Antiretroviral agent categories according to FDA
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"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:"6397",leadTitle:null,fullTitle:"Free Radicals, Antioxidants and Diseases",title:"Free Radicals, Antioxidants and Diseases",subtitle:null,reviewType:"peer-reviewed",abstract:"The current book entitled Free Radicals, Antioxidants, and Diseases gives an idea of detecting free radicals in vivo by newer techniques and provides insights into the roles played by various antioxidants in combating diseases caused by oxidative stress. The chapters included in this volume showcase new investigation in this field by the research groups around the world.",isbn:"978-1-78923-565-4",printIsbn:"978-1-78923-564-7",pdfIsbn:"978-1-83881-452-6",doi:"10.5772/intechopen.70075",price:119,priceEur:129,priceUsd:155,slug:"free-radicals-antioxidants-and-diseases",numberOfPages:148,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"7b0703d537f4f738f46848aac66f5d34",bookSignature:"Rizvan Ahmad",publishedDate:"August 1st 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6397.jpg",numberOfDownloads:10758,numberOfWosCitations:10,numberOfCrossrefCitations:11,numberOfCrossrefCitationsByBook:2,numberOfDimensionsCitations:16,numberOfDimensionsCitationsByBook:2,hasAltmetrics:1,numberOfTotalCitations:37,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"July 12th 2017",dateEndSecondStepPublish:"August 9th 2017",dateEndThirdStepPublish:"December 3rd 2017",dateEndFourthStepPublish:"January 3rd 2018",dateEndFifthStepPublish:"March 3rd 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"Imam Abdulrahman Bin Faisal University",institutionURL:null,country:{name:"Saudi Arabia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"380",title:"Molecular Biology",slug:"biochemistry-genetics-and-molecular-biology-biochemistry-molecular-biology"}],chapters:[{id:"60923",title:"Introductory Chapter: Basics of Free Radicals and Antioxidants",doi:"10.5772/intechopen.76689",slug:"introductory-chapter-basics-of-free-radicals-and-antioxidants",totalDownloads:2317,totalCrossrefCites:7,totalDimensionsCites:10,hasAltmetrics:0,abstract:null,signatures:"Rizwan Ahmad",downloadPdfUrl:"/chapter/pdf-download/60923",previewPdfUrl:"/chapter/pdf-preview/60923",authors:[{id:"40482",title:null,name:"Rizwan",surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad"}],corrections:null},{id:"59442",title:"Detecting In Vivo Free Radicals in Various Disease Models",doi:"10.5772/intechopen.74106",slug:"detecting-in-vivo-free-radicals-in-various-disease-models",totalDownloads:1281,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"In vivo free radical imaging in pre-clinical models of disease is now possible. Free radicals have traditionally been characterized by ESR or EPR spin trapping spectroscopy. The disadvantage of the ESR/EPR approach is that spin adducts are short-lived due to biological reductive and/or oxidative processes. Immuno-spin trapping (IST) involves the use of an antibody that recognizes macromolecular DMPO-spin adducts (anti-DMPO antibody), regardless of the oxidative/reductive state of trapped radical adducts. The IST approach has been extended to an in vivo application that combines IST with molecular magnetic resonance imaging (mMRI). This combined IST-mMRI approach involves the use of a spin trapping agent, DMPO, to trap free radicals in disease models, and administration of a mMRI probe, an anti-DMPO probe, that combines an antibody against DMPO-radical adducts and a MRI contrast agent, resulting in targeted free radical adduct detection. The combined IST-mMRI approach has been used in several rodent disease models, including diabetes, ALS, gliomas, and septic encephalopathy. The advantage of this approach is that heterogeneous levels of trapped free radicals can be detected directly in vivo and in situ to pin-point where free radicals are formed in different tissues. The approach can also be used to assess therapeutic agents that are either free radical scavengers or generate free radicals. The focus of this review will be on the different applications that have been studied, advantages and limitations, and future directions.",signatures:"Rheal A. Towner and Nataliya Smith",downloadPdfUrl:"/chapter/pdf-download/59442",previewPdfUrl:"/chapter/pdf-preview/59442",authors:[{id:"59098",title:"Dr.",name:"Nataliya",surname:"Smith",slug:"nataliya-smith",fullName:"Nataliya Smith"},{id:"220515",title:"Dr.",name:"Rheal",surname:"Towner",slug:"rheal-towner",fullName:"Rheal Towner"}],corrections:null},{id:"61598",title:"Oxidative Stress and Vascular Diseases: Effect of Physical Exercise",doi:"10.5772/intechopen.76576",slug:"oxidative-stress-and-vascular-diseases-effect-of-physical-exercise",totalDownloads:1152,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Investigations have shown that worldwide the vascular diseases are considered independent risk factors for an increased mortality. Despite these diseases being related to factors such as sedentary lifestyle, poor diet and stress, the oxidative stress been the which most strongly explained the genesis of these vascular diseases. In this sense, the body of evidence involving an analysis and understanding of the factors and preventive variables of these diseases available in the literature is necessary. Considering this, we aimed to available information about the role of the oxidants and antioxidants enzymes in the prevention or causes of vascular diseases, and how the physical exercise can prevent the development of these vascular diseases. It was observed that endothelin-1 is an important oxidant involved in the atherosclerotic process, while the hydrogen sulfide and glutathione peroxidase have an antioxidant role. About the physical exercise, there is greater production of oxidants, however, as a mechanism of compensation, there is also greater production and release of antioxidants such as nitric oxide and glutathiones after some sessions when compared with the baseline. We conclude that the stress oxidative is involved in the vascular disease and the physical exercise could be used like prevention.",signatures:"Aline de Freitas Brito, Caio Victor Coutinho de Oliveira, Glêbia Alexa\nCardoso, Joana Marcela Sales de Lucena, Jordanna di Paula dos\nSantos Sousa and Alesandra Araújo de Souza",downloadPdfUrl:"/chapter/pdf-download/61598",previewPdfUrl:"/chapter/pdf-preview/61598",authors:[{id:"237904",title:"Dr.",name:"Aline",surname:"Brito",slug:"aline-brito",fullName:"Aline Brito"},{id:"246673",title:"MSc.",name:"Caio Victor",surname:"Coutinho De Oliveira",slug:"caio-victor-coutinho-de-oliveira",fullName:"Caio Victor Coutinho De Oliveira"},{id:"246676",title:"Dr.",name:"Glêbia Alexa",surname:"Cardoso",slug:"glebia-alexa-cardoso",fullName:"Glêbia Alexa Cardoso"},{id:"246678",title:"Dr.",name:"Joana Marcela",surname:"Sales De Lucena",slug:"joana-marcela-sales-de-lucena",fullName:"Joana Marcela Sales De Lucena"},{id:"246679",title:"Prof.",name:"Jordanna Di Paula",surname:"Dos Santos Sousa",slug:"jordanna-di-paula-dos-santos-sousa",fullName:"Jordanna Di Paula Dos Santos Sousa"},{id:"246680",title:"MSc.",name:"Alesandra",surname:"Araújo De Souza",slug:"alesandra-araujo-de-souza",fullName:"Alesandra Araújo De Souza"}],corrections:null},{id:"59536",title:"EPR Analysis of Antioxidant Compounds",doi:"10.5772/intechopen.74294",slug:"epr-analysis-of-antioxidant-compounds",totalDownloads:1082,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"A free radical is a molecular species having an unpaired electron and it is a highly reactive entity and unstable. A free radical is a molecule with one or more unpaired electrons in its outer shell. Free radicals can be formed by chemical bond breakage from molecules or by redox reactions. When cells use oxygen, the oxidative stress occurs. The oxidative stress causes free radical formation. Free radicals can also be generated from ionizing radiations, ozone, heavy metal poisoning, cigarette smoking, and chronic alcohol intake. These free radicals are highly reactive and oxidize biomolecules leading to tissue injury and cell death. They also cause toxic effects and diseases. Antioxidants neutralize free radicals resulting from oxidative stress. Antioxidants play an important role in the treatment of diseases. The most suitable method for the analysis of free radicals is the electron paramagnetic resonance (EPR) spectroscopy method. The EPR method detects a paramagnetic center with a single electron. It gives information about the interactions with other nuclei around one electron. It provides information on the structure and environment of radicals.",signatures:"Betül Çalişkan and Ali Cengiz Çalişkan",downloadPdfUrl:"/chapter/pdf-download/59536",previewPdfUrl:"/chapter/pdf-preview/59536",authors:[{id:"199110",title:"Dr.",name:"Betül",surname:"Çalişkan",slug:"betul-caliskan",fullName:"Betül Çalişkan"},{id:"208732",title:"Dr.",name:"Ali Cengiz",surname:"Çalişkan",slug:"ali-cengiz-caliskan",fullName:"Ali Cengiz Çalişkan"}],corrections:null},{id:"60997",title:"Oxidative Stress in Type 1 Diabetes Mellitus: Ethnic Aspects",doi:"10.5772/intechopen.76512",slug:"oxidative-stress-in-type-1-diabetes-mellitus-ethnic-aspects",totalDownloads:917,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Numerous researches show that data on an ethnic origin can give additional information for the personified approach in treatment of different diseases. The aim of this study was to evaluate the level of some lipid peroxidation components and antioxidant defense system in Mongoloid and Caucasian patients with Type 1 diabetes mellitus. Conjugated dienes, ketodienes and conjugated trienes, thiobarbituric acid reactants, total antioxidant activity, α-tocopherol, retinol, superoxide dismutase activity, reduced and oxidized glutathione, and oxidative stress coefficient levels were evaluated in 65 patients with type 1 diabetes (38 Mongoloids and 27 Caucasians) and in 82 healthy people (42 Mongoloids and 40 Caucasians). Spectrophotometric and fluorometric methods were used. The intensity of LPO in Mongoloid patients was lower than in Caucasians: the level of primary and intermediate products was by lower 1.53 and 1.83 times, while total antioxidant activity was elevated by 1.44 times, and decreased α-tocopherol level by 1.32 times, which was also supported by oxidative stress coefficient (1.35 in Mongoloids and 2.32 in Caucasians). Activity of the POL-AOD system in Mongoloids is low, which is probably due to the increase of antioxidant defense system work. These results are consistent with clinical characteristics of type 1 diabetes mellitus with infrequent development of complications in Mongoloids living in Eastern Siberia.",signatures:"Lyubov I. Kolesnikova, Marina A. Darenskaya, Lyudmila A.\nGrebenkina, Svetlana V. Gnusina and Sergey I. Kolesnikov",downloadPdfUrl:"/chapter/pdf-download/60997",previewPdfUrl:"/chapter/pdf-preview/60997",authors:[{id:"220094",title:"Dr.",name:"Marina",surname:"Darenskaya",slug:"marina-darenskaya",fullName:"Marina Darenskaya"}],corrections:null},{id:"59213",title:"Dimethylformamide Reduces Cerebral Ischaemia in Diabetic Rats Hours after Its Occurrence; A New Horizon",doi:"10.5772/intechopen.73700",slug:"dimethylformamide-reduces-cerebral-ischaemia-in-diabetic-rats-hours-after-its-occurrence-a-new-horiz",totalDownloads:1019,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The antioxidant properties of dimethylformamide (DMF) depend on its interference with the hydroxyl-radical-transduction pathway. Diabetes is a risk factor of cerebral ischaemia (CI), and both entities are associated with oxidative stress (OS). We evaluated DMF’s effects on CI in non-diabetic rats (NDRs) and in diabetic rats (DRs). One hour after CI, the animals were divided into two treatment groups (300 μl subcutaneous): either DMF or isotonic saline solution. Treatment effects were analysed in NDRs or DRs without CI. Eight hours after CI, a neurophysiologic score (NS) was determined; CI and OS biomarkers were measured in the ischaemic cerebral hemisphere. Infarct/oedema volumes were measured on dyed brain slices. DMF reduced infarct volume in NDRs and DRs but only improved the NS in DRs. Basal concentrations of all the biomarkers were similar in the NDRs and DRs. Metalloproteinase 9 (MMP9) did not change with DMF. Malondialdehyde (MDA) increased with CI, and DMF only reduced it in DRs. RAGE, nitrite/nitrate and nitrotyrosine increased with CI only in DRs (all prevented by DMF). We conclude that DMF’s benefits on CI were greater in the DRs due to a higher susceptibility of diabetic animals to the OS produced by CI. The results open a new horizon in CI treatment since DMF has not been investigated before.",signatures:"Julio Amadeo Mendoza-Betancourt, Robert David Kross, Maria\nAngeles Moro, Ignacio Lizasoain, Luis Humberto Pérez-Astudillo,\nArturo Alva-Félix-Díaz and Cleva Villanueva",downloadPdfUrl:"/chapter/pdf-download/59213",previewPdfUrl:"/chapter/pdf-preview/59213",authors:[{id:"178299",title:"Dr.",name:"Cleva",surname:"Villanueva",slug:"cleva-villanueva",fullName:"Cleva Villanueva"},{id:"178301",title:"Dr.",name:"Robert",surname:"Kross",slug:"robert-kross",fullName:"Robert Kross"},{id:"178302",title:"Dr.",name:"Luis",surname:"Perez-Astudillo",slug:"luis-perez-astudillo",fullName:"Luis Perez-Astudillo"},{id:"222060",title:"MSc.",name:"Julio",surname:"Mendoza-Betancourt",slug:"julio-mendoza-betancourt",fullName:"Julio Mendoza-Betancourt"},{id:"222061",title:"Dr.",name:"Maria Angeles",surname:"Moro",slug:"maria-angeles-moro",fullName:"Maria Angeles Moro"},{id:"222062",title:"Dr.",name:"Ignacio",surname:"Lizasoain",slug:"ignacio-lizasoain",fullName:"Ignacio Lizasoain"},{id:"222065",title:"Dr.",name:"Emmanuel",surname:"Martinez Lara",slug:"emmanuel-martinez-lara",fullName:"Emmanuel Martinez Lara"},{id:"222073",title:"Mr.",name:"Arturo",surname:"Alva Felix Diaz",slug:"arturo-alva-felix-diaz",fullName:"Arturo Alva Felix Diaz"}],corrections:null},{id:"61344",title:"Cardioprotective Effects of S-Nitrosothiols in Ischemia- Reperfusion: Role for Mitochondria and Calcium Channels",doi:"10.5772/intechopen.77003",slug:"cardioprotective-effects-of-s-nitrosothiols-in-ischemia-reperfusion-role-for-mitochondria-and-calciu",totalDownloads:1134,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The most important clinical consequence of coronary disease is acute myocardial infarction caused by an occlusion that limits the irrigation to the heart. Although the gold standard treatment is to restore blood flow, this reperfusion causes inherent damage by increasing the size of the infarcted area primarily through the opening of the mitochondrial permeability transition pore (MPTP). The cardioprotective effect of nitric oxide (NO) has been described to operate through S-nitrosylation of several important proteins in the cardiomyocytes such as the calcium channels RyR2 and the L-type Ca2+ channel and mitochondrial proteins, including the MPTP. In this sense, an attractive strategy to prevent the ischemia-reperfusion damage is to increase the bioavailability of endogenous S-nitrosothiols. S-nitrosoglutathione reductase (GSNOR) is an enzyme involved in the metabolism of NO through denitrosylation, which would limit the cardioprotective effect of NO. Although inhibition of GSNOR has been studied in different organs, its effects on myocardial reperfusion have not yet been fully elucidated. In this chapter, we review the pathophysiology underlying myocardial reperfusion injury and the opening of the MPTP along with the cardioprotective role of S-nitrosothiols and the potential role for GSNOR.",signatures:"Oscar Arriagada, Adriana V. Treuer and Daniel R. González",downloadPdfUrl:"/chapter/pdf-download/61344",previewPdfUrl:"/chapter/pdf-preview/61344",authors:[{id:"54305",title:"Dr.",name:"Daniel",surname:"Gonzalez",slug:"daniel-gonzalez",fullName:"Daniel Gonzalez"},{id:"177980",title:"Dr.",name:"Adriana",surname:"Treuer",slug:"adriana-treuer",fullName:"Adriana Treuer"},{id:"215747",title:"MSc.",name:"Oscar",surname:"Arriagada",slug:"oscar-arriagada",fullName:"Oscar Arriagada"}],corrections:null},{id:"60407",title:"Antimicrobial and Antioxidant Properties of Essential Oil Isolated from Coleus zeylanicus under Normal and Salinity Stress Conditions",doi:"10.5772/intechopen.73966",slug:"antimicrobial-and-antioxidant-properties-of-essential-oil-isolated-from-coleus-zeylanicus-under-norm",totalDownloads:984,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Essential oils can be used as antibacterial additives and are generally recognized as safe. Coleus zeylanicus is one of the medicinal aromatic plant serves as a source of essential oils. Antimicrobial and antioxidant activities of essential oils obtained from the control and salinity stressed Coleus zeylanicus plant was investigated in the present study. Essential oils from the control and salinity stressed Coleus zeylanicus plant was extracted using Clevenger apparatus. The composition of essential oils was identified using gas chromatography mass spectrometry, which showed a few compounds expressed differentially. The antibacterial activity of the isolated essential oils was studied by using the agar well diffusion method, showing potent inhibitory activity against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. The antioxidant and antimicrobial constituents of the essential oils were spotted using the bioautography method, revealing that the antioxidant and antimicrobial properties in the essential oils of Coleus zeylanicus were increased upon exposure to salinity stress.",signatures:"Divya Kotagiri, Khasim Beebi Shaik and Viswanatha Chaitanya\nKolluru",downloadPdfUrl:"/chapter/pdf-download/60407",previewPdfUrl:"/chapter/pdf-preview/60407",authors:[{id:"227207",title:"Dr.",name:"Kolluru",surname:"Viswanatha Chaitanya",slug:"kolluru-viswanatha-chaitanya",fullName:"Kolluru Viswanatha Chaitanya"},{id:"227209",title:"Ms.",name:"Divya",surname:"Kotagiri",slug:"divya-kotagiri",fullName:"Divya Kotagiri"},{id:"227210",title:"Prof.",name:"Sheik",surname:"Khasim Beebi",slug:"sheik-khasim-beebi",fullName:"Sheik Khasim Beebi"}],corrections:null},{id:"59088",title:"Vascular Calcification and Oxidative DNA Damage as Nontraditional Cardiovascular Risk Factors in Chronic Renal Disease",doi:"10.5772/intechopen.73095",slug:"vascular-calcification-and-oxidative-dna-damage-as-nontraditional-cardiovascular-risk-factors-in-chr",totalDownloads:872,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The number of CKD sufferers that require renal replacement techniques (RRTs) is increasing. The severity of cardiovascular disease (CVD) is disproportionate in these kinds of patients and contributes considerably to mortality in CKD patients. We evaluated the association between oxidative DNA damage, antioxidant activity and vascular calcification (VC) in CKD. An analytical cross-sectional study was performed. Two simple plaques were taken for each patient (pelvis-hip, and hands-wrists). The presence of VC was scored as presence (1) and absence (0). Oxidative stress was determined by activity of catalase, superoxide dismutase (SOD) and oxidative DNA damage by determination of 8-OHdG marker. Eighty-one patients were included. The RRT type was similar for hemodialysis (HD) and peritoneal dialysis (PD). Thirty-eight patients (47%) presented VC (p < 0.01); in 61%, the VC was severe (≥3 points). VC prevalence in women was significantly higher, (67%) (p < 0.001), and (29%) men. Sixty four percent of the patients submitted to HD presented VC and 27% to PD (p < 0.001). The activity of the catalase enzyme was significantly decreased in CKD vs. the healthy control (HC) (p < 0.0001). The oxidative DNA damage in CKD was greater vs. HC (p < 0.0001). In conclusion, the VC was frequent (47%) in CKD, and decreased catalase activity and greater oxidative DNA damage.",signatures:"Edith Viridiana Alatorre-Moreno, José Ignacio Cerrillos-Gutiérrez,\nJorge Andrade-Sierra, Enrique Rojas-Campos, Sandra Carrillo-Ibarra,\nSonia Sifuentes-Franco, Andrés García-Sánchez and Alejandra\nGuillermina Miranda-Díaz",downloadPdfUrl:"/chapter/pdf-download/59088",previewPdfUrl:"/chapter/pdf-preview/59088",authors:[{id:"178033",title:"Dr.",name:"Alejandra Guillermina",surname:"Miranda-Diaz",slug:"alejandra-guillermina-miranda-diaz",fullName:"Alejandra Guillermina Miranda-Diaz"},{id:"202798",title:"Dr.",name:"Jorge",surname:"Andrade-Sierra",slug:"jorge-andrade-sierra",fullName:"Jorge Andrade-Sierra"},{id:"208589",title:"Dr.",name:"Sonia",surname:"Sifuentes-Franco",slug:"sonia-sifuentes-franco",fullName:"Sonia Sifuentes-Franco"},{id:"208590",title:"Dr.",name:"Sandra",surname:"Carrillo-Ibarra",slug:"sandra-carrillo-ibarra",fullName:"Sandra Carrillo-Ibarra"},{id:"208591",title:"Dr.",name:"José Ignacio",surname:"Cerrillos-Gutiérrez",slug:"jose-ignacio-cerrillos-gutierrez",fullName:"José Ignacio Cerrillos-Gutiérrez"},{id:"208595",title:"Dr.",name:"Enrique",surname:"Rojas-Campos",slug:"enrique-rojas-campos",fullName:"Enrique Rojas-Campos"},{id:"222295",title:"Dr.",name:"Edith Viridiana",surname:"Alatorre-Moreno",slug:"edith-viridiana-alatorre-moreno",fullName:"Edith Viridiana Alatorre-Moreno"},{id:"222296",title:"Mr.",name:"Andrés",surname:"García-Sánchez",slug:"andres-garcia-sanchez",fullName:"Andrés García-Sánchez"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"5121",title:"Free Radicals and Diseases",subtitle:null,isOpenForSubmission:!1,hash:"9f5f123060d6e78a2f4bb7d37e781d92",slug:"free-radicals-and-diseases",bookSignature:"Rizwan Ahmad",coverURL:"https://cdn.intechopen.com/books/images_new/5121.jpg",editedByType:"Edited by",editors:[{id:"40482",title:null,name:"Rizwan",surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"779",title:"Protein Purification",subtitle:null,isOpenForSubmission:!1,hash:"8aa371cf1ed6990c6ede21238f467547",slug:"protein-purification",bookSignature:"Rizwan Ahmad",coverURL:"https://cdn.intechopen.com/books/images_new/779.jpg",editedByType:"Edited by",editors:[{id:"40482",title:null,name:"Rizwan",surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10803",title:"Reactive Oxygen Species",subtitle:null,isOpenForSubmission:!1,hash:"176adcf090fdd1f93cb8ce3146e79ca1",slug:"reactive-oxygen-species",bookSignature:"Rizwan Ahmad",coverURL:"https://cdn.intechopen.com/books/images_new/10803.jpg",editedByType:"Edited by",editors:[{id:"40482",title:null,name:"Rizwan",surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3203",title:"Oxidative Stress and Chronic Degenerative Diseases",subtitle:"A Role for Antioxidants",isOpenForSubmission:!1,hash:"7014dbaa632114f7220802475ccd0402",slug:"oxidative-stress-and-chronic-degenerative-diseases-a-role-for-antioxidants",bookSignature:"José A. 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Reaching the virtual worldwide eradication of vertical transmission (prevention of mother-to-child transmission [PMTCT]) is among such goals.
This chapter will address topics related mainly to diagnostic and therapeutic aspects that have been proven to be useful in the prevention of HIV vertical transmission (VT). The aim is to provide the reader with a clinical guideline for the management of an HIV(+) pregnant woman based on levels of evidence, grading of recommendation, and experts’ opinions and to individualize those healthcare strategies that have demonstrated to be effective in the reduction of HIV vertical transmission. Such achievement will highlight the importance of ordering an HIV test to all pregnant women during prenatal control visit. The latter, in case of carrier status, will help to decrease viral load in HIV(+) mothers to undetectable or almost undetectable levels. It will also enable the formulation of a management strategy based on clinical and laboratory parameters, with the use of the most adequate pharmacological management, thus decreasing exposure of the newborn of an HIV(+) mother, to blood, genital secretions, or amniotic fluid, and to identify the best opportunity to program delivery and termination of breastfeeding.
This Clinical Guideline is intended for midwives, medical students, gynecology and obstetrics fellows/residents, maternal-fetal medicine fellows/residents, obstetricians serving at level 2 and 3 hospitals, and specialists in maternal-fetal medicine, who aim at updating their knowledge on the diagnosis and management of gestations affected by HIV/AIDS.
All the aforementioned will bring insights on why healthcare strategies intended to prevent fetal infection have become a paradigm of perinatal medicine since the application of such biomedical interventions has been proven to be successful in the prevention of HIV transmission from an infected pregnant woman to her child, decreasing risk levels to 2%, as observed in the United States.
The attempt at improving epidemiological rates of HIV/AIDS through the prevention and treatment of the disease is one of the eight Millennium Development Goals proposed by the World Health Organization. Worldwide, the virtual eradication of mother-to-child transmission is one of the goals to be accomplished [1, 2].
The present guide will be developed based on the method proposed by Harbour et al., which in turn is based on the formulation of various questions that will be answered according to levels of evidence, grading of recommendation, and experts’ opinions [3].
Vertical transmission (VT) of HIV is defined as that occurring from mother to child during gestation, delivery, or breastfeeding. The VT rates range between 13% and 48%. [4-7]. Preventive strategies have been set out to lower VT rates to less than 2%. Pregnancy, delivery, and breastfeeding are the most susceptible periods for VT of HIV [8, 9]. Maternal viral load (VL) is the main independent risk factor for transmission. Certain sexually transmitted diseases (STD) also increase the risk of VT. Likewise, low maternal CD4 cell counts also constitute a risk factor for VT, which is independent from VL [10].
The prevalence of vertical transmission (VT) in the various regions of the world varies according to geographic site and specifically according to the contribution of economic resources invested by different countries worldwide in the various strategies for healthcare policies, aiming at the prevention and treatment of infected mothers [2].
In countries with low infection prevalence rates such as Chile, efforts have been targeted to the decrease of vertical transmission (VT), which is responsible for 99% of HIV infections among children younger than 13 years old [5, 11].
Mother-to-child transmission as route of exposure has decreased, from rates of approximately 30% in 1996, prior to the first VT prevention protocol (ACTG 076), to 0.7% for HIV and 0.6% for AIDS, during the 2006-2010 period [4, 12-14].
To optimize prevention of VT, the clinical approach to a seropositive pregnant woman must be based on a thorough assessment of her initial health status, with a full physical examination, focusing particularly on those signs that point toward an opportunistic infectious condition and evaluating her current immune status.
The strategy for prevention of VT has been based on the continuous review of the pooled evidence and has followed the impact factor of such evidence to suggest valid recommendations from expert opinions. It is of key importance to further evaluate new behaviors tending to identify, among other aspects: the eventual induction of resistance and toxicity of antivirals both in the pregnant mother as well as in the newborn, and their potential effect on subsequent quality of life, the use of micronutrients and the identification of their impact on VT decrease, and the evaluation of vaginal delivery as an option in pregnant women with a low viral load [2, 14-20].
Once the effectiveness of biomedical patient benefits in VT prevention has been demonstrated, it is important to ensure the collection of epidemiological history in order to generate an adequate means of notification, which constitutes data required for reassessing the design and the effectiveness of preventive programs. To attain such goals, it is key to maintain and improve diagnosis and primary prevention of infection in women in childbearing age. Furthermore, it is important to avoid the high rate of unwanted pregnancies and abortions, which represent indirect indicators of risk behaviors in such population. Likewise, one should aim at reaching 100% of screening during the first trimester, at the possibility of repeating such screening during the third trimester and at training maternity staff in rapid testing for the detection of carrier status during labor for pregnant women not having previously undergone such screening [2].
Most women discover their carrier status or disease during pregnancy or after delivery upon the detection of the infection in the newborn. With regard to the latter, and despite the fact that there is no consensus on the recommendation of universal screening to all women upon their pre- and/or postconception visit, the American College of Obstetricians and Gynecologists and the Royal College of Obstetricians and Gynecologists United kingdom recommend performing the test on a routine basis, a behavior commonly adopted in many countries worldwide [21, 22]. In fact, most of such countries have also integrated a mandatory pretest counseling, the need for an informed consent, and the willfulness of people upon deciding to undergo the testing. Thus, sample collection requires the participation of staff trained in “counseling”. The latter has reinforced the decision of women to undergo the test and has resulted in a significant rise of adhesion to preventive behaviors and therapy (Uganda and Rwanda) [23, 29, 30].
The recommended test for screening is the fourth-generation ELISA. Such laboratory examination enables the simultaneous detection of Ag p24 and its respective antibodies, and therefore the window period is reduced to approximately 30 days with a sensitivity of 99.9% and a specificity of 99.5%. Despite the latter, it is important to stress that the positive predictive value of such test during pregnancy is approximately 50%, as a result of being applied on a low prevalence population. Thus, a confirmation test is required, and therefore patients with positive ELISA test should undergo a confirmatory test with Western blot. The confirmatory Western blot technique is carried out with a nitrocellulose strip onto which HIV envelope proteins have been added. When patient serum is transferred to the strips, any antibody against the virus present in serum will bind to the respective specific antigen on the strip. Western blot results are interpreted by observing the colored bands that are identified according to their position and particular characteristics. When results are indeterminate, a new sample must be ordered after 3 months to reevaluate eventual positivity [2, 31, 32, 36].
Furthermore, for pregnant patients with unknown serological status that seek healthcare because of labor initiation or medical situations in which pregnancy interruption is imminent, health services should be equipped with rapid diagnostic techniques (visual or instrumental). Despite their nonoptimal specificity and sensitivity, in the event of being positive, such techniques would enable the recommendation of peripartum preventive measures, with prior provision of the informed consent by the patient. Such emergency evaluations may be performed even by individuals lacking a specific training when other human resources are unavailable [33-36].
With regard to the indication of universal HIV testing for women at their preconception consultation and/or at the beginning of their antenatal follow-up visit, the American College of Obstetricians and Gynecologists recommends that it is carried out on a routine basis, as it is the common practice in many countries of the world. In fact, most women are aware of their carrier status during pregnancy or during the puerperium upon screening for neonatal infection. As for the latter, it has been demonstrated that ordering the test together with pre- and posttest counseling improves awareness on the disease, adherence to therapy, and development of behaviors in the carrier to prevent transmission to her individual environment [22-27]. With regard to pre- and postconception counseling, defined as a “confidential conversation between a patient and a counselor that aims at the acquisition by the former of skills to face the stress related to an eventual carrier status, at achieving HIV/AIDS-related decision making during pregnancy, and learning of strategies for the prevention of vertical transmission,” it is advisable to address the following topics:
Information about basic aspects of HIV/AIDS transmission and prevention
Signature of the informed consent or statement of declination of the test
Evaluation of the HIV detection test final result, with posttest counseling
Reinforcement of preventive strategies for HIV and other STD during pregnancy
Supply of emotional support in the case the result of one or both tests is reactive or positive
Provision of information on pregnancy control and/or follow-up procedures at the specialties level and consequent referral in cases with reactive or positive test results
Support to therapy adherence, exams, and periodic follow-up if applicable
Record of the activity in the pertaining documents
The trend worldwide regarding HIV test ordering has progressed toward mandatory programs. These are more efficient and less harmful than those that are voluntary or the routine programs with implicit but revocable consent. International organizations (WHO/UNAIDS) recommend guidelines regarding avoidance of compulsoriness of HIV testing and prioritization of guidance, education, and advise for its performance [25, 27, 28]. The recommendations/guidelines should be undertaken regardless of seropositivity prevalence in the population. Such management protocols would enable an adequate control of mother-to-child transmission at the population health level, while protecting mother rights and preventing stigmatization and discrimination. To the WHO, national policies and practices regarding compulsoriness of HIV testing should be reviewed to eliminate any testing that is not voluntary. Mandatory testing or testing under coercion on individuals belonging to vulnerable groups or groups with high risk of infection such as pregnant women should not be performed. Voluntary testing amplification and counseling must include a better protection of risk behavior and seropositivity related stigma and discrimination. Additionally, more support for bonding and connection to prevention, treatment, care, and support services should be provided. Despite the latter and the trends seen in both poor as well as in developed countries, there are some exceptions, such as several states at the United States of America and countries like Chile. In Chile, the HIV/AIDS law has been in force since 2005 but does not accept compulsoriness; however, the 2011 Decree of the Ministry of Health indicates that HIV testing is mandatory for pregnant women [23-27].
It is imperative, therefore, for women at the last trimester or those at due date with unknown serology for HIV antibodies to undergo an urgent HIV screening rapid test. Similarly, counseling must be offered in this case and the corresponding informed consent obtained [23-27]. Should such test be reactive, the vertical transmission prevention protocol should be applied immediately (Level 4 evidence) [19-21, 35, 36].
Based on experts’ opinion, HIV testing should be offered to all pregnant women by their second control visit at the latest. Should the result of the test be negative, the latter should be repeated between 32 and 34 weeks of gestation in women under higher risk of acquiring HIV during the first trimester of pregnancy (pathological alcohol consumption, drug addiction, sex workers, multiple sexual partners, etc.), i.e., Grade D recommendation.
Every patient with confirmed serology should be referred to consultation, and immediate coordination should be implemented in order to provide the patient with assessment by a multidisciplinary team (Grade D recommendation).
Routine exams different from those performed on the nonpregnant HIV-positive women are not justified in the pregnant patient with recent positive serology, with the exception of those clinically warranted (Grade D recommendation).
Other STDs should be actively ruled out. Hepatitis B and hepatitis C serology as well as tuberculin skin testing (PPD) should also be performed (Grade D recommendation). Lymphocyte count, viral load, and viral genotyping should be ordered by the immunologist or the infectologist (Grade D recommendation).
The following are listed laboratory tests that should be routinely carried out [2]:
Rubella serology: both IgG and IgM are evaluated to evidence current or past infection. If there is no evident immunity against rubella, postpartum vaccination is recommended.
Urine culture: aiming at ruling out an infection of the urinary tract.
Hepatitis B virus surface antigen: to evaluate the presence of disease, since the transmission mechanism and the risk of vertical transmission are similar, and in the event of a synergic effect in disease progression
RPR or VDRL: these are nontreponemic tests for syphilis detection. They are highly sensitive but poorly specific. Therefore, if a positive result is obtained, it should be confirmed with a more specific test detecting antibodies against
Hepatitis C serology: the purpose of this test is to rule out the carrier status since it is common among HIV-infected patients. It is considered an opportunistic infection and might be patient death cause.
PPD (purified protein derivative) testing for tuberculosis: to evaluate a tuberculosis diagnosis. In HIV-carrier patients, a cutaneous reaction measuring 5 mm is enough to be considered positive (at least 10 mm should be seen in the remainder of patients). False-positive results may exist, for instance, in patients previously vaccinated with BCG (bacillus Calmette-Guérin). This infectious association should be considered since it worsens patient prognosis.
Cytomegalovirus cytology: CMV is the most common viral opportunistic disease in AIDS. It is associated with severe immunosuppression, and the reactivation of a latent disease is its usual form of onset. The disease usually has high mortality rates.
Gonococcus, chlamydia, mycoplasma, and Ureaplasma cultures: since they share in common their mechanism of transmission, other sexually transmitted infections should be ruled out.
These are prognostic factors for vertical transmission, and they are determinant factors for the appropriate time to initiate ART. They are also parameters for the assessment of the therapeutic response.
Its evaluation is critical to assess resistance to antiretroviral therapy.
This information indicates that HIV(+) pregnant women should be assessed and treated by a multidisciplinary medical team (Infectologist, immunologist, pharmacist, obstetrician, and neonatologist) (Level 4 evidence) [16-21]. Additionally, as previously mentioned, screening for various STDs found to be related with increased VT is of key importance. Such screening should include herpes simplex virus 2 and
In pregnant HIV carriers, the transmission of the infection to the fetus can occur mainly during delivery (65%), but also during pregnancy and breastfeeding with approximate rates of 35% and 15%, respectively. Such risk for transmission increases with certain factors such as maternal primary infection during pregnancy, intercurrent sexually transmitted infections, decreased CD4 counts, and high viral loads (27). In relation with the latter, and despite the fact that viral loads lower than 1000 copies/ml present a significantly lower risk for vertical transmission, there is no viral load exemption from VT risk. Thus, triple-drug highly active antiretroviral therapy (HAART) regimens have been proven to reach the goal of undetectable viral load levels with a reasonable risk versus benefit quotient, especially during the peripartum period where the risk of infection of the product of conception is higher. It is during that same period that it is advised to incorporate zidovudine to the regimen, since it has demonstrated its efficacy in abbreviated regimens prescribed during the intrapartum and postpartum periods [2, 37-50].
Moreover, the study of the teratogenic risks entailed by the different drugs used in ART regimens has not evidenced a higher incidence of congenital defects than that observed in general population. Likewise the APRI (Antiretroviral Pregnancy Registry International) study on the prevalence of congenital defects was 2.2 per 100 live births when assessing the use of ART at any stage of pregnancy and was 3% when therapy was used during the first trimester. With the exception of efavirenz, which is categorized by the FDA as D, because of its association with neural tube defects, the rest of ARV is categorized as B or C [2]. There are reports in which AZT might be related to an increase of hypospadia rates among the exposed human population, and others where delavirdine might be associated with increased cardiac septal defects in animals [46-49].
The following drugs or combinations should not be indicated during pregnancy: efavirenz, nelfinavir, and the association of d4T (stavudine) and ddI (didanosine). They all share teratogenicity and the risk of toxicity to the mother-child binomial [46-51]. Finally, to optimize the update in side effects, it is essential to fully and continuously report to the competent organizations such as APRI about the possible secondary teratogenic effects and to comply strictly with regulations on the indication for therapy initiation and drug choice according to the stage of pregnancy [46-49, 51].
Although it is true that the first attempt to control VT with a successful pharmacological regime was achieved by the protocol known as ACTG 076, a protocol attaining a decrease in VT from 29% to 5.6% in 2001, new evidence has demonstrated that triple ART was more effective than monotherapy or bitherapy in VT prevention [14, 42-45]. Thus, a protocol that associated biomedical preventive measures (cesarean section and elimination of breastfeeding) with the indication of a combination of three antiretroviral drugs (nucleosidic and nonnucleosidic inhibitors of reverse transcriptase and protease inhibitors, regimens known together as Highly Active Antiretroviral Therapy or HAART) was designed [14, 42-45].
The purpose of pharmacological therapy during pregnancy is to prevent vertical transmission through the reduction of the viral load in the mother to undetectable levels without resulting in teratogenic effects on the fetus. There are currently 14 commonly prescribed antiretroviral drugs (Table 1) that should be used to customize regimens in which selection is based on the eventual prior treatment of the pregnancy, the status of the disease, the viral load, CD4 cell counts, and the associated toxic and teratogenic effects according to FDA (Tables 1 and 2). Despite other drugs having been demonstrated efficacious in preventing vertical transmission, it is advisable to include the use of zidovudine within the antiretroviral scheme since it is the only drug that has proven efficacy and, most of the times, to be innocuous to the fetus in protocolized regimens (AIDS Clinical Protocol 076-ACTG 076) [2].
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
Nucleoside reverse transcriptase inhibitors | \n\t\t|
Abacavir | \n\t\t\tC | \n\t\t
Didanosine (ddl) | \n\t\t\tB | \n\t\t
Lamivudine (3TC) | \n\t\t\tC | \n\t\t
Lamivudine + zidovudine (Combivir) | \n\t\t\tC | \n\t\t
Stavudine (d4T zalcitabine) | \n\t\t\tC | \n\t\t
Zidovudine (ZDV, AZT) | \n\t\t\tC | \n\t\t
Nonnucleoside reverse transcriptase inhibitors | \n\t\t|
Delavirdine | \n\t\t\tC | \n\t\t
Evavirenz | \n\t\t\tX | \n\t\t
Nevirapine | \n\t\t\tC | \n\t\t
Protease inhibitors | \n\t\t|
Amprenavir | \n\t\t\tX | \n\t\t
Indinavir | \n\t\t\tC | \n\t\t
Nelfinavir | \n\t\t\tX | \n\t\t
Ritonavir | \n\t\t\tB | \n\t\t
Saquinavir | \n\t\t\tB | \n\t\t
Antiretroviral agent categories according to FDA
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
A | \n\t\t\tControlled studies fail to demonstrate risk | \n\t\t
B | \n\t\t\tNo evidence of risk for humans | \n\t\t
C | \n\t\t\tThe existence of risk cannot be ruled out; should only be used when potential benefits justify potential risk to the fetus | \n\t\t
D | \n\t\t\tProven risk | \n\t\t
X | \n\t\t\tContraindicated in pregnancy | \n\t\t
FDA pregnancy categories
One of the aspects that need to be assessed for the selection of a pharmacological therapy is the eventual toxic effect of such medications on the mother-child binomial. Thus, studies have reported that approximately 80% of treated pregnant women developed certain side effects such as anemia, nausea, vomiting, abnormal liver enzyme results, or hyperglycemia [44-49]. As a consequence of the aforementioned, it is essential to know the side and toxic effects of the drugs generally used (Table 3) in order to identify them and act accordingly in the event of using them.
In the general population, protease inhibitors have been linked to the induction of variable degrees of carbohydrate intolerance. The latter should be considered when prescribing the patient such drugs to the pregnant woman since they might trigger the development of gestational diabetes [44-49].
There is evidence that nucleoside reverse transcriptase inhibitors may induce mitochondrial dysfunction by virtue of their high affinity for gamma DNA-polymerase found in mitochondria. Among the drugs of such family that are more intensely related to such adverse effect are d4T (stavudine) and ddI (didanosine) and, to a lesser extent, ZDV (Zidovudine), 3TC (lamivudine), ABC (abacavir), and TDF (tenofir). The association between such type of drugs and lactic acidosis with or without concomitant liver steatosis is also known. Such conditions are more commonly seen in association with the use of d4T (stavudine) (0.8%-1.2%) [44-49]. The clinical picture resulting from such entity is similar to Hellp syndrome, a condition that may or may not be associated to polyneuropathies, fatty liver, myopathies, cardiopathies, and lactic acidosis. Finally, there are literature reports on children from mothers exposed to zidovudine or zidovudine/lamivudine (AZT/3TC) who developed mitochondrial dysfunction-related symptoms, a finding that was not observed in the cohort of patients following the ACTG/076 protocol [2].
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
AZT | \n\t\t\tAnemia - Neutropenia | \n\t\t\tGastrointestinal-headache-rash | \n\t\t
d4T | \n\t\t\tPolyneuropathy, lipoatrophy, lactic acidosis | \n\t\t\tPancreatitis, hepatic steatosis | \n\t\t
3TC | \n\t\t\t- | \n\t\t\tGastrointestinal-headache | \n\t\t
ddl | \n\t\t\tPancreatitis, polyneuropathy | \n\t\t\tGastrointestinal, Hyperuricemia | \n\t\t
Abacavir | \n\t\t\tHypersensitivity reaction | \n\t\t\tGastrointestinal | \n\t\t
Tenofovir | \n\t\t\t- | \n\t\t\tGastrointestinal, Renal | \n\t\t
Efavirenz | \n\t\t\tCNS: Vertigo, Psychosis | \n\t\t\tRash, hepatotoxicity, dyslipidemia | \n\t\t
Nevirapine | \n\t\t\tRash, Hepatotoxicity | \n\t\t\t\n\t\t |
PI (except for Atanazavir) | \n\t\t\tLipodystrophy, dyslipidemia, diabetes | \n\t\t\tLiver toxicity, gastrointestinal, osteonecrosis | \n\t\t
Indinavir | \n\t\t\tMetabolic, hyperbilirubinemia, kidney stones | \n\t\t\tGastrointestinal | \n\t\t
Atanazavir | \n\t\t\tHyperbilirubinemia, rash | \n\t\t\tGastrointestinal | \n\t\t
Antiretroviral agent toxicity
Several cohort studies show that the late initiation of ART is associated both with higher VT as well as with longer duration of VT. The latter is based on the fact that when therapy duration was 9.5 weeks, VT was significantly higher than when therapy duration was 16 weeks (
A pregnant woman without prior therapy should initiate ART from 20 weeks of gestation (Grade B recommendation).
When VL is higher than 100,000 copies/ml, ART should be initiated by week 14 (Grade B recommendation).
If the pregnant woman has clinical or immunological criteria for ART initiation, or if seroconversion occurs during gestation, ART must be initiated immediately (Grade B recommendation).
A low frequency of VT (5%) has been observed during the second trimester of pregnancy. Thirty-four percent of VT occurs during the antepartum and 66% occurs during delivery [2, 7, 10, 12]. However, placental transmission may occur from 13 weeks (Level 2++ evidence C).
Triple ART or HAART (highly active antiretroviral therapy) is the preferred choice. The use of zidovudine (AZT) in association with lamivudine (3TC) 600 and 300 mg per day, respectively, is recommended for the prevention of HIV vertical transmission. A preparation including both drugs in a fixed drug combination of 300 mg AZT and 150 mg 3TC is commercially available (grade of recommendation: A). Lopinavir/ritonavir (800/200 mg daily) or saquinavir/ritonavir (2000/200 mg daily) are recommended as a third drug (Grade C recommendation). The use of nevirapine (NVP) as a third drug may be considered in patients with CD4 T-cell counts lower than 250 cells/mm3 (200-400 mg daily) (Grade C recommendation).
A higher incidence of malformations failed to be demonstrated on 3,000 pregnancies exposed to AZT and 3TC. The 3TC+AZT combination has evidenced a higher efficacy in the prevention of VT than AZT as monotherapy. Cohort studies have reported a reduction in HIV mortality and transmission with the use of AZT+3TC (Level 2+ evidence). There is not enough comparative evidence of the efficacy of other ARV combinations on VT prevention (Level 2+ evidence) [19, 20, 43, 45].
The use of NVP in pregnant women with CD4 T-cell counts between 250 and 350 cells/mm3 failed to confirm an increase of the risk of suffering severe adverse effects. The benefits of using NVP in pregnant women outweigh the risks (Level 2+ evidence) [19, 20, 43, 45].
Efficacy of ART is measured through the decrease of viral load. ART is effective if the decrease is near 1 log of VL 2 weeks after the initiation of therapy and 1.5 log at 4 weeks. Achieving a decrease of 2 logs between 28 and 34 weeks of gestation is also considered effective [19]. The viral load should be assessed upon the first control visit. Viral load should be controlled 2 and 4 weeks after the initiation of therapy or after a change in therapy. Subsequently, VL should be controlled on a monthly basis until becoming undetectable. At gestation weeks 34-36, a VL assessment should be performed to define the route of delivery, eventual additional ART, and to plan ART for the newborn (Grade D recommendation).
In patients starting ART before week 24, a VL every 2 months (8 weeks) and at week 34 is recommended (Grade D recommendation).
Several clinical guidelines propose such management based on expert recommendations (Level 4 evidence) [15-17, 19-21].
A cesarean section should be indicated at 38 weeks of gestation in women with HIV infection without ART during pregnancy, in women without a VL result at gestation week 34, or in cases of VL >1,000 copies/ml (Grade B recommendation).
A vaginal delivery may be allowed in mothers under ART from 24 weeks of gestation or earlier, with VL <1,000 copies/ml at week 34, CD4 T-cell counts above 250, and that additionally meet the following conditions:
Gestational age greater than 37 weeks
Single fetus in cephalic presentation
Favorable obstetric conditions
Care provided by specialist physician
Informed consent from the patient
Invasive maneuvers (amniocentesis, chorionic villus biopsy, internal monitoring, artificial rupture of membranes) and instrumental delivery (forceps, spatulas) should be avoided (Grade D recommendation) though oxytocin may be used for labor guidance. The use of methylergonovine for the management of uterine inertia should be avoided if the patient is using protease inhibitors.
Elective cesarean section at 38 weeks of gestation, before an eventual rupture of membranes or initiation of spontaneous labor, substantially reduces the risk of HIV transmission. On its own, elective cesarean section reduces the risk of HIV transmission in 50%. Cesarean section together with antiretroviral therapy during the antenatal period, during delivery and administered to the newborn with the addition of termination of breastfeeding, achieves decreases close to 90% with final vertical transmission rates under 2% (Level 2++ evidence) [52-57].
Studies with large patient numbers have failed to show benefits in favor of cesarean section in women undergoing ART with VL <1,000 copies/ml. Shapiro showed transmission rates for vaginal delivery of 0.8 v/s 0.5 for cesarean section (OR 1.4 (0.2-6.4)) in patients with viral load lower than 1,000 copies/ml. (Level 2+ evidence) [53]. Moreover, cesarean section has been seen to cause 7-10-fold increases in morbidity, mainly infectious, as compared to vaginal delivery (Level 2+ evidence) [57]. Obstetric procedures that increase the risk of fetal exposure to maternal blood such as amniocentesis, villus biopsy, and invasive monitoring have been implicated by some researchers as transmission risk factors (Level 2+ evidence) [30]. The use of oxytocin is not contraindicated; however, ergot derivatives accumulate in patients receiving protease inhibitors because of the inhibitory action of the latter on cytochrome 3A4, and exaggerated vasoconstriction and ischemia have been described in relation with their use in association (Level 4 evidence) [15-20].
Intrapartum intravenous AZT shall be used in the indicated dose, regardless of the chosen route for delivery (Grade B recommendation), as follows:
Loading dose: 2 mg/kg, infused over 1 h (in case of cesarean, 4 h prior to surgery)
Maintenance dose: 1 mg/kg/h during cesarean section (to run 3 h after the loading dose) or during labor, until the cord is clamped
In case AZT 200 mg is unavailable, the oral administration of AZT/3TC upon the initiation of labor or 4 h prior to scheduled cesarean section is recommended
Nevirapine 200 mg single dose before cesarean section shall be added in any of the following settings (Grade B recommendation):
The late initiation of the protocol (later than 34 weeks and patients that failed to complete 4 weeks of ART upon delivery)
VL week 34 >1,000 copies/ml
Intrapartum HIV (+) diagnosis that did not receive ART
When NVP is used intrapartum, AZT/3TC should be added for 7 days postpartum to decrease the risk of developing resistance to NVP (Grade B recommendation).
The use of IV AZT during delivery enables reaching effective fetal plasma levels thus generating a preexposure prophylaxis. The latter, together with the oral administration of AZT suspension to the newborn for 6 weeks, enables a postexposure prophylaxis that as a whole has an impact on VT regardless of the patient having received AZT within her ART regimen during pregnancy or even, in the case of an eventual resistance to AZT (Level 2++ evidence) [53-55].
Pharmacological cessation of breastfeeding shall proceed in all HIV(+) women even if such result is just from the rapid intrapartum test (Grade B recommendation). Based on four studies in which mothers acquired HIV-1 after birth, the estimated risk of transmission is 29% (95% CI 16-42%). The analysis of five studies showed that when the mother became infected before delivery, the additional risk of transmission through breastfeeding, beyond
A CD4 T-cell count, a VL, and a viral genotyping study are recommended in women previously exposed to ART and who discontinued therapy. The latter will enable designing the therapeutic regimen based on patient history and current genotype. Viral load should be assessed after 4 to 6 weeks of the initiation of ART, and a new genotyping study should be performed in case of failure, for adjustment of the latter. Zidovudine should be included in the ART regimen when possible (Grade D recommendation).
Several clinical guidelines propose such management based on expert recommendations (Level 4 evidence) [15-20].
Women undergoing ART who become pregnant are recommended to maintain ART if their VL is undetectable. If the regimen includes drugs that increase toxicity (D4T) or contains Efavirenz, these should be withdrawn and replaced with lopinavir/ritonavir or by saquinavir/ritonavir, including, when possible, AZT in the regimen (Grade D recommendation). The WHO guidelines do not recommend the use of the antiretroviral medication efavirenz (EFV) during the first trimester of pregnancy because of its potential fetal teratogenic effects, mostly involving defects of neural tube closure. Nevertheless, there are no categorical studies supporting such recommendation (Level 3 evidence). Likewise, the use of the ddl/d4T combination should be terminated [15-21].
The genotyping study should be performed on pregnant women undergoing ART with VL >1,000 copies/ml, particularly in pregnancies that have not achieved such goal at 34 weeks of gestation. Moreover, the addition of a single dose of nevirapine at the moment of delivery is suggested (Grade D recommendation).
Several clinical guidelines propose such management based on expert recommendations (Level 4 evidence) [15-21].
In pregnant women reaching the 32nd week of gestation or more without ART, it is recommended to assess CD4 T-cell levels and VL and to initiate immediately ART with AZT/3TC coformulated, together with a protease inhibitor (PI). Nevirapine (NVP) can be used instead of a reinforced PI when CD4 T-cell counts are lower than 250 cells/mm3 (Grade D recommendation).
There is wide experience on the use of NVP during pregnancy. The drug has a risk of severe hepatotoxicity with CD4 >250 cells/mm3, especially in coinfection with HBV and HCV. Several clinical guidelines propose such management based on expert recommendations. When NVP is used during delivery, AZT/3TC needs to be used subsequently to prevent drug resistance induced by NVP (Level 4 evidence) [15-21].
The following are to be observed:
Ideally assess CD4 T cells and VL.
Intravenous zidovudine as per regimen.
Single dose of nevirapine.
Resolution of delivery through cesarean section.
Use AZT/3TC for 1 week, add PI, until evaluating the best regimen to continue therapy (Grade D recommendation).
Several clinical guidelines propose such management based on expert recommendations (Level 4 evidence) [15-21].
Because of the potential teratogenesis of ribavirin, its preconception withdrawal for at least 4 months in women and at least for 7 months in case the couple had received such drug should be counseled. In case of an eventual use during pregnancy, it should be immediately withdrawn, and a consultation visit should be arranged to assess maternal liver function.
The administration of IV AZT 2 mg/kg/h, together with tocolytic therapy, during the first hour followed by 1 mg/kg/h until dynamics ease up, according to ART administration policy during delivery, is recommended in the presence of regular uterine dynamics, despite cervical modifications being scarce. If unable to slow down the situation and if delivery is triggered and/or rupture of membranes ensues, a cesarean section shall be performed sufficiently in advance (Grade C recommendation).
Premature delivery constitutes a risk factor for perinatal transmission of the virus: a maternal viral load (VL) of <400 c/ml in a delivery occurring before 34 weeks was related to an 8-fold increase in the risk of transmission as compared to term delivery (Level 2+ evidence) [58].
All patients should receive ART and undergo the usual control and therapeutic measures such as the administration of prophylactic antibiotics, steroids, and eventually the use of magnesium sulfate as neuroprotector. In case of a suspected infection or loss of fetal well-being, pregnancy interruption must be carried out. The recommended delivery route is cesarean section. The management of each case depends on the gestational age (Grade D recommendation).
In pregnancies of less than 26 weeks, a conservative therapy is recommended in view of the risk of severe sequels as a result of prematurity and high neonatal mortality (Grade D recommendation). Between weeks 26 and 30, each case shall be evaluated according to maternal and fetal status, the virological status of the mother, if she has been administered a therapy or not, and the neonatal outcomes of the center (Grade D recommendation). Between 30 and 34 weeks, the general behavior that is recommended is to terminate pregnancy. In view of the higher tendency to an increase of reported VT in premature deliveries with PROM even while receiving ART, the preferred route for delivery shall be cesarean section (Grade D recommendation)
There is a clear difference in the risk of severe sequels between gestational ages (61.5% at week 23 and 10% at week 28). In view of the higher risk of VT in preterms, a cesarean section shall be considered (Level 2+ evidence) [21, 56, 58].
Before the use of ART during pregnancy, several studies found a relationship between the duration of the rupture of membranes and the VT, particularly if such duration was greater than 4 h. In women with less than 24 h since the rupture of membranes, for every hour that elapses after the rupture, the risk of vertical transmission rises in 2%. Because the risk of fetal infection in patients with PROM and very low plasmatic viral load and/or under ART is unknown, treatment of PROM has not been fully clarified. Several clinical guidelines propose such management based on expert recommendations (Level 4 evidence) [15-21].
Recommendations and protocols discussed above are easy to implement in countries with adequate resources, consolidated healthcare systems, and proven functional system with trained healthcare personnel and high literate population. Countries must strategically choose their models for the provision of services, taking into consideration the type of epidemics, cost-effectiveness, equity in access, and available resources. The WHO at present collaborates with poor countries, proposing a “Health Systems Platform for HIV/AIDS.” Such idea comprises the following areas that are considered as crucial: (1) labor systems that ensure the availability of a sufficient number of trained healthcare providers that work in an adequate facility and in safe conditions, (2) systems to purchase and distribute medications and other supplies, (3) fair funding systems to prevent people from being pushed into poverty when they become ill, and (4) healthcare information systems to alert the administrators of healthcare assistance and those in charge of elaborating policies addressing risks for persons in situations that might severely worsen. Of all these necessities, the most urgent is the availability of a sufficient number of health professionals. Nevertheless, there are some experiences gained through the participation of untrained personnel in some stages of the process; for instance, in the diagnosis of the condition of HIV carrier, this should not be de-emphasized.
In a 1996 paper written by Bernand Bertossa, who was Attorney General of the Republic and Canton of Geneva at the time, it was highlighted that representative democracy and respect for the decisions of an independent Judiciary prevent (through the dissemination of power and the meticulous control of its exercise) the emergence of a fertile ground for corruption [1]. In Brazil, on the other hand, the internationally known
In fact, President Jair Bolsonaro was elected as a consequence of Operation Car Wash and now—after 4 years of decrease in institutional standards and aware of the electoral polls which indicates his defeat to political rival Luis Inácio Lula da Silva [2]—is trying to delegitimize the very system that elected him in 2018 [3]. As has been increasingly reported, the democratic regime may be at risk in Brazil [4, 5] and the turning point in this direction took place with the instrumentalization of the criminal process to withdraw his main political opponent from the 2018 electoral dispute.
From that premise an important lesson can be extracted, one that most of the advanced democracies have already learned, whether from their own or through foreign experience: a nation’s criminal procedure structure is the thermometer of the elements of its Constitution ([6], p. 67). When it comes to corruption—especially the one more directly related to the functioning of the democratic regime, which is corruption within the context of politics, the overlap between the criminal procedure model and the regime is even more intense and arises in an especially latent way. Indeed, the shallow and simplistic discourse of the mass media and punitive agencies in the sense that social ills all derive from the relation between “honest” and “corrupt” stifles the conflicts of interests and ideals that serve as the foundation of real power bases of society ([7], p. 419).
This agenda discourages the political participation of the citizen, who begins to understand (and to belittle) democracy itself as a political regime more susceptible to corrupt practices due to the greater opportunity for an interface between political agents, economic agents, and individuals—although what gains strength when compared to authoritarian regimes is not corruption itself, but its possibility of visibility and dissemination ([7], pp. 419–421). Therefore, it is not surprising, at least under a retrospective lens, that Brazilian democratic institutionality has so rapidly degraded. The analysis of the context, the development, and the surprising and melancholic end of Operation Car Wash, with the bias of its main judge recognized nationally [8] and internationally [9, 10], however, seems to be of extreme value, including and especially for the international community. In this case, Brazil has a lot to teach. By means of bad example.
The Brazilian criminal procedure suffers from serious historical problems. The Brazilian Criminal Procedure Code dates from 1941 and was reportedly inspired by the 1930s Fascist Italy’s
Felipe Lazzari da Silveira ([12], p. 22) explains that although the Brazilian state has never been a fascist state, in the criminal procedural field, it fully incorporated the rationality created by Mussolini’s jurists. Its
The Brazilian authoritarian and dictatorial culture was reinforced by political and military groups, in addition to expressive intellectuals, such as Oliveira Viana (1883–1951) and Francisco Campos (1891–1968), the latter did not hesitate to join the forces that articulated the conditions for the 1937 coup, nor in actively participating in the formatting and legal consolidation of both the
Although by various means, both Italian fascism and the Brazilian
Francisco Campos was the Brazilian counterpart of Alfredo Rocco, the Minister of Justice of Fascist Italy. Endowed with a strong personality, both jurists, with great diligence, took on this new way of legislating and were responsible for the constitutional reforms that shifted the political regimes of their countries to the authoritarian spectrum ([15], p. 171, 172). In turn, the collaborators of these legislative endeavors were not jurists consecrated by the professorship or by theoretical writings, but practical applicators of Law, which made coexistence with the authoritarian environment possible and without major constraints: not for nothing, the vast majority of Italian jurists and all the Brazilian jurists involved came from the Judiciary and the Public Prosecutor Office ([15], p. 172, 173).
This overlap between technicality and practicality certainly helped to legitimize the new criminal law and criminal procedure before the Brazilian judges and criminal courts. But not only. It helped to spread the new system also to the legal literature, which was uncritically fed back through the jurisprudence made by themselves—after all, many of the authors of legal works on the Criminal Procedure Code of 1941 were also its practical applicators.
As Francisco Campos later highlighted, he and his assistants (recognized jurists, such as Nelson Hungria, Antônio Vieira Braga, Narcélio de Queirós, and Cândido Mendes de Almeida) intended to develop a criminal process that did not make society’s right to defend itself a mere illusion and that offered the necessary means to ascertain the “real truth” so that to the judge was granted a wide margin of maneuver for the evidentiary initiative—which did not mean an authorization to decide contrary to the law, but only that the body of evidence could be freely evaluated, including through the search for new evidence when necessary and always in accordance with the interests of the State ([12], p. 189).
In that conception of criminal procedure, the simple fact of being tried by a judge was, in itself, the greatest guarantee against injustice that a defendant could obtain ([12], p. 192). The mere existence of a judge was enough for the criminal process to be understood as a fair and impartial procedure. Hence the difficulty in obtaining recognition of judicial partiality in Brazilian forensic practice, even in Operation Car Wash—which gave abundant signs of Federal Judge Sérgio Moro’s bias to the detriment of Luís Inácio Lula da Silva from the first day and, even so, the Courts (the Regional Federal Court of the 4th Region and the Superior Court of Justice) did not recognize it.
The partiality of Federal Judge Sérgio Moro was not acknowledged until the publication of the series of articles by the Intercept Brazil containing the messages he exchanged, via Telegram app, with one of the Federal Prosecutors responsible for Operation Car Wash [16]. The content of the messages, however, was not formally considered by the Federal Supreme Court when it came to recognizing the judicial bias of Federal Judge Sérgio Moro [17], which demonstrates that the exterior signs were sufficient to conclude in those terms (although until then those outside marks had not yet been declared). Not even the authoritarian matrix of the Brazilian criminal process was able to deny the judicial partiality that came to the eyes of Brazil and the world with the series of reports known as
Both in Italy and Brazil, the criminal procedural models were orchestrated with the objective of legitimizing the neutralization of fundamental guarantees, and this structure continued to guide legal literature, jurisprudence, and legislative reforms even after the end of the authoritarian regimes that promoted them: Italians only forsook it in 1988, with a new Code of Criminal Procedure; Brazilians, however, continue with inquisitorialism to this day ([12], p. 191).
Despite the legislative reforms carried out with the alleged aim of democratizing the Brazilian criminal procedure to adapt it to the Federal Constitution of 1988, it is undoubted that they were all late and insufficient to produce any significant change to the spirit of the Criminal Procedure Code of 1941 and that, despite them, jurisprudence has developed in the sense of violating the accusatory system ([18], p. 526). According to Jacinto Nelson de Miranda Coutinho ([19], p. 11), this is because none of them reached the core of the 1941 Criminal Procedure Code system, which is completely out of step with the 1988 Federal Constitution.
Indeed, the center of the inquisitorial system consists in enabling the criminal judge to
The rationality that authorizes and legitimates this sort of procedure is the same that guides the premise that there is in fact a “real truth” and that it can be found through human knowledge, especially through criminal proceedings. Part of the doctrine distinguishes “real truth” from “formal truth,” which is a serious mistake because, according to Francesco Carnelutti ([20], p. 4, 5), the truth is obviously unique and can never be reached by human beings, regardless of the method chosen to do so.
Lenio Luiz Streck ([21], p. 290, 291) cuts across and demonstrates that the concept of real truth is not sustainable because it proclaims something “real” and that, therefore, is justified by itself at the same time that it does not obviate the need for an interpreter to give it meaning—which leads to the judicial protagonism that makes fundamental guarantees more flexible for the sake of public or social interest that cannot be precisely defined. Consequently, according to Salah Khaled H. Jr. ([22], p. 1), the search for truth is nothing more than an unlimited search for confirmation of a hypothesis previously chosen by the magistrate.
The great problem of the inquisitorial system (in general and of the Brazilian criminal procedure in particular), therefore, lies in the legitimation of the search for the truth that, by reflecting the past in an integral way, at least in theory, certainly distinguishes and accurately determines innocents and guilty. Hence the reason why, in the name of this absolute truth, all flexibilization of fundamental guarantees and all judicial abuse are legitimized, whether in the search for evidence or its subsequent evaluation.
Operation Car Wash took place after the enactment of the so-called Clean Record Law (Supplementary Law 135/2010), which prevents anyone criminally convicted by a collegiate body from running for any elective office for 8 years. Without this restriction limiting the will of the electorate, Operation Car Wah would probably not have caused so much institutional turmoil: after all, the mere non-definitive conviction by a collegiate body would not have removed the leader of the polls from the 2018 electoral dispute.
Mariana Mota Prado and Marta R. de Assis Machado explain that in July 2013 there were huge protests against corruption and an increase in the attention of the press and institutions responsible for accountability to the issue, which may have created a window of opportunity for changes ([23], p. 10).
Structured and publicized since the beginning (2014) as the biggest operation against corruption in the history of Brazil, Operation Car Wash clearly had a predestined aim: to strike the Workers’ Party (PT), which at the time occupied the Presidency of the Republic with Dilma Rousseff (she was impeached in 2016), and especially former President Luiz Inácio Lula da Silva, who would seek reelection in 2018 (when he was leading the polls [24]) but ended up in prison for 580 days due to a non-definitive conviction—and without evidence—delivered by an admittedly biased judge.
One of the changes referred by Mariana Mota Prado and Marta R. de Assis Machado may be directly linked to the very definition of corruption. The Brazilian Penal Code describes corruption as two distinct crimes: active corruption (supply side) and passive corruption (demand side). Former President Luiz Inácio Lula da Silva was convicted of passive corruption—a crime that requires the actions of requesting, receiving, or accepting a promise of undue advantage on behalf of the public function in exchange for an action, an omission, or a delay in its performance—for allegedly receiving gifts from private companies. As the authors point out, when substantiating the conviction Federal Judge Sérgio Moro expressly highlighted out that it was unnecessary for those private companies to have received any advantage in retribution for those treats for the setting of the crime of passive corruption. He acknowledged that this was a controversial interpretation of the crime of passive corruption but maintained it, arguing that it was necessary to tackle high-level corruption ([23], pp. 13–14).
Although the Brazilian Penal Code is not entirely clear on the matter, until recently the tendency of the courts was to demand proof of the existence of a connection between the payment promised or made by the private agent and the benefit received by the public official (in a word:
According to Mariana Mota Prado and Marta R. de Assis Machado, to criminally convict Luís Inácio Lula da Silva, Federal Judge Sérgio Moro went even further: the conviction was based on indicia that private companies were planning to give him a triplex in Guarujá/SP, but the only substantial evidence was that the senior managers of Petrobras (the Brazilian petroleum corporation)—who is not even appointed by the President of the Republic but by the board of directors of the state company—favored the companies that were supposedly providing the gift. There was no direct relationship between the triplex and the performance of Luís Inácio Lula da Silva as President of the Republic—the link was established through the following chain: the board of directors of Petrobras appointed individuals (senior managers) recommended by a government minister, in turn, appointed by the President of the Republic ([23], p. 15).
In the words of the authors, the assumption was that Luís Inácio Lula da Silva appointed high-level officials “who would, in turn, appoint corrupt directors, who would then strike the deal for overpriced contracts between construction companies and Petrobras.” ([24], p. 16). However, it was not demonstrated that the appointments had this deviation purpose, much less that Luis Inácio Lula da Silva had any knowledge about the corruption scheme inside Petrobras. The conviction was based on a presumption against the defendant, not on substantial evidence.
The vices of that sentence are numerous. João Paulo Allain Teixeira, Gustavo Ferreira Santos, and Marcelo Labanca Corrêa de Araújo ([25], p. 67) stated that “In espousing and courting public opinion fostered by the national mass media, Judge Moro transformed evidence into mere procedure details. When the evidence (or lack of it) does not speak for itself, any verdict is unpredictable, depending on the whims and convenience of the moment.” “A decision that appears nothing like a judicial sentence. It is more like a long—as it has more than 200 pages—personal opinion in relation to the accused,” in the words of João Ricardo W. Dornelles ([25], p. 68).
Pedro Estevam Alves Pinto Serrano, Anderson Medeiros Bonfim, and Juliana Salinas Serrano ([26], p. 42, 43) demonstrate that, if in the United States of America and continental Europe it is possible to identify both a clear jurisprudence of the Criminal Law of exception and measures of exception in special laws on the subject of national security (terrorist threats), in Brazil the enemy is fought by the criminal law and criminal procedure of every day, reinterpreted in an exceptional way, so that the criminal justice system (magistrates, public prosecutors, and police precinct chiefs) became—with the fundamental support of the media—the sovereign author of the exceptional measures.
Also according to the authors ([27], p. 43), the exceptional jurisdiction is characterized by the simplification of the judicial decision itself, which is no longer mediated by Law—in fact, it temporarily suspends it in specific situations, without any coherence or rationality (so much that it does not produce jurisprudence, since changing the actors involved or the political purpose, also changes the decision, which can return to Law or produce a new exception).
It is difficult to interpret Operation Car Wash otherwise. Pedro Estevam Alves Pinto Serrano
For Brazilian democracy, as already exposed, the direct consequence was the removal of Luís Inácio Lula da Silva from the electoral dispute (he was leading the polls even at the pinnacle of Operation Car Wash) with the consequent election of Jair Bolsonaro in 2018. For the anti-corruption agenda, the consequence was its discredit in front of the perception that it is in fact a speech easily used against political opponents by chance. This feeling became even stronger when Federal Judge Sérgio Moro left the Judiciary a month after the elections to join the newly elected government as Minister of Justice and Public Security [29]. When he later announced his departure from Jair Bolsonaro’s government [30] and tried to run in the 2022 presidential election [31], it was already clear to everyone that his political project had begun much earlier.
In addition to specific problems related to the way in which the turn state’s evidence (institute on which the convictions in Operation Car Wash were built) was envisioned in Brazil through Law 12.850/2013, Federal Judge Sérgio Moro took advantage of circumstances and structural deficiencies of the Brazilian criminal procedure to reach the conviction of Luiz Inácio Lula da Silva. The manipulation of the electoral process through the criminal procedure was only possible in Brazil because (i) the punitive agencies joined the mass media for the spectacular dissemination of excerpts of turn state’s evidence in order to garner the support of the population against politicians and great businessmen (similar to what happened in Operation
The intention of this article was to demonstrate that the constant disrespect for criminal procedural guarantees in large cases of political corruption is particularly harmful to democracy, especially when Law is used to interdict the popular will expressed in polls for voting intentions.
Through the Operation Car Wash, the Brazilian case is the reference of a bad example in this sense, as former President Luis Inácio Lula da Silva was convicted and held in custody for 580 days when he was leading the voting intentions in 2018 only to be recognized by the Supreme Court, after the election of the new President Jair Bolsonaro, the partiality of Federal Judge Sérgio Moro. A judicial bias that was already clearly perceptible from the beginning for those with a minimum knowledge of criminal procedure.
The construction of the conviction of a popular former President was only possible because:
The mass media aligned itself with the interests of the Federal Prosecutors to receive first-hand information and publish it in a sensationalist way;
Over the precedent years, a shallow and banalized perception that political activity is impregnated with corrupt people had already been created;
The Brazilian Criminal Procedure Code (1941), inspired by the
The authoritarian spirit of the 1941 Brazilian Criminal Procedure Code was spread to doctrine and jurisprudence, having crystallized over the decades;
The legal reforms after the 1988 Federal Constitution were not enough to change the core of the original Brazilian Criminal Procedure.
Considering that the now President Jair Bolsonaro took anti-political speech to extreme levels, that after winning the elections he started to delegitimize the electronic voting system and that it is already beginning to be said that he can even bar the October 2022 elections [33], it is possible to correlate the disrespect for individual guarantees operated by Operation Car Wash with political and institutional instability that recalls the worst moments of recent Brazilian history.
It is important to emphasize that legal sanctions against acts of political corruption are necessary and healthy for democracy and for the very realization of social rights. But due process of law can never be neglected; Law cannot be manipulated to achieve political and punitive purposes in a specific case, even under the pretext of fighting corruption. Otherwise, democratic institutions—including the Judiciary—shall become weakened.
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\n\nPlease consult our Open Access Funding page to explore some of these funding opportunities and learn more about how you could finance your IntechOpen publication. Keep in mind that this list is not definitive, and while we are constantly updating and informing our Authors of new funding opportunities, we recommend that you always check with your institution first.
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This has compromised the ability of the environment to foster life and render its intrinsic values. Heavy metals are known to be naturally occurring compounds, but anthropogenic activities introduce them in large quantities in different environmental compartments. This leads to the environment’s ability to foster life being reduced as human, animal, and plant health become threatened. This occurs due to bioaccumulation in the food chains as a result of the nondegradable state of the heavy metals. Remediation of heavy metals requires special attention to protect soil quality, air quality, water quality, human health, animal health, and all spheres as a collection. Developed physical and chemical heavy metal remediation technologies are demanding costs which are not feasible, time-consuming, and release additional waste to the environment. This chapter summarises the problems related to heavy metal pollution and various remediation technologies. A case study in South Africa mines were also used.",book:{id:"6534",slug:"heavy-metals",title:"Heavy Metals",fullTitle:"Heavy Metals"},signatures:"Vhahangwele Masindi and Khathutshelo L. Muedi",authors:[{id:"225304",title:"Dr.",name:"Vhahangwele",middleName:null,surname:"Masindi",slug:"vhahangwele-masindi",fullName:"Vhahangwele Masindi"},{id:"241403",title:"M.Sc.",name:"Khathutshelo",middleName:"Lilith",surname:"Muedi",slug:"khathutshelo-muedi",fullName:"Khathutshelo Muedi"}]},{id:"37067",doi:"10.5772/35482",title:"Fourier Transform Infrared Spectroscopy for Natural Fibres",slug:"fourier-transform-infrared-spectroscopy-for-natural-fibres",totalDownloads:9282,totalCrossrefCites:166,totalDimensionsCites:399,abstract:null,book:{id:"2270",slug:"fourier-transform-materials-analysis",title:"Fourier Transform",fullTitle:"Fourier Transform - Materials Analysis"},signatures:"Mizi Fan, Dasong Dai and Biao Huang",authors:[{id:"104647",title:"Prof.",name:"Mizi",middleName:null,surname:"Fan",slug:"mizi-fan",fullName:"Mizi Fan"}]},{id:"42566",doi:"10.5772/53706",title:"Challenges and Opportunities for Spark Plasma Sintering: A Key Technology for a New Generation of Materials",slug:"challenges-and-opportunities-for-spark-plasma-sintering-a-key-technology-for-a-new-generation-of-mat",totalDownloads:9164,totalCrossrefCites:99,totalDimensionsCites:211,abstract:null,book:{id:"3478",slug:"sintering-applications",title:"Sintering Applications",fullTitle:"Sintering Applications"},signatures:"M. Suárez, A. Fernández, J.L. Menéndez, R. Torrecillas, H. U. Kessel, J. Hennicke, R. Kirchner and T. Kessel",authors:[{id:"102383",title:"Dr.",name:"Marta",middleName:null,surname:"Suárez",slug:"marta-suarez",fullName:"Marta Suárez"},{id:"103822",title:"Dr.",name:"J.L",middleName:null,surname:"Menendez",slug:"j.l-menendez",fullName:"J.L Menendez"},{id:"103833",title:"Prof.",name:"Ramón",middleName:null,surname:"Torrecillas",slug:"ramon-torrecillas",fullName:"Ramón Torrecillas"},{id:"162633",title:"Dr.",name:"Adolfo",middleName:null,surname:"Fernández",slug:"adolfo-fernandez",fullName:"Adolfo Fernández"}]},{id:"23617",doi:"10.5772/24118",title:"Collagen- vs. Gelatine-Based Biomaterials and Their Biocompatibility: Review and Perspectives",slug:"collagen-vs-gelatine-based-biomaterials-and-their-biocompatibility-review-and-perspectives",totalDownloads:9450,totalCrossrefCites:63,totalDimensionsCites:204,abstract:null,book:{id:"1487",slug:"biomaterials-applications-for-nanomedicine",title:"Biomaterials",fullTitle:"Biomaterials Applications for Nanomedicine"},signatures:"Selestina Gorgieva and Vanja Kokol",authors:[{id:"55577",title:"Prof.",name:"Vanja",middleName:null,surname:"Kokol",slug:"vanja-kokol",fullName:"Vanja Kokol"},{id:"61285",title:"BSc",name:"Selestina",middleName:null,surname:"Gorgieva",slug:"selestina-gorgieva",fullName:"Selestina Gorgieva"}]},{id:"46243",doi:"10.5772/57255",title:"Corrosion Inhibitors – Principles, Mechanisms and Applications",slug:"corrosion-inhibitors-principles-mechanisms-and-applications",totalDownloads:13727,totalCrossrefCites:40,totalDimensionsCites:161,abstract:null,book:{id:"3817",slug:"developments-in-corrosion-protection",title:"Developments in Corrosion Protection",fullTitle:"Developments in Corrosion Protection"},signatures:"Camila G. Dariva and Alexandre F. Galio",authors:[{id:"169261",title:"Dr.",name:"Camila",middleName:"G.",surname:"Dariva",slug:"camila-dariva",fullName:"Camila Dariva"},{id:"170138",title:"Dr.",name:"Alexandre",middleName:"Ferreira",surname:"Galio",slug:"alexandre-galio",fullName:"Alexandre Galio"}]}],mostDownloadedChaptersLast30Days:[{id:"76780",title:"Basics of Clay Minerals and Their Characteristic Properties",slug:"basics-of-clay-minerals-and-their-characteristic-properties",totalDownloads:1930,totalCrossrefCites:16,totalDimensionsCites:25,abstract:"Clay minerals such as kaolinite, smectite, chlorite, micas are main components of raw materials of clay and formed in presence of water. A large number of clays used to form the different structure which completely depends on their mining source. They are known as hydrous phyllosilicate having silica, alumina and water with variable amount of inorganic ions like Mg2+, Na+, Ca2+ which are found either in interlayer space or on the planetary surface. Clay minerals are described by presence of two-dimensional sheets, tetrahedral (SiO4) and octahedral (Al2O3). There are different clay minerals which are categorized based on presence of tetrahedral and octahedral layer in their structure like kaolinite (1:1 of tetrahedral and octahedral layers), smectite group of clay minerals (2:1 of tetrahedral and octahedral layers) and chlorite (2:1:1 of tetrahedral, octahedral and octahedral layers). The particle size of clay minerals is <2microns which can be present in form of plastic in presence of water and solidified when dried. The small size and their distinctive crystal structure make clay minerals very special with their unique properties including high cation exchange capacity, swelling behavior, specific surface area, adsorption capacity, etc. which are described in this chapter. Due to all these unique properties, clay minerals are gaining interest in different fields.",book:{id:"10949",slug:"clay-and-clay-minerals",title:"Clay and Clay Minerals",fullTitle:"Clay and Clay Minerals"},signatures:"Neeraj Kumari and Chandra Mohan",authors:[{id:"258132",title:"Dr.",name:"Chandra",middleName:null,surname:"Mohan",slug:"chandra-mohan",fullName:"Chandra Mohan"},{id:"352399",title:"Dr.",name:"Neeraj",middleName:null,surname:"Kumari",slug:"neeraj-kumari",fullName:"Neeraj Kumari"}]},{id:"51535",title:"An Introduction to Hydrogels and Some Recent Applications",slug:"an-introduction-to-hydrogels-and-some-recent-applications",totalDownloads:11734,totalCrossrefCites:70,totalDimensionsCites:140,abstract:"Hydrogels have existed for more than half a century, and today they have many applications in various processes ranging from industrial to biological. There are numerous original papers, reviews, and monographs focused on the synthesis, properties, and applications of hydrogels. This chapter covers the fundamental aspects and several applications of hydrogels based on the old and the most recent publications in this field.",book:{id:"5251",slug:"emerging-concepts-in-analysis-and-applications-of-hydrogels",title:"Emerging Concepts in Analysis and Applications of Hydrogels",fullTitle:"Emerging Concepts in Analysis and Applications of Hydrogels"},signatures:"Morteza Bahram, Naimeh Mohseni and Mehdi Moghtader",authors:[{id:"179718",title:"Prof.",name:"Morteza",middleName:null,surname:"Bahram",slug:"morteza-bahram",fullName:"Morteza Bahram"},{id:"185713",title:"Dr.",name:"Naimeh",middleName:null,surname:"Mohseni",slug:"naimeh-mohseni",fullName:"Naimeh Mohseni"},{id:"185714",title:"Dr.",name:"Mehdi",middleName:null,surname:"Moghtader",slug:"mehdi-moghtader",fullName:"Mehdi Moghtader"}]},{id:"70661",title:"Bioremediation Techniques for Polluted Environment: Concept, Advantages, Limitations, and Prospects",slug:"bioremediation-techniques-for-polluted-environment-concept-advantages-limitations-and-prospects",totalDownloads:2672,totalCrossrefCites:10,totalDimensionsCites:27,abstract:"Environmental pollution has been rising in the past few decades due to increased anthropogenic activities. Bioremediation is an attractive and successful cleaning technique to remove toxic waste from polluted environment. Bioremediation is highly involved in degradation, eradication, immobilization, or detoxification diverse chemical wastes and physical hazardous materials from the surrounding through the all-inclusive and action of microorganisms. The main principle is degrading and converting pollutants to less toxic forms. Bioremediation can be carried out ex-situ and in-situ, depending on several factors, which include but not limited to cost, site characteristics, type, and concentration of pollutants. Hence, appropriate bioremediation technique is selected. Additionally, the major methodologies to develop bioremediation are biostimulation, bioaugmentation, bioventing, biopiles, and bioattenuation provided the environmental factors that decide the completion of bioremediation. Bioremediation is the most effective, economical, eco-friendly management tool to manage the polluted environment. All bioremediation techniques have its own advantage and disadvantage because it has its own specific applications.",book:{id:"9343",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",title:"Trace Metals in the Environment",fullTitle:"Trace Metals in the Environment - New Approaches and Recent Advances"},signatures:"Indu Sharma",authors:[{id:"301262",title:"Associate Prof.",name:"Indu",middleName:null,surname:"Sharma",slug:"indu-sharma",fullName:"Indu Sharma"}]},{id:"18275",title:"Modeling and Identification of Parameters the Piezoelectric Transducers in Ultrasonic Systems",slug:"modeling-and-identification-of-parameters-the-piezoelectric-transducers-in-ultrasonic-systems",totalDownloads:10197,totalCrossrefCites:3,totalDimensionsCites:5,abstract:null,book:{id:"201",slug:"advances-in-ceramics-electric-and-magnetic-ceramics-bioceramics-ceramics-and-environment",title:"Advances in Ceramics",fullTitle:"Advances in Ceramics - Electric and Magnetic Ceramics, Bioceramics, Ceramics and Environment"},signatures:"Pawel Fabijanski and Ryszard Lagoda",authors:[{id:"13086",title:"Dr.",name:"Pawel",middleName:null,surname:"Fabijański",slug:"pawel-fabijanski",fullName:"Pawel Fabijański"}]},{id:"60680",title:"Environmental Contamination by Heavy Metals",slug:"environmental-contamination-by-heavy-metals",totalDownloads:16251,totalCrossrefCites:187,totalDimensionsCites:407,abstract:"The environment and its compartments have been severely polluted by heavy metals. This has compromised the ability of the environment to foster life and render its intrinsic values. Heavy metals are known to be naturally occurring compounds, but anthropogenic activities introduce them in large quantities in different environmental compartments. This leads to the environment’s ability to foster life being reduced as human, animal, and plant health become threatened. This occurs due to bioaccumulation in the food chains as a result of the nondegradable state of the heavy metals. Remediation of heavy metals requires special attention to protect soil quality, air quality, water quality, human health, animal health, and all spheres as a collection. Developed physical and chemical heavy metal remediation technologies are demanding costs which are not feasible, time-consuming, and release additional waste to the environment. This chapter summarises the problems related to heavy metal pollution and various remediation technologies. A case study in South Africa mines were also used.",book:{id:"6534",slug:"heavy-metals",title:"Heavy Metals",fullTitle:"Heavy Metals"},signatures:"Vhahangwele Masindi and Khathutshelo L. Muedi",authors:[{id:"225304",title:"Dr.",name:"Vhahangwele",middleName:null,surname:"Masindi",slug:"vhahangwele-masindi",fullName:"Vhahangwele Masindi"},{id:"241403",title:"M.Sc.",name:"Khathutshelo",middleName:"Lilith",surname:"Muedi",slug:"khathutshelo-muedi",fullName:"Khathutshelo Muedi"}]}],onlineFirstChaptersFilter:{topicId:"14",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"83035",title:"Breaking the Property Trade-Offs by Using Entropic Conceptions",slug:"breaking-the-property-trade-offs-by-using-entropic-conceptions",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.106532",abstract:"Entropic conception has been used as an effective strategy for developing materials to break the property recordings of current materials, for example, breaking the trade-off between the high-strength and low-ductility structural alloys. The performance of materials usually under a complex circumstance, a balance of multiple properties, for example, combined the high-strength, high ductility, high conductivity, high corrosion resistance, high irradiation resistance, etc., the strategy of high-entropy-alloy (HEA) will provide a materials design and development technology to realize the goal. Magnetic materials usually exhibit excellent magnetic properties but weak mechanical properties and corrosion resistance. The reported unique behaviors of HEAs, for example, self-healing effects may be the mechanism for the high irradiation resistance of the HEAs, and self-sharpening behaviors of the tungsten-based HEAs main closely be related to the serration behaviors.",book:{id:"11468",title:"High Entropy Materials - Microstructures and Properties",coverURL:"https://cdn.intechopen.com/books/images_new/11468.jpg"},signatures:"Yong Zhang and Xuehui Yan"},{id:"82929",title:"Prediction of Solubility and Miscibility Parameters of Bismuth-Arsenic Complex and Amorphous Mineral Compounds Using Molecular Dynamics Simulation",slug:"prediction-of-solubility-and-miscibility-parameters-of-bismuth-arsenic-complex-and-amorphous-mineral",totalDownloads:3,totalDimensionsCites:0,doi:"10.5772/intechopen.106316",abstract:"Bismuth is one of the most difficult impurities to remove in mining concentrates and low concentrations generate problems in silver and copper refineries. Therefore, financial penalties are established when concentrations exceed 0.05%. Some researchers had used arsenic to remove bismuth with results of up to 52% of extraction. Unfortunately, this mechanism is not yet fully understood. The objective of this research was to obtain the solubility parameters of amorphous mineral compounds, including bismuth-based compounds, through computational simulation using molecular dynamics. The composition of the mineral sample was determined by X-ray diffraction and the crystalline species were obtained and modeled using Materials Studio software. The nanostructures were optimized by an energy minimization methodology using the Broyden-Fletcher-Goldfarb-Shanno algorithm and were validated using the figure of merit equation and density. Simulations were performed using the Universal Force Field at constant pressure and temperature. The results of the minerals identified in the sample were compared with arsenic trioxide, indicating miscibility between As2O3 and Bi2O3, possible miscibility with 10 other minerals, and immiscibility with the rest. The results indicate that As2O3 can be successfully used for the removal of Bi2O3 without a negative effect on the recovery of other minerals of higher commercial value.",book:{id:"11467",title:"Bismuth-Based Nanostructured Materials",coverURL:"https://cdn.intechopen.com/books/images_new/11467.jpg"},signatures:"Francisco Adrián De la Torre-Martínez, Efren Delgado, María Dolores Josefina Rodríguez Rosales, Hiram Medrano-Roldán, Javier López-Miranda and Damián Reyes-Jáquez"},{id:"82940",title:"Role of Surface Defects and Optical Band-gap Energy on Photocatalytic Activities of Titanate-based Perovskite Nanomaterial",slug:"role-of-surface-defects-and-optical-band-gap-energy-on-photocatalytic-activities-of-titanate-based-p",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.106253",abstract:"In recent years, water pollution has become one of the major challenges faced by humans because of consistent rise in population and industrial activities. Water pollution due to discharge from cosmetics and pharmaceutical wastes, organic dyes, and heavy metal seen as carcinogens has the potential to disrupt hormonal processes in the body. Different approaches such as chlorination, aerobic treatment, aeration, and filtration have been deployed to treat wastewaters before being discharged into the streams, lakes, and rivers. However, more attention has been accorded to treatment approaches that involve use of nanomaterial due to non-secondary pollution, energy efficiency, and ease of operation. Titanate-based perovskite (TBP) is one of the most frequently studied nanomaterials for photocatalytic applications because of its stability and flexibility in optical band-gap modification. This chapter provided an overview of basic principles and mechanisms of a semiconductor photocatalyst, and current synthesis techniques that have been used in formulating TBP nanomaterial. The effect of reaction conditions and approaches such as doping, codoping, composites, temperature, pH, precursor type, surface area, and morphology on surface defects and optical band-gap energy of TBP nanomaterial was highlighted. Importantly, the impact of surface defects and optical band-gap energy of TBP on its photocatalytic activities was discussed. Finally, how to enhance the degradation efficiency of TBP was proposed.",book:{id:"11469",title:"Recent Advances in Perovskite Materials",coverURL:"https://cdn.intechopen.com/books/images_new/11469.jpg"},signatures:"Izunna Stanislaus Okeke, Priscilla Yahemba Aondona, Amoge Chidinma Ogu, Eugene Echeweozo and Fabian Ifeanyichukwu Ezema"},{id:"82718",title:"Refractories for the Cast Iron Melting",slug:"refractories-for-the-cast-iron-melting",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.105973",abstract:"Refractory is a very important component in economically successful melting of cast iron. Refractory is used to line the furnace or any other vessel used for melting or holding of the molten metal. This chapter has discussed the different type of furnaces used for the melting of cast iron, the special features of those furnaces and the operational parameters of those furnaces with special emphasis on the coreless induction furnace, which is most commonly used. It has dealt with the installation practices of the refractory lining and also has discussed the mode of failure of the refractory lining and the precautions to be taken during installation and during use.",book:{id:"11766",title:"Cast Iron - Production, Properties, Characterization, and Casting Defects Analysis",coverURL:"https://cdn.intechopen.com/books/images_new/11766.jpg"},signatures:"Prasunjit Sengupta"},{id:"82988",title:"Optimization of Retained Austenite and Corrosion Properties on EN-31 Bearing Steel by Cryogenic Treatment Process",slug:"optimization-of-retained-austenite-and-corrosion-properties-on-en-31-bearing-steel-by-cryogenic-trea",totalDownloads:8,totalDimensionsCites:0,doi:"10.5772/intechopen.106317",abstract:"In this work, the percentage of retained austenite and corrosion rate presented on EN 31 bearing steel was identified by which cryogenic treatment processes. Further investigation carried out the possible mechanism brought in by which treatment has significantly improving the properties of the EN-31 bearing steel. The hardness values of CHT and DCT were compared by using the microstructure view of the CHT and DCT samples. The optimised cryotreated samples were prepared for metallographic examination as per ASTM E3-01. Then, the specimen were subjected to factor level settings such as cooling rate, soaking period, soaking temperature and tempering temperature at various conditions. Moreover, the precipitation of fine carbides and the transformation of retained austenite to martensite showed considerable variations in the hardness of the optimised DCT samples compared with the CHT samples. 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The structure of this chapter is obedient to the conventional framework in materials science, and several topics would be covered, including composition and structure design, heat treatment and solidification processing, and some properties and performances, such as mechanical and electrochemical corrosion behaviors and high-temperature oxidation characteristics. A conclusion and outlook of the CALPHAD method are also provided at the end of this chapter. 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"243698",title:"Dr.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:null,institution:null},{id:"7227",title:"Dr.",name:"Hiroaki",middleName:null,surname:"Matsui",slug:"hiroaki-matsui",fullName:"Hiroaki Matsui",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Tokyo",country:{name:"Japan"}}},{id:"312999",title:"Dr.",name:"Bernard O.",middleName:null,surname:"Asimeng",slug:"bernard-o.-asimeng",fullName:"Bernard O. 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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",institutionURL:null,country:{name:"India"}}},editorTwo:null,editorThree:null,series:{id:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188"},editorialBoard:[{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",institutionString:null,institution:{name:"Grenoble Alpes University",institutionURL:null,country:{name:"France"}}},{id:"188219",title:"Prof.",name:"Imran",middleName:null,surname:"Shahid",slug:"imran-shahid",fullName:"Imran Shahid",profilePictureURL:"https://mts.intechopen.com/storage/users/188219/images/system/188219.jpeg",institutionString:null,institution:{name:"Umm al-Qura University",institutionURL:null,country:{name:"Saudi Arabia"}}},{id:"214235",title:"Dr.",name:"Lynn",middleName:"S.",surname:"Zijenah",slug:"lynn-zijenah",fullName:"Lynn Zijenah",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSEJGQA4/Profile_Picture_1636699126852",institutionString:null,institution:{name:"University of Zimbabwe",institutionURL:null,country:{name:"Zimbabwe"}}},{id:"178641",title:"Dr.",name:"Samuel Ikwaras",middleName:null,surname:"Okware",slug:"samuel-ikwaras-okware",fullName:"Samuel Ikwaras Okware",profilePictureURL:"https://mts.intechopen.com/storage/users/178641/images/system/178641.jpg",institutionString:null,institution:{name:"Uganda Christian University",institutionURL:null,country:{name:"Uganda"}}}]},onlineFirstChapters:{paginationCount:20,paginationItems:[{id:"82800",title:"Repurposing Drugs as Potential Therapeutics for the SARS-Cov-2 Viral Infection: Automatizing a Blind Molecular Docking High-throughput Pipeline",doi:"10.5772/intechopen.105792",signatures:"Aldo Herrera-Rodulfo, Mariana Andrade-Medina and Mauricio Carrillo-Tripp",slug:"repurposing-drugs-as-potential-therapeutics-for-the-sars-cov-2-viral-infection-automatizing-a-blind-",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Molecular Docking - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11451.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"82582",title:"Protecting Bioelectric Signals from Electromagnetic Interference in a Wireless World",doi:"10.5772/intechopen.105951",signatures:"David Marcarian",slug:"protecting-bioelectric-signals-from-electromagnetic-interference-in-a-wireless-world",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Biosignal Processing",coverURL:"https://cdn.intechopen.com/books/images_new/11153.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"82586",title:"Fundamentals of Molecular Docking and Comparative Analysis of Protein–Small-Molecule Docking Approaches",doi:"10.5772/intechopen.105815",signatures:"Maden Sefika Feyza, Sezer Selin and Acuner Saliha Ece",slug:"fundamentals-of-molecular-docking-and-comparative-analysis-of-protein-small-molecule-docking-approac",totalDownloads:26,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Molecular Docking - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11451.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"82184",title:"Biological Sensing Using Infrared SPR Devices Based on ZnO",doi:"10.5772/intechopen.104562",signatures:"Hiroaki Matsui",slug:"biological-sensing-using-infrared-spr-devices-based-on-zno",totalDownloads:10,totalCrossrefCites:0,totalDimensionsCites:0,authors:[{name:"Hiroaki",surname:"Matsui"}],book:{title:"Biosignal Processing",coverURL:"https://cdn.intechopen.com/books/images_new/11153.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"82122",title:"Recent Advances in Biosensing in Tissue Engineering and Regenerative Medicine",doi:"10.5772/intechopen.104922",signatures:"Alma T. 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