Interactions of medications used in the treatment of COVID-19.
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\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:"5367",leadTitle:null,fullTitle:"Cryopreservation in Eukaryotes",title:"Cryopreservation in Eukaryotes",subtitle:null,reviewType:"peer-reviewed",abstract:"Since accidentally discovering the ability of glycerol on protecting cells from freezing damage, many researchers have been pursuing to develop cryopreservation methods of a very wide range of cells and some tissues, and these have found widespread applications in biology and medicine. From the point of view of living organisms, cryopreservation is a useful tool for ex situ conservation of genetic resources together with its contribution on conservation of their biodiversity. Cryopreservation in Eukaryotes includes totally 12 chapters, which have been written by the expert researchers in the field. The chapters are a comprehensive collection of the most frequently used methods for eukaryotes. With this book, every researcher will better understand the principles, background, and current status of cryopreservation in particular organisms.",isbn:"978-953-51-2780-2",printIsbn:"978-953-51-2779-6",pdfIsbn:"978-953-51-4143-3",doi:"10.5772/62605",price:119,priceEur:129,priceUsd:155,slug:"cryopreservation-in-eukaryotes",numberOfPages:228,isOpenForSubmission:!1,isInWos:1,isInBkci:!0,hash:"e542ca854409964cc9a1a9b33d061601",bookSignature:"Francisco Marco-Jiménez and Hülya Akdemir",publishedDate:"November 30th 2016",coverURL:"https://cdn.intechopen.com/books/images_new/5367.jpg",numberOfDownloads:23875,numberOfWosCitations:21,numberOfCrossrefCitations:16,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:28,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:65,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 8th 2016",dateEndSecondStepPublish:"March 29th 2016",dateEndThirdStepPublish:"July 3rd 2016",dateEndFourthStepPublish:"October 1st 2016",dateEndFifthStepPublish:"October 31st 2016",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,8,9",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"178775",title:"Dr.",name:"Francisco",middleName:null,surname:"Marco-Jimenez",slug:"francisco-marco-jimenez",fullName:"Francisco Marco-Jimenez",profilePictureURL:"https://mts.intechopen.com/storage/users/178775/images/4920_n.jpg",biography:"Professor Francisco Marco-Jiménez holds an Agronomy Engineer degree (2003) and a PhD degree (2007) from the Polytechnic University of Valencia (Spain), where he is currently working as Professor of Animal Physiology and Biotechnology of Reproduction in the Institute for Animal Science and Technology. His research interests are mainly related in reproductive biology and technology specifically in embryo and gamete cryopreservation.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Universitat Politècnica de València",institutionURL:null,country:{name:"Spain"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"154662",title:"Dr.",name:"Hulya",middleName:null,surname:"Akdemir",slug:"hulya-akdemir",fullName:"Hulya Akdemir",profilePictureURL:"https://mts.intechopen.com/storage/users/154662/images/4919_n.jpg",biography:"Dr. Hülya Akdemir holds a BS degree in Biology from the Istanbul University (Turkey) and MSc and PhD degrees from Gebze Technical University (Turkey), where she is currently working as a researcher. Her research interests are mainly related to different aspects of plant biotechnology including micropropagation and cryopreservation of ornamental and woody plants, assessment of genetic integrity in the plants by DNA-based molecular markers, development of genetic transformation techniques, as well as gene expression profiling of cell wall–related genes.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Gebze Technical University",institutionURL:null,country:{name:"Turkey"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"414",title:"Cytology",slug:"cytology"}],chapters:[{id:"52895",title:"Isolation and Cryopreservation of Trypanosomes and their Vectors for Research and Development in Resource‐ Constrained Settings",doi:"10.5772/65283",slug:"isolation-and-cryopreservation-of-trypanosomes-and-their-vectors-for-research-and-development-in-res",totalDownloads:1642,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Biorepositories for biological samples have increasingly become very important in supporting biomedical research since the 1990s. The Kenya Trypanosomiasis Research Institute Cryo‐bank for trypanosomes and their vectors was established in the 1970s with the aim of providing research materials to scientists. Over 2000 trypanosome isolates have been collected and stored in dewars under liquid nitrogen. Recent collections include tsetse flies—vectors of human and animal trypanosomiasis. Challenges encountered include distances to remote field sites and impassable roads and the cost of collection, preparation, storage, and maintenance under resource‐constrained settings. Under these settings, the challenges can be overcome through strategic leadership that ensures availability and sustainability of resources, appropriate institutional policies, adoption of multidisciplinary approach where appropriate, working with different sectors such as human health, livestock, and wildlife, and environmental conservation in order to leverage on capacities in these sectors, and acknowledging the role of communities from which materials are collected.",signatures:"Murilla Grace, Ndung’u Kariuki, Joanna Auma, Purity Gitonga and\nThuita John",downloadPdfUrl:"/chapter/pdf-download/52895",previewPdfUrl:"/chapter/pdf-preview/52895",authors:[{id:"187555",title:"Dr.",name:"Grace",surname:"Murilla",slug:"grace-murilla",fullName:"Grace Murilla"},{id:"194209",title:"Dr.",name:"John",surname:"Thuita",slug:"john-thuita",fullName:"John Thuita"}],corrections:null},{id:"52184",title:"Microscopic Evaluation of Necrotic Cell Death in the Cartilage Destined for Experimental Tracheal Allografts: Lyophilization vs Cryopreservation",doi:"10.5772/65014",slug:"microscopic-evaluation-of-necrotic-cell-death-in-the-cartilage-destined-for-experimental-tracheal-al",totalDownloads:1581,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Tracheal replacement remains an important unmet need for patients with extensive lesions. Tracheal allografts treated by cryopreservation and lyophilization have been used as experimental methods for replacing long segments of the trachea. We compare the effect of lyophilization and cryopreservation on the canine tracheal cartilage by microscopic evaluation of necrotic cell death. Canine tracheal segments were rinsed and randomly divided into a control group (G1) and two biopreservation groups: lyophilization (G2) [−70–55°C/10 mmBar] and cryopreservation (G3) [RPMI-1640 + 10%DMSO + 10%SBF, −70°C/−196°C]. After tracheal segments were rehydrated (G2) or thawed (G3), the central ring was obtained from each tracheal segment and processed for histological evaluation with hematoxylin and eosin and for caspase-3 expression by immunohistochemistry. Compared with the control group, chondrocytes without apparent abnormalities, nucleus with karyorrhexis, and caspase-3 expression decreased significantly with the effect of lyophilization and cryopreservation (p < 0.001, ANOVA + Tukey, chi-square, Kruskal-Wallis), while a significant decrease in pyknotic nuclei was observed only with the effect of the lyophilization as well as an increase in the nucleus with karyolysis and empty lacunae (p < 0.001, ANOVA + Tukey). The mean percentages of normal chondrocytes and empty lacunae were significantly affected by lyophilization compared with cryopreservation (p < 0.01, ANOVA + Tukey). Our results strongly suggest that lyophilization has a deleterious impact on the tracheal cartilage.",signatures:"Avelina Sotres-Vega, Jaime Villalba-Caloca, Miguel O. Gaxiola-\nGaxiola, Miriam Mendoza-Santiago, Juan A. Morales-Tiburcio,\nClaudia Hernández-Jiménez and Francisco Figueroa-Cavero",downloadPdfUrl:"/chapter/pdf-download/52184",previewPdfUrl:"/chapter/pdf-preview/52184",authors:[{id:"35115",title:"Dr.",name:"Jaime",surname:"Villalba-Caloca",slug:"jaime-villalba-caloca",fullName:"Jaime Villalba-Caloca"},{id:"187401",title:"Ph.D.",name:"Avelina",surname:"Sotres-Vega",slug:"avelina-sotres-vega",fullName:"Avelina Sotres-Vega"},{id:"194051",title:"Dr.",name:"Miguel O.",surname:"Gaxiola-Gaxiola",slug:"miguel-o.-gaxiola-gaxiola",fullName:"Miguel O. Gaxiola-Gaxiola"},{id:"194052",title:"Dr.",name:"Miriam",surname:"Mendoza-Santiago",slug:"miriam-mendoza-santiago",fullName:"Miriam Mendoza-Santiago"},{id:"194053",title:"Dr.",name:"Juan A.",surname:"Morales-Tiburcio",slug:"juan-a.-morales-tiburcio",fullName:"Juan A. Morales-Tiburcio"},{id:"194054",title:"Dr.",name:"Claudia",surname:"Hernández-Jiménez",slug:"claudia-hernandez-jimenez",fullName:"Claudia Hernández-Jiménez"},{id:"194056",title:"Dr.",name:"Francisco",surname:"Figueroa-Cavero",slug:"francisco-figueroa-cavero",fullName:"Francisco Figueroa-Cavero"}],corrections:null},{id:"52273",title:"Isolation and Cryopreservation of Animal Mesenchymal Stromal Cells",doi:"10.5772/64949",slug:"isolation-and-cryopreservation-of-animal-mesenchymal-stromal-cells",totalDownloads:1779,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Scientific progress in cellular and molecular biotechnology has led to the development of advanced therapies, such as gene therapy, cell therapy, and tissue engineering. The application of stem cells as therapeutic agents has been investigated for several years in human medicine and, more recently, the same approach has been considered in the veterinary field as a novel opportunity for the treatment of animal diseases. Mesenchymal stem cell (MSC)-based therapies seem to contribute to the healing process by several mechanisms due to their peculiar biological features. It has been shown that MSCs could effectively differentiate into the required cell type to replace the damaged tissue. Furthermore, due to their autocrine and paracrine secretory activities, these cells are a powerful source of trophic mediators, growth factors, cytokines, and extracellular matrix components. The clinical application of MSCs needs great amounts of cells designed for in vivo implantation that can be obtained following their in vitro isolation, serial subcultivations, cryopreservation, and thawing. These procedures could determine their feature changes which could interfere with the therapeutic outcome. For these reasons, to preserve MSCs after in vitro manipulation for future applications, standardized quality controls and a reliable long-term cryopreservation method are required.",signatures:"Tina Lombardo, Sabrina Renzi, Silvia Dotti, Stefano Cinotti and\nMaura Ferrari",downloadPdfUrl:"/chapter/pdf-download/52273",previewPdfUrl:"/chapter/pdf-preview/52273",authors:[{id:"186219",title:"Dr.",name:"Maura",surname:"Ferrari",slug:"maura-ferrari",fullName:"Maura Ferrari"},{id:"187114",title:"Dr.",name:"Tina",surname:"Lombardo",slug:"tina-lombardo",fullName:"Tina Lombardo"},{id:"187173",title:"Dr.",name:"Sabrina",surname:"Renzi",slug:"sabrina-renzi",fullName:"Sabrina Renzi"},{id:"187174",title:"Dr.",name:"Silvia",surname:"Dotti",slug:"silvia-dotti",fullName:"Silvia Dotti"},{id:"194159",title:"Prof.",name:"Stefano",surname:"Cinotti",slug:"stefano-cinotti",fullName:"Stefano Cinotti"}],corrections:null},{id:"52111",title:"Semen Cryopreservation in Brazilian Freshwater Fish: Advances and Main Challenges",doi:"10.5772/65037",slug:"semen-cryopreservation-in-brazilian-freshwater-fish-advances-and-main-challenges",totalDownloads:1726,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Studies on semen cryopreservation in Brazilian freshwater fish have been growing in number of publications and investigated species. Despite this apparent increase in research, standardization of cryoprotocols is still missing, making it clear that the grounds on the quality of cryopreserved semen has not yet reached a level that guarantee satisfactory results for its replication. This chapter aims to make a critical and reflective analysis on the ways cryopreservation of freshwater fish semen has been conducted in Brazil. The difficulties in standardizing protocols, broodstock, and selection of genetically superior animals; the barriers in transferring technology from laboratory benches to the field and make feasible the use of cryopreserved semen on a commercial scale; the formation of germplasm banks and the responsible use of cryopreserved material are also discussed. We have no intention to point out the successes and mistakes that may have been committed in pursuing development of cryopreservation protocols, but a reflection on the future directions considering what should be pondered on this subject with objectivity and scientific consolidation.",signatures:"Raycon R.F. Garcia, Danilo P. Streit, Elsa Cabrita and Leandro C.\nGodoy",downloadPdfUrl:"/chapter/pdf-download/52111",previewPdfUrl:"/chapter/pdf-preview/52111",authors:[{id:"75412",title:"Dr.",name:"Danilo Pedro",surname:"Streit Junior",slug:"danilo-pedro-streit-junior",fullName:"Danilo Pedro Streit Junior"},{id:"186231",title:"M.Sc.",name:"Raycon",surname:"Garcia",slug:"raycon-garcia",fullName:"Raycon Garcia"},{id:"187448",title:"Dr.",name:"Leandro Cesar",surname:"Godoy",slug:"leandro-cesar-godoy",fullName:"Leandro Cesar Godoy"},{id:"187449",title:"Dr.",name:"Elsa",surname:"Cabrita",slug:"elsa-cabrita",fullName:"Elsa Cabrita"}],corrections:null},{id:"51798",title:"Cryopreservation of Nile Tilapia (Oreochromis niloticus) Sperm",doi:"10.5772/64835",slug:"cryopreservation-of-nile-tilapia-oreochromis-niloticus-sperm",totalDownloads:1718,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The main aim of this study is to determine the effect of the straw volume (0.25 vs. 0.5 mL) on Nile tilapia sperm quality after cryopreservation. Sperm was frozen according to conventional slow freezing procedure and diluted at ratio of 1:3 with ionic extender containing 350 mM glucose and 30 mM Tris containing 10% dimethylacetamide. Diluted semen was equilibrated at 4°C for 10 min and drawn into 0.25-mL or 0.5-mL plastic straws and sealed with polyvinyl alcohol. Samples were frozen 3 cm above of the liquid nitrogen surface and exposed to the liquid nitrogen vapor (≈−140°C) for 10 min. After this, frozen sperm cells were kept into the liquid nitrogen container (−196°C). The frozen sperm in different volume of straws were thawed in a water bath at 30°C for 20 s (0.25-mL straws) or at 30°C for 30 s (0.5-mL straws), respectively. Fertilization was conducted using 1 ×105 spermatozoa/egg ratio with each straw type. The findings of the present study indicated that cryopreservation of sperm in glucose-Tris–based extender using 0.5-mL straws improved post-thaw progressive motility, duration of progressive motility, and fertilization results (P<0.01). On the other hand, differences in term of post-thaw cell viability was not significant among the treatments (P>0.01). In conclusion, our results suggest that Nile tilapia sperm can be successfully cryopreserved in Tris-based extenders supplemented with glucose containing 10% dimethylacetamide in 0.5-mL straws.",signatures:"Yusuf Bozkurt and İlker Yavaş",downloadPdfUrl:"/chapter/pdf-download/51798",previewPdfUrl:"/chapter/pdf-preview/51798",authors:[{id:"90846",title:"Prof.",name:"Yusuf",surname:"Bozkurt",slug:"yusuf-bozkurt",fullName:"Yusuf Bozkurt"},{id:"119796",title:"Associate Prof.",name:"İlker",surname:"Yavaş",slug:"ilker-yavas",fullName:"İlker Yavaş"}],corrections:null},{id:"52099",title:"Long‐Term Storing of Frozen Semen at −196°C does not Affect the Post-Thaw Sperm Quality of Bull Semen",doi:"10.5772/64948",slug:"long-term-storing-of-frozen-semen-at-196-c-does-not-affect-the-post-thaw-sperm-quality-of-bull-semen",totalDownloads:2265,totalCrossrefCites:5,totalDimensionsCites:7,hasAltmetrics:0,abstract:"Today, it is theoretically assumed that frozen storage of semen doses in liquid nitrogen guarantees sperm functionality indefinitely. However, there are few studies that objectively evaluate the effects of long‐term storage on sperm quality parameters. In this study, we show a freezability analysis of bull semen stored for 1, 10, 25, 40 and 45 years at −196°C. Sperm viability and full sperm motility were analyzed by CASA system, and acrosome integrity was assessed with Coomassie blue staining. Our results showed that sperm viability and total sperm motility were not affected by long‐term cryopreservation at −196°C. Specifically, we did not find any significant differences (p > 0.05) associated between different long‐time storing analyzed; both parameters showed optimal values of sperm viability and total sperm motility (both over 60%). Additionally, the acrosomal integrity parameter was not affected, showing an optimal range (87±1.6 - 95±0.5%). We conclude that the sperm quality of bovine semen is not affected by long-term storage at −196°C. However, future field trials will be necessary in order to validate that both fertility and embryo viability are maintained for the times analyzed.",signatures:"Alfredo Ramírez‐Reveco, Jorge Luis Hernández and Pablo Aros",downloadPdfUrl:"/chapter/pdf-download/52099",previewPdfUrl:"/chapter/pdf-preview/52099",authors:[{id:"186477",title:"D.Sc.",name:"Alfredo",surname:"Ramírez-Reveco",slug:"alfredo-ramirez-reveco",fullName:"Alfredo Ramírez-Reveco"},{id:"194256",title:"Mr.",name:"Jorge Luis",surname:"Hernández",slug:"jorge-luis-hernandez",fullName:"Jorge Luis Hernández"},{id:"194257",title:"Mr.",name:"Pablo",surname:"Aros",slug:"pablo-aros",fullName:"Pablo Aros"}],corrections:null},{id:"52750",title:"The Roles of Antioxidants and Fatty Acids in Sperm Cryopreservation",doi:"10.5772/65571",slug:"the-roles-of-antioxidants-and-fatty-acids-in-sperm-cryopreservation",totalDownloads:2323,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Despite research developments in the area of sperm storage, it has become inevitable to realize a marked reduction in the quality of fresh semen following cryopreservation. As a result, research has continued and will also continue in the future looking forward for a much better and improved methods of sperm cryopreservation along with better understanding of the physical and biochemical challenges that the sperm has to face to survive during freezing. Among the various attempts made to improve the cryopreservation process and subsequently result in superior quality of sperm after thawing include manipulating the composition of semen extenders by addition of exogenous products including antioxidants and fatty acids. While fatty acids are added to strengthening plasma membrane stability, Antioxidants are incorporated to compensate the reduction in the endogenous antioxidants level of seminal plasma due to dilution as well as to combat with the excess reactive oxygen species (ROS) production during freezing. In this chapter, the roles of antioxidants and fatty acids in mammalian sperm cryopreservation, both from endogenous and exogenous perspectives, will be discussed with reference to the latest research findings.",signatures:"Nurhusien Yimer, Asmatullah Kaka, Rosnina Yusoff and Abdul\nWahid Haron",downloadPdfUrl:"/chapter/pdf-download/52750",previewPdfUrl:"/chapter/pdf-preview/52750",authors:[{id:"187074",title:"Dr.",name:"Nurhusien",surname:"Yimer",slug:"nurhusien-yimer",fullName:"Nurhusien Yimer"},{id:"194393",title:"Dr.",name:"Asmatullah",surname:"Kaka",slug:"asmatullah-kaka",fullName:"Asmatullah Kaka"},{id:"194397",title:"Dr.",name:"Rosnina",surname:"Yusoff",slug:"rosnina-yusoff",fullName:"Rosnina Yusoff"},{id:"194398",title:"Prof.",name:"Abdul Wahid",surname:"Haron",slug:"abdul-wahid-haron",fullName:"Abdul Wahid Haron"}],corrections:null},{id:"52222",title:"Cryopreservation of Epididymal Sperm",doi:"10.5772/65010",slug:"cryopreservation-of-epididymal-sperm",totalDownloads:2106,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"The recovery and cryopreservation of epididymal sperm are essential tools to preserve genetic stocks of valuable domestic or wild animals under adverse conditions and also as an alternative source of gametes in cases of human infertility. This technique is recommended after death or when it is not possible to recover semen by usual methods. Sperm from the epididymis has been studied by many authors in different species. Cryopreservation is the most effective method for long-term preservation of genetic material from valuable breeding individuals. The protocols and diluents used for cryopreservation of conventional semen are well established, but many challenges remain working with sperm extracted directly from the epididymis. The spermatozoa retrieved from the cauda epididymis have special features, such as the absence of seminal plasma and large numbers of distal cytoplasmic droplets, which necessitate special handling, both for cryopreservation and for fertilization. For these reasons, it is important to describe in detail the features needed to cryopreserve sperm from the epididymis.",signatures:"Melina A.F. Bertol",downloadPdfUrl:"/chapter/pdf-download/52222",previewPdfUrl:"/chapter/pdf-preview/52222",authors:[{id:"187705",title:"Ph.D.",name:"Melina",surname:"Bertol",slug:"melina-bertol",fullName:"Melina Bertol"}],corrections:null},{id:"52201",title:"Cryopreservation of Embryos and Gametes: Past, Present, and Future",doi:"10.5772/65123",slug:"cryopreservation-of-embryos-and-gametes-past-present-and-future",totalDownloads:2257,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The need to find an efficient method to store gametes and embryos was driven both by medical and agricultural necessities. Gametes were the first cells used in early attempts of cryopreservation, yet these proved to be the most elusive. This chapter details the story of the development of techniques for gamete and embryo freezing, starting with hot air balloons and ending with cryotop open vitrification systems. Since gametes were the first cells to be frozen and the last to successfully thaw, their story provides an overview of the development of the science of cryopreservation.",signatures:"Julia Szeptycki and Yaakov Bentov",downloadPdfUrl:"/chapter/pdf-download/52201",previewPdfUrl:"/chapter/pdf-preview/52201",authors:[{id:"191290",title:"Dr.",name:"Yakov",surname:"Bentov",slug:"yakov-bentov",fullName:"Yakov Bentov"},{id:"194318",title:"Dr.",name:"Julia",surname:"Szeptycki",slug:"julia-szeptycki",fullName:"Julia Szeptycki"}],corrections:null},{id:"52097",title:"Cryopreservation of Human Gametes and Embryos: Current State and Future Perspectives",doi:"10.5772/64950",slug:"cryopreservation-of-human-gametes-and-embryos-current-state-and-future-perspectives",totalDownloads:2671,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Cryopreservation of human gametes and embryos is an important and widely used method in most embryology laboratories. During last years, the practice of single embryo transfer was a greater demand for reliable cryostorage of surplus embryos. Currently, there are two basic principally different methods usable for cryopreservation: slow freezing and vitrification. Vitrification is a very promising method with massive use in embryology. Nowadays, this method is also suitable for cryopreservation of human mature oocytes (one of the most problematic cell in cryobiology). This progress in the field of cryopreservation opens new perspectives in assisted reproduction. Recent effective oocyte vitrification systems have a significant impact on clinical practice. This chapter gives a view of human gametes (sperms, oocytes) and embryos cryopreservation application and possibilities. Indications and methods of cryopreservation and thawing are mentioned.",signatures:"Jeseta Michal, Zakova Jana, Ventruba Pavel, Bartosz Kempisty and\nCrha Igor",downloadPdfUrl:"/chapter/pdf-download/52097",previewPdfUrl:"/chapter/pdf-preview/52097",authors:[{id:"138948",title:"Dr.",name:"Michal",surname:"Jeseta",slug:"michal-jeseta",fullName:"Michal Jeseta"},{id:"187507",title:"Dr.",name:"Jana",surname:"Zakova",slug:"jana-zakova",fullName:"Jana Zakova"},{id:"187508",title:"Prof.",name:"Pavel",surname:"Ventruba",slug:"pavel-ventruba",fullName:"Pavel Ventruba"},{id:"187510",title:"Dr.",name:"Igor",surname:"Crha",slug:"igor-crha",fullName:"Igor Crha"},{id:"194204",title:"Dr.",name:"Bartosz",surname:"Kempisty",slug:"bartosz-kempisty",fullName:"Bartosz Kempisty"}],corrections:null},{id:"52351",title:"Quality Control Factors Influencing the Successful and Reliable Implementation of Oocyte and Embryo Vitrification",doi:"10.5772/65332",slug:"quality-control-factors-influencing-the-successful-and-reliable-implementation-of-oocyte-and-embryo-",totalDownloads:1910,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Clinical vitrification evolved slowly, with interests and acceptance being commercially driven by the development of unique devices, safer solutions, and the misconception that ultra‐rapid cooling in an “open” system was a necessity to optimizing vitrification success. Furthermore, the dogma surrounding the importance of cooling rates has led to unsafe practices subject to excessive technical variation and risky modifications to create closed‐storage devices. The aim of this chapter is to highlight important quality control factors (e.g., ease of use, repeatability, reliability, labeling security, and cryostorage safety) into the selection process of which device/solution to use, independent of commercial manipulations. In addition, we provide clinical and experimental evidence in support of warming rates being the most important factor determining vitrification survival. Lastly, we exhibit indisputable support that aseptic, closed vitrification systems, specifically microSecure vitrification (μS‐VTF), can achieve success with attention to quality control details often lacking in open vitrification devices.",signatures:"Mitchel C. Schiewe",downloadPdfUrl:"/chapter/pdf-download/52351",previewPdfUrl:"/chapter/pdf-preview/52351",authors:[{id:"186485",title:"Prof.",name:"Mitchel",surname:"Schiewe",slug:"mitchel-schiewe",fullName:"Mitchel Schiewe"}],corrections:null},{id:"52653",title:"Cryopreservation of Orchid Genetic Resources by Desiccation: A Case Study of Bletilla formosana",doi:"10.5772/65302",slug:"cryopreservation-of-orchid-genetic-resources-by-desiccation-a-case-study-of-bletilla-formosana",totalDownloads:1902,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Many native orchid populations declined yearly due to economic development and climate change. This resulted in some wild orchids being threatened. In order to maintain the orchid genetic resources, development of proper methods for the long‐term preservation is urgent. Low temperature or dry storage methods for the preservation of orchid genetic resources have been implemented but are not effective in maintaining high viability of certain orchids for long periods. Cryopreservation is one of the most acceptable methods for long‐term conservation of plant germplasm. Orchid seeds and pollens are ideal materials for long‐term preservation (seed banking) in liquid nitrogen (LN) as the seeds and pollens are minute, enabling the storage of many hundreds of thousands of seeds or pollens in a small vial, and as most species germinate readily, making the technique very economical. This article describes cryopreservation of orchid genetic resources by desiccation and a case study of Bletilla formosana. We hope to provide a more practical potential cryopreservation method for future research needs.",signatures:"Rung‐Yi Wu, Shao‐Yu Chang, Ting‐Fang Hsieh, Keng‐Chang\nChuang, Ie Ting, Yen‐Hsu Lai and Yu‐Sen Chang",downloadPdfUrl:"/chapter/pdf-download/52653",previewPdfUrl:"/chapter/pdf-preview/52653",authors:[{id:"187594",title:"Mrs.",name:"Rung Yi",surname:"Wu",slug:"rung-yi-wu",fullName:"Rung Yi Wu"},{id:"194404",title:"MSc.",name:"Shao-Yu",surname:"Chang",slug:"shao-yu-chang",fullName:"Shao-Yu Chang"},{id:"194405",title:"Dr.",name:"Ting-Fang",surname:"Hsieh",slug:"ting-fang-hsieh",fullName:"Ting-Fang Hsieh"},{id:"194406",title:"MSc.",name:"Yen-Hsu",surname:"Lai",slug:"yen-hsu-lai",fullName:"Yen-Hsu Lai"},{id:"194407",title:"Prof.",name:"Yu-Sen",surname:"Chang",slug:"yu-sen-chang",fullName:"Yu-Sen Chang"},{id:"195111",title:"MSc.",name:"Keng-Chang",surname:"Chuang",slug:"keng-chang-chuang",fullName:"Keng-Chang Chuang"},{id:"195112",title:"BSc.",name:"Ie",surname:"Ting",slug:"ie-ting",fullName:"Ie Ting"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"2617",title:"Molecular Regulation of Endocytosis",subtitle:null,isOpenForSubmission:!1,hash:"dfd1b4de49c737272c722b73a0d7facb",slug:"molecular-regulation-of-endocytosis",bookSignature:"Brian Ceresa",coverURL:"https://cdn.intechopen.com/books/images_new/2617.jpg",editedByType:"Edited by",editors:[{id:"48114",title:"Dr.",name:"Brian",surname:"Ceresa",slug:"brian-ceresa",fullName:"Brian Ceresa"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"729",title:"Metabolomics",subtitle:null,isOpenForSubmission:!1,hash:"4fae9ba692c101455b3001980a3d85b4",slug:"metabolomics",bookSignature:"Ute Roessner",coverURL:"https://cdn.intechopen.com/books/images_new/729.jpg",editedByType:"Edited by",editors:[{id:"85077",title:"Dr.",name:"Ute",surname:"Roessner",slug:"ute-roessner",fullName:"Ute Roessner"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3545",title:"Autophagy - A Double-Edged Sword",subtitle:"Cell Survival or Death?",isOpenForSubmission:!1,hash:"62f2a3697cfbfa51f5d78b86b07140aa",slug:"autophagy-a-double-edged-sword-cell-survival-or-death-",bookSignature:"Yannick Bailly",coverURL:"https://cdn.intechopen.com/books/images_new/3545.jpg",editedByType:"Edited by",editors:[{id:"164577",title:"Dr.",name:"Yannick",surname:"Bailly",slug:"yannick-bailly",fullName:"Yannick Bailly"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"570",title:"Cell Metabolism",subtitle:"Cell Homeostasis and Stress Response",isOpenForSubmission:!1,hash:"1edda5867b826ab2fd845eff2da7a11f",slug:"cell-metabolism-cell-homeostasis-and-stress-response",bookSignature:"Paula Bubulya",coverURL:"https://cdn.intechopen.com/books/images_new/570.jpg",editedByType:"Edited by",editors:[{id:"47827",title:"Dr.",name:"Paula",surname:"Bubulya",slug:"paula-bubulya",fullName:"Paula Bubulya"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2860",title:"Cell Interaction",subtitle:null,isOpenForSubmission:!1,hash:"07b45b340578c983659c4376a7bd0e57",slug:"cell-interaction",bookSignature:"Sivakumar Gowder",coverURL:"https://cdn.intechopen.com/books/images_new/2860.jpg",editedByType:"Edited by",editors:[{id:"118572",title:"Dr.",name:"Sivakumar Joghi",surname:"Thatha Gowder",slug:"sivakumar-joghi-thatha-gowder",fullName:"Sivakumar Joghi Thatha Gowder"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4695",title:"Cell Death",subtitle:"Autophagy, Apoptosis and Necrosis",isOpenForSubmission:!1,hash:"cd1952ac488c47339209a54f512e975c",slug:"cell-death-autophagy-apoptosis-and-necrosis",bookSignature:"Tobias M. 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Many POPs are currently used as pesticides, pharmaceuticals, solvents, and industrial chemicals. Because of their persistence, POPs bioaccumulate and adversely affect human health and the environment. Persistent Organic Pollutants (POPs) - Monitoring, Impact and Treatment deals with several aspects of POP monitoring, occurrence, impact, and treatment technologies. The book is divided into two sections containing nine chapters that address such topics as the effect of POPs on wildlife, their role in hepatocarcinogenesis, treatment of POPs in wastewater, and much more.",isbn:"978-1-83968-207-0",printIsbn:"978-1-83968-206-3",pdfIsbn:"978-1-83968-208-7",doi:"10.5772/intechopen.95151",price:119,priceEur:129,priceUsd:155,slug:"persistent-organic-pollutants-pops-monitoring-impact-and-treatment",numberOfPages:172,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"f5b1589f0a990b6114fef2dadc735dd9",bookSignature:"Mohamed Nageeb Rashed",publishedDate:"April 13th 2022",coverURL:"https://cdn.intechopen.com/books/images_new/10843.jpg",keywords:null,numberOfDownloads:841,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 10th 2021",dateEndSecondStepPublish:"July 8th 2021",dateEndThirdStepPublish:"September 6th 2021",dateEndFourthStepPublish:"November 25th 2021",dateEndFifthStepPublish:"January 24th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"a year",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:"Edited by",kuFlag:!1,biosketch:"Prof. Mohamed Nageeb Rashed enrolled among Top 2% Scientists Around the World from Stanford University, USA, 2020 in the field of Environmental Sciences.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"63465",title:"Prof.",name:"Mohamed Nageeb",middleName:null,surname:"Rashed",slug:"mohamed-nageeb-rashed",fullName:"Mohamed Nageeb Rashed",profilePictureURL:"https://mts.intechopen.com/storage/users/63465/images/system/63465.gif",biography:"Prof. Mohamed Nageeb Rashed is Professor of Analytical and Environmental Chemistry and former vice-dean for environmental affairs, Faculty of Science, Aswan University, Egypt. He received his Ph.D. in Environmental Analytical Chemistry from Assiut University, Egypt, in 1989. His research interest is in analytical and environmental chemistry with special emphasis on: (1) monitoring and assessing biological trace elements and toxic metals in human blood, urine, water, crops, vegetables, and medicinal plants; (2) relationships between environmental heavy metals and human diseases; (3) uses of biological indicators for monitoring water pollution; (4) environmental chemistry of lakes, rivers, and well water; (5) water and wastewater treatment by adsorption and photocatalysis techniques; (6) soil and water pollution monitoring, control, and treatment; and (7) advanced oxidation treatment. Prof. Rashed has supervised several MSc and Ph.D. theses in the field of analytical and environmental chemistry. He served as an examiner for several Ph.D. theses in analytical chemistry in India, Kazakhstan, and Botswana. He has published about ninety scientific papers in peer-reviewed international journals and several papers in national and international conferences. He participated as an invited speaker at thirty international conferences. Prof. Rashed is the editor-in-chief and an editorial board member for several international journals in the fields of chemistry and environment. He is a member of several national and international societies. He received the Egyptian State Award for Environmental Research in 2001 and the Aswan University Merit Award for Basic Science in 2020. Prof. Rashed was recognized in Stanford University’s list of the World’s Top 2% Scientists in 2020 and 2021.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"5",institution:{name:"Aswan University",institutionURL:null,country:{name:"Egypt"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"133",title:"Environmental Pollution",slug:"environmental-pollution"}],chapters:[{id:"79742",title:"Endocrine Disruptor Impact on Zebrafish Larvae: Posterior Lateral Line System as a New Target",slug:"endocrine-disruptor-impact-on-zebrafish-larvae-posterior-lateral-line-system-as-a-new-target",totalDownloads:17,totalCrossrefCites:0,authors:[{id:"354033",title:"Dr.",name:"Ahmed",surname:"Nasri",slug:"ahmed-nasri",fullName:"Ahmed Nasri"},{id:"420855",title:"Prof.",name:"Patricia",surname:"Aïssa",slug:"patricia-aissa",fullName:"Patricia 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Dubey"},{id:"446429",title:"Dr.",name:"Dev Vrat",surname:"Kamboj",slug:"dev-vrat-kamboj",fullName:"Dev Vrat Kamboj"}]},{id:"79879",title:"Impact of PCBs, Furan and Dioxin on Hepatocarcinogenesis",slug:"impact-of-pcbs-furan-and-dioxin-on-hepatocarcinogenesis",totalDownloads:107,totalCrossrefCites:0,authors:[{id:"226635",title:"Prof.",name:"Amany",surname:"El-Sikaily",slug:"amany-el-sikaily",fullName:"Amany El-Sikaily"},{id:"424992",title:"Dr.",name:"Mohamed",surname:"Helal",slug:"mohamed-helal",fullName:"Mohamed Helal"},{id:"435668",title:"Dr.",name:"Sara",surname:"Ghanem",slug:"sara-ghanem",fullName:"Sara Ghanem"}]},{id:"79056",title:"Persistent Organic Pollutants in the Bizerte Lagoon Ecosystem: Occurrence, Distribution, and Ecotoxicological Assessment Using Marine 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Since the end of 2019, when the first cases were documented in Wuhan (China), the corona virus disease 2019 (COVID-19), a zoonotic infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly and rampantly, raising major concerns regarding public health, while applying an unprecedented, continuous strain, on the global medical infrastructure. COVID-19 was officially declared a pandemic by the World Health Organization on 11 March 2020 [1], and since then it has affected over 400 million people worldwide, with a cumulative mortality rate of under 2% [2] and recent alleviation of clinical outcomes due to the development and widespread implementation of efficient vaccination. Taking into account the extreme polymorphism of clinical presentations, ranging from asymptomatic to severe systemic effects, mainly involving the respiratory and cardiovascular systems, and fatal, rapidly progressing, acute respiratory distress syndrome (ARDS), the containment of transmission, at least in the pre-vaccination era, and the therapeutic management of COVID-19 and its systemic complications, has proven to be quite a challenge for clinicians, especially in the case of high-risk patients [3].
A novel member of the β-coronavirus genus, group 2, the enveloped, positive-sense RNA single-stranded SARS-CoV-2, has established itself as the third emerging, highly pathogenic coronavirus, to infect humans and cause a large-scale outbreak since the early 2000s, after severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) [4]. Even though mortality rates are lower for SARS-CoV2 than for previous related coronavirus outbreaks (>35% for MERS-CoV and > 10% for SARS-CoV), contagiousness is much higher (MERS-CoV and SARS-CoV had only 10000 cumulative cases between them), as transmission is mainly airborne (via respiratory droplets), with multiple alternative mechanisms being reported (aerosols, direct contact with contaminated surfaces, and fecal-oral transmission [4]).
From a genomic viewpoint, SARS-CoV-2 shares ~80% sequence identity with SARS-CoV and ~ 50% with MERS-CoV, encoding 16 nonstructural proteins (that make up the replicase complex), 9 accessory proteins, and 4 structural proteins – spike (S), envelope (E), membrane (M), and nucleocapsid (N). The SARS-CoV-2 life cycle revolves around the envelope S protein. Direct contact between the Spike receptor-binding domain and the innate cellular receptor (angiotensin-converting enzyme 2 – ACE2), if provided adequate cleavage of the viral Spike S1/S2 polybasic cleavage site by host-cell proteolytic enzymes, will ensure Spike activation in endosomes and virus-cell membrane fusion (cell surface and endosomal compartments), allowing viral RNA to be released into the host-cell cytosol. Viral replication ensues, with subsequent expulsion into the intercellular space [4]. In fact, the S gene of SARS-CoV-2 represents the distinguishing genomic feature from SARS-CoV, sharing <75% nucleotide identity [4].
The main tissue tropism of SARS-CoV-2 is pulmonary, targeting high ACE2 expression cells (airway/alveolar epithelial cells, vascular endothelial cells, and alveolar macrophages) [5]. Even so, higher levels of ACE2 messenger RNA expression can be found in many extra-pulmonary tissues as well and nearly undetectable amounts of ACE2 still support viral host-cell entry. Therefore, additional, underappreciated, cell-intrinsic factors must also be involved in host-cell entry [4]. Noteworthy, a subpopulation of human type II alveolar cells has been documented, which manifest abundant ACE2 expression, and concomitant high levels of messenger RNA, specific to certain cellular proviral genes (coding elements of the, SARS-CoV-2 cell entry facilitating, and endosomal transport system) [6]. Also, ACE2 expression regulation must be considered, as, during viral infection, ACE2 gene expression in human airway epithelial cells is upregulated by type I and II interferons [5].
Considering the multitude of the medical literature written on the topic of multisystem impairment occurred during the infection with the SARS-CoV-2 virus, the purpose of our research was to summarize the opinions of experts concerning the cardiovascular alterations associated with COVID-19, and for this aim we reviewed the most significant articles published on PubMed, Medline, and Research gate on these topics and provided individualized summaries of expert opinions.
The COVID-19 pandemic greatly challenged clinicians, both due to the sheer number of patients, but also because of the lack of therapeutic consensus and incomplete understanding of disease pathogenesis. Most fatal cases of COVID-19 relate to a severe atypical pneumonia, accompanied by a sudden systemic deterioration, despite therapeutic intervention in the hospital setting.
The infection with the SARS-CoV-2 virus primarily affects the respiratory structures, but the involvement of the cardiovascular system is also frequent. Cardiovascular complications in addition to respiratory disease may develop in all phases of COVID-19, which can start with the dramatic picture of acute heart failure (ACF), acute coronary syndrome (ACS), pulmonary venous thromboembolism (VTE), or even sudden cardiac death, as shown in Figure 1. The pathophysiological mechanisms underlying these disproportionate effects of the SARS-CoV-2 infection on patients with cardiovascular comorbidities, however, remain incompletely understood [7]. Thromboembolic events, usually accompanied by violent, pulmonary, and/or systemic complications, have been described from early on, since the beginning of the pandemic, with infectious inflammatory response patterns rapidly shifting into a typical systemic inflammatory response syndrome (SIRS) or ARDS, which could potentially induce multi-organ failure (MOF) and, subsequently, death. As we enter the third year of the pandemic, COVID-19 pathophysiology is slowly unraveling as we begin to better comprehend the complex interplay between the direct cytotoxic effects of SARS-CoV-2 on pneumocytes and endothelial cells, the emerging local and systemic inflammatory response, and the ways in which these responses interact with hemostatic homeostasis, a mechanism which has been deemed as central and, at least to this extent, unprecedented [8].
Main COVID-19-associated cardiovascular complications and underlying pathophysiological mechanisms.
COVID-19 was initially considered to be solely a respiratory disease, yet clinical outcomes quickly revealed that, undeniably, this infection implies multi-organ involvement. Perhaps most notably, the heart has been shown to represents a target organ for SARS-CoV-2-related pathogenesis, with a high prevalence of cardiac injury following COVID-19, often diagnosed only through biomarker evaluation. Beyond subclinical myocardial damage, SARS-CoV-2 infection may also cause more aggressive, clinically apparent modifications, such as myocarditis, accompanied by a subsequent diastolic dysfunction or severe reduction of left ventricle ejection fraction, not to mention the fact that heart failure may represent a short−/long-term consequence of COVID-19-related inflammatory cardiomyopathy, with dramatic consequences regarding prognosis [9].
Regarding myocardial damage in COVID-19, although the full pathophysiology is still incompletely understood, multiple mechanisms are most likely incriminated (see Figure 2), which, globally, can be divided into two main groups: direct, specific modifications, related to the cytopathic effects of SARS-CoV-2 infection, and indirect, general modifications, commonly seen in other severe infections, as well [10].
Pathophysiology of COVID-19-related myocardial injury [
The aforementioned ACE2, a type I transmembrane protein, highly expressed in different organs (heart, lungs, gut, and kidneys), mediates SARS-CoV-2 entry into the host cells, with different clinical implications, depending on the targeted organ, and represents the key molecular entity involved in the direct cytopathic effects of SARS-CoV-2 infection within the cardiac tissue. After entering the host cell through the host ACE2 receptor, SARS-CoV-2 utilizes the host’s RNA-dependent RNA polymerase to replicate its own structural proteins, which are then assembled, and the newly formed virions are released from the infected cells, perpetuating the viral life cycle. Theoretically, as a consequence of this process, infected cells may become damaged/destroyed [11].
This idea is supported by a recent autopsy study, analyzing cardiac tissue from 39 consecutive patients who died as a consequence of COVID-19, which found viral genome in the myocardial tissue, yet in situ hybridization showed that the most likely localization of SARS-CoV-2 not to be in the cardiomyocytes, but rather in interstitial cells or macrophages invading the myocardial tissue [12]. Even so, in engineered heart tissue models of COVID-19 myocardial pathology, SARS-CoV-2 demonstrated the ability to directly infect cardiomyocytes through ACE2, resulting in contractile deficits, cytokine production, sarcomere disassembly, and cell death [9].
Furthermore, ACE2 must not be viewed as a mere bystander in the pathophysiology of COVID-19 myocardial injury, seeing as, besides being the host cell receptor of SARS-CoV-2, ACE2 is an enzyme involved in the renin-angiotensin-aldosterone system (RAAS). Specifically, ACE2 cleaves angiotensin II, a very potent vasoconstrictor, into angiotensin 1–7, which manifests vasodilator and anti-inflammatory effects. ACE2 also demonstrates a weak affinity for angiotensin I (or proangiotensin, formed by the action of renin on angiotensinogen), competitively limiting angiotensin II synthesis by ACE. Angiotensin I is converted by ACE2 into the nonapeptide angiotensin 1–9, which will manifest vasodilator effects through subsequent angiotensin type 2 (AT2) receptor stimulation. Therefore, ACE2 can counteract the undesirable effects of angiotensin II, demonstrating vasodilator, antioxidant, and anti-fibrotic effects [13]. In the context of SARS-CoV-2 infection, after S protein binding is complete, the virus attaches ACE2 through membrane fusion and invagination, causing a downregulation of ACE2 enzymatic activity [13]. Additionally, ACE2 also demonstrates immunomodulatory properties, both directly, via its interactions with macrophages, and indirectly, as it reduces expression of angiotensin II, which stimulates inflammation [14]. Thus, ACE2 downregulation in the context of SARS-CoV-2 infection may increase angiotensin II levels, favoring AT1 receptor activity, with a subsequent vasoconstriction, fibrotic, proliferative, and pro-inflammatory effects [10].
As is the case with all severe respiratory infections, COVID-19 has a general deleterious effect on the cardiovascular system, with fever and sympathetic activation causing tachycardia and implicitly increasing myocardial oxygen consumption [9, 10], while prolonged bed rest and systemic inflammation will favor coagulation disorders, as supported by clinical findings – both venous and atypical arterial thromboembolic events have been documented in COVID-19 patients (see subchapter 3.4. Thromboembolic events and bleeding risk). Hypoxemia, another hallmark of COVID-19, will determine enhanced oxidative stress and increased production of reactive oxygen species, with subsequent intracellular acidosis, mitochondrial damage, and cell death [7, 9].
Moreover, another series of indirect mechanisms for COVID-19-related myocardial damage appears as a result of the abnormal inflammatory response which may be elicited by SARS-CoV-2 infection (i.e. a pro-inflammatory surge, the so-called “cytokine storm,” which may occur as early as 1 week after the initial exposure and infection) [15].
Indeed, individual immune response is the cardinal element behind SARS-CoV-2 infection progression. Upon viral genome expulsion into the host cytosol, SARS-CoV-2 viral replication begins, with aberrant RNA sequences, byproducts of replication, being, in turn, detected by intracellular receptors, which activate the cellular antiviral response, involving enhanced leukocyte chemotaxis and transcriptional induction of type I and III interferons (IFN-I/-III), followed by under-regulation of IFN-stimulated genes [16]. Lung cell damage incurred during replication will also activate the local immune response, resulting in monocyte/macrophage recruitment [16], while chemokines will induce specific leukocyte subset recruitment and coordination [16]. Circulating immune cell relocation in the pulmonary tissue will determine additional cytokine/chemokine production, while also creating multiple imbalances in immune cell populations – increased leukocyte count and neutrophil-lymphocyte ratio, with decreased lymphocytes (especially T cells [17]), thus setting the scene for immune response dysregulation [3].
In fact, the relationship between SARS-CoV-2 infection and extensive activation of inflammation signaling pathways has been well documented, representing the main immunopathological mechanism through which severe forms occur, in susceptible individuals. During the acute phase of the infection, a disproportionate response occurs between T helper cell populations (types 1 and 2), characterized by high circulating levels of interleukin (IL)-1β, IL-1RA, IL-2, IL-6, IL-7, IL-8, IL-9 IL-10, interferon gamma-induced protein-10 (CXCL10), monocyte chemoattractant protein-1 (CCL2), macrophage inflammatory protein 1α (CCL3) and 1β (CCL4), granulocyte colony-stimulating factor, vascular endothelial growth factor (VEGF), and tumor necrosis factor (TNF) α [16, 18, 19], which mediate widespread lung inflammation, in an attempt to eradicate the pathogen [3]. The resulting hyper-inflammatory status, as well as the individual excessive levels of certain circulating cytokine species, have been independently associated with an unfavorable evolution and increased mortality [20]. This hyper-inflammatory state seems, at least intuitively, to be pivotal in the development of cardiac injury, seeing as positive correlations have been established between the increase in inflammatory markers and myocardial damage in COVID-19 [21, 22]. Indeed, this idea is additionally supported by previous studies, in other septic conditions, evidencing that the release of pro-inflammatory cytokines such as TNFα and IL-1β, were responsible for myocardial cells depression through modulation of calcium channel activity and nitric oxide production [23].
It may also be the case that the cytokine storm following SARS-CoV-2 infection determines the AHF, recurrently seen in severe COVID-19, as the inflammatory activation and oxidative stress background are similarly expressed generally in heart failure, predisposing to a more severe clinical course [24].
Lastly, the aforementioned marked inflammatory changes will also take place in the endothelium, as shown in postmortem histological studies, evidencing lymphocytic endotheliitis with apoptotic bodies and viral inclusion in multiple organs [7, 25]. Endotheliitis can lead to disseminated intravascular coagulation, with small or large vessels thrombosis and infarction, and will determine significant new vessel growth through a mechanism of intussusceptive angiogenesis [25].
After becoming infected, roughly 20% of COVID-19 patients will be incapable of controlling/halting viral replication through their initial immune response, which may be aberrant/insufficient or overwhelmed by a high initial viral load, or both [26]. This subgroup of patients will thus progress to a more severe disease phenotype, with aggravating symptomatology secondary to uncontrolled viral replication, leading to host pneumocyte and endothelial cell apoptosis, which in turn will activate platelets, induce procoagulant factor expression (fibrinogen, factors V, VII, VIII, X, and von Willebrand), and increase inflammatory response, as the body tries and fails to keep the infection localized to the lungs [27]. This sequence of host responses will additionally damage the pulmonary parenchyma (through further destruction of pneumocytes, microangiopathy, and inflammatory microthrombi), causing even more severe symptoms and hindering oxygenation, thus imposing the need for an additional oxygen supply. Even so, at this point, a relative balance between procoagulant and anticoagulant (but also pro-inflammatory/anti-inflammatory) factors is still maintained. In only approximately 5% of symptomatic patients, the pro-inflammatory processes involved in the immune response to SARS-CoV-2 infection will derail into the so-called “cytokine storm,” which will fuel pro-inflammatory and pro-coagulatory processes even further, resulting in systemic endotheliitis and capillary leakage, cellular dysfunction, organ dysfunction (including ARDS), and overt activation of the (systemic) coagulation cascade resulting in the need for critical organ support [28]. In fact, SARS-CoV-2 infection may trigger endothelial dysfunction not only through the direct cytopathic effect of invasion on vascular endothelial cells but also through indirect mechanisms, such as hypoxia and the induced inflammatory response [27]. Moreover, some patients have also manifested antiphospholipid antibodies [28].
Therefore, all factors of the classic Virchow triad are influenced during the course of COVID-19, and they contribute synergically to the risk of thromboembolic events: hemodynamic changes (increased blood viscosity due to elevated fibrinogen, but also venous stasis due to hospitalization and disease-related immobilization); hypercoagulability (due to an overwhelming inflammatory state, occurring early after infection); and endothelial injury/dysfunction (ACE2 receptor expression on endothelial cells allows viral entry and cytopathic effects – endotheliitis) [3].
It is generally accepted that viral infections, and corona viruses even more, are a common cause of myocarditis, frequently associated with congestive heart failure (CHF), and an increased risk to sudden death due to ventricular arrhythmias [29]. Emerging data suggest an increased association between myocarditis and COVID-19, observed more frequently in hospitalized patients, associated with an increased risk of adverse outcome, including higher mortality rates [30].
According to Dallas criteria, acute myocarditis is defined as “inflammatory infiltrate of the myocardium with necrosis and/or degeneration of adjacent myocytes not typical for the ischemic damage associated with coronary artery disease.” Proposed pathophysiological pathways are myocardial injury due to the direct action of the virus, mediated via ACE2 receptors, and an intense, prolonged inflammatory response resulting in the release of high amounts of cytokines [29, 31, 32] together with additional factors such as hypoxia, increased metabolic demands, and physiological stress. At biopsy, myocyte and interstitial cells necrosis and mononuclear cell infiltrates were detected.
The real prevalence of acute myocarditis in patients infected with the SARS-CoV-2 virus is difficult to establish. In the medical literature, in these patients, the estimated incidence of acute myocarditis ranges from 12–17% or even 22–31% in ICU patients [33]. The symptoms vary from mild, nonspecific ones: palpitations, breathlessness, chest pain, common in influenza, to the dramatic picture of AHF with dyspnea, arrhythmias, or even sudden cardiac death. On the electrocardiogram (ECG), there are nonspecific ST, PR, and T-wave abnormalities, but signs mimicking an ACS, tachyarrhythmias, and conduction disturbances associated or not with left ventricular echocardiographic alterations and elevated levels of high sensitive troponins are also frequently seen [31, 33]. Another aspect is that the main diagnostic criteria require endomyocardial biopsy and cardiac magnetic resonance imaging (MRI), which are sometimes difficult or even impossible to access in COVID-19 patients due to the increased risk of contamination [33, 34]. It has been discussed that the prevalence of myocarditis rose parallel with the evolving strains of the SARS-CoV-2 virus being higher in patients infected in 2021 than in 2020 [30].
The incidence of pericarditis in COVID-19 patients ranges from 3% to 4.8% [35, 36]. It is often associated with myocarditis in COVID-19 patients with pneumonia and elevated inflammatory markers, as demonstrated by Diaz et al. in a meta-analysis performed on 33 studies, mainly case reports. The principal mechanism seems to be an autoreactive, inflammatory response [36].
Pericarditis manifests itself with a variety of symptoms, such as chest pain, fever, and dyspnea [36]. Pericardial friction rub is seldom encountered (9.3%) [36]. The predominant characteristic of this type of pericarditis is pericardial thickening observed at transthoracic echocardiography (TTE) persisting several weeks during recovery [37]. Over 50% of patients have pericardial effusion, mostly small to moderate in size, with 34% having large pericardial effusion, and even pericardial tamponade developed in about half of this last subset of patients [36]. On the ECG, 60% of patients present the typical four-stage evolution: diffuse ST elevation with depression of the PR segment, normalization of ST elevation, diffuse T-wave inversion, and in the end, normalization of the ECG [66]. Some patients presented unspecific signs, such as diffuse ST elevation, PR depression, and focal T-wave inversion [36].
The treatment of acute pericarditis consists in high doses of nonsteroidal anti-inflammatory drugs (NSAIDs) such as Ibuprofen, Indomethacin, or Naproxen recommended until symptom relief is achieved, and in addition, colchicine is recommended to be used for 3 to 6 months. Aspirin may be an alternative to NSAIDs [36]. Although low to moderate doses of steroids could be recommended in patients with SARS-CoV-2 infection, in most cases, this therapy is started sooner because of the associated viral myocarditis [36]. Furthermore, steroids can also be added to NSAIDs and colchicine as triple therapy for patients with an incomplete response. In the case of cardiac tamponade, pericardial drainage represents the standard of care [36]. Usually, the evolution of pericarditis associated with COVID-19 is benign.
An increased incidence of ACS has been reported in several viral infections such as influenza, SARS, and MERS, being associated with a 3- to 10-fold increased risk, but in COVID-19 exact data are lacking [31, 32]. As principal potential pathophysiological pathways are considered: destabilization of atherosclerotic plaques due to systemic inflammation with an increased release of pro-inflammatory cytokines, the “cytokine storm,” associated microangiopathy, activation of prothrombotic factors, as well as other specific changes of immune cell polarization toward more unstable phenotypes. Contributing factors also are myocardial oxygen supply/demand mismatch in the context of increased metabolic demands due to tachycardia/arrhythmias, fever, and hypoxia. These factors probably represent also the best explanation for the increased troponin levels observed in many patients with acute COVID-19 in the absence of typical cardiovascular manifestations (chest pain, specific ischemic electrocardiographic modification, and parietal hypokinesia at TTE) [31, 32], the more so as some other complications such as myopericarditis may have similar symptoms, and often patients with COVID-19 may not have typical angina symptoms.
Patients already suffering with coronary artery disease and heart failure may be exposed in a greater extent to ACS as a consequence of coronary plaque rupture or stent thrombosis in the context of systemic inflammation [31, 32]. For this reason, it is strongly recommended that in patients with a previous history of coronary artery disease and especially in those with coronary interventions, antiplatelet therapy should be continued, eventually even intensified, together with other plaque stabilizing agents such as statins, beta-blockers, and angiotensin-converting enzyme inhibitors [27, 30, 38, 39].
In this global health systems crisis, an adequate diagnosis and management of ACS is complicate and health care institutions worldwide have reexamined their protocols considering the increased risk of contamination of healthcare personal and the high requirements for protective equipment [34, 40, 41]. However, risk stratification is difficult due to limited bedside approach for an accurate ECG and TTE examination [31, 42]. The treatment of acute myocardial infarction (AMI) in COVID-19 patients is even more controversial. While in patients diagnosed with non-ST elevation myocardial infarction (non-STEMI), the result of a PCR testing could be expected prior to cardiac catheterization, in cases with ST elevation myocardial infarction (STEMI), the American College of Cardiology (ACC) recommends reconsidering fibrinolysis in patients with “low-risk STEMI” such as inferior without right ventricular extension, or lateral STEMI without altered hemodynamic. Thus percutaneous coronary intervention (PCI) remains the most indicated therapy, remaining the best option also in non-STEMI patients who are hemodynamically unstable [34, 42, 43].
In a large meta-analysis, DeLuca et al. concluded that COVID-19 pandemic has significantly impacted the therapy of patients with STEMI, with a 19% reduction in PCI procedures leading to increased morbidity and mortality, aspects evidenced also in other studies [34, 40, 43].
Arrhythmias were observed precociously in COVID-19 patients worldwide, several centers reporting a large spectrum of electrocardiographic abnormalities [31, 32]. In most cases, sinus tachycardia due to multiple, concomitant causes (hypoperfusion, fever, hypoxia, and anxiety) was observed, but also atrial tachycardia and fibrillation (AF), and less frequently atrioventricular block (AVB) and polymorphic ventricular tachycardia (VT), significantly increasing the morbidity and mortality, and explaining at least in part, the increased number of cardiac arrests noticed in out-of-hospital patients [44, 45]. It was considered that underlying mechanisms are myocardial injury, inflammation, coexisting hypoxia, electrolytic (especially hypokalemia) and acid–base imbalances, and activation of the sympathetic nervous system, which is contributing the medication used to treat this disease such as hydroxychloroquine, azithromycin, and antivirals that prolong the QT interval [46, 47].
Perhaps the most comprehensive study written on this topic is the one of Coromilas et al. who analyzed data collected from over 4000 patients with COVID-19 and arrhythmias, from 4 continents and 12 countries, and concluded that the majority of them (81.8%) developed supraventricular arrhythmias including AF and atrial flutter, 21% of subjects had ventricular arrhythmias, and 22.6% developed bradyarrhythmias [47]. They also observed that arrhythmias were more frequent in patients over 60 years old, male gender prevailed, and frequently systemic hypertension and diabetes mellitus were associated comorbidities [33, 46, 47].
Treatment of arrhythmias should follow the standard guidelines for the management of arrhythmias focusing on the underlying pathophysiological mechanisms, and addressing as much as possible the reversible causes, especially electrolyte abnormalities. In the case of recurrent, uncontrolled ventricular arrhythmias not responding to antiarrhythmic therapy, implantable cardioverter defibrillators may be recommended, and for persistent high-degree AVB transvenous pacemaker insertion [48].
As the pandemic unravels, medical literature has provided robust insight into the unique mechanisms of and specific propensity for COVID-19 thrombogenicity, identified as considerably different from other severe infectious and non-infectious diseases. The relationship between SARS-CoV-2 infection and subsequent dysregulation of coagulation homeostasis is reflected in the various rates of occurrence of major venous and arterial thromboembolic/thrombotic events, which, in more extreme cases, have been documented to occur concomitantly. A recent comparative study, which retrospectively evaluated thromboembolic risk in large patient cohorts of COVID-19 and Influenza, found that COVID-19 was independently associated with a higher 90-day risk for venous thrombosis, but not arterial thrombosis, as compared to Influenza, with secondary analysis showing a similar risk for ischemic stroke and myocardial infarction, and a higher risk for deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with COVID-19 [49].
In spite of early thromboprophylaxis, most frequently, VTE negatively impacts clinical outcomes in COVID-19 hospitalized patients, and the risk seems to be greatest in the intensive care unit (ICU) setting, among the critically ill [50]. Major arterial thrombotic events and VTE have been reported at a higher frequency, in COVID-19 ICU patients, as compared to non-ICU patients, over a 30-day period, despite a thromboprophylaxis rate of 85–90% [51]. Moreover, a recent meta-analysis of 12 studies, in which all patients were under thromboprophylaxis, with either low molecular weight or unfractionated heparin, still showed a 31% pooled prevalence of VTE for ICU admissions [52]. Very recently, an overall incidence of 17.3% for VTE among hospitalized COVID-19 has been reported (~2/3 DVT), with significant discrepancies between pooled incidences of VTE for ICU admissions as compared to general ward patients (27.9% vs. 7.1%, respectively), while including catheter-associated thromboembolism, isolated distal DVT, and isolated pulmonary emboli reached the highest incidence rates. Even so, VTE incidence was higher when assessed within a screening strategy (33.1% vs. 9.8% by clinical diagnosis), meaning that, in clinical practice, it is very likely that many COVID-19 patients with subclinical VTE remain undiagnosed [53]. Moreover, VTE prevalence in COVID-19 patients varies widely depending on the subpopulation evaluated, seemingly correlating well with disease severity and preexisting metabolic and cardiovascular comorbidities, a statement reflected by the variability of occurrence rates reported: <3% in non-ICU patient [51], >30% for ICU cases, with DVT and subsequent PE representing the most common thrombotic complication in the ICU setting [54], while autopsy findings of COVID-19 fatalities suggest it may reach nearly 60% [55].
Interestingly, amounting data suggest that the majority of so-called PE diagnoses occur without a recognizable source of venous embolism and may be better defined as primary in situ pulmonary arterial thrombosis, a direct consequence of the SARS-CoV-2 pulmonary disease, entailing thrombotic occlusion of small−/mid-sized pulmonary arteries, which will result in the infarction of afferent lung parenchyma [56]. This may explain why PE is the most prevalent thrombotic event seen in COVID-19 patients [54] and why screening yielded a higher incidence of VTE than clinical evaluation of asymptomatic patients. In a recent investigation, duplex ultrasound was performed for clinical suspicion of DVT, reporting 41.58% confirmed DVT, 6.93% superficial thrombophlebitis and, surprisingly, 23.76% PE (mostly involving distal pulmonary vessels), yet only 7.92% had PE and concomitant, associated DVT, meaning that 2/3 of PE occurred in the absence of a recognizable DVT, suggesting a causal mechanism of primary thrombosis rather than embolism [56]. Additionally, postmortem analyses of COVID-19 fatalities have frequently documented thrombosis of small- and mid-sized pulmonary arteries, a lesion capable of causing hemorrhagic necrosis, fibrosis, disruption of pulmonary circulation, acute pulmonary hypertension (PH), and ultimately death [55]. Other severe morphopathological modifications of pulmonary tissue architecture have also been frequently reported in COVID-19 autopsy reports, such as severe endothelial injury, with disruption of cell membranes, rampant vascular thrombosis, and significant angiogenesis [25], while other organs also showed microthrombotic lesions on autopsy, but at a lower rate (cardiac thrombi, epicardial coronary artery thrombi and microthrombi in myocardial capillaries, arterioles, and small muscular arteries) [55].
An aforementioned study, analyzing 184 COVID-19 ICU cases, all receiving thromboprophylaxis, demonstrated a 31% cumulative incidence of the defined vascular complication composite outcome (PE, DVT, ischemic stroke, ACS, or systemic arterial embolism). The main independent predictors of thrombotic complications identified were age, with an adjusted hazard ratio (aHR) of 1.05/per year, and coagulopathy [54]. Conversely, regarding VTE, an extensive meta-analysis (44 studies/14,866 hospitalized COVID-19 patients), on the topic acute complications and mortality, reported a much lower prevalence of 15% for VTE, than previously reported. This value may be influenced not only by cohort size but also by other factors such as heterogeneous reporting between the studies evaluated and increased risk of bias, resulting in very low-quality evidence [57].
On the other hand, as seen in the above-mentioned studies, VTE can still occur in noncritically ill COVID-19 patients; therefore, rigorous elaboration of adequate screening and risk stratification protocols for VTE, especially for mild and moderate COVID-19 phenotypes, will be essential, as these patients are much less likely to undergo tromboprophylaxis.
Regarding arterial thromboembolism (ATE), incidence rates among COVID-19 diagnosed patients have consistently been reported as being much lower than for VTE, since the early days of the pandemic (3.7%) to date [54]. Unsettlingly, large-vessel strokes in young and generally healthy people, which became infected with SARS-CoV-2, have been consistently reported [25, 55]. Early retrospective studies, seemingly corroborated these findings, claiming that acute, new-onset, cerebrovascular disease was not uncommon in COVID-19 patients – out 219 consecutive COVID-19 patients, 10 (4.6%) developed acute ischemic stroke and 1 (0.5%) had intracerebral hemorrhage [58] –,and that SARS-CoV-2 infection carried an increased risk of ACS, especially via coronary stent thromboses [59]. Nevertheless, investigations involving a much larger sample size showed that the actual incidence of ATE (thrombotic/embolic) is, in fact, much lower than initially reported in earlier studies [51, 60]. A large cohort retrospective study, evaluating 1114 COVID-19 patients with independently adjudicated thrombotic/embolic events, found stroke and ACS incidence were 0.1% (1/1114) and 1.3% (14/1114), respectively [51]. Most authors agree that thrombotic events occur early in the evolution of COVID-19, and in order to combat the hypercoagulable and prothrombotic state, administration of anticoagulants is recommended to reduce this risk [27].
Of great importance is the fact that, due to several factors such as thrombocytopenia, hyperfibrinolytic state, consumption of coagulation factors, which initiate their action later on, after 1 to 3 weeks, COVID-19 patients may also become prone to bleeding. This must be taken into account, especially in severe COVID-19 cases, where concomitant administration of anticoagulants as thromboprophylaxis is very likely to occur [61]. Additionally, critically ill COVID-19 patients have an even more increased bleeding risk, due to thrombocytopenia/platelet dysfunction or coagulation factor deficiencies, or both [62], which are frequent occurrences in this clinical population. Thus, it has become increasingly difficult to establish an adequate, integrative, anticoagulant prophylaxis strategy for COVID-19.
As opposed to the numerous investigations debating over thromboembolic events, there are much fewer articles focusing on major bleedings and just a few case reports on hematomas in COVID-19. Al-Shamkary et al. reported an overall incidence of 4.8–8% referring to bleeding events, and of 3.5% for major bleedings [62], being mostly associated with advanced age, comorbidities and apparently, more frequent in males.
All in all, thromboembolic events are a frequent morbidity encountered in COVID-19 patients, especially in those with severe forms and comorbidities. For their prophylaxis/treatment anticoagulant therapy is recommended, thus increasing the risk of bleedings. Both thromboembolic events and hemorrhagic complications aggravate the evolution of these patients, representing significant negative prognostic factors and increasing the morbidity and mortality associated with COVID-19.
The important contribution of COVID-19 in the pathogenesis of acute cardiovascular involvements is now well established, but because this pandemic is a new disease, long-term data on post-COVID-19 complications were not available [63, 64]. However, more and more studies revealed that the infection with the SARS-CoV-2 virus also causes chronic cardiac complications, even when the viral load is normalized [63, 64], explaining the persistence of symptoms during recovery observed in an increasing number of individuals [65]. In some patients, myocarditis, subacute pericarditis, persisting arrhythmias, pulmonary hypertension, or heart failure have been observed raising serious concerns and indicating that in symptomatic patients, a comprehensive evaluation and a regular long-term follow-up are needed for effective therapeutic regime and to prevent a worse evolution of these cardiovascular complications.
It is well known that pulmonary hypertension (PH) may occur during the acute phase of the SARS-CoV-2 infection as a consequence of extensive lung injury and of altered pulmonary circulation, frequently leading to right heart failure (RHF), shearing common pathophysiological mechanisms with other complications encountered in this illness, and significantly increasing the mortality [66, 67].
In COVID-19 patients, the prevalence of PH varies wildly, depending on the studied population, ranging from 7.69% to 12–13,4% or even 22% in severe COVID-19 cases [67, 68]. While this topic was largely debated in the medical literature, information over its outcome is less available. It has been observed that some patients are predisposed to develop interstitial lung disease (ILD) frequently associated with persisting PH and explaining, at least partially, the persisting symptoms observed in patients with subacute and long COVID-19 [69, 70]. The backgrounds of this disease are complex and multifactorial, including a large variety of pathophysiological types, ranging from arterial PH (group 1), PH of group 3 – due to ILD, to chronic thromboembolism (group 4 PH) or even of group 2 PH (secondary left heart disease) [70, 71]. In their study, Suzuki et al., observed a unique hystopathological finding identified only at the autopsy of COVID-19 patients, namely thickened pulmonary vascular walls, considered an important hallmark of arterial PH [71]. This finding suggests that COVID-19, depending on the severity of the lung injury and the inflammatory responses, could favor the development of PH, and some of these patients may develop in the future signs and symptoms of PH and RHF [71].
The diagnosis of PH is difficult and implies right heart catheterization, which is limited during the pandemic considering the risk of contamination and shortness of personal and resources. In patients infected with SARS-CoV-2, TTE allows an accurate estimation of the systolic pressure in the pulmonary artery, being the most utilized method for the diagnostic and follow-up of these patients. A specific therapy for this type of PH has not been described, and future studies are needed to clarify its management.
AHF may appear precocious in the evolution of the SARS-CoV-2 infection, in some cases being even the first manifestations. Since COVID-19 and AHF/worsening of CHF shear similar symptoms, distinguishing these two pathologies is challenging, the more so as these two conditions may coexist. Some studies describe an increased prevalence of ACH (23% or even 33%) in patients hospitalized for COVID-19 being associated with an increased risk of mortality [63]. In many cases, it is difficult to establish if AHF is the consequence of a new myocarditis/cardiomyopathy or it represents the exacerbation of previously undiagnosed CHF. Responsible pathophysiological mechanisms of AHF in COVID-19 may include acute myocardial injury due to inflammation (myocarditis), tachyarrhythmia or ischemia, or to acute respiratory failure, acute kidney injury, and hypervolemia [9, 29, 31]. Importantly, RHF may also be present especially in patients with severe pulmonary injury and PE contributing to the increased mortality of these patients [37].
Diagnosis may be difficult, but clinical presentation, history of preexisting cardiovascular comorbidities, evidence of cardiomegaly, and/or bilateral pleural effusion on chest radiography are suggestive. Increased levels of B-type natriuretic peptide (BNP)/N-terminal B-type natriuretic peptide (NT-proBNP) could be an important clue for AHF/worsened CHF, although elevated BNP/NT-proBNP values were also found in COVID-19 patients in the absence of AHF. An important contribution offers TTE demonstrating enlarged cardiac cavities, impaired systolic performance, and other important signs [34, 49, 72].
Therapy of AHF in COVID-19 patients should be performed according to guidelines [63] based on the same recommendation as in subjects without COVID-19, with special attention to early detection and treatment of complications, especially hypoxia, thrombotic/bleeding events, and cardiac arrhythmias. It is important to consider AHF/CHF when administering intravenous fluids avoiding excessive fluid replacement and to be conscious on the cardiac adverse effects of medications used in the treatment of COVID-19 [9, 31, 64].
Referring to patients already diagnosed with CHF, it is well known that they are predisposed to develop more severe forms of COVID-19, being predisposed to a higher mortality. The SARS-CoV-2 infection may also unmask a latent CHF, particularly heart failure with preserved ejection fraction (HFpEF) which is common among elderly overweight, hypertensive patients. In addition, as a consequence of myocardial injury, cardiac fibrosis may occur, explaining the increased frequency of diastolic dysfunction identified on TTE. The risk to develop overt CHF is present both during the acute phase of COVID-19 and during the recovery from the acute illness in survivors [31, 33, 72, 73].
Another aspect is that the COVID-19 pandemic negatively impacted the outcome of patients with CHF who avoided or delayed hospital controls or admissions due to fear of contamination. They presented themselves to the hospital only when their condition was severe, which lead to an increased mortality worldwide [9, 74].
The relationship between the infection with the SARS-CoV-2 virus and systemic hypertension is very complicated and difficult to establish. While it is generally accepted that COVID-19 patients with a history of cardiovascular diseases, especially systemic hypertension, have a worse outcome and increased mortality [29, 75], it is very difficult to establish if there is a new onset or a worsening of a chronic hypertension in the context of this illness, since a previous comprehensive evaluation is not available in the majority of cases. A meta-analysis of Lippi et al. evidenced a nearly 2.5-fold increase of severity and mortality of severe COVID-19 in patients with associated systemic hypertension, especially in those older than 60 years with other comorbidities [75].
Other large meta-analyses focused on the impact of hypertension’s severity and its control and the outcomes but failed to document significant connections [76]. It was concluded that hypertension is associated with endothelial dysfunction strongly impacted in COVID-19, and patients with more severe forms have more advanced atherosclerosis and consecutive complications, thus increasing the morbidity and mortality. As the concerns regarding therapy with ACE inhibitors were not found to be justified, treatment should be given according to guidelines to optimize blood pressure values [77].
The postural tachycardia syndrome (POTS) is the result of an autonomic dysregulation which determines increased vasoconstriction when standing, resulting in blood pooling within the splanchnic vasculature and limbs, with reduced venous return to the heart. An excessive compensatory tachycardia and increased plasma noradrenaline levels contribute to symptoms, the commonest of which are fatigue, palpitations, light-headedness, headache, and nausea symptoms reported by many of patients with long-COVID (between 15% and 50% according to some studies) [78]. Although orthostatic intolerance is common among patients recovering from a COVID-19 infection, not all have POTS, some of them have only orthostatic hypotension [78].
The exact pathophysiological mechanism of POTS is not fully clarified, and there are several mechanisms involved, including hypovolemia, autonomic denervation, hyperadrenergic stimulation, and autoimmune pathology. It is not well established whether the same recognized pathophysiology of POTS is also present in patients with long COVID further studies being necessary [78].
From the early stages of the infection with the SARS-CoV-2 virus, it became evident that underlying cardiovascular diseases, obesity, diabetes mellitus, and more advanced age are associated with a higher risk for severe COVID-19 infection [34]. Individuals already suffering from cardiovascular diseases were more likely to be infected with the virus, and the virus infection was likely to determine the deterioration of basic heart disease [79]. Apparently, among COVID-19 patients, there were almost 50% diagnosed with chronic diseases, 40% of them with cardiovascular and cerebrovascular disorders, chronic kidney failure, and chronic obstructive pulmonary disease, having an increased risk of morbidity or even death related to this infection. A large study from the USA reported that the most common comorbidities among patients with COVID-19 were systemic hypertension (56.6%), obesity (41.7%), diabetes (33.8%), coronary artery disease (11.1%), and CHF (6.9%) [33], and a retrospective cohort study in China conducted on patients with cardiovascular comorbidities evidenced a fivefold higher mortality risk (10.5%). Based on these results, hypertension and cardiovascular comorbidities can be considered as risk factors for persons with severe symptoms of the disease.
In COVID-19 cases, it is important to recognize the clinical characteristics of infected persons to identify and effectively treat the associated comorbidities and the newly developed cardiovascular complications as well to reduce patients’ morbidity and mortality. Since many antiviral drugs may determine cardiac insufficiency, arrhythmia or other cardiovascular disorders, therefore, during the therapy of this illness, especially with antiviral therapy, the risk of cardiac toxicity needs to be closely monitored [79].
Another aspect is that of the long-term outcome of patients who suffered from a SARS-CoV-2 infection. In a recent and comprehensive study realized on over 150000 individuals recovering from COVID-19 [80], Xie et al. highlighted that beyond the first month after infection, people with COVID-19 experienced at 12 months an increased morbidity risks and burdens of cardiovascular diseases, including cerebrovascular disorders, dysrhythmias, inflammatory heart disease, ischemic heart disease, heart failure, thromboembolic disease, and other cardiac disorders [80]. These risks were obvious regardless of age, race, gender, and associated cardiovascular risk factors, including obesity, hypertension, diabetes, chronic kidney disease, and hyperlipidemia, being evident even in individuals without history of cardiovascular pathology before the SARS-CoV-2 virus infection, raising concerns that these risks might be present even in people at low risk of cardiovascular disease [80]. These risks and associated burdens increased parallel to the severity of the acute phase of COVID-19: from non-hospitalized individuals – who were the majority – to hospitalized patients, especially to those admitted to the intensive care units [80].
It has been observed that many of the medications used for the treatment of COVID-19 strongly interfere with other medications used in the therapy of cardiovascular diseases, such as anticoagulants, antiplatelets, statins, antihypertensives, and especially antiarrhythmics favoring the occurrence of arrhythmias [31]. Some antibiotics (azithromycin), corticosteroids, antimalarials (chloroquine, hydroxychloroquine), newly developed therapies, still under study such as antivirals (remdesivir, ribavirin, lopinavir/ritonavir, and favipiravir), and biologics (tocilizumab) determine cardiotoxicity, interact with electrolyte metabolism, and many of them, especially Lopinavir/ritonavir, may cause QT and PR prolongation favoring the occurrence of arrhythmias or conduction disturbances, mainly in patients already treated with drugs prolonging the QT interval. Data over the mechanism of action and potential effects of main medication used in the treatment of COVID-19 is presented in Table 1 [31].
Medication | Mechanism of action | Cardiovascular effects and drug interactions |
---|---|---|
Azithromycin | Interacts with the synthesis of proteins and binds to 50s ribosome |
|
Chloroquine and Hydroxychloroquine | Alterations in the pH of endosomal/organelle |
|
Methylprednisolone | Anti-inflammatory |
|
Remdesivir | Inhibitor of RNA polymerases |
|
Ribavirin | Inhibits RNA and DNA virus replication |
|
Lopinavir/Ritonavir | Lopinavir inhibits protease and Ritonavir inhibits CYP3A metabolism |
|
Favipiravir | Inhibits RNA-dependent RNA polymerases |
|
Interferon | Immune system activation |
|
Tocilizumab | Inhibits IL-6 |
|
Interactions of medications used in the treatment of COVID-19.
After the introduction of mRNA COVID-19 vaccines a higher incidence of myocarditis in vaccine recipients. A study performed on the data basis from an Israeli national database concluded that the incidence of myocarditis after two doses of the BNT162b2 mRNA vaccine was reduced (risk ratio = 3.24), significantly lower than after COVID-19 (risk ratio = 18.28), but higher than in unvaccinated individuals. The risk of myocarditis was higher after the second dose of vaccine and in young male recipients [81].
Similar results were also reported by other researcher, with an elevated risk of myocarditis, pericarditis, and myopericarditis observed particularly among young males with 39–47 expected cases of per million second mRNA COVID-19 vaccine doses administered [82]. They reported an increased risk of myocarditis after the first dose of ChAdOx1 and BNT162b2 vaccines and the first and second doses of the mRNA-1273 vaccine [82].
The impairment of the cardiovascular system in COVID-19 comprises a wide spectrum of dysfunctions, ranging from mild to severe, or even life-threatening forms, often having an acute onset, sometimes continuing during recovery or even resulting in chronic pathologies. Individuals are affected regardless of age, race, gender, and associated cardiovascular risk factors, but those with a history of cardiovascular pathology prior to the SARS-CoV-2 virus infection have a worse outcome. Therefore, a comprehensive cardiologic evaluation, including TTE, is justified to assess the involvement of the cardiovascular system, for initiating a proper therapy as soon as possible and to schedule a follow-up program particularly in patients at high risk.
IntechOpen - where academia and industry create content with global impact
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\n\nSara Uhac, COO
\n\nSara Uhac was appointed Managing Director of IntechOpen at the beginning of 2014. She directs and controls the company’s operations. Sara joined IntechOpen in 2010 as Head of Journal Publishing, a new strategically underdeveloped department at that time. After obtaining a Master's degree in Media Management, she completed her Ph.D. at the University of Lugano, Switzerland. She holds a BA in Financial Market Management from the Bocconi University in Milan, Italy, where she started her career in the American publishing house Condé Nast and further collaborated with the UK-based publishing company Time Out. Sara was awarded a professional degree in Publishing from Yale University (2012). She is a member of the professional branch association of "Publishers, Designers and Graphic Artists" at the Croatian Chamber of Commerce.
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\n\nDr Alex Lazinica
\n\nAlex Lazinica is co-founder and Board member of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his Ph.D. in Robotics at the Vienna University of Technology. There, he worked as a robotics researcher with the university's Intelligent Manufacturing Systems Group, as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and, most importantly, co-founded and built the International Journal of Advanced Robotic Systems, the world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career since it proved to be the pathway to the foundation of IntechOpen with its focus on addressing academic researchers’ needs. Alex personifies many of IntechOpen´s key values, including the commitment to developing mutual trust, openness, and a spirit of entrepreneurialism. Today, his focus is on defining the growth and development strategy for the company.
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She is now a lecturer at the University of Witwatersrand, South Africa, and a principal researcher at the Health Economics and Epidemiology Research Office (HE2RO), South Africa. Dr. Moolla holds a Ph.D. in Psychology with her research being focused on mental health and resilience. In her professional work capacity, her research has further expanded into the fields of early childhood development, mental health, the HIV and TB care cascades, as well as COVID. She is also a UNESCO-trained International Bioethics Facilitator.",institutionString:"University of the Witwatersrand",institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"342152",title:"Dr.",name:"Santo",middleName:null,surname:"Grace Umesh",slug:"santo-grace-umesh",fullName:"Santo Grace Umesh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/342152/images/16311_n.jpg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"333647",title:"Dr.",name:"Shreya",middleName:null,surname:"Kishore",slug:"shreya-kishore",fullName:"Shreya Kishore",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333647/images/14701_n.jpg",biography:"Dr. Shreya Kishore completed her Bachelor in Dental Surgery in Chettinad Dental College and Research Institute, Chennai, and her Master of Dental Surgery (Orthodontics) in Saveetha Dental College, Chennai. She is also Invisalign certified. She’s working as a Senior Lecturer in the Department of Orthodontics, SRM Dental College since November 2019. She is actively involved in teaching orthodontics to the undergraduates and the postgraduates. Her clinical research topics include new orthodontic brackets, fixed appliances and TADs. She’s published 4 articles in well renowned indexed journals and has a published patency of her own. Her private practice is currently limited to orthodontics and works as a consultant in various clinics.",institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"323731",title:"Prof.",name:"Deepak M.",middleName:"Macchindra",surname:"Vikhe",slug:"deepak-m.-vikhe",fullName:"Deepak M. Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Univeristy of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:null},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:null},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. 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Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. 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