Causes of portal hypertension related to site of increased resistance to portal blood flow
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"9873",leadTitle:null,fullTitle:"Strategies of Sustainable Solid Waste Management",title:"Strategies of Sustainable Solid Waste Management",subtitle:null,reviewType:"peer-reviewed",abstract:"The world is currently experiencing increased environmental contamination with solid waste, which is one of the greatest environmental threats today. Although solid waste is harmful, proper management and profitable recycling can make it beneficial to the environment. In this regard, estimation of the true quantities of solid wastes generated annually in developed and developing countries is important for evaluating suitable strategies for economic and sustainable procedures of waste management. This book presents an interesting review of the economics of solid waste management in various developing and developed countries. It examines several economic applications of solid waste, such as innovative methods to generate bioelectricity from organic waste using microbial fuel cells and using solid waste as an alternative fuel in cement kilns.",isbn:"978-1-83962-560-2",printIsbn:"978-1-83962-559-6",pdfIsbn:"978-1-83962-561-9",doi:"10.5772/intechopen.87682",price:119,priceEur:129,priceUsd:155,slug:"strategies-of-sustainable-solid-waste-management",numberOfPages:170,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"59b5ceeeedaf7449a30629923569388c",bookSignature:"Hosam M. Saleh",publishedDate:"April 21st 2021",coverURL:"https://cdn.intechopen.com/books/images_new/9873.jpg",numberOfDownloads:6734,numberOfWosCitations:5,numberOfCrossrefCitations:10,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:26,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:41,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 12th 2020",dateEndSecondStepPublish:"July 3rd 2020",dateEndThirdStepPublish:"September 1st 2020",dateEndFourthStepPublish:"November 20th 2020",dateEndFifthStepPublish:"January 19th 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"144691",title:"Prof.",name:"Hosam M.",middleName:null,surname:"Saleh",slug:"hosam-m.-saleh",fullName:"Hosam M. Saleh",profilePictureURL:"https://mts.intechopen.com/storage/users/144691/images/system/144691.png",biography:"Hosam M. Saleh is a Professor of Radioactive Waste Management in the Radioisotope Department, Atomic Energy Authority, Egypt. He obtained an MSc and Ph.D. in Physical Chemistry from Cairo University, Egypt. He has more than 25 years of experience in hazardous waste management with an emphasis on treatment and developing new matrixes for the immobilization of these wastes. He is also interested in studying innovative economic and environmentally friendly techniques for the management of hazardous and radioactive wastes. He has authored many peer-reviewed scientific papers and chapters and served as an editor of several books. He was selected among the top 2% of scientists in the world according to the Stanford University report for 2020 and 2021.",institutionString:"Egyptian Atomic Energy Authority",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"15",totalChapterViews:"0",totalEditedBooks:"14",institution:{name:"Egyptian Atomic Energy Authority",institutionURL:null,country:{name:"Egypt"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"891",title:"Solid Waste",slug:"solid-waste"}],chapters:[{id:"74478",title:"Introductory Chapter: Solid Waste",doi:"10.5772/intechopen.95327",slug:"introductory-chapter-solid-waste",totalDownloads:359,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Hosam M. Saleh and Amal I. Hassan",downloadPdfUrl:"/chapter/pdf-download/74478",previewPdfUrl:"/chapter/pdf-preview/74478",authors:[{id:"144691",title:"Prof.",name:"Hosam M.",surname:"Saleh",slug:"hosam-m.-saleh",fullName:"Hosam M. Saleh"},{id:"218811",title:"Prof.",name:"Amal I.",surname:"Hassan",slug:"amal-i.-hassan",fullName:"Amal I. Hassan"}],corrections:null},{id:"73477",title:"Reflections on the Influence of Family Demographics on Food Waste Generation among the City of Tshwane Households, Republic of South Africa",doi:"10.5772/intechopen.93755",slug:"reflections-on-the-influence-of-family-demographics-on-food-waste-generation-among-the-city-of-tshwa",totalDownloads:337,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This chapter presents the influence of households’ demographics on food waste generation. A mixed method research approach consisting of meta-analysis, survey (structured interviews), and experimental were used to collect opinions and weigh the amount of waste generated in each household. Although not all demographic variables were investigated, the influence of: (1) family size, (2) household monthly income, (3) employment status, (4) educational level, and (5) age of respondents on food waste generation were analyzed. The results of the study confirmed that age and family size are positive factors that influence the amount of food waste generated in households of the City of Tshwane, as opposed to the level of education, employment status, and monthly income levels. It should be noted, however, that this study does not conclusively exclude the other factors as not having an influence in food waste generations. However, their influence in the current food waste generation quantities was not conclusive. Further studies with larger sample size are thus recommended.",signatures:"Machate Machate",downloadPdfUrl:"/chapter/pdf-download/73477",previewPdfUrl:"/chapter/pdf-preview/73477",authors:[{id:"326045",title:"Prof.",name:"Machate",surname:"Machate",slug:"machate-machate",fullName:"Machate Machate"}],corrections:null},{id:"74039",title:"Sustainable Pathway for Closing Solid Waste Data Gaps: Implications for Modernization Strategies and Resilient Cities in Developing Countries",doi:"10.5772/intechopen.94384",slug:"sustainable-pathway-for-closing-solid-waste-data-gaps-implications-for-modernization-strategies-and-",totalDownloads:405,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This chapter addresses three peculiar challenges in the solid waste management system of developing countries, namely: the chronic lack of reliable data for planning purposes, the absence of participatory engagement strategies in data gathering for wider ownership and usage, and the lack of monitoring of the climate change burden of existing waste disposal practices. A team of researchers has collaborated with system managers and a responsible philanthropic organization to engage key stakeholders to address these gaps in a sustainable manner. The strategy deployed has been to work in a participatory and evidenced-based frame to solicit support, enhance capacities, empower each other to understand the problems and find for ourselves the practical routes by which solid waste data gaps can be closed in the greater Accra region of Ghana. Stakeholders have participated in a comprehensive waste audit and landfill emission monitoring exercise to develop a baseline, and have used local resources and ideas to recommend steps to sustain reliable data flows and the development of a climate action plan for purposes of modernization. The methodological processes and research outcomes suggest that structural collaboration between researchers and system stakeholders is necessary to break the vicious circle of chronic data gaps and substitute virtuous circles of reliable data for planning purposes.",signatures:"Kwaku Oduro-Appiah and Abraham Afful",downloadPdfUrl:"/chapter/pdf-download/74039",previewPdfUrl:"/chapter/pdf-preview/74039",authors:[{id:"324899",title:"Dr.",name:"Kwaku",surname:"Oduro-Appiah",slug:"kwaku-oduro-appiah",fullName:"Kwaku Oduro-Appiah"},{id:"330032",title:"Mr.",name:"Abraham",surname:"Afful",slug:"abraham-afful",fullName:"Abraham Afful"}],corrections:null},{id:"73972",title:"Guide for Organising a Community Clean-up Campaign",doi:"10.5772/intechopen.94515",slug:"guide-for-organising-a-community-clean-up-campaign",totalDownloads:889,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"While it is the government’s and municipality’s mandate to ensure that its citizens stay in a clean and safe environment, it is of concern that waste management remains a big challenge in urban areas especially in developing countries. Increased economic development, rapid population growth and improvement of living standards are among the factors attributed to increased quantity and complexity of solid waste being generated. On the other hand, while people generate wastes, they continue to be looked at as passive recipients of municipality services. Ultimately, citizens fail to recognise their role in waste management and become unwilling to either pay for service delivery or participate in clean-up campaigns. Waste dumps are prime breeding sites for communicable disease vectors such as rodents, mosquitoes and houseflies, which can exacerbate the prevalence of water, food and waterborne diseases such as cholera and typhoid. This chapter thus describes the methodology of successfully conducting a community-led cleanup campaign. It is based on experience gained during implementation of an urban water, sanitation and hygiene (WASH) project. Ward level clean-up campaigns were organised and conducted by community members and local leaders. Besides clearing illegal dumpsites, the activity was also used to raise awareness on the consequence of waste dumping. The experience showed that organising a clean-up campaign only requires careful timeous planning. Overall, it was concluded that not only does the activity serve the practical purpose of cleaning, but it also creates a greater sense of unity and friendship among community members. Additionally, the power of beautification in a clean-up campaign wold naturally motivate residents to believe that their problems could be solved, resulting in a shared responsibility for sustainable management of waste and commons at local level.",signatures:"Innocent Rangeti and Bloodless Dzwairo",downloadPdfUrl:"/chapter/pdf-download/73972",previewPdfUrl:"/chapter/pdf-preview/73972",authors:[{id:"171647",title:"Mr.",name:"Innocent",surname:"Rangeti",slug:"innocent-rangeti",fullName:"Innocent Rangeti"},{id:"327929",title:"Dr.",name:"Bloodless",surname:"Dzwairo",slug:"bloodless-dzwairo",fullName:"Bloodless Dzwairo"}],corrections:null},{id:"74647",title:"Economics of Solid Waste Management: A Review",doi:"10.5772/intechopen.95343",slug:"economics-of-solid-waste-management-a-review",totalDownloads:821,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Solid Waste Management is one of the importance environmental issues at many developing countries. There is a lack of studies on economic analysis of solid waste management in the many cities at the national and international level. Most of the Municipal Corporation or city management is the major responsibility for better waste management. However, the local governments has been allocated budget for solid waste management without analysing cost and benefit of solid waste. Although, waste management budget is focusing on collected waste but, uncollected waste has been creating a number of socio, economic and health issues. Therefore, this chapter has presents a details review on economics of solid waste management at the various developing and developed countries. The main policy implication of the paper is to emphasis on better understanding of economic importance of solid waste management to the local policy makers.",signatures:"Muniyandi Balasubramanian",downloadPdfUrl:"/chapter/pdf-download/74647",previewPdfUrl:"/chapter/pdf-preview/74647",authors:[{id:"275432",title:"Dr.",name:"Muniyandi",surname:"Balasubramanian",slug:"muniyandi-balasubramanian",fullName:"Muniyandi Balasubramanian"}],corrections:null},{id:"73967",title:"Sustainable Solid Waste Management in Morocco: Co-Incineration of RDF as an Alternative Fuel in Cement Kilns",doi:"10.5772/intechopen.93936",slug:"sustainable-solid-waste-management-in-morocco-co-incineration-of-rdf-as-an-alternative-fuel-in-cemen",totalDownloads:346,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The management of municipal solid waste (MSW) is a major obstacle for the majority of municipalities in developing countries because of the impacts related to the landfilling of waste. Garbage is an energy-rich material. As a result, energy recovery is considered to be a sustainable waste management method. In Morocco, 7.4 million tons are produced annually; most of the waste is landfilled without any recovery despite the impacts related to this method of disposal. The objective of this chapter is to characterize combustible fractions (RDF) from household waste in Morocco and to study the economic and environmental benefits of their use as alternative fuels in cement kilns. The results of this research show that the combustible fractions contained in household waste in Morocco constitute a potential sustainable energy source with a high lower calorific value (4454 kcal/kg). The study of the advantages of co-incineration shows that the substitution of pet coke by 15% RDF reduces the pollution linked to gaseous emissions. In addition, the cement plant can make financial savings 389 USD/h by minimizing the use of fossil fuels.",signatures:"Aziz Hasib, Abdellah Ouigmane, Otmane Boudouch, Reda Elkacmi, Mustapha Bouzaid and Mohamed Berkani",downloadPdfUrl:"/chapter/pdf-download/73967",previewPdfUrl:"/chapter/pdf-preview/73967",authors:[{id:"166445",title:"Prof.",name:"Aziz",surname:"Hasib",slug:"aziz-hasib",fullName:"Aziz Hasib"},{id:"237725",title:"Prof.",name:"Reda",surname:"Elkacmi",slug:"reda-elkacmi",fullName:"Reda Elkacmi"},{id:"325462",title:"Dr.",name:"Abdellah",surname:"Ouigmane",slug:"abdellah-ouigmane",fullName:"Abdellah Ouigmane"},{id:"325463",title:"Prof.",name:"Otmane",surname:"Boudouch",slug:"otmane-boudouch",fullName:"Otmane Boudouch"},{id:"325528",title:"Prof.",name:"Mustapha",surname:"Bouzaid",slug:"mustapha-bouzaid",fullName:"Mustapha Bouzaid"},{id:"325529",title:"Prof.",name:"Mohammed",surname:"Berkani",slug:"mohammed-berkani",fullName:"Mohammed Berkani"}],corrections:[{id:"74392",title:"Corrigendum to: Sustainable Solid Waste Management in Morocco: Co-Incineration of RDF as an Alternative Fuel in Cement Kilns",doi:null,slug:"corrigendum-to-sustainable-solid-waste-management-in-morocco-co-incineration-of-rdf-as-an-alternativ",totalDownloads:null,totalCrossrefCites:null,correctionPdfUrl:null}]},{id:"74238",title:"Effectiveness of Anaerobic Technologies in the Treatment of Landfill Leachate",doi:"10.5772/intechopen.94741",slug:"effectiveness-of-anaerobic-technologies-in-the-treatment-of-landfill-leachate",totalDownloads:601,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Improper Solid Waste Management leads to the generation of landfill leachate at the landfills. To reduce the negative impacts of highly toxic and recalcitrant leachate on the environment, several techniques have been used. A lot of research is conducted to find suitable methods for the treatment of landfill leachate such as biological processes, chemical oxidation processes, coagulation, flocculation, chemical precipitation, and membrane procedures. The biological process is still being used widely for the treatment of leachate. The current system of leachate treatment consists of various unit processes which require larger area, energy and cost. In addition, the current aerobic treatment is not able to treat entirely the pollutants which require further treatment of the leachate. Anaerobic wastewater treatment has gained considerable attention among researchers and sanitary engineers primarily due to its economic advantages over conventional aerobic methods. The major advantages of anaerobic wastewater treatment in comparison to aerobic methods are: (a) the lack of aeration, which decreases costs and energy requirements; and (b) simple maintenance and control, which eliminates the need for skilled operators and manufacturers. Several anaerobic processes have been used for leachate treatment such as up-flow anaerobic sludge blanket (UASB) reactor, anaerobic filter, hybrid bed reactor, anaerobic sequencing batch reactor and Anaerobic baffled reactor. The following chapter provides an insight to the solid waste management at the landfills, generation of leachate and details of some of the highly efficient anaerobic treatment systems that are used for the overall treatment of landfill leachate.",signatures:"Imran Ahmad, Norhayati Abdullah, Shreeshivadasan Chelliapan, Ali Yuzir, Iwamoto Koji, Anas Al-Dailami and Thilagavathi Arumugham",downloadPdfUrl:"/chapter/pdf-download/74238",previewPdfUrl:"/chapter/pdf-preview/74238",authors:[{id:"237449",title:"Dr.",name:"Shreeshivadasan",surname:"Chelliapan",slug:"shreeshivadasan-chelliapan",fullName:"Shreeshivadasan Chelliapan"},{id:"324168",title:"Ph.D. Student",name:"Imran",surname:"Ahmad",slug:"imran-ahmad",fullName:"Imran Ahmad"},{id:"332462",title:"Dr.",name:"Norhayati",surname:"Abdullah",slug:"norhayati-abdullah",fullName:"Norhayati Abdullah"},{id:"338893",title:"Dr.",name:"Ali",surname:"Yuzur",slug:"ali-yuzur",fullName:"Ali Yuzur"},{id:"338894",title:"Dr.",name:"Iwamoto",surname:"Koji",slug:"iwamoto-koji",fullName:"Iwamoto Koji"},{id:"338895",title:"Dr.",name:"Anas",surname:"Al-Dailami",slug:"anas-al-dailami",fullName:"Anas Al-Dailami"},{id:"343758",title:"Dr.",name:"Thilagavathi",surname:"Arumugham",slug:"thilagavathi-arumugham",fullName:"Thilagavathi Arumugham"}],corrections:null},{id:"74004",title:"Hydrometallurgical Recovery of Gold from Mining Wastes",doi:"10.5772/intechopen.94597",slug:"hydrometallurgical-recovery-of-gold-from-mining-wastes",totalDownloads:743,totalCrossrefCites:0,totalDimensionsCites:3,hasAltmetrics:1,abstract:"Gold is a highly required material for a wide range of personal and industrial applications. The high demand for gold, together with the shortage of natural resources and high pollution potential of wastes generated during mining and ore processing activities led to search for alternative sources of gold. A possible source is represented by mine wastes resulting from the processing of polymetallic or sulfidic ores. The reprocessing of wastes and old tailings with moderate to low content of gold offers not only a business opportunity, but also enhances the quality of the surrounding environment, changes the land use and offers a wide range of socio-economic benefits. Cyanidation, the most widespread Au leaching option, is progressively abandoned due to the high risk associated with its use and to the low public acceptance. Therefore, alternative methods such as thiocyanate, thiourea, thiosulphate and halide leaching gained more and more interest. This chapter presents the most important features of some Au leaching methods, emphasizing their advantages, limitations and potential applications.",signatures:"Emilia Neag, Eniko Kovacs, Zamfira Dinca, Anamaria Iulia Török, Cerasel Varaticeanu and Erika Andrea Levei",downloadPdfUrl:"/chapter/pdf-download/74004",previewPdfUrl:"/chapter/pdf-preview/74004",authors:[{id:"324453",title:"Dr.",name:"Erika Andrea",surname:"Levei",slug:"erika-andrea-levei",fullName:"Erika Andrea Levei"},{id:"335075",title:"Dr.",name:"Emilia",surname:"Neag",slug:"emilia-neag",fullName:"Emilia Neag"},{id:"335077",title:"MSc.",name:"Eniko",surname:"Kovacs",slug:"eniko-kovacs",fullName:"Eniko Kovacs"},{id:"335078",title:"Dr.",name:"Zamfira",surname:"Dinca",slug:"zamfira-dinca",fullName:"Zamfira Dinca"},{id:"335080",title:"Dr.",name:"Anamaria Iulia",surname:"Török",slug:"anamaria-iulia-torok",fullName:"Anamaria Iulia Török"},{id:"335081",title:"BSc.",name:"Cerasel",surname:"Varaticeanu",slug:"cerasel-varaticeanu",fullName:"Cerasel Varaticeanu"}],corrections:null},{id:"74827",title:"Bioelectricity from Organic Solid Waste",doi:"10.5772/intechopen.95297",slug:"bioelectricity-from-organic-solid-waste",totalDownloads:464,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Resource recovery and recycling of organic waste is a great challenge in the world. The unmanaged organic waste causes a great damage to the environment and the public health both in the developing countries and industrial parts of the world. In this research, an innovative method was adopted to generate bioelectricity from the organic waste by using the Microbial Fuel Cell (MFC). Various types of organic wastes such as livestock waste, food waste, fruit waste were used as the substrates of the microbial fuel cell. All the experiments were carried out in the same sized one chamber microbial fuel cell and the similar electrode materials. It was observed that all the organic wastes can be used to generate bioelectricity through microbial fuel cell. The generated electricity can be used in several environmental monitoring sensors and can be used as an alternate power source in the developing countries. The by-products of the bioelectricity generation can be used as soil conditioner in the organic depleted soil and agricultural fields.",signatures:"M. Azizul Moqsud",downloadPdfUrl:"/chapter/pdf-download/74827",previewPdfUrl:"/chapter/pdf-preview/74827",authors:[{id:"7199",title:"Dr.",name:"Md.Azizul",surname:"Moqsud",slug:"md.azizul-moqsud",fullName:"Md.Azizul Moqsud"}],corrections:null},{id:"73517",title:"Agricultural Solid Wastes: Causes, Effects, and Effective Management",doi:"10.5772/intechopen.93601",slug:"agricultural-solid-wastes-causes-effects-and-effective-management",totalDownloads:1769,totalCrossrefCites:6,totalDimensionsCites:15,hasAltmetrics:1,abstract:"The role of the agricultural sector in human development and economic development cannot be overemphasized. Awareness for increased agricultural production is on the increase, arising from the need to feed the ever-increasing human population. Interestingly, almost all agricultural activities generate wastes, which are generated in large quantities in many countries. However, these wastes may constitute a serious threat to human health through environmental pollution and handling them may result in huge economic loss. Unfortunately, in many developing countries where large quantities of these wastes are generated, they are not properly managed because little is known about their potential risks and benefits if properly managed. There are studies that address some of the challenges of agricultural solid wastes as well as suggestions on how they can be properly managed. In this chapter, we intend to explore the major sources of agricultural solid wastes, their potential risks, and how they can be properly managed.",signatures:"Isaac Oluseun Adejumo and Olufemi Adebukola Adebiyi",downloadPdfUrl:"/chapter/pdf-download/73517",previewPdfUrl:"/chapter/pdf-preview/73517",authors:[{id:"276527",title:"Dr.",name:"Isaac Oluseun",surname:"Adejumo",slug:"isaac-oluseun-adejumo",fullName:"Isaac Oluseun Adejumo"},{id:"328699",title:"Dr.",name:"O.A.",surname:"Adebiyi",slug:"o.a.-adebiyi",fullName:"O.A. Adebiyi"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"8580",title:"Municipal Solid Waste Management",subtitle:null,isOpenForSubmission:!1,hash:"e3554c02569fe3ac8afa79cb02daae97",slug:"municipal-solid-waste-management",bookSignature:"Hosam El-Din Mostafa Saleh",coverURL:"https://cdn.intechopen.com/books/images_new/8580.jpg",editedByType:"Edited by",editors:[{id:"144691",title:"Prof.",name:"Hosam M.",surname:"Saleh",slug:"hosam-m.-saleh",fullName:"Hosam M. Saleh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6534",title:"Heavy Metals",subtitle:null,isOpenForSubmission:!1,hash:"a7573426a162c18f39acc575c1e69f67",slug:"heavy-metals",bookSignature:"Hosam El-Din M. Saleh and Refaat F. Aglan",coverURL:"https://cdn.intechopen.com/books/images_new/6534.jpg",editedByType:"Edited by",editors:[{id:"144691",title:"Prof.",name:"Hosam M.",surname:"Saleh",slug:"hosam-m.-saleh",fullName:"Hosam M. Saleh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2383",title:"Polyester",subtitle:null,isOpenForSubmission:!1,hash:"79fd9d6314f8e1abd60d7e21896ce878",slug:"polyester",bookSignature:"Hosam El-Din M. Saleh",coverURL:"https://cdn.intechopen.com/books/images_new/2383.jpg",editedByType:"Edited by",editors:[{id:"144691",title:"Prof.",name:"Hosam M.",surname:"Saleh",slug:"hosam-m.-saleh",fullName:"Hosam M. 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\r\n\tThe evaluation of the seismic hazard of a particular site represents the principal input data needed to develop the seismic code regulations and to perform structural building design worldwide. Being the actual trend of automatization of structural designs using various available software, it is imperative that structural engineers also study the estimation of earthquake ground motions and the associated risk of their designs, and seismologists envision in their research interests the structural analysis of buildings as well. Merging these technical fields would result in a new educational curriculum that would fulfill the actual research trends and demand practices. This book will address the recent advances, new perspectives, and applications of seismic hazard and risk evaluation based on the following topics: Tectonics, seismicity evaluation, ground motion prediction equations GMPEs, seismic hazard probabilistic methods, and site effects evaluation, including but not limited to inversion analysis on strong motion data and geophysical prospecting; development of structural fragility curves and seismic risk estimation.
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Portal hypertension leads to the formation of porto-systemic collaterals including gastro-oesophageal varices. The development of portal hypertension can also herald the development of other complications of liver cirrhosis such as ascites formation, hepatic encephalopathy and when varices occur, their bleeding. However it should be noted that portal hypertension also occurs in non-cirrhotic conditions, such as: Budd-Chiari, myeloproliferative diseases and extra-hepatic portal vein obstruction.
Variceal haemorrhage is a serious life-threatening complication of portal hypertension, with overall mortality rates historically reported as 30-50% [1]. Although mortality can be up to 40% at 6 weeks, it can be up to 70% at 1 year [2]. With the generally improved management of the critically ill cirrhotic patient, together with vasoactive therapy and new endoscopic techniques for managing variceal haemorrhage, overall mortality has reduced, with one centre in Europe showing a reduction from 42% in 1980 to 14% in 2000 [3]. The treatment of gastric varices has also evolved over recent years with the introduction of adhesive compounds such as N-butyl-2-cyanoacrylate and thrombin, and the increased use of Transjugular Intrahepatic Portosystemic Shunts (TIPS) in variceal bleeding and early in rebleeding. New self-expanding oesophageal stents have been developed for oesophageal haemorrhage in the ever expanding endoscopic armamentarium against variceal bleeding. Earlier emergency access to endoscopy performed by skilled endoscopists has coincided with the decline in use of tamponade equipment such as Sengstaken-Blakemore tubes, and the virtual extinction of emergency surgical procedures of oesophageal transection or porto-caval shunt formation.
This chapter addresses the aetiology and pathogenesis of oesophageal and gastric varices, the strategy of primary prophylaxis against variceal bleeding, and reviews the medical and endoscopic treatment of variceal haemorrhage and rebleeding thereafter.
Portal hypertension is a key factor in the development of oesophageal or gastric varices. The endoscopic appearances of oesophageal and gastric varices can be seen in Figures 1 and 2 respectively.
Quiescent column of oesophageal varices
Gastric varix seen on retroflexion of the endoscope in fundus of the stomach with the classical “hanging grapes” appearance (courtesy of Dr Branislav Kunčak, University of Trnava and Nové Zámky Hospital, Nové Zámky, Slovakia at www.Endoatlas.sk)
The portal pressure is the pressure in the portal vein and portal vein tributaries. Normal portal pressure is 1-5 mmHg. When the portal pressure gradient (difference in pressure between the pressure in the portal vein and hepatic vein) exceeds 10-12mmHg, varices will form. The causes of portal hypertension categorised by anatomical site are summarised in Table 1.
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
PRE-HEPATIC | \n\t\t\tPortal vein/ splenic vein thrombosis Extrinsic compression of portal vein Portal vein congenital abnormalities (stenosis) | \n\t\t
INTRA-HEPATIC | \n\t\t\tAny cause of cirrhosis (alcoholic, metabolic, viral, biliary, autoimmune) Acute alcoholic hepatitis Veno-occlusive disease Hepatocellular carcinoma Chronic active hepatitis Acute fatty liver of pregnancy Amyloidosis Chronic Hypervitaminosis A Polycystic disease Nodular regenerative hyperplasia Granulomatous liver diseases (TB, sarcoidosis, schistosomiasis) | \n\t\t
POST-HEPATIC | \n\t\t\tTricuspid valve disease / severe right heart failure Constrictive pericarditis Inferior vena cava thrombosis/ congenital malformations Hepatic vein thrombosis (Budd Chiari) | \n\t\t
Causes of portal hypertension related to site of increased resistance to portal blood flow
Irrespective of the site of resistance to portal blood flow, there are different mediators involved in the development of portal hypertension as outlined in Figure 3.
Portal hypertension can develop from structural changes within the liver, altering the architecture and thus leading to distortion of the blood flow through the liver. This results in increased vascular resistance. Such structural changes are the main cause for increased intrahepatic vascular resistance. Nodule generation, sinusoidal capillarization (development of a basal membrane around the sinusoid in the Space of Disse and fibrous tissue accumulation), sinusoidal collapse and hepatocyte enlargement all lead to shrinking and narrowing of the sinusoid unit leading to increased intrahepatic vascular resistance. Once these pathological changes occur, they can be an irreversible / fixed component of the development of portal hypertension. Depending on the aetiology and thus treatment of disease, degrees of fibrosis can in some cases be partially reversed.
Overview of the mechanisms in the development of portal hypertension. (NO = nitric oxide)
Activated hepatic stellate cells (HSCs) are key mediators in the production of peri-sinusoidal hepatic fibrous tissue and the laying down of extracellular matrix [4]. Such deposition of fibrous tissue around the sinusoids can be the initial event in sinusoidal capillarization [5]– whereby extracellular matrix is deposited in the Space of Disse, and furthermore this can result in sinusoidal endothelial cells producing less nitric oxide (NO), which activates HSCs further. Any underlying liver disease promoting a fibrosis architecture of the liver can lead to portal hypertension [6]. As the fibrosis persists and progresses, liver cirrhosis can ensue.
The development of portal hypertension leading to collateral formation and varices relies not only on structural changes within the liver, but also on increased vascular tone within the liver. The alterations in vascular tone are dynamic changes. The HSCs are activated and can constrict as fibrosis and cirrhosis develop leading to a further vasoconstriction at the sinusoidal level. The mechanisms by which this occurs are multifactorial but include a change of HSC from a quiescent phenotype to a myofibroblast-like phenotype [6], which has greater contractile properties, and an up-regulation of calcium-channel receptors that mediate constriction [6,7]. In addition to the activation of HSCs, there is an increase in mediators of vasoconstriction including Thromboxane A2, Angiotensin II, RhoA, endothelin, and eicanosoid, which have been shown at experimental level to increase intravascular intrahepatic tone [8-11]. The increase in vasoconstrictors is coupled with a reduction of vasodilators such as homocysteine and NO, with the latter being a key mediator in portal circulation vasodilatation [12] and in the formation of collateral vessels [13,14]. The production of NO is promoted by vascular endothelial growth factor, which also promotes porto-collateral vessel formation [15].
Vasodilatation of the arterial splanchnic vessels is an important factor in the development of portal hypertension. Chronic vasodilatation leads to increased blood flow to the porto-venous system and development of porto-systemic collateral formation and varices [16]. Increased portal pressure is the most important risk factor for the development of varices [2]. Varices develop once a hepatic venous pressure gradient (HVPG), a surrogate marker for sinusoidal portal hypertension, exceeds 10-12mm Hg [17]. Lowering the portal pressure is a key target in the prevention of variceal formation, in the prevention of variceal bleeding, and in the management of acutely bleeding varices [18]. One other major feature in portal hypertension is the development of the hyperdynamic circulatory syndrome, which is associated with the development of varices [16]. This is characterised by a decreased mean arterial pressure, increased cardiac output and decreased systemic vascular resistance. The hyperdynamic circulation again is a target for drug therapies including beta-blockers to reduce portal hypertension, with the main driver for the vasodilatation and subsequent hyperdynamic circulation being NO [16].
Once portal hypertension ensues, there is development of porto-systemic collateral formation in an attempt to decompress the rising portal pressure. Two basic mechanisms lead to: (1) neo-angiogenesis and (2) dilatation of pre-existing embryonic channels between the portal and systemic circulations [19, 20]. Gastro-oesophageal varices develop as part of cephalad collaterals formed after dilatation of the left gastric (coronary) vein and the short gastric veins. Once established, varices can remain indolent or grow in size, and also cause life-threatening haemorrhage. When the portal pressure is above 10 mmHg, the median time for the development of varices is 4 years [21] while some studies show a
Variceal size is a predictor of haemorrhage, as predicted by La Place’s law, whereby wall tension increases with variceal radius and transmural variceal pressure. The mean risk of haemorrhage from larger varices (>5mm) is 30% at 2 years, compared to 10% from small varices at 2 years [24,25]. Risk factors for the dilatation of varices include: an increase in portal pressure [26], alcohol consumption [27], circadian rhythm [28], prandial blood flow bursts [29] and also Child-Pugh class at baseline and its deterioration during follow-up [30, 31]. The rate of yearly increase in size of varices varies from a range of 8% to 31% [32, 33].The two main locations of varices that may rupture are the lower oesophagus and the stomach.
Oesophageal varices are long columns of dilated veins (Figure 1), usually occurring within the lower third of the oesophagus, immediately above the gastro-oesophageal junction (GOJ). Oesophageal varices can be graded endoscopically according to size [34] (Table 2/ Figure 4), while the American Association for the Study of Liver Diseases (AASLD) recommends the classification into small and large oesophageal varices based on a cut-off of 5mm [35].
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
1 (small) | \n\t\t\tSmall straight varices | \n\t\t
2 (medium) | \n\t\t\tEnlarged tortuous varices occupying less than one third of the lumen | \n\t\t
3 (large) | \n\t\t\tLarge coil-shaped varices occupying more than one third of the lumen | \n\t\t
Grading of oesophageal varices according to Italian liver cirrhosis project. (Reference 34)
Grading of oesophageal varices endoscopically (adapted from reference 24)
The major blood supply to oesophageal varices is from the left gastric vein. There are 4 layers of veins in the oesophagus (Figure 5). The intra-epithelial veins are the most superficial veins and correlate with the red spots seen at time of endoscopy. These red spots have been shown to be predicative of variceal rupture (along with variceal size and Child-Pugh class [25]). Deeper to these veins is the superficial venous plexus, which then drains into deeper intrinsic veins. These in turn are then connected via perforating veins to the deepest adventitia plexus. It is the main trunks of the deep adventitia plexus that large oesophageal varices arise from.
An area of common oesophageal variceal rupture is at the GOJ - the palisade zone – an area of venous tributaries between the gastric zones and perforating zone (in the oesophagus). This area is a watershed between the azygous and portal blood flow systems, where venous flow is bidirectional with turbulent flow – which may explain frequent rupture [36] – and thus why when banding, oesophageal bands should be applied as close to the GOJ as possible.
The anatomy of veins within the oesophagus from which oesophageal varices arise.
Gastric varices are supplied by the short gastric veins, draining into the deep intrinsic veins of the lower oesophagus, and can be classified according to site by the Sarin classification of gastric varices [37] (Figure 6 / Table 3).
Sarin classification of gastric varices (adapted from reference 37)
Gastric varices account for 10-30% of variceal haemorrhage and can occur in up to 20% of patients with portal hypertension [17, 38]. Management of bleeding gastric varices differs from that of the more common situation of bleeding oesophageal varices (see later in chapter).
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
Gastro-Oesophageal Varices -1 (GOV-1) | \n\t\t\tContinuation from oesophageal varices and extend on lesser curve | \n\t\t
Gastro-Oesophageal Varices -2 (GOV-2) | \n\t\t\tExtend along lesser curve and more tortuous than GOV-1 | \n\t\t
Isolated Gastric Varices-1 (IGV-1) | \n\t\t\tOccur in absence of oesophageal varices, and occur in the fundus, and are tortuous and complex | \n\t\t
Isolated Gastric Varices-2 (IGV-2) | \n\t\t\tOccur in absence of oesophageal varices, in the body, antrum or pylorus | \n\t\t
Sarin classification of gastric varices (adapted from reference 37).
Since patients with cirrhosis may have portal hypertension and varices, there is a rationale for screening of such patients to identify those with varices who might benefit from primary prophylaxis against variceal haemorrhage. Thus those patients who have a diagnosis of cirrhosis either clinically, biochemically or on liver biopsy, should be offered Oesopho-Gastro-Duodenoscopy (OGD) looking for gastro-oesophageal varices [39]. When cirrhosis is diagnosed, any factors causing the continuing insult to the liver must be addressed – such as treatment of the underlying condition (e.g. viral /autoimmune or ongoing alcohol intake in alcoholic liver disease). In those cirrhotic patients who do not have varices diagnosed on initial endoscopy, a follow up endoscopy has been recommended after 2-3 years [40] particularly if hepatic synthetic function worsens (i.e. worsening in Child-Pugh status). Primary prophylaxis aims to prevent variceal haemorrhage in patients who have varices but who have not had a previous bleeding episode. Strategies used in primary prophylaxis can be broadly divided into pharmacological and endoscopic therapies.
Drug therapies are used to prevent variceal bleeding, and if well tolerated by patients can be effective. Isosorbide mononitrate (ISMN) is a potent vasodilator used in ischaemic heart disease and reduces vascular tone. There are theoretical reasons why ISMN should help to prevent variceal bleeding. In randomised control trials ISMN has been shown to reduce HVPG by 7.5% [41,42], and to augment the splanchnic vasoconstrictive effects of the non-selective beta-blocker propranolol [42]. It has been used when there are contra-indications to, or intolerance of beta-blocker drugs in patients with varices. However a double-blind randomised controlled trial in patients intolerant of beta-blockers, compared ISMN with placebo and found that ISMN was ineffective at preventing a first variceal bleed [43].
Non-selective beta-blockers are the mainstay of treatment in the prevention of variceal bleeding once varices have been identified. Non-selective beta-blockers not only block beta-1 receptors, reducing cardiac output and thus portal blood flow, but also block the adrenergic dilatory tone in the mesenteric arterioles, resulting in unopposed alpha-adrenergic vasoconstriction and a decrease in portal blood flow [44]. Nadolol or propanolol can reduce HVPG measurements by up 10% [45,46] and are effective in reducing variceal bleeding rates and mortality when compared to placebo [47,48]. Their roles have been firmly established in guidelines [2,35] with the choice between them dependent on institutional practice. Carvedilol is a potent non-selective beta-blocker, with weak vasodilating effects due to alpha-1-blockade [49]. This leads to a reduction in hepatic vascular tone and hepatic resistance [50]. Carvedilol has been shown in multiple studies to reduce portal pressure and HVPG significantly more than propranolol [51-54], but its role in primary prophylaxis is not yet been established [2]. Once beta-blocker therapy has been instituted, patients with varices who are compliant with their medication do not require further endoscopy unless bleeding occurs. However some US centres prefer to repeat endoscopy annually in varices patients on beta-blockers and consider changing to a programme of endoscopic variceal band ligation (EVBL) if the varices increase in size. This latter strategy, however, is non-evidence based.
Side-effects of beta-blockers include bronchoconstriction, heart failure and impotence, and these can often limit a patient’s tolerability of the drug. The safety of beta-blockers in cirrhotic patients with refractory ascites has also been questioned in a prospective study of 151 patients in such a cohort [55]. The 1-year probability of survival was significantly lower in patients who received propranolol [19% (95% CI = 9%-29%)] versus those who did not [64% (95% CI = 52%-76%), p< 0.0001]. Further studies in this area are required as this initial study was not a randomised controlled trial. It has been postulated that beta-blockers are only beneficial during a set time window in the progression of cirrhosis with portal hypertension [56]. There may be no benefit in early cirrhosis when there is less risk of bacterial translocation, no increase in sympathetic nervous system activity and when the cardiac compensatory reserve remains intact. However as cirrhosis progresses with increasing bacterial translocation and increased sympathetic nervous system activity, there is an increased risk of variceal haemorrhage, and beta-blockers become beneficial in not only reducing variceal bleeding but also reducing bacterial translocation. The window then closes in advanced cirrhosis as beta-blockers exert a negative impact on cardiac compensatory reserve.
Endoscopic treatments can be used to obliterate/thrombose oesophageal varices. Injection sclerotherapy involves the injection of a sclerosant (usually ethanolamine) via a needle-catheter directly into a varix to thrombose it. Although intuitively the obliteration of varices before they have a chance to bleed would seem to be a logical strategy, injection sclerotherapy is not without complication. In fact when sclerotherapy for primary prophylaxis against variceal bleeding was formally studied in a randomised trial, patients with varices randomised to sclerotherapy had a higher mortality than patients with varices in the control arm [57]. Consequently injection sclerotherapy should not be used as primary prophylaxis against variceal bleeding. Injection sclerotherapy for oesophageal varies has largely been superseded by EVBL in the past 2 decades. EVBL is an alternative to non-selective beta-blockers, in those intolerant to the medication or for those often with medium or large varices (Figure 7). EVBL should be performed by an endoscopist who has expertise in variceal band ligation to minimise complications in day-case endoscopy patients.
EVBL can be used to treat acutely or recently bleeding oesophageal varices, or can be performed electively to obliterate varices and thus prevent bleeding or rebleeding. Once a diagnostic OGD has been performed and has identified oesophageal varices, the most distal level of variceal location is noted, and the endoscope removed. A single-use, multiband ligator incorporating up to 10 bands, is then loaded onto the endoscope. A cap fitting over the endoscope’s tip holds the mounted bands, and is connected through the accessory port of a standard endoscope, with the firing handle mounted close to the endoscope’s operating wheels. Once the ligator has been loaded onto the endoscope, the oesophagus is re-intubated. The ligator’s cap may make intubation and subsequent endoscopic views a little more difficult.
The first varix to be banded should be the largest one with stigmata of recent/active haemorrhage, or if quiescent then the most distal varix just above the GOJ, since varices at/just above the GOJ are those most likely to bleed. Furthermore, if a proximal varix is banded first, it may be difficult to then pass the endoscope beyond it without dislodging the band. Suction is applied, aspirating the varix into the cap, until the varix is completely sucked up (as seen by a red-out on the screen). Operating the firing handle releases a band onto the varix neck, and release of suction allows the banded varix to be viewed (Figure 7). Thereafter, additional variceal banding can be continued in a cranial direction. Complications of EVBL include band-induced ulceration (which may present as a re-bleed requiring urgent endoscopy), transient dysphagia or chest pain, and rarely oesophageal stricturing.
Endoscopic variceal band ligation of oesophageal varices (courtesy of Dr Branislav Kunčak, 2nd Dept. of Internal Medicine, Faculty of Health and Social Work, University of Trnava and Nové Zámky Hospital, Nové Zámky, Slovakia. at www.Endoatlas.sk)
The role of EVBL in patients with medium or large varices has been studied in several trials, and has also been compared to beta-blockers. Meta-analyses show that for primary prophylaxis, both beta-blockade and EVBL have similar efficacy and mortality [53, 58-63]. Guidelines currently do not recommend combination therapies with both EVBL and non-selective beta-blockers [2,35,40]. Local factors including availability of endoscopic procedures, and technicians able to perform EVBL may influence choices between beta-blockade and EVBL as primary prophylaxis. The cost of endoscopy with EVBL is higher than the cost of beta-blocker medication, particularly since banding programmes require follow-up endoscopies to ensure variceal eradication (with up to 22% recurrence post-EVBL reported in one study [59]). Guidelines recommend EVBL every 1-2 weeks after initial OGD until the varices are obliterated, and then 6-12 monthly check endoscopies [35].
Current Baveno V guidelines on portal hypertension [2] recommend primary prophylaxis with non-selective beta-blockers for patients with small oesophageal varices and red wale marks or Child C cirrhotic patients. These guidelines also suggest that patients with small oesophageal varices but without signs of increased risk of haemorrhage or Child C cirrhosis could be considered for treatment with non-selective beta-blockers, although further studies are necessary. Patients with medium or large oesophageal varices can be treated with either beta-blockers or EVBL. Current American Association for the Study of Liver Diseases (AASLD) guidelines [35] similarly recommend prophylaxis with non-selective beta-blockers for patients with compensated cirrhosis and small oesophageal varices with or without features of likely increased haemorrhage risk. The AASLD guidelines also recommend non-selective beta-blockers or EVBL for those with medium or large varices.
For gastric varices, injection of N-Butyl-2-Cyanoacrylate glue has been studied in the primary prophylaxis setting. This long-chain cyanoacrylate glue polymerises and solidifies within seconds following contact with aqueous media such as blood within a varix. This leads to obliteration of the varix from which the cast extrudes after 2-4 weeks. Mixing the cyanoacrylate with the oily agent Lipiodol delays polymerisation. The glue treatment was compared with beta-blockers or no therapy in a randomised controlled trial [64], with significantly reduced probabilities of bleeding in patients treated with glue compared to beta-blockers or no therapy (13% v 28% and 45% respectively). However the use of the glue for gastric varices has complications (see later in chapter in “Endoscopic treatment of acute gastric variceal haemorrhage” section) and its role in primary prophylaxis against gastric variceal bleeding has not yet been established [2]. Although there is a paucity of data from prophylactic studies on gastric variceal bleeding, there is current consensus that using beta-blockers to reduce portal pressure is appropriate in this setting [2].
Variceal haemorrhage is a life-threatening emergency with a mortality of 20-40% at 6-weeks (65). Factors predictive of death within 6 weeks of index bleeding in patients with cirrhosis include: site of bleed is varices (instead of other pathology), level of bilirubin, underlying alcoholic liver disease, presence of encephalopathy or coagulopathy and the need for balloon tamponade [2,40,65]. If haematemesis or melena occurs in patients known to have cirrhosis or stigmata of chronic liver disease, variceal bleeding should be considered. AASLD guidelines recommend such patients should be managed in an intensive care setting [35]. Tracheal intubation should be considered if the patient has a reduced Glasgow Coma Scores (GCS) or signs of hepatic encephalopathy, since these increase the risk of aspiration. Furthermore, subsequent endoscopy to diagnose and treat the bleeding point is safer in an intubated patient. General measures include wide-bore venous access or central venous access, and fluid resuscitation with either colloid or blood products. Blood resuscitation to maintain a haemoglobin level of approximately 8g/dl has been recommended [40], as experimental studies have shown the total restoration of all lost blood may raise portal pressure higher than that of baseline [66], with subsequent higher rates of re-bleeding and mortality [67]. There must however be adequate arterial pressure to maintain renal perfusion (and prevent acute kidney injury and the development of hepato-renal syndrome). Clotting and platelet deficiencies should be corrected.
Bacterial infections are common in cirrhotic patients, and antibiotics have been shown to reduce bacterial infections, recurrent bleeding and mortality in patients bleeding from oesophageal varices [68,69]. Broad-spectrum antibiotic prophylaxis is recommended [35]. Local antibiotic policy and a patient’s nil-by-mouth status are important influences, but the antibiotic used should be either an oral quinolone, or else a 3rd generation intravenous cephalosporin in patients who have advanced cirrhosis, or previously received quinolone prophylaxis, or live in areas of high quinolone resistance [2].
Bleeding oesophageal varices (courtesy of ELLA-CS, Hradec Kralove, Czech Republic)
The use of vasoactive drugs to lower portal pressure is paramount in the initial management of variceal bleeding. Such drugs should be given prior to endoscopy if the source of upper gastrointestinal bleeding is suspected to be varices [2, 70]. Vasopressin and terlipressin cause constriction of the splanchnic arterioles, thus leading to increased resistance to inflow of blood to the gut. This leads to a lowering of portal venous pressure. Side effects however include myocardial ischaemia and these vasoconstrictors are contraindicated in peripheral vascular disease. Vasopressin has been shown to achieve haemostasis in 60-80% of patients, but has limited effects on reducing early rebleeding and does not improve survival from active variceal haemorrhage [71]. Vasopressin has largely been superseded by terlipressin in countries where it is available (not the USA). Terlipressin (triglycyl-lysine vasopressin) is a synthetic analogue of vasopressin administered at an initial dose of 2mg, then 1mg intravenously every four hours. Meta-analysis shows that terlipressin reduces all-cause mortality when compared to placebo [71, 72] and it should be instituted early and continued for up to 5 days, as this is the period during which rebleeding is common. When compared to somatostatin analogues such as octreotide, the haemodynamic effects of terlipressin on portal pressure are more sustained [73], suggesting terlipressin may have a more prolonged benefit in bleeding varices.
Somatostatin and somatostatin analogues (e.g. the long-acting analogue octreotide) act by increasing splanchnic arterial resistance, and inhibit vasoactive peptides such as glucagon. Octreotide is used as first-line vasoactive therapy in the USA (where terlipressin is unavailable). It is given intravenously as a 50 microgram bolus followed by a continuous infusion of 50 micrograms per hour. Octreotide causes a transient reduction in portal pressure and azygous blood flow lasting up to only 5 minutes despite continuous infusion [74]. However additional effects are via inhibition of glucagon and other peptides that increase post-prandial mesenteric blood flow [75]. The mesenteric blood flow increases in variceal bleeding due to the high protein gut loading from the intraluminal blood [76], and octreotide can reduce the hormone-induced changes for up to 38 hours [77]. Somatostatin has fewer side effects than terlipressin (0% vs. 10%) and a higher relative risk (1.62) for achieving initial control of bleeding, but no survival benefit [78]. Thus vasoactive drugs are part of the initial therapy in variceal haemorrhage and one of these drugs should be continued for 2- 5 days [2].
Prior to endoscopy a tamponading balloon such as the Sengstaken-Blakemore tube or Minnesota tube can be considered, but the advent of 24-hour endoscopy services, vasoactive drugs and TIPS has largely obviated the need for this intervention. Balloon tamponade should be only be used in massive haemorrhage as a bridge to endoscopy [2]. Complications of tube insertion include upper airway obstruction, inadvertent tracheal intubation, lower oesophagus ulceration and even oesophageal rupture if the gastric balloon is wrongly inflated in the oesophagus.
OGD is the investigation of choice in the diagnosis of variceal bleeding, and it offers endoscopic therapeutic capability at the time. After general measures covered earlier in the chapter have been instituted in a patient with variceal bleeding, an urgent OGD should be carried out within 12 hours of presentation [2]. Some experts recommend tracheal intubation prior to OGD in all patients suspected of having variceal bleeding, to prevent aspiration of blood into the airway. Endoscopic therapy for bleeding varices largely depends on the type of varix that is bleeding – oesophageal or gastric. The mainstays of endoscopic therapy for bleeding oesophageal varices include injection sclerotherapy and EVBL.
Endoscopic sclerotherapy for oesophageal varices has mainly been performed using the sclerosant ethanolamine. Cyanoacrylate glue and thrombin have also been used. Sclerotherapy is done using a catheter with a retractable needle introduced through the endoscope’s operating channel. Under endoscopic vision, the sclerosant is directly injected into the bleeding oesophageal varix. Local complications can include bleeding, stricture formation, ulceration, oesophagitis, mediastinitis and oesophageal perforation.
Sclerotherapy controls active bleeding from oesophageal varices in 62-100% of patients and is more effective than treatment with placebo, vasoactive therapy or balloon tamponade [40]. A meta-analysis of 5 studies (Laine L, personal communication in Baveno IV consensus statements [40]) of 251 patients comparing sclerotherapy with sham sclerotherapy, balloon tamponade and/or vasopressive therapies showed significant benefits of sclerotherapy in terms of initial haemostasis, in patient re-bleeding (OR=0.36, 0.21-0.62) and mortality (OR=0.57, 0.33-0.98) [79-83]. A meta-analysis suggested that sclerotherapy was the “gold standard” in acute variceal bleeding [84]. Despite the efficacy of endoscopic sclerotherapy for actively bleeding oesophageal varices, endoscopic therapy has switched to EVBL. In part this switch may have been extrapolated from the negative outcomes when sclerotherapy was used as primary prophylaxis against variceal bleeding[57], but subsequent comparative trials detailed below have pointed to a superiority of EVBL.
EVBL has evolved as the recommended standard of treatment for bleeding oesophageal varices (Baveno IV guidelines) [40], and sclerotherapy is only recommended if ligation is technically difficult. In a meta-analysis of 10 randomized controlled trials comparing EVBL with sclerotherapy, there was an almost significant benefit of EVBL in achieving initial haemostasis compared to sclerotherapy (pooled relative risk of 0.53 with CI 0.28-1.01) [85]. In one of the studies in the meta-analysis, HVPG increased significantly immediately after both EVBL and sclerotherapy, but the HVPG remained elevated for the duration of the study (5 days) in the sclerotherapy group while returning to baseline levels by 48 hours after EVBL group [86]. Another meta-analysis however found no difference in initial haemostasis rates between sclerotherapy and EVBL (RR 1.1, 95% CI: 0.4-2.9) [87], but the actively bleeding patients represented a small subset from larger trials, and were thus not truly from pure randomized controlled trials in this population [40]. EVBL is associated with fewer adverse effects than sclerotherapy. By consensus, EVBL is the preferred form of endoscopic therapy for acute oesophageal variceal bleeding, although sclerotherapy is recommended in patients in whom EVBL is not technically feasible.
Combination therapies of vasoactive drugs and direct endoscopic therapies have been studied, with dual therapy conferring the potential benefits of pharmacological reduction in portal pressure together with the direct local haemostasing effects of either sclerotherapy or EVBL. Combination is now recommended as a standard of care in oesophageal variceal bleeding [2,40]. The combined effect of initial haemostasis was initially difficult to assess due to heterogeneity of trials and definitions of immediate haemostasis. A meta-analysis of 4 trials including 559 patients, concluded that combined therapy was associated with a higher rate of initial haemostasis than endoscopic therapy alone (88% v 76%, RR: 1.12, 95% CI: 1.02-1.23) [88]. Five-day haemostasis rates were studied in the Baveno IV consensus statements [40]. Pooling of results of 939 patients demonstrated that combination therapy achieved greater haemostasis rates than endoscopic therapy alone (77% v 58%, RR: 1.28, 95% CI: 1.18-1.39) with a number needed to treat of 5 (95% CI 4-8) [89-96]. However no significant differences were found in 5-day or 42-day mortality when combined vasoactive drug and endoscopic therapy was compared to endoscopic therapy alone in 2 meta-analyses [88, 89]. Two pooled randomized controlled trial results of combination therapy versus pharmacological therapy alone showed combination therapy improved control of bleeding (RR: 3.1, 95% CI: 1.2-8.3) but with no influence on mortality [88, 89].
More recently self-expanding oesophageal metallic stents have been developed and used in oesophageal variceal bleeds. They have been developed from their role in oesophageal malignancy, and act by applying direct tamponading pressure to the distal oesophageal mucosa and any associated varices. Stents were used in a pilot study in 20 patients who failed to achieve haemostasis with pharmacological or endoscopic techniques [92]. Immediate haemostasis was achieved in 100% of these patients. Such stents seem a promising option in the situation of refractory oesophageal haemorrhage, but further evaluation is needed.
A bleeding gastric varix seen on retroflexion of the gastroscope (courtesy of Dr Adrian Stanley, Glasgow Royal Infirmary, 2006)
Self-expanding oesophageal metallic stent (courtesy of ELLA-CS, Hradec Kralove, Czech Republic)
Radiological therapies have been used in acute oesophageal variceal bleeding, with TIPS the most commonly studied and available radiological modality. TIPS involves the placement of a needle catheter via the transjugular route into the hepatic vein, and wedging it there under fluoroscopic guidance. The needle is then advanced through the liver parenchyma to the intrahepatic portion of the portal vein, creating a “side-to-side” anastomotic shunt. A stent is then positioned across the liver, connecting the portal vein and hepatic veins, and allowing blood to flow normally from the portal vein through the liver with a drop in the portal pressure. TIPS was initially used as therapy for uncontrolled bleeding and achieved control of bleeding in 90-95% of patients and a 4-week survival of 50-60% [93]. Early TIPS placement has been shown to have beneficial effect in patients with a HVPG > 20mmHg presenting with a variceal bleed [94]. TIPS reduced treatment failures, hospital stay and 1-year mortality. Other studies have confirmed the role of TIPS in variceal bleeding which cannot be controlled by endoscopy or vasoactive drugs [95-97]. Complications of TIPS include haemorrhage, infection, intravascular haemolysis and worsening of hepatic encephalopathy [95-97].
Although less common than oesophageal variceal bleeding, gastric variceal haemorrhage is often torrential with an associated high mortality (Figure 9). Re-bleeding is also common with reported figures of up to 43-89% after a gastric variceal bleed [37, 98-101]. Gastric varices can occur alone or in combination with oesophageal varices. They are often large and located deep in the submucosa, making EVBL or injection therapy more difficult than that for oesophageal varices. Gastric varices can remain quiescent and predicting which gastric varix is likely to bleed can be difficult. Factors that are associated with a high risk of gastric variceal bleeding include: red colour sign, large varices, or a rapid increase in size [102-104].
Therapeutic options for bleeding gastric varices include injection sclerotherapy, banding, TIPS and other radiological interventions. Endoscopic sclerotherapy was first applied in the treatment of a bleeding gastric varix in 1984 [105] and results in endothelial damage with subsequent sclerosis of the varix. Variceal obliteration rates of 71.6% (mean follow up 24.2 +/-22.9 months) in gastric variceal bleeds treated with sclerotherapy have been reported [101], but there are often high re-bleeding rates of 60-90% following sclerotherapy for gastric varices [106, 107].
There are limited data on EVBL in the management of gastric variceal bleeding. EVBL can be useful for varices extending from the oesophagus along the proximal lesser curve (Sarin GOV-1), but it is problematic for other types of gastric varices. High rates of gastric variceal recurrence following EVBL may be due to a more superficial effect compared with obturation therapy [108]. This, together with the technical difficulty of banding in a retroflexed endoscope position has meant EVBL for gastric varices has largely been superseded by obturation therapies using cyanoacrylate and thrombin injection.
Cyanoacrylate injection is effective for bleeding gastric varices, yet remains unapproved in the USA. Injection of cyanoacrylate is not without complications including endoscope damage due to blockage of the injection channel, detachment of the injection needle into a varix, cerebral embolism, pulmonary embolism, splenic infarcts, mediastinitis and local abscesses. Although most reports of this therapy for gastric varices have limited follow-up, immediate haemostasis rates of 92-100% have been reported with variable re-bleeding rates [108-113]. Cyanoacrylate glue has been compared with ethanol injection in a randomised study with the former showing faster rates of variceal obliteration with a smaller injection volume, improved efficacy in control of acute gastric oesophageal variceal bleeding and reduced need for rescue surgery [114]. Another randomised study concluded that the obliteration of gastric varices using EVBL was more difficult and less effective than cyanoacrylate glue injection [115]. Early haemostasis rates were 87% with cyanoacrylate and 45% with EVBL, and re-bleeding rates were 31% and 54% respectively. Cyanoacrylate injection is also superior to beta-blockers in preventing gastric variceal re-bleeding [116]. When 77 patients who had bled from gastric varices were assigned to either beta-blockers or cyanoacrylate, those whose varices were injected with cyanoacrylate had lower rebleeding rates (15% v 55%), and lower mortality (3% v 25%) [116]. The addition of beta-blockers to cyanoacrylate therapy for secondary prevention after a cyanoacrylate-treated index bleed, does not confer any additional benefit [117].
Thrombin is another obturation therapy advocated for acutely bleeding gastric varices in some United Kingdom centres. It converts fibrinogen to a fibrin clot and causes platelet aggregation [118]. There have been small case-series of its use with haemostasis rates between 70-100% using bovine thrombin [119-122]. However there was concern that this material of bovine origin might present a potential risk of prion transmission. Short-term small studies of human-derived thrombin have demonstrated initial haemostasis rates of 100% but a high mortality from re-bleeding [123-125].
Interventional radiological procedures for the treatment of gastric varices include TIPS [126-128] and Balloon-occluded Retrograde Transvenous Obliteration (BRTO) [127-129] as salvage or rescue therapy when obturation therapy fails. BRTO is an interventional radiological technique used mostly in Far East Asia for gastric variceal bleeding. The gastro-renal shunts often seen in such patients can be occluded with sclerosant via a balloon catheter approach via the left renal vein [129]. BRTO may become an alternative to TIPS in patients with active gastric variceal bleeding in whom a gastrorenal shunt is present [130].
Current Baveno V guidelines [2] suggest early TIPS within 72 hours (ideally < 24 hours) in patients at high risk of treatment failure (Child-Pugh class C < 14 points or Child-Pugh class B with active bleeding) after initial pharmacology and endoscopic therapy in patients with variceal bleeding. This recommendation is derived from the pivotal study from Barcelona in which 63 cirrhotic patients with variceal bleeding were treated with vasoactive drugs and endoscopic therapy and then randomised to treatment with a TIPS within 72 hours (“early-TIPS”) or else continuation of vasoactive drugs for 3 to 5 days followed by non-selective beta-blockers and long-term EVBL with insertion of a TIPS only if required as a rescue therapy [132]. Rebleeding or failure to control bleeding occurred in only 1 of the “early-TIPS” patients and in 14 of the vasoactive drug/EVBL group (p<0.001). Overall mortality was lower in the “early-TIPS” group (12 patients versus 4, p = 0.01) with 1-year survival 61% in the vasoactive drug/EVBL group versus 86% in the “early-TIPS” group (p <0.001).
The improvement in survival from index variceal bleeds using the therapies discussed has focussed attention on prevention of rebleeding. 60-80% of patients who bleed from varices will rebleed if not treated [18, 40,133, 134], and the risk of rebleeding is greatest in the first 10 days (131,132), during which 50% of those who are going to rebleed, do so. The risk of rebleeding gradually falls over the first month when an additional 10% rebleed [133, 134]; the risk after the first six weeks then plateaus out. Despite the advent of endoscopic therapies and early pharmacological therapies, rebleeding rates are still higher early on, with factors predictive of early rebleeding /treatment failure at 5 days including: active bleeding at index endoscopy, severity of liver disease (Child-Pugh class), severity of bleed, and severity of portal hypertension [132, 135]. HVPG is one of the best predictors of identifying those who will re-bleed. After an index variceal bleed, a reduction of HVPG to less than 12mm Hg or by at least 20%, reduces the risk of rebleeding from 46-65% to 0.13% [136]. HVPG measurement is usually limited to specialist centres.
Strategies to prevent rebleeding historically included surgical portocaval shunts, but currently involve pharmacological and endoscopic therapies. Pharmacological therapies include non-selective beta-blockers, and endoscopic therapies include sclerotherapy or EVBL. Beta-blockers significantly reduce rebleeding rates and improve survival at 2 years when compared to placebo [24,137]. Factors associated with a risk of rebleeding in patients treated with beta-blockers included a lack of compliance or a lack of reduction of heart rate [138]. Injection sclerotherapy reduces the risk of rebleeding from 65% to 35% but does not appear to reduce overall mortality and is associated with complications such as oesophageal ulceration [40]. When sclerotherapy was compared with beta-blockers there was less rebleeding in the sclerotherapy group, but significantly more side effects and no impact on mortality [136, 139]. EVBL has been shown to be superior to sclerotherapy in reducing the risk of rebleeding to a greater level with fewer side effects [87]. The combination of EVBL and sclerotherapy was no more effective than EVBL alone [140]. A combination of beta-blocker therapy with either EVBL or sclerotherapy has been found to reduce all bleeding, rebleeding from varices and variceal recurrence but not mortality, when compared to any single modality of therapy [141]. TIPS has been studied in early rebleeding with excellent results as mentioned previously in the chapter [132].
In summary, current Baveno V guidelines [2] suggest secondary prophylaxis should start on day 6 of the index bleed. A combination of beta-blocker therapy and EVBL is recommended over either treatment alone as there are lower re-bleed rates with combination therapy. In patients who are unwilling to have EVBL, beta-blockers with ISMN is recommended [2]. In patients intolerant of beta-blockers, EVBL alone is recommended. In patients who re-bleed despite endoscopic and pharmacological therapies, TIPS is recommended. Transplantation should be considered in those who are appropriate candidates.
Variceal haemorrhage remains a life-threatening emergency, and a cause of decompensation of patients with portal hypertension or cirrhosis. Prevention of the development of portal hypertension where possible remains key in halting the development of oesophageal or gastric varices. However when portal hypertension has developed, it is important to identify those at risk of varices and enter them into a screening programme. Those found to have varices should be offered primary prophylaxis if required. Once a varix bleeds, urgent specialist care is required to potentially save life. In addition to fluid and blood resuscitation to stabilise conditions before endoscopy, vasoactive medications to reduced portal pressure and antibiotics should be administered. At urgent endoscopy performed by an experienced endoscopist, EVBL is the preferred endoscopic technique to achieve haemostasis in oesophageal variceal haemorrhage, and injection of cyanoacrylate glue is the preferred endoscopic technique to achieve haemostasis in gastric variceal haemorrhage. If endoscopic therapy is difficult, or does not halt the bleeding then TIPS can be performed, although self-expanding tamponading stents may be useful in refractory oesophageal variceal bleeding and BRTO may be useful in refractory gastric variceal bleeding. Survivors of variceal bleeding should receive secondary prophylaxis with beta-blocker medication, together with EVBL in the case of oesophageal varices.
The authors would like to acknowledge those permitting the reprint of images in the chapter: Dr Adrian Stanley, Consultant Gastroenterologist, Glasgow Royal Infirmary, Scotland; the company ELLA-CS, Hradec Kralove, Czech Republic; and Dr Branislav Kunčak, 2nd Dept. of Internal Medicine, Faculty of Health and Social Work, University of Trnava and Nové Zámky Hospital, Nové Zámky, Slovakia.
Zoonosis (due to viruses [45%], bacteria [28%], parasites [20%], and fungi [7%]) cause damage to health because they represent 70% of the infectious pathologies that affect human beings and with a significant compromise of animal health (of 1 415 pathogenic agents for humans, 868 zoonosis have been described, and 80% of the latter are capable of affecting different species of animals), which implies a considerable economic burden for the countries, fundamentally derived from their health system [1, 2, 3].
In addition, the underreporting of zoonosis in many countries, especially those with low incomes, is notable, among other things, to deficiencies in health promotion and education, poor health coverage, limited hospital and laboratory infrastructure, poor inter-institutional interaction and, especially the application of deficient sanitary control programs [4, 5].
These diseases are often underestimated as a public health problem despite their significant impact on morbidity and mortality (43.6% are distributed throughout the world, of which 63.3% appear in Africa) compared to other pathologies that affect humans and animals [3, 6, 7, 8, 9].
Mainly due to the lack of knowledge of the real magnitude of the problem (good records are not kept), the noncompliance in the application of the control programs that already exist in each country, and because of the key concepts that constitute the theoretical framework of zoonoses as an area of knowledge They are scattered in various bibliographic sources, which makes access difficult [3, 6, 7, 8, 9].
The objective of the present written is to make a compilation of information on the last point, that is, a concentration and updating of relevant aspects that exist in the world literature on the subject based on a narrative approach. Since solid knowledge is that health professionals can achieve significant achievements in the prevention, control, and eradication of zoonosis [3, 6, 7, 8, 9].
The present work was based on the documentary review of scientific literature in electronic and physical format on aspects of zoonosis based on the systematic analysis and narrative description of what was found, for which virtual databases were used (Bireme/PAHO, Medline, PudMed, and Scielo) from descriptors related to the topic. Repeated documents and those without clear conclusions and without originality were excluded. All original articles published up to December 2021 were included. The relevant ideas were grouped into four aspects that can be read independently, in order to facilitate their review:
The concept of zoonosis,
General aspects of zoonosis,
Overview of zoonosis in the world, and
Theoretical and methodological interventions of zoonosis.
Finally, and as a contribution from the researchers, conclusions are provided.
This word derives from the Greek roots zoos (animal) gnosis (disease). Its origin is attributed to Rudolf Virchowe, since in the nineteenth century he used this word to refer to diseases shared between man and animals. In 1956 (in the twentieth century) the World Health Organization defined zoonosis as any disease that is naturally transmitted from vertebrate animals to man in a man-centered concept, therefore, three years later this international organism of health reformulates the concept of diseases that are transmitted between animals and man [10, 11].
This last definition of zoonosis is followed by the proposal by Schwalbe, which from the operational-administrative perspective gives it the following meaning: "… those infections and infestations that in nature are shared by man and other lower vertebrate animals" [10, 11, 12]. Subsequently, the concepts zoo anthropozoonosis (when the infection is transmitted from animals to humans) and anthropozoonosis (when the infection is transmitted from humans to animals) appear [11, 12].
According to the characteristics of their transmission cycle, zoonosis is classified into (Table 1):
Transmission cycle | Type |
---|---|
Direct cycle | Only one vertebrate involved. |
Cyclozoonosis | More than one vertebrate is involved. |
Metazoonosis | A vertebrate and an invertebrate participate. |
Saprozoonosis | Requires an inert element to complete its transmission cycle. |
Types of zoonosis according to their transmission cycle.
Source: Schwalbe (10), Acha (1986), Bastidas (2018).
In addition, the transmission of a zoonosis between animals and humans can be:
Direct due to systematic or circumstantial coexistence (they group together a large part of the best-known zoonoses);
Indirect when different elements of the environment, such as soil, water, organic matter, food, and vectors (abundant in etiology and versatile in their form of transmission), intervene;
Those that can be transmitted directly or indirectly [10, 13, 14].
Due to their form of transmission, zoonosis is divided into:
Direct (they are transmitted by contact between vertebrate animals and humans, and vice versa), and
Indirect (includes living or inanimate intermediaries).
They can also be
Emerging (unknown so far or the result of infection) evolution or modification of pathogenic agents whose pathogenicity, transmitter, or host is known),
Re-emerging (these are known diseases whose prevalence increases considerably), or
Exotic (known but never before presented in a certain region).
A disease can be placed in more than one category. In addition, these infections can be:
Synanthropic (urban cycle) or
Exoanthropic (sylvatic cycle), and
Even be mixed [15].
Emerging and re-emerging zoonosis are considered neglected diseases because their prevalence is particularly high in marginalized populations with low incomes without access to health services and where official health institutions neglect to attend to their health needs. In addition, among the conditioning factors of the emergence and re-emergence of zoonosis, demography, ecological and climatic changes, and human behavior are mentioned [16, 17].
The key element to describe the epidemiological behavior of zoonosis is the information registry. However, its quality (complete and up-to-date) can be seriously compromised in countries with low economic income, due to poor investment of financial resources and technical difficulties, as well as the frequent political and social conflicts that occur in many of these countries, because private health institutions do not keep records or do so partially or incompletely, and because of the subclinical behavior of some zoonosis that prevents their registration on time [6, 18, 19].
In countries with low economic income, economic support, and the availability of human talent and favorable political will toward the health sector are constantly changing, which has a negative influence on the control and eradication of zoonosis, since they mark periodic cycles of advances and setbacks in the fight with these diseases. Likewise, the scarce or absent intersectoral coordination and the non-perception of zoonosis as an important public health problem by health authorities contribute to the stagnation in the control of these diseases. The need for care and the institutional response to zoonosis control allow it to be grouped into three categories as shown in Table 2 [6, 20]:
Zoonosis | Health action |
---|---|
With significant morbidity and/or mortality | It is present in the epidemiological records. With a sanitary control and epidemiological surveillance program incorporated into the organizational structure of the country’s health system. With technical regulations and legal framework. With infrastructure and financing. |
Sporadic outbreaks, but in longitudinal follow-up, they are more or less frequent. | With direct or indirect evaluations of its incidence by not necessarily official institutions of the health sector. They lack health control programs. |
Rarely therefore its importance for public health is unknown. | They are recorded as isolated and insignificant events, generally by private care services. |
Zoonosis according to its importance, is a health problem.
Source: Modified from Matamoros [6].
The control and eradication of zoonosis are seriously compromised by a series of factors that ensure their spread, among which are mentioned:
The ability of some pathogens to infect a wide variety of species,
The appearance of new zoonosis,
Immunosuppression of the susceptible (due to chemotherapy, use of steroids, and HIV),
The tendency of the diseases to remain in a latent or subclinical phase,
The chronic course of many of them,
The damage to health and the severe economic losses that they produce,
The complexity of the re-emergence of multiple zoonosis,
The underestimation of clinical diagnosis and the frequent disarticulation between human and animal health in the approach to zoonosis [21, 22, 23, 24].
In addition, the control of zoonosis is affected:
By not being addressed in a particular way despite the existence of common elements,
By the constant demographic growth (with greater animal exploitation in an attempt to cover food needs),
By globalization (with an increase in the displacement of people, animals, and their derivatives),
Due to the increase in occupational accidents (brucellosis, hepatitis, and tuberculosis, among others),
Due to climate and ecological change (allows the adaptation of pathogens to new territories),
Due to the tendency to adopt animals wild as pets, and the resistance of pathogens to the drugs used to combat them (by indiscriminate use) [21, 22, 23, 25, 26, 27].
In Latin America and the Caribbean, for example, there are 26 priority zoonotic diseases (Table 3):
Rabies Leptospirosis Brucellosis Tuberculosis Hydatidosis Campylobacteria Influenza Chagas Leishmaniosis Venezuelan Equine Encephalitis Hantavirus Plague Anthrax Chikungunya Equine Encephalitis Dengue Helminths Food Borne Illness Toxoplasmosis Fasciolosis Erysipelas COVID-19 |
Zoonosis is considered priorities for health authorities in Latin America and the Caribbean.
Source: Drawn from Maxwell [28].
In the world, there are several zoonosis, considered emerging and priority among them are H5N1 and H1N1 influenza, SARS, and most recently Ebola and Zika [28]. Likewise, the stages through which zoonosis goes through to become pandemics are currently described (see Table 4).
Expansion within the host population. The spread to a new region. It is transmitted to another non-host population. That reaches the human being. Large-scale agricultural or demographic changes, such as transport of livestock, to the region where the infectious agent has a niche or movement of wildlife to other regions in search of food, result in multidirectional transmission. For example, transmission like this can be between livestock and non-human primates and that can increase the probability that the pathogen reaches humans and spreads among different populations. Advance to the second stage??. become large outbreaks. They can be limited (for example, Ebola virus) or not (for example, Hendra virus) |
Strategies to try to predict potential pandemics are also described (Table 5):
Determining the relationship between the species of the pathogenic agent and the host. This is particularly important because the species closely related to each other favor the transmission of the etiological agent, that is, it passes easily from one host to another, however, in living beings human emerging pathogen species can come from closely related or distant hosts. The key to transmission to occur is contact. |
The emergence of pathogens can be predicted based on the analysis of phylogenetic relationships. In this sense, it is known that wild pathogens that are more closely related to those that affect humans are more certain to infect people in contrast to those distant. Likewise, the analysis of the phylogenetic relationship allows for determining the pathogenesis. |
The potential of emerging pathogens across a wide range of hosts (plasticity), thus, emerging pathogens have the ability to successfully transmit between different host taxa, thus increasing the probability of transmission to humans. Hence, the need for a constant study of these mechanisms in order to establish predictions. |
The presence of factors that facilitate the passage of a pathogen between different host species (evolutionary capacity), although these aspects are little known, they are related to the ability to mutate. The understanding of these mechanisms facilitates the explanation of the high capacity for jumping between hosts that some species of pathogens have. High transmission efficiency is often related to the ability of the pathogen to employ new transmission routes, hence, massive or generalized epidemic outbreaks are correlated with high transmission efficiency. |
The prediction of ligand-receptor binding requires an understanding of the interactions involved between common elements (already existing) or new ones because the binding at the cellular level between the pathogen and the host cell is the initial and indispensable step (binding to the receptor is necessary but not sufficient condition to ensure infection since other factors are required) and it is usually associated with changes in the tropism of the host’s tissues. Despite the fact that there are many technological and scientific advances, only the cellular receptor of a little less than half of the pathogens that affect human beings is known. Highly species-specific receptors are considered as a barrier to infection between pathogens and unusual or new hosts. |
The prediction of the transmissibility (virulence) of pathogens to humans is the greatest challenge to face in the study of pandemics since pathogen species that behave benignly in their natural hosts can trigger severe or lethal inflammatory responses in the host. New host coevolution patterns. |
Zoonosis is approached, studied, and intervened by classical or conventional epidemiology through the positivist paradigm that is based on the risk approach in the search for explanations about the health-disease process and about the circumstances that imply damage to human health and animal, due to the economic losses generated by the high figures of morbidity and mortality attributed to zoonotic transmission diseases, which undoubtedly hinder the development of countries [10, 30].
The advances and contributions achieved with the methods and theories of classical epidemiology are great and important, however, for the management of zoonoses, an integral vision is required that allows understanding of the complexity of the relationship between animals and human beings due to ecosystem and intervening social variables since it is necessary to go beyond the mere identification of infectious agents, pathogenesis, transmission, control, and treatment, in this sense, the paradigms of complexity and chaos have been used for the study of zoonosis [30, 31, 32, 33, 34].
The single and multi-causality approaches to risk are not enough to understand and explain the complex interactions that occur in zoonosis, paradigms are required that go beyond system theories, structural functionalism, the inability to control the pathogenic agent, the articulation of the epidemiological discourse to health policies, the ecosystem approach and the social component (behavior and culture in the relationship between equals, social determinants, and inequities in health), in this sense, a holistic approach to zoonoses (prevents the fragmentation and decontextualization of the health problem by considering it broad and complex) [30, 35, 36, 37, 38, 39, 40, 41].
Hence, international health organizations issue general and comprehensive recommendations that contribute to adequate surveillance and response capacity in the event of the emergency and re-emergence of zoonosis (see Table 6).
Recommendations |
|
Recommendations for comprehensive surveillance and adequate response to zoonosis.
Source: Ministry of Health [42].
These recommendations seek to prevent, monitor, and control zoonosis to reduce its impact on health, but to achieve this, the joint participation of animal health, human health, and the environmental sector are required.
This writing constitutes a brief but concise compendium on zoonosis that starts from the meaning of the word, goes through its general aspects, through the epidemiological panorama, and finally through the theoretical and methodological interventions that it has been the object of, it can then serve as a tool for health professionals and for the community in general in acquiring knowledge about zoonosis or for updating them in the fight against these diseases because with the information it offers, the dynamics of the factors that condition or determine their emergence can be understood, re-emergence, prevalence, and distribution in the animal and human population.
However, in the field of health control of zoonosis and from what is stated in this paper, it is concluded that the approach to zoonosis requires cross-cutting, multidisciplinary, and inter-institutional health care, in addition to the incorporation of social, cultural, and economic concepts that define the animal-man relationship, as well as the consideration of the circumstances that imply the involuntary contact between both actors (often ignored) as a result of mutual coexistence and the incorporation in the epidemiological surveillance of diseases of this type that have a low frequency of appearance.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. 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Dual-beam platforms, combining a high-resolution scanning electron microscope (HR-SEM) and an FIB column, additionally equipped with precursor-based gas injection systems (GIS), micromanipulators, and chemical analysis tools (such as energy-dispersive spectra (EDS) or wavelength-dispersive spectra (WDS)), serve as multifunctional tools for direct lithography in terms of nano-machining and nano-prototyping, while advanced specimen preparation for transmission electron microscopy (TEM) can practically be carried out with ultrahigh precision. Especially, when hard materials and material systems with hard substrates are concerned, FIB is the only technique for site-specific micro- and nanostructuring. 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In addition, the colloidal nanoparticles produced by laser ablation have very high purity—they are free from surfactants and reaction products or by-products. In this chapter, nanosecond, picosecond and femtosecond laser pulse durations are compared in laser material processing. 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Electron diffraction patterns are used to obtain quantitative data including phase identification, orientation relationship and crystal defects in materials, etc. At first, a general introduction including a geometrical and quantitative approach to electron diffraction from a crystalline specimen, the reciprocal lattice and electron diffraction in the electron microscope are presented. The scattering process by an individual atom as well as a crystal, the Bragg law, Laue conditions and structure factor are also discussed. Types of diffraction patterns such as ring pattern, spot pattern and Kikuchi pattern, and general and unique indexing diffraction patterns are explained. The procedure for indexing simple, complicated and imperfect patterns as well as Kikuchi lines and a combination of Kikuchi lines and spots is outlined. The known and unknown materials are identified by indexing patterns. Practical comparisons between various methods of analysing diffraction patterns are also described. The basic diffraction patterns and the fine structure in the patterns including specimen tilting experiments, orientation relationship determination, phase identification, twinning, second phases, crystallographic information, dislocation, preferred orientation and texture, extra spots and streaks are described in detail. 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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. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,annualVolume:11410,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,annualVolume:11411,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. 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He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. 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In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. 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We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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