cattle’s. The reports of clinical picture of MCF in the species kept in zoos are quite old [62, 63]. MCF is considered more emerging and non-endemic in Poland; therefore, no current data exists. However, it was well documented that the exposure of American bison to sheep-associated MCFV is frequently fatal [64, 65]. In 2018, an outbreak of fatal MCF in European bison enclosure in Switzerland was consulted with European Bison Pedigree Book department at the Białowieża National Park; however no report was published officially (Baumgartner, personal communication).
\nThe twenty-first century brings new challenges of the protection of animal health, including free living. Social and economic changes, globalization, intensification of intra- and intercontinental trade and travels, and environment and climate change contributed to the observed increase in the risk of emergence and re-emergence of pathogens [66]. The last few years have brought an increase in the importance of new pathogens, completely unknown before or not present in a given geographical latitude [67, 68], which may also have a significant impact on the health of an endangered species such as the European bison. It is related to processes related to human activity or changes in the environment but also to the development of science, improvement of disease diagnostics, and the introduction of new cognitive techniques, such as metagenomics and next-generation sequencing (NGS). Due to the habitat and the maintenance of a part of the European bison population in captivity, they are exposed to pathogens from both wild and domestic animals. Along with climate change, infections caused by pathogens transmitted by vectors such as arthropods (ticks, biting midges, mosquitoes) are more and more frequently reported in our part of Europe. In 2007, the first cases of infection with bluetongue virus (BTV) serotype 8 (BTV-8) causing significant mortality in European bison at an enclosure in Hardehausen occurred. The virus is transmitted by the blood-sucking midges of the family of
BTV, EHDV, and SBV insect vectors: biting midges of
After the bluetongue epizootics (BTV) in 2007 [67], a new pathogen named Schmallenberg virus (SBV) was identified in Europe in 2011 [74], which spread very quickly across the continent. The first SBV infection in cattle in Poland was found in 2012, and in the same year, virus transmission to the ruminants of free-living ruminants in the Białowieża Forest, including European bison, was observed [75]. The first case of acute SBV infection in wild animals was actually confirmed in a fallen elk calf rescued by the animal keepers of the Białowieża National Park [76, 77]. This was the first report on the identification of the SBV virus in a free-living animal that began an international discussion on the importance of free-living animals as a reservoir of this new virus [77]. It proceeded the subsequent surveillance of European bison and other wild ruminants at Białowieża Forest, what allowed to determined that the transmission of SBV occurred during 2012
Since the transmission of arthropod-borne pathogens involves environmental factors, entomological and virological studies of the midges near European bison were performed between 2014 and 2015 [73]. Using specially designed ultraviolet (UV) light traps (Figure 7c) placed near European bison resting places at Białowieża National Park abundance, species composition and virus exposure were tested. The wood midges of
Further studies suggest that European bison may be an important reservoir of tick-borne Lyme disease, since
The last emerging disease with high epizootic potential we would like to discuss shortly is hepatitis E. The pigs including wild boar are the main reservoirs of hepatitis E virus (HEV); however, cases of virus to humans through cervid meat have been also reported. In a recent study, none of the European bison had antibodies against HEV [87]; however, the sensitivity of the methods to ruminants is debatable, and therefore the studies are being continued.
\nEuropean bison survived to the present times, only thanks to human care and protection. Because Europe, unlike the Americas, was significantly more populated in the Middle Ages, European bison conservation by the Polish kings saved this species from total extinction, as was the case outside the Kingdom of Poland. Successive rulers continued to protect the species, but warfare led to the total depopulation of the last surviving free-living population in the Białowieża Primeval Forest. Thanks to the efforts of scientists and naturalists, the current global population of European bison which was founded by 12 individuals is over 7000. This is undoubtedly a success, but without the supervision of the health of European bison, it would be impossible. European bison, in general opinion, is characterized by a decreased resistance to infections due to their low genetic heterogeneity after passing through the “bottleneck.” Except for
The publishing of the chapter was funded by KNOW (Leading National Research Centre) Scientific Consortium “Healthy Animal-Safe Food,” decision of Ministry of Science and Higher Education no. 05-1/KNOW2/2015. The collection of some data was funded from the project: ‘
We declare no conflict of interest exists for this publication.
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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. 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