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Healthcare",slug:"improving-improvement-by-refocusing-learning-experiences-from-an-initially-unsuccessful-six-sigma-pr",signatures:"Svante Lifvergren and Bo Bergman",authors:[{id:"25348",title:"Dr.",name:"Svante",middleName:null,surname:"Lifvergren",fullName:"Svante Lifvergren",slug:"svante-lifvergren"},{id:"25352",title:"Prof.",name:"Bo",middleName:null,surname:"Bergman",fullName:"Bo Bergman",slug:"bo-bergman"}]},{id:"38084",title:"Project Costs and Risks Estimation Regarding Quality Management System Implementation",slug:"project-costs-and-risks-estimation-regarding-quality-management-system-implementation",signatures:"Adela-Eliza Dumitrascu and Anisor Nedelcu",authors:[{id:"52709",title:"Prof.",name:"Anisor",middleName:null,surname:"Nedelcu",fullName:"Anisor Nedelcu",slug:"anisor-nedelcu"},{id:"145737",title:"Dr.",name:"Dumitrascu",middleName:null,surname:"Adela-Eliza",fullName:"Dumitrascu Adela-Eliza",slug:"dumitrascu-adela-eliza"}]},{id:"38087",title:"What Quality Management 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Training for Quality",slug:"competence-education-and-training-for-quality",signatures:"Vidoje Moracanin",authors:[{id:"147905",title:"PhD.",name:"Vidoje",middleName:null,surname:"Moracanin",fullName:"Vidoje Moracanin",slug:"vidoje-moracanin"}]},{id:"38091",title:"The Integration of TQM and Six-Sigma",slug:"the-integration-of-tqm-and-six-sigma",signatures:"Ching-Chow Yang",authors:[{id:"11862",title:"Prof.",name:"Ching-Chow",middleName:null,surname:"Yang",fullName:"Ching-Chow Yang",slug:"ching-chow-yang"}]},{id:"38085",title:"Qualitative and Quantitative Analysis of Six Sigma in Service Organizations",slug:"qualitative-and-quantitative-analysis-of-six-sigma-in-service-organizations",signatures:"Ayon Chakraborty and Kay Chuan Tan",authors:[{id:"147160",title:"Dr.",name:"Ayon",middleName:null,surname:"Chakraborty",fullName:"Ayon Chakraborty",slug:"ayon-chakraborty"},{id:"148315",title:"Dr.",name:"Kay Chuan",middleName:null,surname:"Tan",fullName:"Kay Chuan Tan",slug:"kay-chuan-tan"}]},{id:"38089",title:"Lean Six Sigma - Making It 'Business as Usual'\"",slug:"lean-six-sigma-making-it-business-as-usual-",signatures:"Graham Cartwright and John Oakland",authors:[{id:"151090",title:"Prof.",name:"John",middleName:null,surname:"Oakland",fullName:"John Oakland",slug:"john-oakland"},{id:"153931",title:"Mr.",name:"Graham",middleName:null,surname:"Cartwright",fullName:"Graham Cartwright",slug:"graham-cartwright"}]}]}]},onlineFirst:{chapter:{type:"chapter",id:"72704",title:"The Potential Role of Renin Angiotensin System (RAS) and Dipeptidyl Peptidase-4 (DPP-4) in COVID-19: Navigating the Uncharted",doi:"10.5772/intechopen.92837",slug:"the-potential-role-of-renin-angiotensin-system-ras-and-dipeptidyl-peptidase-4-dpp-4-in-covid-19-navi",body:'Coronavirus (CoV) is a positive-sense single-strand RNA genome, which is the largest known RNA virus, constitutes Riboviria of Coronaviridae family and Orthocoronavirinae subfamily with a genome size of 27–34 kilobases. The name coronavirus is derived from the Latin word corona, meaning crown or halo, which is the feature appearance under electron microscope. Regarding COVID-19, it is similar to the other RNA viruses with additional endoribonuclease and exoribonuclease terminal caps (Figure 1) [1].
Structure of SARS-CoV2.
Formerly different researches were done to identify the cause of obscure respiratory tract infections. The identified novel agents were severe acute respiratory syndrome coronavirus (SARS-CoV) and human coronavirus NL63 (HCoV-NL63) [2] CoV causes human acute respiratory infection in about 5–30% of the total respiratory infection. In the past, between 2002 and 2003, an epidemic had been shown caused by SARS-CoV, which causes severe acute respiratory syndrome in 8000 subjects with 750 deaths. SARS-CoV is a second coronavirus group, while HCoV-NL63 is called group 1 coronavirus [3, 4].
On December 2019, a number of cases with a novel coronavirus (COVID-19) led to infected pneumonia in Wuhan in central China. Four cases with pneumonia of unknown etiology were reported on 29 December 2019, which heralds the similar outbreak of 2003 SARS-CoV [5].
At this time, no vaccines or effective antiviral agents are approved for the treatment or prevention of human COVID-19. Therefore, the emergence of COVID-19 is regarded as a priority by the World Health Organization (WHO), Center for Disease Control and Prevention (CDC), and health agencies for the developing a therapeutic effective drug against COVID-19. In general COVID-19 as other positive-sense RNA virus is characterized by high genetic plasticity and mutations due to short replication time, with a higher rate of recombination. These criteria limit and challenge for discovering novel antiviral agents [6, 7]. However, nucleotide and nucleoside analogue inhibitors (NIs) may be an effective agent by the reduction of genetic mapping of COVID-19 [8]. NIs such as ribavirin, remdesivir, and beta-D-N4-hydroxycytidine could be effective agents despite emergence of rapid resistance [9].
Previously, it has been reported by Li et al. [11] and Kuba et al. [10] that the entry-point receptor for SARS-CoV is angiotensin-converting enzyme 2 (ACE2) at the lung [10, 11]. Besides, Eckerle et al. reported that dipeptidyl peptidase-4 (DPP-4) which cluster of differentiation 26 (CD26) is widely expressed on the surface of human cells which acts as a receptor for Middle East respiratory syndrome coronavirus (MERS-CoV) [12]. Since there is a 80% similarity between MERS-CoV and SARS-CoV with SARS-CoV-2, this study was planned to review the potential link between the incidence and severity of COVID-19 regarding the modulation of DPP-4 and ACE2 by DPP-4 and renin angiotensin system (RAS) inhibitors, respectively.
In general, an endeavor of this study article was to present a mini review concerning DPP-4 and RAS and their inhibitors in relation to the incidence and severity of COVID-19. Evidences and substantiations from experimental, preclinical, and clinical studies are assessed, given the nature and character of the subject area; it remains clear that this literature search cannot be considered as a systemic review. A multiplicity and array of search policy took on and are assumed, which is integrated by electronic database searches of Scopus, Web of Science, Medline, Cochrane Central Register of Controlled Trials (CCTR), and PubMed using MeSH terms, keywords, and title words during the search. The terms used for these searches were as follows: COVID-19 or coronavirus or SARS-CoV-2 and DPP-4 OR renin angiotensin system; COVID-19 or SARS-CoV-2 and DPP-4 inhibitors or sitagliptin, vildagliptin, and insulin resistance; incidence of COVID-19 or coronavirus or SARS-CoV-2; and hypertension or orphan drugs or glucagone-like peptide 1 (GLP-1) or dipeptidyl peptidase-IV inhibitors (DPPIV) or thiazolidinediones (TZDs).
Reference lists of previous and recent notorious articles were reviewed. In addition, only English articles were measured, and case reports were also of concerned in this review. The key features of predictable and suitable search studies were considered, and the conclusions were summarized and summed up in a mini review.
RAS is a signaling pathway for the regulation of blood pressure, blood volume, natriuresis, and other vascular functions [13]. RAS consists of different effector peptides that control the dynamic vascular functions. Angiotensinogen from the liver is converted to angiotensin I (AngI), which is converted to angiotensin II (AngII) by angiotensin-converting enzyme 1(ACE1). AngII activates two types of receptors which are AT1 (vasoconstrictor) 90% and AT2 (vasodilator) 10%. The overall effect of AngII is vasoconstriction with sympathetic activation and aldosterone release. Excess of AngII is metabolized by ACE2 into vasodilator Ang (1–7) which act on specific receptor called MAS receptor (Figure 2). AngII can also be converted to angiotensin A by mononuclear leukocyte-derived aspartate decarboxylase (MLDAD), leading to the formation of alamandine, which has been shown to bind to the mas-related G protein-coupled receptor D [14].
Renin angiotensin system (RAS).
In COVID-19, SARS-CoV-2 binds ACE2 which is highly expressed by the epithelial cells of the blood vessel, intestine, and lung. The expression of ACE2 is augmented by angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) (Figure 3) [15] as well as ibuprofen and thiazolidinediones, and cigarette smoking also increases the expression of ACE2 at epithelial cells of the lung. Therefore, hypertensive patients on ACEIs or ARBs are at higher risk for COVID-19 [16, 17].
Role of angiotensin-converting enzyme 2 (ACE2).
Recently, Zhou et al. [18] found that the COVID-19 genome is 96% identical to the bat CoV, so spike glycoprotein (S protein) and receptor binding domain (RBD) of both SARS-CoV-2 and bat CoV bind ACE2, which might explain the cross-species transmission, which means from bat to human and from human to human [19]. In addition, the affinity of COVID-19-RBD to ACE2 is approximately 10–20 times more than that of SARS-CoV [20]. It has been shown that smoking upregulates ACE2 via activation of pulmonary platelet factor and induction of oxidative stress and inflammatory reactions. Increased ACE activity also contributes to impaired vascular relaxation observed in smokers. Irbesartan, an AT1R antagonist (also known as angiotensin receptor blocker), was found to reduce arterial stiffness in hypertensive patients. When stratified by smoking status, smokers were found to have stiffer arteries before treatment, and irbesartan was able to reduce arterial stiffness to a greater extent in smokers than in nonsmokers, indicating that overactivity of the RAS contributes to increased arterial stiffness in smokers. On the other hand, overexpression and upregulation of ACE2 is regarded as a protective measure via the reduction of pro-inflammatory cytokines mainly tumor necrosis factor (TNF-α) which is augmented in smoker subjects [21]. Therefore, active cigarette smoking subjects are at high risk for COVID-19 regardless of gender difference (Figure 4).
Nicotine smoking and ACE2.
The activity of RAS is high in the lung, which is the main source of circulating AngII due to higher expression of ACE. Lung ACE2 controls the balance of RAS activation through regulating AngII/Ang 1–7 ratio. Local pulmonary AngII provokes vascular permeability, causing pulmonary edema [22]. However, in acute respiratory distress syndrome (ARDS), the activation of RAS is necessary to maintain oxygenation since ACE2 knockout mice illustrated more sever pulmonary damage than the controls. Thereby, pulmonary ACE2 seems to be a protective defense pathway during ARDS [23]. In addition, ACE2 has an important anti-inflammatory action, and so ACE2 therapy is effective in the treatment of hypertension and diabetic nephropathy through attenuation of AngII-induced inflammation and oxidative stress [24]. Even so recombinant ACE2 is effective in the management of animal model ARDS, the inhibition of ACE2 may lead to fatal outcomes due to the reduction of vasodilator Ang1–7. However, chronic intravenous administration of Ang1–7 or MAS agonists leads to vasodilatation independent of circulating AngII levels [25].
Depending on these observations, different studies illustrate that RAS inhibitors might be of value in the reduction of ARDS, respiratory failure, and acute pneumonia that are induced by SARS-CoV-2 [26]. Though Wang [27] confirms that RAS inhibitors increase the risk of COVID-19 due to the upregulation of pulmonary ACE2, this study recommends stopping RAS inhibitors during COVID-19 outbreak. Nonetheless, all recruited patients with COVID-19 developed ARDS without any evidence of AKI [27]. Thus, RAS system mainly ACE2/Ang1–7 grows to be the focus and meeting point of different researches to implicate this pathway in the pathogenesis of COVID-19.
Guo et al. found that the expression of ACE2 is higher renal tubules than in lung tissues; nevertheless COVID-19 leads to ARDS in much at higher than that of acute kidney injury (AKI), suggesting other mechanism other than ACE2 binding in the pathogenesis of COVID-19 [28]. AT2 receptor is activated by ACE2 and Ang1–7 that oppose the activity of AT1 receptor [29]. Similarly, AT2 receptors are highly expressed in lung epithelial cells compared with kidney tissues. Pulmonary AT2 receptors mediate lung injury through the augmentation of pulmonary inflammation and vascular permeability as well as the development of pulmonary fibrosis [30]. Consequently, pulmonary AT2 receptor antagonists are regarded as a novel pathway in COVID-19-induced pneumonia and ARDS. This finding does not rule out the responsibility of ACE2, since the activation of ACE2 by SARS-CoV-2 causes considerable activation of pulmonary AT2 receptors (Figure 5).
Role of AT2 receptors in COVID-19.
Amid myriad literature survey, polymorphism of ACE2 has been associated with different cardio-metabolic disorders; thus, the implication of ACE2 and AT2 receptors in COVID-19-induced pneumonia should be considerably regarded with ACE2 polymorphisms [31]. Furthermore, the expression of ACE2 might not be necessary for COVID-19 infection and viral entry, as the absence of SARS-CoV-2 in some ACE2 expressing cell types as well; this infection was observed in some cell line lacking ACE2, suggesting a vague pathway, and cofactors might be necessary for human infection [32]. Amusingly, Gurwitz [33] animal model study shows that pulmonary COVID-19 infection leads to significant lung injury through the downregulation of ACE2, which is attenuated by the administration of ARB. This study suggests the protective role of RAS inhibitors in COVID-19-induced ARDS [33]. Indeed, most of reported data from various social media during this dangerous outbreak was not legitimate due to overwhelming lay press and sparked concerns. Therefore, the high incidence of COVID-19 in patients receiving ACEIs or ARBs might be not because of these drugs but because those patients were often older, hypertensive, or diabetic which in fact increase the risk of COVID-19 infection. In addition, a recent clinical trial on the effectiveness of recombinant ACE2 (rACE) in the management of COVID-19 infection has been started [34], and we are waiting for these results. Thus, according to the guideline for the management of hypertension, RAS inhibitors should be used irrespective of COVID-19 infection, as sudden withdrawal of these therapeutic regimens may increase the risk of deleterious outcomes in critically ill patients.
Regarding gender differences in the expression of ACE2, ACE2 gene is located on the X chromosome, which gives the possibility of gender differences in the susceptibility for COVID-19 infection. Females have lower levels of ACE2 compared with males, which gives a clue of male vulnerability to COVID-19 infection as compared with females [35]. In addition, Shenoy et al. report that estrogen attenuates AngII-induced pulmonary fibroblast proliferation due to the upregulation of ACE2 [36]. The expression of ACE2 is regulated by different endogenous hormones and peptides; both endothelin-1 and aldosterone downregulate ACE2 expression in a rat model. So, RAS inhibitors may improve ACE2 expression via suppression of endogenous endothelin-1 and aldosterone (Figure 6) [37].
Potential effects of endothelin-1 and aldosterone on the expression of ACE2.
Moreover, ACE2 contains ectodomain and endodomain at cytoplasmic membrane; the shedding part (ectodomain) is essential for the replication of SARS-CoV-2 (Figure 7) [38].
Shedding of ACE2 during SARS-CoV-2 entry.
At the heart of the dilemma, extensive researches are recommended to explore the specific role of ACE2 and RAS inhibitors during precarious COVID-19 worldwide outbreak.
DPP4, also called adenosine deaminase complexing protein 2 (ADCP2) or adenosine deaminase binding protein (ADBP), is widely distributed on the surface of human cells. DPP4 is involved in the regulation of blood glucose, oxidative stress, inflammation, immune system, cell adhesion, and apoptosis [39]. The substrates of DPP4 are glucagone-like peptide 1 (GLP-1), stromal cell-derived factor 1 (SDF-1), brain natriuretic peptide (BNP), substance P, and neuropeptide Y (NPY). Furthermore, DPP4 interacts with different ligands such as caveolin-1, chemokine receptor type 4 (CXCR4), adenosine deaminase (ADA), and fibronectin [40].
DPP4 inhibitors (DPP4i) such as sitagliptin, saxagliptin, and vildagliptin are approved in the management of type 2 diabetes mellitus (T2DM). Additionally, DPP4i have a potential therapeutic effect regarding hypertension, endothelial dysfunction, cardioprotection, and connective tissue diseases (Figure 8) [41].
Metabolic effects of DDP-4 inhibitors.
Regarding the role of DPP4 in viral entry and replication, Widagdo et al. [42] found that DPP4 is an important receptor for MERS-CoV transmission. DPP4 receptors are found in the human upper respiratory tract epithelium. Lacking of these receptors may restrict the transmission of MERS-CoV.
S protein of MERS-CoV binds specifically to DPP4 receptors. These interactions provoke proteolytic activation for viral entry and fusion of viral membrane with the cell membrane [43].
It has been observed that polymorphism in DPP4 gene is concerned with different cardio-metabolic disorders and transmission of MERS-CoV [44]. The polymorphism in DPP4 reduces the interactions between S proteins of MERS-CoV with cellular membranes. The difference in the incidence between Arabian and African MERS-CoV is mainly related to the genotype polymorphism of DPP4 [45].
Since there is a higher genomic similarity between SARS-CoV-2 and SARS-CoV, the implication of DPP4 as a receptor or a pathogenetic pathway in COVID-19-induced ARDS is reasonable. In COVID-19 infection, ARDS is developed due to massive cytokine release (cytokine storm), due to uncontrolled systemic inflammatory response, and due to the release of pro-inflammatory cytokine, including INF-α-, IL-6, IL-12, IL-33, etc., which cause multiple organ failure [46].
It has been reported that DPP4 is highly expressed on alveolar cells (type I and type II), alveolar macrophage, pleural mesothelium, and vascular endothelium. Besides, pulmonary vascular endothelial cells (PVECs) are the main source of pro-inflammatory cytokines in ARDS. DPP4 is upregulated in pneumonia, asthma, and ARDS; therefore, DPP4 inhibitors may reduce the inflammatory reaction and cytokine release in acute lung injury and ARDS through immune-modulation effect [47].
Different studies illustrated that DPP4 inhibitors inhibit the release of IL-6 and TNF-α in ARDS without effect on the blood glucose when used in a small dose [48]. Therefore, DPP4 inhibitors might be a therapeutic option in the management of COVID-19-induced ARDS.
DPP4 is involved in the activation of T-cell, so the activated T-cell can synthesize and secret AngII by local RAS. So, AngII-dependent T-cell activation is inhibited by DPP4i, leading to a significant reduction of endothelial inflammation and vasoconstriction [49]. Similarly, Bengsch et al. [50] disclosed that DPP4 receptors are highly expressed on Th17 which induced AngII release during ARDS. High circulating AngII level leads to the activation of inflammatory reactions via activation of the release of IL-18, 1 L-17, IL-6, and TNF-α. These mediators are essential for the induction of epithelial and endothelial cell injury during ARDS. DPP4i plays an integral role in the attenuation of IL-6 and TNF-α and associated inflammation and endothelial damage [51].
Therefore, DPP4i interferes with RAS at different levels; as teneligliptin attenuates AngII action, liraglutide downregulates AT1 and upregulates AT2 receptors during intravenous AngII infusion. Besides, exenatide inhibits the secretion of renin, AngII, and angiotensinogen [52].
What is more, DPP4i has a nephroprotective effect through the regulation of sodium and water reabsorption. Both DPP4i and GLP-1 increase sodium excretion through direct effect on proximal renal tubules or indirect effect via the activation of brain natriuretic peptide (BNP) (Figure 9) [53].
Metabolic effects of DDP-4 inhibitors regarding obesity and insulin resistance.
Consequently, DPP4i exerts protective effects on the lung and kidney which are the main tropism of COVID-19 through direct modulation of inflammatory reactions or indirectly through the attenuation of AngII. The interaction between DPP4i and RAS inhibitors seems to augment the expression of AT2 receptor which is under extensive researches to find the pathophysiological pathway of COVID-19 infection. Indeed, this interaction sheds light for possible attenuation of COVID-19-induced ARDS and AKI mainly in critically ill patients with systemic hypertension.
ACE2 is regarded as a portal entry-point for SARS-CoV-2; however, human cell lines with higher expression of ACE2 are not infected by this virus. The overexpression of AT2 receptors by ACE2 and Ang1–7 is regarded as a novel pathway in COVID-19-induced pneumonia and ARDS. Females have lower levels of ACE2 than males, which give a clue of male vulnerability to COVID-19 infection as compared with females. Even so, ACE2 is regarded as a protective pathway which reduces COVID-19-induced acute inflammatory reactions. RAS inhibitors and DPP4i increase the expression of pulmonary ACE2, so the implication of RAS inhibitors and DPP4i as augmenters of COVID-19 is not practical. Therefore, addition of, DPP4i to RAS inhibitors in hypertensive patients with COVID-19 may reduce the risk of ARDS and AKI.
Nil.
Nil.
"I work with IntechOpen for a number of reasons: their professionalism, their mission in support of Open Access publishing, and the quality of their peer-reviewed publications, but also because they believe in equality. Throughout the world, we are seeing progress in attracting, retaining, and promoting women in STEMM. IntechOpen are certainly supporting this work globally by empowering all scientists and ensuring that women are encouraged and enabled to publish and take leading roles within the scientific community." Dr. Catrin Rutland, University of Nottingham, UK
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\\n\\nOur reputation – Everything we publish goes through a two-stage peer review process. We’re proud to count Nobel laureates among our esteemed authors. We meet European Commission standards for funding, and the research we’ve published has been funded by the Bill and Melinda Gates Foundation and the Wellcome Trust, among others. IntechOpen is a member of all relevant trade associations (including the STM Association and the Association of Learned and Professional Society Publishers) and has a selection of books indexed in Web of Science's Book Citation Index.
\\n\\nOur expertise – We’ve published more than 4,500 books by more than 118,000 authors and editors.
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\\n\\nOur services – The support we offer our authors and editors is second to none. Each book in our program receives the following:
\\n\\nOur end-to-end publishing service frees our authors and editors to focus on what matters: research. We empower them to shape their fields and connect with the global scientific community.
\\n\\n"In developing countries until now, advancement in science has been very limited, because insufficient economic resources are dedicated to science and education. These limitations are more marked when the scientists are women. In order to develop science in the poorest countries and decrease the gender gap that exists in scientific fields, Open Access networks like IntechOpen are essential. Free access to scientific research could contribute to ameliorating difficult life conditions and breaking down barriers." Marquidia Pacheco, National Institute for Nuclear Research (ININ), Mexico
\\n\\nInterested? Contact Ana Pantar (book.idea@intechopen.com) for more information.
\\n"}]'},components:[{type:"htmlEditorComponent",content:'We have more than a decade of experience in Open Access publishing. The advantages of publishing with IntechOpen include:
\n\nOur platform – IntechOpen is the world’s leading publisher of OA books, built by scientists, for scientists.
\n\nOur reputation – Everything we publish goes through a two-stage peer review process. We’re proud to count Nobel laureates among our esteemed authors. We meet European Commission standards for funding, and the research we’ve published has been funded by the Bill and Melinda Gates Foundation and the Wellcome Trust, among others. IntechOpen is a member of all relevant trade associations (including the STM Association and the Association of Learned and Professional Society Publishers) and has a selection of books indexed in Web of Science's Book Citation Index.
\n\nOur expertise – We’ve published more than 4,500 books by more than 118,000 authors and editors.
\n\nOur reach – Our books have more than 130 million downloads and more than 108,170 Web of Science citations. We increase citations via indexing in all the major databases, including the Book Citation Index at Web of Science and Google Scholar.
\n\nOur services – The support we offer our authors and editors is second to none. Each book in our program receives the following:
\n\nOur end-to-end publishing service frees our authors and editors to focus on what matters: research. We empower them to shape their fields and connect with the global scientific community.
\n\n"In developing countries until now, advancement in science has been very limited, because insufficient economic resources are dedicated to science and education. These limitations are more marked when the scientists are women. In order to develop science in the poorest countries and decrease the gender gap that exists in scientific fields, Open Access networks like IntechOpen are essential. Free access to scientific research could contribute to ameliorating difficult life conditions and breaking down barriers." Marquidia Pacheco, National Institute for Nuclear Research (ININ), Mexico
\n\nInterested? Contact Ana Pantar (book.idea@intechopen.com) for more information.
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She performed research in perioperative autotransfusion and obtained the degree of PhD in 1993 publishing Peri-operative autotransfusion by means of a blood cell separator.\nBlood transfusion had her special interest being the president of the Haemovigilance Chamber TRIP and performing several tasks in local and national blood bank and anticoagulant-blood transfusion guidelines committees. Currently, she is working as an associate professor and up till recently was the dean at the Albert Schweitzer Hospital Dordrecht. She performed (inter)national tasks as vice-president of the Concilium Anaesthesia and related committees. \nShe performed research in several fields, with over 100 publications in (inter)national journals and numerous papers on scientific conferences. \nShe received several awards and is a member of Honour of the Dutch Society of Anaesthesia.",institutionString:null,institution:{name:"Albert Schweitzer Hospital",country:{name:"Gabon"}}},{id:"83089",title:"Prof.",name:"Aaron",middleName:null,surname:"Ojule",slug:"aaron-ojule",fullName:"Aaron Ojule",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Port Harcourt",country:{name:"Nigeria"}}},{id:"295748",title:"Mr.",name:"Abayomi",middleName:null,surname:"Modupe",slug:"abayomi-modupe",fullName:"Abayomi Modupe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/no_image.jpg",biography:null,institutionString:null,institution:{name:"Landmark University",country:{name:"Nigeria"}}},{id:"94191",title:"Prof.",name:"Abbas",middleName:null,surname:"Moustafa",slug:"abbas-moustafa",fullName:"Abbas Moustafa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94191/images/96_n.jpg",biography:"Prof. Moustafa got his doctoral degree in earthquake engineering and structural safety from Indian Institute of Science in 2002. He is currently an associate professor at Department of Civil Engineering, Minia University, Egypt and the chairman of Department of Civil Engineering, High Institute of Engineering and Technology, Giza, Egypt. He is also a consultant engineer and head of structural group at Hamza Associates, Giza, Egypt. Dr. Moustafa was a senior research associate at Vanderbilt University and a JSPS fellow at Kyoto and Nagasaki Universities. He has more than 40 research papers published in international journals and conferences. He acts as an editorial board member and a reviewer for several regional and international journals. His research interest includes earthquake engineering, seismic design, nonlinear dynamics, random vibration, structural reliability, structural health monitoring and uncertainty modeling.",institutionString:null,institution:{name:"Minia University",country:{name:"Egypt"}}},{id:"84562",title:"Dr.",name:"Abbyssinia",middleName:null,surname:"Mushunje",slug:"abbyssinia-mushunje",fullName:"Abbyssinia Mushunje",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Fort Hare",country:{name:"South Africa"}}},{id:"202206",title:"Associate Prof.",name:"Abd Elmoniem",middleName:"Ahmed",surname:"Elzain",slug:"abd-elmoniem-elzain",fullName:"Abd Elmoniem Elzain",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Kassala University",country:{name:"Sudan"}}},{id:"98127",title:"Dr.",name:"Abdallah",middleName:null,surname:"Handoura",slug:"abdallah-handoura",fullName:"Abdallah Handoura",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"École Supérieure des Télécommunications",country:{name:"Morocco"}}},{id:"91404",title:"Prof.",name:"Abdecharif",middleName:null,surname:"Boumaza",slug:"abdecharif-boumaza",fullName:"Abdecharif Boumaza",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Abbès Laghrour University of Khenchela",country:{name:"Algeria"}}},{id:"105795",title:"Prof.",name:"Abdel Ghani",middleName:null,surname:"Aissaoui",slug:"abdel-ghani-aissaoui",fullName:"Abdel Ghani Aissaoui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/105795/images/system/105795.jpeg",biography:"Abdel Ghani AISSAOUI is a Full Professor of electrical engineering at University of Bechar (ALGERIA). He was born in 1969 in Naama, Algeria. He received his BS degree in 1993, the MS degree in 1997, the PhD degree in 2007 from the Electrical Engineering Institute of Djilali Liabes University of Sidi Bel Abbes (ALGERIA). He is an active member of IRECOM (Interaction Réseaux Electriques - COnvertisseurs Machines) Laboratory and IEEE senior member. He is an editor member for many international journals (IJET, RSE, MER, IJECE, etc.), he serves as a reviewer in international journals (IJAC, ECPS, COMPEL, etc.). He serves as member in technical committee (TPC) and reviewer in international conferences (CHUSER 2011, SHUSER 2012, PECON 2012, SAI 2013, SCSE2013, SDM2014, SEB2014, PEMC2014, PEAM2014, SEB (2014, 2015), ICRERA (2015, 2016, 2017, 2018,-2019), etc.). His current research interest includes power electronics, control of electrical machines, artificial intelligence and Renewable energies.",institutionString:"University of Béchar",institution:{name:"University of Béchar",country:{name:"Algeria"}}},{id:"99749",title:"Dr.",name:"Abdel Hafid",middleName:null,surname:"Essadki",slug:"abdel-hafid-essadki",fullName:"Abdel Hafid Essadki",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"École Nationale Supérieure de Technologie",country:{name:"Algeria"}}},{id:"101208",title:"Prof.",name:"Abdel Karim",middleName:"Mohamad",surname:"El Hemaly",slug:"abdel-karim-el-hemaly",fullName:"Abdel Karim El Hemaly",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/101208/images/733_n.jpg",biography:"OBGYN.net Editorial Advisor Urogynecology.\nAbdel Karim M. A. El-Hemaly, MRCOG, FRCS � Egypt.\n \nAbdel Karim M. A. El-Hemaly\nProfessor OB/GYN & Urogynecology\nFaculty of medicine, Al-Azhar University \nPersonal Information: \nMarried with two children\nWife: Professor Laila A. Moussa MD.\nSons: Mohamad A. M. El-Hemaly Jr. MD. Died March 25-2007\nMostafa A. M. El-Hemaly, Computer Scientist working at Microsoft Seatle, USA. \nQualifications: \n1.\tM.B.-Bch Cairo Univ. June 1963. \n2.\tDiploma Ob./Gyn. Cairo Univ. April 1966. \n3.\tDiploma Surgery Cairo Univ. Oct. 1966. \n4.\tMRCOG London Feb. 1975. \n5.\tF.R.C.S. Glasgow June 1976. \n6.\tPopulation Study Johns Hopkins 1981. \n7.\tGyn. Oncology Johns Hopkins 1983. \n8.\tAdvanced Laparoscopic Surgery, with Prof. Paulson, Alexandria, Virginia USA 1993. \nSocieties & Associations: \n1.\t Member of the Royal College of Ob./Gyn. London. \n2.\tFellow of the Royal College of Surgeons Glasgow UK. \n3.\tMember of the advisory board on urogyn. FIGO. \n4.\tMember of the New York Academy of Sciences. \n5.\tMember of the American Association for the Advancement of Science. \n6.\tFeatured in �Who is Who in the World� from the 16th edition to the 20th edition. \n7.\tFeatured in �Who is Who in Science and Engineering� in the 7th edition. \n8.\tMember of the Egyptian Fertility & Sterility Society. \n9.\tMember of the Egyptian Society of Ob./Gyn. \n10.\tMember of the Egyptian Society of Urogyn. \n\nScientific Publications & Communications:\n1- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Asim Kurjak, Ahmad G. Serour, Laila A. S. Mousa, Amr M. Zaied, Khalid Z. El Sheikha. \nImaging the Internal Urethral Sphincter and the Vagina in Normal Women and Women Suffering from Stress Urinary Incontinence and Vaginal Prolapse. Gynaecologia Et Perinatologia, Vol18, No 4; 169-286 October-December 2009.\n2- Abdel Karim M. El Hemaly*, Laila A. S. Mousa Ibrahim M. Kandil, Fatma S. El Sokkary, Ahmad G. Serour, Hossam Hussein.\nFecal Incontinence, A Novel Concept: The Role of the internal Anal sphincter (IAS) in defecation and fecal incontinence. Gynaecologia Et Perinatologia, Vol19, No 2; 79-85 April -June 2010.\n3- Abdel Karim M. El Hemaly*, Laila A. S. Mousa Ibrahim M. Kandil, Fatma S. El Sokkary, Ahmad G. Serour, Hossam Hussein.\nSurgical Treatment of Stress Urinary Incontinence, Fecal Incontinence and Vaginal Prolapse By A Novel Operation \n"Urethro-Ano-Vaginoplasty"\n Gynaecologia Et Perinatologia, Vol19, No 3; 129-188 July-September 2010.\n4- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Laila A. S. Mousa and Mohamad A.K.M.El Hemaly.\nUrethro-vaginoplasty, an innovated operation for the treatment of: Stress Urinary Incontinence (SUI), Detursor Overactivity (DO), Mixed Urinary Incontinence and Anterior Vaginal Wall Descent. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/ urethro-vaginoplasty_01\n\n5- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamed M. Radwan.\n Urethro-raphy a new technique for surgical management of Stress Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/\nnew-tech-urethro\n\n6- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamad A. Rizk, Nabil Abdel Maksoud H., Mohamad M. Radwan, Khalid Z. El Shieka, Mohamad A. K. M. El Hemaly, and Ahmad T. El Saban.\nUrethro-raphy The New Operation for the treatment of stress urinary incontinence, SUI, detrusor instability, DI, and mixed-type of urinary incontinence; short and long term results. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=urogyn/articles/\nurethroraphy-09280\n\n7-Abdel Karim M. El Hemaly, Ibrahim M Kandil, and Bahaa E. El Mohamady. Menopause, and Voiding troubles. \nhttp://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly03/el-hemaly03-ss\n\n8-El Hemaly AKMA, Mousa L.A. Micturition and Urinary\tContinence. Int J Gynecol Obstet 1996; 42: 291-2. \n\n9-Abdel Karim M. El Hemaly.\n Urinary incontinence in gynecology, a review article.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/abs-urinary_incotinence_gyn_ehemaly \n\n10-El Hemaly AKMA. Nocturnal Enuresis: Pathogenesis and Treatment. \nInt Urogynecol J Pelvic Floor Dysfunct 1998;9: 129-31.\n \n11-El Hemaly AKMA, Mousa L.A.E. Stress Urinary Incontinence, a New Concept. Eur J Obstet Gynecol Reprod Biol 1996; 68: 129-35. \n\n12- El Hemaly AKMA, Kandil I. M. Stress Urinary Incontinence SUI facts and fiction. Is SUI a puzzle?! http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly/el-hemaly-ss\n\n13-Abdel Karim El Hemaly, Nabil Abdel Maksoud, Laila A. Mousa, Ibrahim M. Kandil, Asem Anwar, M.A.K El Hemaly and Bahaa E. El Mohamady. \nEvidence based Facts on the Pathogenesis and Management of SUI. http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly02/el-hemaly02-ss\n\n14- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Mohamad A. Rizk and Mohamad A.K.M.El Hemaly.\n Urethro-plasty, a Novel Operation based on a New Concept, for the Treatment of Stress Urinary Incontinence, S.U.I., Detrusor Instability, D.I., and Mixed-type of Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/urethro-plasty_01\n\n15-Ibrahim M. Kandil, Abdel Karim M. El Hemaly, Mohamad M. Radwan: Ultrasonic Assessment of the Internal Urethral Sphincter in Stress Urinary Incontinence. The Internet Journal of Gynecology and Obstetrics. 2003. Volume 2 Number 1. \n\n\n16-Abdel Karim M. El Hemaly. Nocturnal Enureses: A Novel Concept on its pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecolgy/?page=articles/nocturnal_enuresis\n\n17- Abdel Karim M. El Hemaly. Nocturnal Enureses: An Update on the pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecology/?page=/ENHLIDH/PUBD/FEATURES/\nPresentations/ Nocturnal_Enuresis/nocturnal_enuresis\n\n18-Maternal Mortality in Egypt, a cry for help and attention. The Second International Conference of the African Society of Organization & Gestosis, 1998, 3rd Annual International Conference of Ob/Gyn Department � Sohag Faculty of Medicine University. Feb. 11-13. Luxor, Egypt. \n19-Postmenopausal Osteprosis. The 2nd annual conference of Health Insurance Organization on Family Planning and its role in primary health care. Zagaziz, Egypt, February 26-27, 1997, Center of Complementary Services for Maternity and childhood care. \n20-Laparoscopic Assisted vaginal hysterectomy. 10th International Annual Congress Modern Trends in Reproductive Techniques 23-24 March 1995. Alexandria, Egypt. \n21-Immunological Studies in Pre-eclamptic Toxaemia. Proceedings of 10th Annual Ain Shams Medical Congress. Cairo, Egypt, March 6-10, 1987. \n22-Socio-demographic factorse affecting acceptability of the long-acting contraceptive injections in a rural Egyptian community. Journal of Biosocial Science 29:305, 1987. \n23-Plasma fibronectin levels hypertension during pregnancy. The Journal of the Egypt. Soc. of Ob./Gyn. 13:1, 17-21, Jan. 1987. \n24-Effect of smoking on pregnancy. Journal of Egypt. Soc. of Ob./Gyn. 12:3, 111-121, Sept 1986. \n25-Socio-demographic aspects of nausea and vomiting in early pregnancy. Journal of the Egypt. Soc. of Ob./Gyn. 12:3, 35-42, Sept. 1986. \n26-Effect of intrapartum oxygen inhalation on maternofetal blood gases and pH. Journal of the Egypt. Soc. of Ob./Gyn. 12:3, 57-64, Sept. 1986. \n27-The effect of severe pre-eclampsia on serum transaminases. The Egypt. J. Med. Sci. 7(2): 479-485, 1986. \n28-A study of placental immunoreceptors in pre-eclampsia. The Egypt. J. Med. Sci. 7(2): 211-216, 1986. \n29-Serum human placental lactogen (hpl) in normal, toxaemic and diabetic pregnant women, during pregnancy and its relation to the outcome of pregnancy. Journal of the Egypt. Soc. of Ob./Gyn. 12:2, 11-23, May 1986. \n30-Pregnancy specific B1 Glycoprotein and free estriol in the serum of normal, toxaemic and diabetic pregnant women during pregnancy and after delivery. Journal of the Egypt. Soc. of Ob./Gyn. 12:1, 63-70, Jan. 1986. Also was accepted and presented at Xith World Congress of Gynecology and Obstetrics, Berlin (West), September 15-20, 1985. \n31-Pregnancy and labor in women over the age of forty years. Accepted and presented at Al-Azhar International Medical Conference, Cairo 28-31 Dec. 1985. \n32-Effect of Copper T intra-uterine device on cervico-vaginal flora. Int. J. Gynaecol. Obstet. 23:2, 153-156, April 1985. \n33-Factors affecting the occurrence of post-Caesarean section febrile morbidity. Population Sciences, 6, 139-149, 1985. \n34-Pre-eclamptic toxaemia and its relation to H.L.A. system. Population Sciences, 6, 131-139, 1985. \n35-The menstrual pattern and occurrence of pregnancy one year after discontinuation of Depo-medroxy progesterone acetate as a postpartum contraceptive. Population Sciences, 6, 105-111, 1985. \n36-The menstrual pattern and side effects of Depo-medroxy progesterone acetate as postpartum contraceptive. Population Sciences, 6, 97-105, 1985. \n37-Actinomyces in the vaginas of women with and without intrauterine contraceptive devices. Population Sciences, 6, 77-85, 1985. \n38-Comparative efficacy of ibuprofen and etamsylate in the treatment of I.U.D. menorrhagia. Population Sciences, 6, 63-77, 1985. \n39-Changes in cervical mucus copper and zinc in women using I.U.D.�s. Population Sciences, 6, 35-41, 1985. \n40-Histochemical study of the endometrium of infertile women. Egypt. J. Histol. 8(1) 63-66, 1985. \n41-Genital flora in pre- and post-menopausal women. Egypt. J. Med. Sci. 4(2), 165-172, 1983. \n42-Evaluation of the vaginal rugae and thickness in 8 different groups. Journal of the Egypt. Soc. of Ob./Gyn. 9:2, 101-114, May 1983. \n43-The effect of menopausal status and conjugated oestrogen therapy on serum cholesterol, triglycerides and electrophoretic lipoprotein patterns. Al-Azhar Medical Journal, 12:2, 113-119, April 1983. \n44-Laparoscopic ventrosuspension: A New Technique. Int. J. Gynaecol. Obstet., 20, 129-31, 1982. \n45-The laparoscope: A useful diagnostic tool in general surgery. Al-Azhar Medical Journal, 11:4, 397-401, Oct. 1982. \n46-The value of the laparoscope in the diagnosis of polycystic ovary. Al-Azhar Medical Journal, 11:2, 153-159, April 1982. \n47-An anaesthetic approach to the management of eclampsia. Ain Shams Medical Journal, accepted for publication 1981. \n48-Laparoscopy on patients with previous lower abdominal surgery. Fertility management edited by E. Osman and M. Wahba 1981. \n49-Heart diseases with pregnancy. Population Sciences, 11, 121-130, 1981. \n50-A study of the biosocial factors affecting perinatal mortality in an Egyptian maternity hospital. Population Sciences, 6, 71-90, 1981. \n51-Pregnancy Wastage. Journal of the Egypt. Soc. of Ob./Gyn. 11:3, 57-67, Sept. 1980. \n52-Analysis of maternal deaths in Egyptian maternity hospitals. Population Sciences, 1, 59-65, 1979. \nArticles published on OBGYN.net: \n1- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Laila A. S. Mousa and Mohamad A.K.M.El Hemaly.\nUrethro-vaginoplasty, an innovated operation for the treatment of: Stress Urinary Incontinence (SUI), Detursor Overactivity (DO), Mixed Urinary Incontinence and Anterior Vaginal Wall Descent. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/ urethro-vaginoplasty_01\n\n2- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamed M. Radwan.\n Urethro-raphy a new technique for surgical management of Stress Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/\nnew-tech-urethro\n\n3- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamad A. Rizk, Nabil Abdel Maksoud H., Mohamad M. Radwan, Khalid Z. El Shieka, Mohamad A. K. M. El Hemaly, and Ahmad T. El Saban.\nUrethro-raphy The New Operation for the treatment of stress urinary incontinence, SUI, detrusor instability, DI, and mixed-type of urinary incontinence; short and long term results. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=urogyn/articles/\nurethroraphy-09280\n\n4-Abdel Karim M. El Hemaly, Ibrahim M Kandil, and Bahaa E. El Mohamady. Menopause, and Voiding troubles. \nhttp://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly03/el-hemaly03-ss\n\n5-El Hemaly AKMA, Mousa L.A. Micturition and Urinary\tContinence. Int J Gynecol Obstet 1996; 42: 291-2. \n\n6-Abdel Karim M. El Hemaly.\n Urinary incontinence in gynecology, a review article.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/abs-urinary_incotinence_gyn_ehemaly \n\n7-El Hemaly AKMA. Nocturnal Enuresis: Pathogenesis and Treatment. \nInt Urogynecol J Pelvic Floor Dysfunct 1998;9: 129-31.\n \n8-El Hemaly AKMA, Mousa L.A.E. Stress Urinary Incontinence, a New Concept. Eur J Obstet Gynecol Reprod Biol 1996; 68: 129-35. \n\n9- El Hemaly AKMA, Kandil I. M. Stress Urinary Incontinence SUI facts and fiction. Is SUI a puzzle?! http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly/el-hemaly-ss\n\n10-Abdel Karim El Hemaly, Nabil Abdel Maksoud, Laila A. Mousa, Ibrahim M. Kandil, Asem Anwar, M.A.K El Hemaly and Bahaa E. El Mohamady. \nEvidence based Facts on the Pathogenesis and Management of SUI. http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly02/el-hemaly02-ss\n\n11- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Mohamad A. Rizk and Mohamad A.K.M.El Hemaly.\n Urethro-plasty, a Novel Operation based on a New Concept, for the Treatment of Stress Urinary Incontinence, S.U.I., Detrusor Instability, D.I., and Mixed-type of Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/urethro-plasty_01\n\n12-Ibrahim M. Kandil, Abdel Karim M. El Hemaly, Mohamad M. Radwan: Ultrasonic Assessment of the Internal Urethral Sphincter in Stress Urinary Incontinence. The Internet Journal of Gynecology and Obstetrics. 2003. Volume 2 Number 1. \n\n13-Abdel Karim M. El Hemaly. Nocturnal Enureses: A Novel Concept on its pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecolgy/?page=articles/nocturnal_enuresis\n\n14- Abdel Karim M. El Hemaly. 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