Neoadjuvant therapy in HER2-positive breast cancer
\\n\\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:{caption:"IntechOpen Maintains",originalUrl:"/media/original/113"}},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"5834",leadTitle:null,fullTitle:"Role of Neutrophils in Disease Pathogenesis",title:"Role of Neutrophils in Disease Pathogenesis",subtitle:null,reviewType:"peer-reviewed",abstract:"This book highlights the important role of neutrophils in health as well as in the pathogenesis of various diseases. Section 1 provides a general background information regarding the mechanisms and various triggers of neutrophil extracellular traps (NETs) formation and their role in various infectious and noninfectious diseases (such as postinjury inflammation). Section 2 provides recent evidence regarding the role of neutrophils in the pathogenesis as well as a therapeutic target for selected disease conditions such as periodontal diseases, rheumatoid arthritis, and cystic fibrosis. Section 3 describes the anti-inflammatory properties of neutrophils with focus regarding their role in graft versus host disease. This book provides a wider picture with regard to the importance of this immune cell type in various diseases with focus on one of its recently discovered properties, NETs. Therapeutic targets aimed to modulate neutrophil functions might provide novel approaches in the treatment of various diseases of infectious and noninfectious origin.",isbn:"978-953-51-3196-0",printIsbn:"978-953-51-3195-3",pdfIsbn:"978-953-51-4800-5",doi:"10.5772/65581",price:119,priceEur:129,priceUsd:155,slug:"role-of-neutrophils-in-disease-pathogenesis",numberOfPages:180,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"a626ce289341f74b7e3bba3bbcfb2aea",bookSignature:"Maitham Abbas Khajah",publishedDate:"June 7th 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5834.jpg",numberOfDownloads:13945,numberOfWosCitations:24,numberOfCrossrefCitations:21,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:32,numberOfDimensionsCitationsByBook:1,hasAltmetrics:0,numberOfTotalCitations:77,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 10th 2016",dateEndSecondStepPublish:"October 31st 2016",dateEndThirdStepPublish:"January 27th 2017",dateEndFourthStepPublish:"April 27th 2017",dateEndFifthStepPublish:"June 26th 2017",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Kuwait University",institutionURL:null,country:{name:"Kuwait"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1029",title:"Hemorheology",slug:"hemorheology"}],chapters:[{id:"54970",title:"Neutrophil Extracellular Traps in Infectious Human Diseases",doi:"10.5772/intechopen.68443",slug:"neutrophil-extracellular-traps-in-infectious-human-diseases",totalDownloads:2049,totalCrossrefCites:2,totalDimensionsCites:6,hasAltmetrics:0,abstract:"Neutrophils, as the main cells of the first line of host defense against microbial pathogens, are responsible for pathogen recognition, inhibition of pathogen spreading into the host tissue, and finally, killing the invader cells. Neutrophils carry out these functions via numerous mechanisms, including a relatively recently described activity based on a release of neutrophil extracellular traps (NETs), a process called netosis. NETs are structures composed of DNA backbone, decorated with antimicrobial factors, derived from neutrophil granules. The structure of NETs and their enzymatic and microbicidal inclusions enable efficient trapping and killing of microorganisms within the neutrophil extracellular space. However, the efficiency of NETs depends on neutrophil ability to recognize pathogen signals and to trigger rapid responses. In this chapter, we focus on possible pathways involved in the release of NETs and summarize the current knowledge on triggers of this process during bacterial, fungal, protozoan, and viral infections. We also consider the mechanisms used by microorganisms to evade NET-killing activity and analyze the harmful potential of NETs against the host cells and the contribution of NETs to noninfectious human diseases.",signatures:"Marcin Zawrotniak, Andrzej Kozik and Maria Rapala‐Kozik",downloadPdfUrl:"/chapter/pdf-download/54970",previewPdfUrl:"/chapter/pdf-preview/54970",authors:[{id:"198701",title:"Associate Prof.",name:"Maria",surname:"Rapala-Kozik",slug:"maria-rapala-kozik",fullName:"Maria Rapala-Kozik"},{id:"200044",title:"Dr.",name:"Marcin",surname:"Zawrotniak",slug:"marcin-zawrotniak",fullName:"Marcin Zawrotniak"},{id:"200045",title:"Prof.",name:"Andrzej",surname:"Kozik",slug:"andrzej-kozik",fullName:"Andrzej Kozik"}],corrections:null},{id:"55192",title:"Beneficial and Deleterious Effects of Neutrophil Extracellular Traps on Infection",doi:"10.5772/intechopen.68634",slug:"beneficial-and-deleterious-effects-of-neutrophil-extracellular-traps-on-infection",totalDownloads:1542,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Polymorphonuclear neutrophils (PMNs) are the most abundant leukocytes in the blood and are considered as the first line of innate immune defence against infectious diseases. However, PMN cells have a crucial function in both innate and adaptive immune responses. Neutrophils have several mechanisms to control pathogens, and one of them is their capability to form neutrophil extracellular traps (NETs) that may control infection. NETs have the capacity to trap microorganisms, kill them, or avoid their dissemination. The aim of this chapter is to provide a comprehensive review on NETs, the cells that produce them, and some of the mechanisms involved in their formation, their role in the immune response, and the pros and cons of NETs, focusing mainly on infectious diseases.",signatures:"Maximina B. Moreno-Altamirano, Christian E. Cruz-Gómez and\nLluvia E. López-Luis",downloadPdfUrl:"/chapter/pdf-download/55192",previewPdfUrl:"/chapter/pdf-preview/55192",authors:[{id:"197287",title:"D.Sc.",name:"MMaximinaBertha",surname:"Moreno-Altamirano",slug:"mmaximinabertha-moreno-altamirano",fullName:"MMaximinaBertha Moreno-Altamirano"},{id:"206922",title:"Mr.",name:"Christian Eduardo",surname:"Cruz-Gómez",slug:"christian-eduardo-cruz-gomez",fullName:"Christian Eduardo Cruz-Gómez"},{id:"206923",title:"Ms.",name:"Lluvia E",surname:"López-Luis",slug:"lluvia-e-lopez-luis",fullName:"Lluvia E López-Luis"}],corrections:null},{id:"55371",title:"The Role of Neutrophil Extracellular Traps in Post‐Injury Inflammation",doi:"10.5772/intechopen.68906",slug:"the-role-of-neutrophil-extracellular-traps-in-post-injury-inflammation",totalDownloads:1670,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Polymorphonuclear (neutrophil) granulocytes (PMNs) are an essential part of the innate immune responses and key instigators and effectors of the underlying pathological mechanisms (endothelial damage, interstitial histolysis, cytokine production, phagocytosis) leading to post-injury inflammation and secondary tissue injury. In 2004, the formation of neutrophil extracellular traps (NETs) was identified as an additional defence mechanism of PMN against microbes. The understanding of complex regulation of neutrophil functions and NET formation is essential for differentiating between healthy and pathological inflammatory response, which frequently determines if patient recovers uneventfully or develops catastrophic complications. Recent discoveries have revealed the potential role of NETs in the pathogenesis of a wide range of non-infectious diseases, including post-injury sterile inflammation. In such conditions, both spontaneous NET formation and impaired NETosis are documented. In this chapter, we review the evidence for the role of NETs in post-injury inflammation, the key molecular and cellular participants in pathological NET formation, the clinical relevance of NETs in post-injury complications and the therapeutic potential of NET inhibition/clearance.",signatures:"Eszter Tuboly, Gabrielle D. Briggs and Zsolt J. Balogh",downloadPdfUrl:"/chapter/pdf-download/55371",previewPdfUrl:"/chapter/pdf-preview/55371",authors:[{id:"26682",title:"Prof.",name:"Zsolt",surname:"Balogh",slug:"zsolt-balogh",fullName:"Zsolt Balogh"},{id:"205370",title:"Ph.D.",name:"Gabrielle",surname:"Briggs",slug:"gabrielle-briggs",fullName:"Gabrielle Briggs"}],corrections:null},{id:"54543",title:"Neutrophil Role in Periodontal Disease",doi:"10.5772/67789",slug:"neutrophil-role-in-periodontal-disease",totalDownloads:3048,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Oral tissues are constantly exposed to damage from the mechanical effort of eating and from the invasion of foreign microorganisms such as bacteria, fungi, and virus. In healthy oral tissues, there is a balance between symbiotic bacteria and cells from the innate immune system, mainly neutrophils. When this balance is broken, inflammation appears and more immune cells are recruited to the gingiva. Neutrophils form a barrier against dysbiotic bacteria. However, when neutrophils are insufficient, bacteria thrive causing periodontitis, a chronic inflammatory disease that destroys the tooth‐supporting tissues or periodontium. Damage of periodontal tissues leads to tooth loss, and in severe cases, it can also affect systemic health by increasing a person's risk for atherosclerosis, rheumatoid arthritis, diabetes, and even cancer. The mechanisms neutrophil employ to keep a balance with bacteria in order to maintain healthy oral tissues is the focus of this chapter. We discuss how neutrophil antimicrobial functions keep bacteria at check and how some dysbiotic bacteria block neutrophils to promote an inflammatory state. Also, novel therapeutic approaches for periodontitis are discussed.",signatures:"Carlos Rosales and Eileen Uribe‐Querol",downloadPdfUrl:"/chapter/pdf-download/54543",previewPdfUrl:"/chapter/pdf-preview/54543",authors:[{id:"192432",title:"Dr.",name:"Carlos",surname:"Rosales",slug:"carlos-rosales",fullName:"Carlos Rosales"},{id:"198687",title:"Dr.",name:"Eileen",surname:"Uribe-Querol",slug:"eileen-uribe-querol",fullName:"Eileen Uribe-Querol"}],corrections:null},{id:"55356",title:"Neutrophils in Rheumatoid Arthritis: A Target for Discovering New Therapies Based on Natural Products",doi:"10.5772/intechopen.68617",slug:"neutrophils-in-rheumatoid-arthritis-a-target-for-discovering-new-therapies-based-on-natural-products",totalDownloads:2071,totalCrossrefCites:9,totalDimensionsCites:12,hasAltmetrics:0,abstract:"Rheumatoid arthritis (RA) is a systemic autoimmune disorder with an important inflammatory component in joints. Neutrophils are the most abundant leukocytes in inflamed joints, and play an essential role in the initiation and progression of RA. Neutrophil effector mechanisms include the release of proinflammatory cytokines, reactive oxygen and nitrogen species (ROS and RNS), and granules containing degradative enzymes, which can cause further damage to the tissue and amplify the neutrophil response. Therefore, the modulation of neutrophil migration and functions is a potential target for pharmacological intervention in arthritis. The pharmacologic treatment options for RA are diverse. The current treatments are mostly symptomatic and have side effects, high costs, and an increased risk of malignancies. Because of these limitations, there is a growing interest in the use of natural products as therapies or adjunct therapies. Herbal products have attracted considerable interest over the past decade because of their multiple beneficial effects such as their antioxidant, anti-inflammatory, antiproliferative, and immunomodulatory properties. This chapter focuses on the role of neutrophils in the pathogenesis of arthritis and the action of substances from natural products as putative antirheumatic therapies.",signatures:"Elaine Cruz Rosas, Luana Barbosa Correa and Maria das Graças\nHenriques",downloadPdfUrl:"/chapter/pdf-download/55356",previewPdfUrl:"/chapter/pdf-preview/55356",authors:[{id:"64332",title:"Dr.",name:"Maria Das Graças",surname:"Henriques",slug:"maria-das-gracas-henriques",fullName:"Maria Das Graças Henriques"},{id:"197932",title:"Dr.",name:"Elaine",surname:"Rosas",slug:"elaine-rosas",fullName:"Elaine Rosas"},{id:"199677",title:"MSc.",name:"Luana",surname:"Correa",slug:"luana-correa",fullName:"Luana Correa"}],corrections:null},{id:"54594",title:"Role of Neutrophils in Cystic Fibrosis Lung Disease",doi:"10.5772/67798",slug:"role-of-neutrophils-in-cystic-fibrosis-lung-disease",totalDownloads:1700,totalCrossrefCites:3,totalDimensionsCites:5,hasAltmetrics:0,abstract:"Cystic fibrosis (CF) is a genetic syndrome caused by mutations in the CF Transmembrane Conductance Regulator (CFTR) gene. In CF patients, chief morbidity and mortality are due to pulmonary manifestations. CFTR lack/dysfunction brings an altered ion flux through the airway epithelium and ablation of mucociliary clearance, which in turn ensues in colonization and infection by opportunistic bacterial pathogens and subsequent neutrophil‐dominated inflammation. This response eventually leads to the damage of the lung tissue. A host of inflammatory mediators attract, activate, and reprogramme neutrophils to survive (avoiding apoptosis) and produce a wealth of proteases and radical oxygen species. The protease/antiprotease imbalance and oxidative stress have multiple downstream effects, including impaired mucus clearance, increased and self‐perpetuating inflammation, and impaired immune responses, thus facilitating and fostering bacterial infections. On the other hand, CFTR lack or dysfunction is likely responsible for alterations in neutrophils concerning chemotaxis, phagocytosis, oxidative burst, degranulation, and neutrophil extracellular trap (NET) formation. A good opportunity to reveal new and non‐invasive biomarkers of CF lung disease is the evaluation of circulating neutrophils. Indeed, neutrophil responses are now investigated as outcomes of the aetiological therapies in CF, such as hypertonic saline, antiproteases, CFTR correctors and potentiators.",signatures:"Massimo Conese, Stefano Castellani, Susanna D’Oria, Sante Di Gioia\nand Pasqualina Montemurro",downloadPdfUrl:"/chapter/pdf-download/54594",previewPdfUrl:"/chapter/pdf-preview/54594",authors:[{id:"198848",title:"Prof.",name:"Massimo",surname:"Conese",slug:"massimo-conese",fullName:"Massimo Conese"},{id:"199817",title:"Prof.",name:"Stefano",surname:"Castellani",slug:"stefano-castellani",fullName:"Stefano Castellani"},{id:"199818",title:"Dr.",name:"Susanna",surname:"D'Oria",slug:"susanna-d'oria",fullName:"Susanna D'Oria"},{id:"199819",title:"Prof.",name:"Sante",surname:"Di Gioia",slug:"sante-di-gioia",fullName:"Sante Di Gioia"},{id:"199820",title:"Prof.",name:"Pasqualina",surname:"Montemurro",slug:"pasqualina-montemurro",fullName:"Pasqualina Montemurro"}],corrections:null},{id:"54763",title:"Neutrophils Plasticity: The Regulatory Interface in Various Pathological Conditions",doi:"10.5772/68130",slug:"neutrophils-plasticity-the-regulatory-interface-in-various-pathological-conditions",totalDownloads:1866,totalCrossrefCites:4,totalDimensionsCites:5,hasAltmetrics:0,abstract:"It is now known that neutrophils make up a population of complex cells with great plasticity, challenging the old view of neutrophil association with tissue damage and early phases of infection. Here, we discuss different contexts in which these cells can induce anti-inflammatory responses. Although distinct surface markers and cytokines profiles were shown, the most reliable characterization of suppressor neutrophil subtypes relies on their functional characteristics. One important example of inhibitory neutrophils generation comes from in vivo treatment with G-CSF, for 5 days, as for hematopoietic-stem-cell-transplantation (HSCT). In this case,donor blood is enriched in degranulated granulocytes harboring a functional regulatory phenotype, characterized by IL-10 production. These cells, when transferred together with HSCT, are able to reduce graft-versus-host-disease, being influenced by Treg cells and influencing them back. Importantly, this protection is long lasting and specific, keeping immunocompetence to other antigens. This regulation is paramount in HSCT, and represents a simple approach to be applied in humans. In summary, we discuss the interaction of neutrophils with other cell types and its consequence in immunomodulation. We believe these features confer an important bridge between innate and adaptive immune system, building a new knowledge for an underestimated cell type.",signatures:"Suelen Martins Perobelli, Triciana Gonçalves Silva and Adriana\nBonomo",downloadPdfUrl:"/chapter/pdf-download/54763",previewPdfUrl:"/chapter/pdf-preview/54763",authors:[{id:"170492",title:"Dr.",name:"Adriana",surname:"Bonomo",slug:"adriana-bonomo",fullName:"Adriana Bonomo"},{id:"205632",title:"Dr.",name:"Suelen",surname:"Perobelli",slug:"suelen-perobelli",fullName:"Suelen Perobelli"},{id:"205633",title:"MSc.",name:"Triciana",surname:"Gonçalves-Silva",slug:"triciana-goncalves-silva",fullName:"Triciana Gonçalves-Silva"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"7129",title:"Neutrophils",subtitle:null,isOpenForSubmission:!1,hash:"4f71e75cb45249658d48e765d179ce9f",slug:"neutrophils",bookSignature:"Maitham Khajah",coverURL:"https://cdn.intechopen.com/books/images_new/7129.jpg",editedByType:"Edited by",editors:[{id:"173123",title:"Dr.",name:"Maitham",surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2607",title:"Blood Cell",subtitle:"An Overview of Studies in Hematology",isOpenForSubmission:!1,hash:"7c47fe55b6adb4aaadb74f8e977e46e5",slug:"blood-cell-an-overview-of-studies-in-hematology",bookSignature:"Terry E. 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Giving chemotherapy before performing a resection of tumour was initially introduced in locally advanced breast cancer where large inoperable tumour can be converted to operable cancer.
Moreover, at the time of breast cancer diagnosed with 2 to 3 cm in size, the risk of occult metastasis either in axillary lymph node or distant micrometastasis is greater than 50% [1], [2]. There were some evidences demonstrated in animal model that after surgical removal of primary cancer, metastases might be exacerbated [3], [4]. The administration of systemic chemotherapy in this setting might be a benefit to decrease the mortality risk from systemic spreading of the disease. Therefore, control of the disease prior to surgical treatment might produce a better treatment outcome. It was debated that NAC might delay the operation. However, the result from many studies showed that during the course of NAC breast cancer rarely progressed, or if it progressed that likely reflected the aggressive tumour which did not response to chemotherapy postoperatively.
Another main benefit of NAC is monitoring response to the treatment, so as a good model for
Furthermore, increased rate of breast conserving surgery (BCS) was documented in operable breast cancer with lower risk of local recurrence, in particular when pCR was achieved [10].
Preoperative or NAC has been compared with standard adjuvant chemotherapy as the treatment of breast cancer in several phase III studies. The primary end points mainly are disease-free survival (DFS) and OS. These studies showed that using the chemotherapy preoperatively did not improve DFS and OS, compared with using the same regimen as an adjuvant treatment. A pivotal study from the National Surgical Adjuvant Breast and Bowel Project (NSABP18) [11] compared the use of neoadjuvant adriamycin plus cyclophosphamide (AC) with the same regimen administering postoperatively. With 4-cycle of neoadjuvant AC, the complete clinical response rate (cCR) and pathological complete response rate (pCR) were 36% and 13%, respectively. In primarily operable breast cancer, NAC can downstage tumor and lead to small increase of breast conserving rate (60% vs 67%, p = 0.002). Although substantial response was found with neoadjuvant approach, there was no statistically significant difference in terms of DFS and OS at a 9-year follow up [12]. Another study from the European Organization for Research and Treatment of Cancer (EORTC) compared the efficacy of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) preoperatively or postoperatively [13]. Consistent with the NSABP-B18 trial, the OS, PFS and relapse rate were similar between both groups. Also, several smaller studies exploring the benefit of NAC did not find any survival benefit for the neoadjuvant approach [13]-[15].
Recent meta-analysis addressed directly the benefit of neoadjuvant versus adjuvant chemotherapy [16]. This meta-analysis included nine randomized trials with the total of 3946 patients. There was no difference of death and disease progression. Surprisingly, the patients who received neoadjuvant treatment experienced higher local relapse (risk ratio of 1.22, p=0.015). This greater risk of local recurrence mainly occurred in the trials that the patients received radiotherapy without surgery in patients who achieved clinical complete response.
To date, the evidence-based literatures support the benefit of NAC as an approach to convert inoperable breast cancer to an operable tumor, or downstaging to increase breast conserving rate. These seems to be no difference in survival in patients with operable breast cancer whether chemotherapy is given before or after surgery.
There was no inherent reason to believe that a regimen that works postoperatively will not work preoperatively. Therefore, a standard neoadjuvant regimen is an acceptable postoperative regimen. Previously, anthracycline-based chemotherapy was approved as standard of care for adjuvant treatment of operable breast cancer. It is justified to use at least three to four cycles of anthracycline-based regimen and additional cycles may be considered to maximize response. Later, combination of taxane and anthracycline using as an adjuvant treatment has been proven to be superior to anthracycline alone and become a standard of care in node-positive and high-risk node negative breast cancer. Therefore, several clinical trials have explored the different chemotherapy combinations using as the primary systemic treatment. The best type and schedule administration of preoperative taxanes were investigated in several phase III studies.
The study of NSABP-B27 is the largest study to demonstrate the benefit of adding docetaxel to anthracycine-based regimen [17]. Over 2000 patients were randomized to receive 1) 4 cycles of preoperative AC, 2) 4 cycles of neoadjuvant AC followed by 4 cycles of docetaxel and then surgery, and 3) 4 cycles of AC followed by surgery and then 4 cycles of adjuvant docetaxel. The results showed superiority of clinical response, pCR in patients who received the addition of docetaxel preoperatively (14% vs 26%, p<0.001), but similar breast conserving rate (63% vs 62%). Furthermore, adding docetaxel either preoperatively or postoperatively modestly reduced local recurrence rate with comparable DFS and OS [6].
In the Aberdeen trial, the locally-advanced breast cancer patients were initially treated with 4 cycles of the combination of cyclophosphamide, vincristine, adriamycin and prednisolone (CVAP). The patients who had response to CVAP were randomized to receive another 4 cycles of CVAP or 4 cycles of docetaxel. Among total 162 patients, 66 percent experienced clinical response following the CVAP. Of these, changing to docetaxel provided much better response rate (85% vs 64%, p=0.03), pCR rate (31% vs 15%, p=0.06) and 5-year survival rate (97% vs 78%, p=0.04) [18] .
Numerous trials have addressed to answer how best to incorporate taxane to anthracycline-based regimen. The German Preoperative Adriamycin and Docetaxel study II (GEPAR-DUO) [19] and the Arbeitsgemeinschaft Gastroenterologische Onkologie (AGO) study [20] explored whether using taxane sequentially or concurrently with anthracycline is the best approach. Both studies demonstrate significantly higher pCR and breast conserving rate in sequential arm. However, it is impossible to demonstrate that the better outcome of sequential arm is a result of sequential use itself or the higher cumulative dose of chemotherapy and longer duration of treatment with sequential administration. Another randomized study compared the efficacy of paclitaxel administered either weekly or every 3 weeks schedules, followed by the combination of 5-FU, adriamycin and cyclophosphamide (FAC). Weekly schedule associated with better pCR and also breast conserving rates [21].
Taken together, these data support the sequential use of anthracycline and taxane as the neoadjuvant treatment in both locally advanced and operable breast cancer. However, the usage of taxane in low-risk patients or ER-positive patients may provide minimal benefit outrage of the risk of adverse effect. Optimizing chemotherapy regimen should be considered individually based on reliable prognostic factor, patient’s status and their preference after discussing of the risk and benefit of the treatment.
The patients who achieve poor response to initial neoadjuvant chemotherapy, i.e non-responder, have a worse prognosis. Modification of chemotherapy after observing poor response has not resulted in better outcome [22], [24]. In the German Preoperative Adriamycin and Docetaxel Study III (GEPAR-TRIO) study [22], the breast cancer patients who had poor response to 2 cycles of neoadjuvant docetaxel, adriamycin and cyclophosphamide (TAC) were randomized to receive another 4 cycles of TAC or alter to 4 cycles of vinorelbine plus capecitabine (NX). The results showed no difference in terms of breast conserving rate, clinical and pathological response. On the other hand, in the Aberdeen trial, the patients who received docetaxel after achieving poor respond to 4 cycles of cyclophosphamide, vincristine, doxorubicin and prednisolone (CVAP) ultimately had substantial overall response rate (66%) [25]. On the basis of limited benefit to neoadjuvant chemotherapy in non-responders, adjuvant therapy such as hormonal treatment as well as targeted therapy is considered as the standard treatment to improve outcome [26].
Overexpression of human epidermal growth factor receptor (HER2) is found in approximate 20-30 percent of breast cancer. Trastuzumab, a humanized antibody against HER2, combined with chemotherapy improved survival in metastatic HER2-positive breast cancer [27]. Moreover, 1-year of adjuvant trastuzumab has been established as standard treatment in HER2-positive breast cancer based on improvement of overall survival in several studies [28], [29]. With the promising activity of trastuzumab, its combination with neoadjuvant chemotherapy to enhance response has been proposed. There were several small phase II trials explored different combination of preoperative trastuzumab and chemotherapy. The pCR rate ranged from 12-45% [30], [31]. To date, there was a randomized controlled trial evaluated the efficacy of preoperative trastuzumab combined with anthracycline-based chemotherapy [32]. The stage II and III HER2-positive breast cancer patients were treated with 4 cycles of paclitaxel followed by 4 cycles of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) with or without trastuzumab. The patients in trastuzumab arm had significantly higher pCR rate (65% vs 26%, p=0.016), but no difference in breast conserving rate. There was no incidence of clinical congestive heart failure. However, this study does not demonstrate whether preoperative trastuzumab impact survival compared to using trastuzumab postoperatively. Risk of cardiotoxicity and benefit of improving response are needed to be discussed individually.
Recently, there are several clinical trials comparing the efficacy of emerging anti-HER2, lapatinib and pertuzumab, as its efficacy using with chemotherapy or the addition to trastuzumab. The GeparQuinto trial compared the efficacy of lapatinib and trastuzumab, both concurrently with chemotherapy in operable HER2-positive breast cancer [33]. The pCR rate was significantly higher with the treatment of trastuzumab plus chemotherapy (30% vs 22%, p=0.04). However, breast conserving rate was not different and long-term outcomes are awaited. With the hypothesis of using dual anti-HER2 might inhibit HER2 receptor more efficiently, the clinical trials exploring the efficacy of dual anti-HER2, as neoadjuvant therapy in HER2-positive breast cancer were developed. Dual anti-HER2, eg. Lapatinib or pertuzumab plus trastuzumab, did increase pCR rate, but did not increase breast conserving rate compared to the patients who received trastuzumab plus chemotherapy. The studies of HER2-targeted therapy combined with chemotherapy as neoadjuvant setting in HER2-positive breast cancer are summarized in Table 1.
\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\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
Buzdar A et al*[32] | \n\t\t\t42 | \n\t\t\t3wPx4->FECx4 Same CMT+H | \n\t26 65 | \n\t53 57 | \n
NOAH*[34] | \n\t235 | \n\tCMT CMT+H 1 year | \n\t20 39 | \n\tNA | \n
Neosphere*[7] | \n\t417 | \n\tD+T D+T+P T+P D+P | \n\t29 46 17 24 | \n\tNA | \n
Neoaltto*[35] | \n\t455 | \n\tL->wP T->wP L+H->wP | \n25 30 51 | \n31 28 26 | \n
GeparQuinto*[33] | \n\t620 | \n\tECx4->Dx4+H ECx4->Dx4+L | \n30 22 | \n63 59 | \n
Neoadjuvant therapy in HER2-positive breast cancer
Abbrevations: N, number of patients; BCS, breast conserving rate; 3wP, Paclitaxel every 3 weeks; FEC, 5-FU+epirubicin+cyclophosphamide;H, Trastuzumab; CMT, chemotherapy; D, docetaxel; P, pertuzumab; L, lapatinib; wP, weekly paclitaxel; EC, epirubicin+cyclophosphamide; NA, not available; *The studies that reported significant different of pCR rate and breast conserving rate.
Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, was shown to improve response rate and progression-free survival when added to chemotherapy in metastatic HER2-negative breast cancer patients [36], [37]. Two recent phase III trials [38], [39] determined whether the addition of bevacizumab to chemotherapy would increase pCR rate in HER2-negative operable breast cancer. Both studies confirmed that bevacizumab did increase pCR rate. However, there was a controversial result whether which specific subgroups would gain benefit from bevacizumab. It was claimed that bevacizumab added benefit in terms of pCR in only triple-negative patients from GeparQuinto trial [39], whereas only patients with positive estrogen receptor from the NSABP-B40 trial had higher pCR rate following bevacizumab treatment [38]. Because of contradictory results of these trials with premature long-term data as well as economic argument, therefore, bevacizumab is not recommended for neoadjuvant treatment in non-metastatic HER2-negative breast cancer.
Endocrine therapy has been used as a standard treatment in metastatic ER-positive breast cancer with the objective response of 30-40 percent. Because of low profile of toxicity, it is commonly used as the first option in low-risk metastatic breast cancer, ie asymptomatic, long disease-free interval and limited metastatic disease. Conversely, neoadjuvant endocrine therapy is not recommended as a standard of care because of its lower response rate compared with response rate in the study of neoadjuvant chemotherapy. The small studies reported response rate of 0-2 percent following tamoxifen [40], [41] and 2-3 percent after aromatase inhibitor treatment [40], [42]. The studies of neoadjuvant endocrine therapy are summarized in Table 2.
\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t
Eiermann et al*[43] | \n\t\t337 | \n\t\tLetrozole Tamoxifen | \n\t\t55 36 | \n\t\t45 35 | \n\t
Smith et al [44] | \n\t\t330 | \n\t\tAnastrozole Tamoxifen Combine | \n\t\t37 36 39 | \n\t\t46 22 26 | \n\t
Ellis et al*[40] | \n\t\t324 | \n\t\tLetrozole Tamoxifen | \n\t\t60 41 | \n\t\t48 36 | \n\t
Randomized trials comparing different neoadjuvant endocrine therapy
Abbreviations; N, number of patients; ORR, overall response rate; BCS, breast conserving surgery rate; *The randomized studies with the significant difference of overall response rate and breast conserving rate.
Although the objective response of primary endocrine treatment is not promising, endocrine therapy remains a reasonable option in selected ER-positive breast cancer patients, for instance, the elderly patients who are not suitable for chemotherapy, or has organ function impairment, or desires to avoid adverse effect from chemotherapy. According to a randomized study comparing the efficacy of neoadjuvant chemotherapy and aromatase inhibitor in postmenopausal ER-positive breast cancer patients, clinical response and pCR were not significantly different [45] . However, possibility of breast conserving surgery following primary endocrine treatment is still infrequent.
With the rationale of the superiority of aromatase inhibitor to tamoxifen in metastatic setting of postmenopausal woman with breast cancer, the study of aromatase inhibitor in neoadjuvant setting compared to tamoxifen has been performed. Several studies showed higher overall response rate and also breast conserving rate with aromatase inhibitor [40], [43], [44] .
At present, there are no data available about neoadjuvant endocrine therapy in premenopausal woman.
Although, recent chemotherapeutic regimen for NAC treatment in breast cancer containing anthracycline followed sequentially by a taxane can produces the good clinical response rates [46]. A cPR is still less than 30% [46], [47]. However, these chemotherapeutic agents are associated with significant morbidity. Therefore, the main benefit would be maximum if it were possible to identify patients who are most likely to benefit from NAC before or shortly after commencing the treatment. Recently, various biotechnologies, including both imaging and biomolecular platforms, have been investigated in order to find novel biomarkers or tests to predict responses to NAC. These technologies include molecular imaging, PET-CT, scintigraphy, genomics and proteomic platforms [48]. However, there is not any promising result demonstrated so far.
Amongst the above technologies, the most recent and feasible is the use of magnetic resonance imaging (MRI) as a early predictor of response to NAC. In a recent systematic review study, where dynamic contrast enhanced (DCE) MRI performed pre and after 1-2 cycles of NAC were compared, good sensitivity and specificity in predicting response to NAC was demonstrated, depending on various MRI parameters used for interpretation. Substantial reductions in tumour volumecould be accurate parameters in discriminating responders and non-responders after 1-2 cycles of NAC [49].
PET-CT using 18 F-FDG seemed to be a good technology in predicting response to NAC due to its combination of anatomical and functional characteristics of cancer cells. However, in a small study comparing ability of PET-CT, MRI and ultrasonography in predicting response to NAC, MRI was superior to PET-CT and ultrasonography [50].
With the rationale of NAC in term of controlling distant or micrometastasis, NAC should be a good approach in breast cancer for both early and locally advanced disease. However, in some early breast cancer, addition of chemotherapy might be an overtreatment with more harmful than useful. Evidence from various clinical studies confirmed the benefit of NAC by avoiding mastectomy in some responders. In the recent day, therefore, use of NAC is the treatment of choice for locally advanced or some early breast cancer. Combination of NAC and other targeted therapy such as trastuzumab have given even better outcome. Finally, further research is still required in order to predict response to NAC as early as possible so that patient who would not respond well to NAC could be identified early and would allow seeking for the other treatment.
Living organisms are constitutionally wired to store energy for survival in periods of scarcity. Eel and salmon are reported to survive long periods without food [1, 2, 3]. The excess intake of calories leads to energy accumulation in the form of fat, glycogen, or starch. Plants store energy reserves as starch and oil. We were unable to find reports of adverse consequences of excess energy storage in plants and lower organisms. The stored energy helps the organism to tide over periods of calorie scarcity and during hibernation, aestivation, or migration in animals. In higher organisms, deposition of excess calories results in impairment of body functions with adverse effects on health and longevity. Obesity with adverse health effects has been reported in zebrafish [4], reptiles [5, 6], and birds [7].
Energy in humans is stored as glycogen or triacylglycerols (TAGs). Relative to the amount of calories that can be stored as triacylglycerols (TAGs), only a small amount of calories can be stored as glycogen. An adult liver can store up to 120 g glycogen, while the skeletal muscles can store up to 400 g glycogen. Triacylglycerols are hydrophobic energy-dense molecules that can be stored in large amounts in the adipocytes. Adipose tissue is the loose collection of adipocytes in a mesh of collagen fibers, deposited at various sites in the body. Preadipocytes, fibroblasts, vascular endothelial cells, adipose tissue macrophages, and small blood vessels are also present in the adipose tissue.
Increased mass of adipose tissue, abnormal site of deposition, or abnormal size of adipocytes can result in adverse consequences on health and quality of life (Table 1).
Physical problems | 1. Musculoskeletal disorders
|
2. Respiratory problems
| |
3. Lower limb venous disease
| |
4. Skin-related problems | |
5. Stress incontinence in females | |
Metabolic disorders | 1. Hyperglycemia |
2. Dyslipidemia | |
3. Gout Hyperglycemia increases risk of skin infections, eye diseases, and kidney diseases. Both hyperglycemia and dyslipidemia cause insulin resistances, leading to increased risk of type 2 diabetes, cardiovascular disease, stroke, and cancers. | |
Gut-associated diseases | 1. Cholelithiasis |
2. Pancreatitis | |
3. Fatty liver | |
4. Gastroesophageal reflux disease | |
Reproductive Health Issues | A. Males 1. Hypogonadism |
2. Gynecomastia | |
3. Decreased fertility | |
B. Females | |
1. Polycystic Ovarian Syndrome (PCOS) | |
2. Anovulation | |
3. Endometrial hyperplasia | |
C. Increased risk of complications in pregnancy | |
1. Gestational diabetes | |
2. Preeclampsia | |
3. Cesarian section | |
Economic issues | 1. Increased expense on obesity-related diseases |
2. Decreased pay | |
3. Decreased job opportunity | |
Mental and social issues | 1. Social stigma |
2. Bullying | |
3. Binge eating | |
4. Depression | |
Quality of life and mortality | 1. Increased risk of morbidity, mortality decreased quality of life |
Multiple consequences of obesity.
These result from the abnormally high weight of the affected person and are closely related to each other and to the other consequences of obesity including metabolic dysfunction and insulin resistance. For convenience, we have classified them into musculoskeletal disorders, skin-related problems, respiratory problems, lower-limb venous diseases, and urinary incontinence.
These include decreased mobility, loss of balance, and osteoarthritis, which are associated with abnormal increase in body weight (Figure 1).
Association of obesity with musculoskeletal disorders.
Obesity is one of the major causes for the loss of functional mobility. Altered posture and gait resulting from abnormal fat deposition, compromised bone strength, pain, and breathlessness compromise the mobility [8], which must be taken into account by treating physicians advising increased physical activity for weight loss. Decreased mobility results in further increase in weight.
Increased weight, decreased mobility, and altered posture result in loss of balance, increasing the risk of falls and injury [9]. In spite of the cushioning effect of the fat mass, falls in patients with obesity are more serious and require higher treatment costs and specialized care [10].
Progressive loss of articular cartilage and formation of osteophytes (bony spurs usually caused by local inflammation) result in osteoarthritis [11]. Obesity is a risk factor for OA of knee, hands, and wrist (but not of hip) [12]; thus excessive body weight alone cannot fully explain the increased incidence of OA in people with obesity. Increased body mass index (BMI) in obesity results in altered gait and increased strain on the knee, causing biomechanical joint loading [13]. This is associated with increased expression of matrix metalloproteinases in chondrocytes and increased degradation of proteoglycans [14]. Synthesis of DNA, proteoglycans, and collagen is decreased, contributing to the loss of cartilage in joints [14]. Chondrocytes subjected to high loading show increased expression of pro-inflammatory cytokines including TNF-α and IL-1(β), along with an increased expression of cyclooxygenase-2 leading to increased PGE2 (responsible for inflammatory pain) synthesis [15].
Increase in the amount of adipose tissue leads to metabolic dysfunction: obesity-related sarcopenia, deposition of intramuscular lipid, and chronic low-grade systemic inflammation, all of which contribute to osteoarthritis [16].
Insulin resistance, often seen in patients with obesity, causes decreased excretion of uric acid, leading to hyperuricemia [17, 18]. Adipose tissue is known to express all the components of renin-angiotensin system (RAS), including angiotensinogen [19]. The resulting hypertension may cause glomerular arteriolar damage and reduce uric acid excretion. Hyperuricemia and gout have been associated with osteoarthritis [20, 21].
Obesity is associated with various respiratory problems that are correlated with each other (Figure 2).
Association of obesity with respiratory disorders.
Increased fat deposition in the mediastinum and abdominal cavity increases intra-abdominal and pleural pressure, thus reducing compliance of the lungs. Altered breathing pattern, with decrease in expiratory reserve volume (ERV), functional reserve capacity (FRC), and tidal volume (TV), with slight increase in mean respiratory rate have been reported in subjects with obesity [22, 23], Obesity has little effect on the residual volume (RV) and total lung capacity (TLC) [24].
The relationship between obesity and asthma has been established by a meta-analysis involving more than 300,000 adults [25]. The expression of adipokines secreted by adipose tissue is different in persons with obesity. Decreased expression of adiponectin (anti-inflammatory adipokine) and increased expression of leptin (pro-inflammatory adipokine) have been reported in asthmatic patients with obesity [26]. Leptin, an anorexigenic hormone, increases metabolic rate and is involved in surfactant production and neonatal lung development [27]. Sood et al. [28] have reported a strong association between high BMI and high levels of serum leptin with asthma in adults.
Inflammatory cytokines such as TNF-α, IL-8, and monocyte chemoattractant protein-1 (MCP-1) have also been reported to be raised in persons with obesity. However, their role in asthma associated with obesity is not clear [29]. In older patients, abdominal obesity and metabolic syndrome have been reported to be associated with restrictive lung disease [30].
The prevalence of obstructive sleep apnea in adult persons with obesity is about 45%, compared with 25% in persons with normal weight [31]. Increased fat deposit in tissues surrounding the upper airway decreases the size of lumen and increases collapsibility of the upper airway. OSA may cause sleep fragmentation, which may lead to sleep deprivation [32]. Since experimental sleep deprivation and self-reported short sleep have been linked with metabolic dysregulation, it is possible that OSA may also be a contributing factor in metabolic dysregulation associated with obesity.
Venous diseases (blood clots, deep vein thrombosis, superficial venous thrombosis or phlebitis, chronic venous insufficiency or CVI, varicose and spider veins, and venous stasis ulcers) may be caused by one or more of the following factors: immobility (as in bed-ridden patients) leading to stagnation of blood), blood vessel injury caused by trauma/needles/intravenous catheters/infections, central venous hypertension, conditions that increase the blood coagulation, and pregnancy. Different cancers are associated with deep vein thrombosis.
Varicose veins and chronic venous insufficiency are more common in aged women compared with men. Obesity has been found to be associated with all types of lower limb venous diseases (Figure 3). Willenberg et al. [33] showed that lower limb venous flow parameters are different in healthy persons with and without obesity. Various epidemiological studies show that obesity is associated with chronic venous disease, phlebitis, and thromboembolism [34, 35, 36, 37]. Untreated CVI results in increased pressure and swelling leading to rupture of capillaries. The skin may appear reddish-brown and becomes sensitive to bumps and scratches. Burst capillaries may lead to inflammation and even ulcers.
Obesity as a cause of lower limb venous diseases.
Increased intra-abdominal pressure caused by central obesity is transmitted to the extremities via femoral veins leading to resistance to venous return, producing venous valvular insufficiency. The self-perpetuating cycle of worsening venous insufficiency causes venous stasis and distension of veins in the lower limb. Obesity produces a chronic low-grade inflammation, which damages the affected veins and increases the risk of thromboembolism [33].
Different problems of the integumentary system associated with obesity can be classified on the basis of their pathophysiologic origin (Figure 4). Skin lesions associated with mechanical causes include striae, lipodystrophy, plantar hyperkeratosis, and venous insufficiency. Acanthosis nigricans and skin tags or acrochordons are due to insulin resistance. Obesity-related hyperandrogenism may cause acne, hirsutism, and androgenic alopecia. Skin folds created by obesity increase the risk of intertrigo and infections.
Dermatological manifestations associated with obesity.
Striae or stretch marks are a type of scarring of the dermis associated with stretching of the dermis. Striae distensae may appear as a consequence of pregnancy, puberty, or obesity and appear on abdomen, breasts (in females), and shoulders (in body builders). They are more common in females. [38]. Striae atrophicans due to thinning of the skin may appear in adrenal gland disorders [39].
Other dermatological conditions with mechanical causes include intertrigo, conditions associated with chronic venous insufficiency, and lymphedema [40]. Intertrigo is an inflammation of skin resulting from friction between opposing skin surfaces of skin folds. It may have an infectious component. Axilla, groin, intergluteal, and inframammary areas may be involved [41]. Hot, humid climates and obesity (BMI > 30 kg/m2) are known to promote intertrigo. Persons with obesity tend to sweat more.
Dermatologic sequelae of chronic venous insufficiency (discussed above) are often seen in patients with obesity and include pitting edema, varicose veins, telangiectasia, hyperpigmentation, venous stasis ulcers, and scaling of the skin (stasis dermatitis) [42].
Blocking or damage of the lymphatic system resulting in accumulation of lymph in soft tissues, especially legs or arms, is called lymphedema. Obesity is a risk factor for secondary lymphedema [40].
These include skin tags, acanthosis nigricans, keratosis pilaris, hidradenitis suppurativa and hirsutism, and plantar hyperkeratosis.
Skin tags or acrochordons. Skin tags are soft cutaneous growths, usually benign, more commonly seen in persons with obesity, metabolic syndrome, type 2 diabetes, or in persons with family history of skin tags [43]. They occur in both males and females, usually later on in life, but are less common after the seventh decade. The polypoid lesions are skin-colored, brown, or red, 1–5 mm in size (rarely larger) with a loose edematous fibrovascular core, and may be attached to a fleshy stalk. They are more common in skin folds: axilla, groin, eyelids, and neck [44]. Although not painful, they can cause trouble by getting caught in clothing or jewelry, resulting in itching or bleeding. However, skin tags in large numbers may be seen in patients with Birt-Hogg-Dube (BHD) syndrome and tuberous sclerosis, where they appear around the neck: the molluscum pendulum necklace sign [45, 46].
Acanthosis nigricans (AN). Hyperpigmented velvety plaques usually in body folds, neck, knuckles, and scalp may be seen in patients with obesity. The condition was first reported more than an hundred years ago in the Atlas for Rare Skin Diseases. The term acanthosis nigricans was proposed by Paul Gerson Unna and published in 1891 in a case report by Sigmund Pollitzer [47]. Obesity-associated AN was previously called pseudo acanthosis nigricans; however, this term is incorrect. This is because the initial cases identified in Europe were associated with abdominal or pelvic malignancies. Association of AN with obesity was first reported by Robertson and Tasker in 1947 [48]. Like acrochordons, AN is also associated with insulin resistance often seen in obesity. Probably, the hyperinsulinemia seen in insulin resistance leads to direct and indirect activation of the insulin-like growth factor receptor, triggering proliferation of the dermal fibroblast and epidermal keratinocyte [49]. Friction and perspiration may also be involved in the development of AN [50].
Keratosis pilaris (chicken skin) is a benign condition of the skin in which sterile papules occur on the skin (collections of dead skin cells). Though these papules may occur anywhere on the body (except palms and soles), they are more common on the posterior aspect of upper arms, anterior aspects of thighs, face, and buttocks [51].
Hidradenitis suppurativa or acne inversa is a chronic painful condition of the terminal follicular epithelium in the apocrine gland–bearing skin (groin, bottom, axilla, breasts) [51]. It affects about 1% of the population and is strongly associated with smoking and obesity. It is also linked with hyperandrogenemia, as many patients have acne and hirsutism [52].
Hirsutism, acne vulgaris, and androgenic alopecia seen in some female patients with obesity (with or without polycystic ovarian syndrome, PCOS) are due to hyperandrogenemia, often associated with peripubertal obesity [51, 52, 53, 54]. Increased insulin production (hyperinsulinemia) due to insulin resistance in obesity increases IGF-1 levels and augments ovarian androgen production [55]. Hyperinsulinemia produces a decrease in serum level of steroid hormone binding globulin (SHBG), resulting in a further increase in the level of free testosterone. Treatments that reduce insulin levels usually correct hyperandrogenemia and ovulatory dysfunction [56].
Plantar hyperkeratosis (thickening of skin over metatarsophalangeal joints, caused due to increased pressure and mechanical stress placed on the feet) is seen in almost 50% patients with obesity [40]. Increased circulating levels of IGF-1 seen in hyperinsulinemia lead to overactivation of IGF-1 receptors on fibroblasts and keratinocytes. The abnormal IGF-1 signaling causes cellular hyperproliferation (Figure 4).
Obesity has been associated with an increased risk of skin, respiratory tract, and urinary tract infections [57]. An increased risk of community-acquired infections has been reported by Harpsoe et al. [58] in both overweight and underweight women. Obesity alters the function of skin, sebum, and sweat glands, affects the structure of collagen and subcutaneous fat, and slows wound healing. A number of skin infections that are more common in persons with obesity include candidiasis, candida folliculitis, furunculosis, tinea cruris, and folliculitis. Cellulitis is less common [42].
Normal adipose tissue in a nonobese person has a population of anti-inflammatory/regulatory immune cells: M2-macrophages and regulatory T cells. These are replaced by pro-inflammatory cells: M1 macrophages, Th1, Th17, and cytotoxic T cells in adipose tissue in persons with obesity [59]. Systemic immune adaptations in obesity include increased number of circulating monocytes, neutrophils, Th1, Th17, and Th22 cells. The pro-inflammatory cytokines produced by pathogenic adipose tissue (IL-1β, IL-6, IL-17, and IFN-γ) result in a chronic low-grade inflammation. Skin conditions such as psoriasis, atopic dermatitis, and eczema are strongly associated with obesity [60]. Hashba et al. [61] have suggested the association of lichen planus with obesity.
Urinary incontinence may be of different types: stress incontinence when pregnancy, childbirth, etc., weaken the muscles supporting and controlling bladder; urge incontinence caused by involuntary action of bladder muscles; and mixed incontinence that shares the causes of both stress and urge incontinence. Thyroid problems, uncontrolled diabetes, and medicines such as diuretics can worsen the problem of UI. High BMI, especially BMI higher than 40 kg/m2, has been strongly associated with stress predominant incontinence including mixed incontinence [62]. Central obesity increases the abdominal pressure, which increases the bladder pressure and urethral mobility, leading to UI. Chronic strain and stretching seen in pregnancy and abdominal obesity weaken the muscles and other structures of the pelvic floor. Surgical and non-surgical weight loss has been reported to decrease incontinence and improved quality of life.
Adipose tissue is a loose connective tissue in which about half the cells are adipocytes, the remaining is stromal vascular fraction containing preadipocytes, fibroblasts, endothelial cells, and macrophages [63]. The adipose tissue may be considered the largest endocrine gland in the body.
Based on the metabolic features of the adipocytes, adipose tissue (AT) can be white adipose tissue (WAT), which stores excess energy as fat, and brown adipose tissue (BAT), which dissipates stored energy as heat (Figure 5). Both WAT and BAT are present in mammals and are formed throughout life. In humans, WAT development begins during early to mid-gestation period. WAT adipocytes contain a large single (unilocular) droplet of triacylglycerols occupying 90% of the cell volume, with the cytoplasm and the nucleus squeezed to the periphery. Adipocytes of BAT are smaller, multilocular, and contain mitochondria and uncoupling protein-1 (UCP-1), which is involved in non-shivering thermogenesis. The brown appearance of BAT is due to high vasculature and high mitochondrial content. It has a high density of noradrenergic parenchymal fibers. BAT is 5–10 times more vascularized than WAT. A third type of adipose tissue, the beige or brite (brown in white) adipose tissue with paucilocular adipocytes is dispersed in the WAT [64, 65, 66]. Browning of WAT has been suggested under the influence of the hormone irisin, which is produced by the skeletal muscle during exercise [67]. Adipocytes of WAT and beige adipose tissue are predominantly derived from the Myf 5 negative progenitor cells, while adipocytes of BAT are predominantly from Myf 5 positive progenitor cells. Myf 5 or myogenic factor 5 is a gene for transcriptional factor expressed during embryonic myogenesis [68]. Brown and beige AT show anatomical decline with aging and protect from obesity and type 2 diabetes mellitus (T2DM).
Types of adipose tissue.
Based on the location of the white adipose tissue, it is broadly classified as subcutaneous and visceral (Figure 5). The subcutaneous adipose tissue (SAT) stores excess energy, provides insulation from heat and cold, and functions as an endocrine organ. Visceral adipose tissue (VAT) provides a protective padding around organs. Specialized adipose tissue is associated with the bone marrow, breast, retroorbital adipose tissue, and epicardium [69]. In persons having the same BMI, females tend to have more adipose tissue than males. Females also have more subcutaneous adipose tissue (SAT) compared with males. Localized fat pads, e.g., the synovia are considered as SAT. The SAT of lower trunk and gluteal-thigh region is further organized in two separate layers: the superficial SAT, SSAT (evenly distributed around the circumference of the abdomen), and the deep SAT, DSAT (most of which is located in the posterior half of the abdomen). The SSAT and DSAT are separated by the fascia of Scarpa. SSAT has a higher expression of metabolic regulatory genes, while DSAT has a higher level of expression of inflammatory genes and higher lipolytic activity. Thus, higher volume of DSAT is associated with higher levels of free fatty acids [70].
Bone marrow contains adipose tissue called the marrow adipose tissue (MAT), which increases in amount in periods of calorie restriction, in contrast to adipose tissue present at other sites in the body. Exercise results in decrease in the size of MAT, as well as of the adipocytes present in MAT. Adipocytes of MAT develop from the mesenchymal stem cells.
In some persons there is a variable lack of adipose tissue, which may be generalized or specific (abnormal distribution of adipose tissue). This condition is called lipodystrophy. Lack of sufficient adipose tissue results in increased levels of fatty acids in blood, as they cannot be stored as TGs in the adipocytes. Raised levels of fatty acids cause lipotoxicity, characterized by ectopic fat deposition in the muscle, liver, and pancreas, thus contributing to T2DM [71].
The mechanism of development of insulin resistance is complicated and is influenced by diverse factors, including the location and type of adipose tissue that increases in mass.
Depending on the location, WAT is further classified into different types (Figure 5) [72, 73]. Excess calorie intake leads to enlargement of adipocytes (hypertrophy) as well as increase in the number of adipocytes (hyperplasia) [74]. The new adipocytes may develop from preadipocytes or from adipocytes of BAT. Adipogenesis through differentiation of progenitor cells to adipocytes occurs through transcription factors such as peroxisome proliferator-activated receptor-γ (PPAR-γ), and CCAAT/enhancer binding protein-α [75]. Increase in the size of the adipocytes is associated with insulin resistance and inflammation. Adipose hypertrophy seen in morbid adiposity results in heterogeneity of cell size within the same depot of adipose tissue, with cell size ranging from 20 microns to 300 microns [76]. Usually, SAT contains more preadipocytes compared with VAT, so adipose hypertrophy is less in SAT [77]. Normal adipose tissue produces adipokines (leptin, adiponectin) that regulate appetite and energy metabolism and cytokines. Pro-inflammatory cytokines include TNF-α, visfatin, resistin, angiotensin II, serum amyloid alpha, plasminogen activator inhibitor, and IL-6, while anti-inflammatory cytokines include apelin, transforming growth factor beta (TGFβ), IL-10, IL-4, IL-13, and IL-1 receptor antagonist (IL-1Ra) [78]. Male hormones promote hypertrophy, while female hormones promote hyperplasia [79]. In lean adipose tissue, the adipose cells are 5–10% of all cells in the tissue; in obese adipose tissue, this number is as high as 60% [80]. Although the life span of adipocytes is about 8 years, increase in size beyond a critical cell size and nutrient excess produce endoplasmic reticulum stress, hypoxia, and death of adipocyte, attracting infiltration of macrophages. This is more in VAT. Adipocyte remnants are absorbed by macrophages, which become activated. In lean adipose tissue, the adipose tissue macrophages (ATMs) are predominantly M2 (anti-inflammatory) type. Pathologic adipose has greater number of M1 ATMs, which are pro-inflammatory and produce cytokines in large amounts after absorbing dead adipocytes. This results in chronic low-grade inflammation and insulin resistance.
In some persons with obesity, excess calories are preferentially stored in SAT, which does not produce inflammation. This type of obesity is also called metabolically healthy obesity (MHO) [81]. In contrast, increase in VAT is associated with abnormal blood lipid profile, i.e., dyslipidemia, insulin resistance, metabolic syndrome, type 2 diabetes, and hypertension. This type of obesity is called metabolically unhealthy obesity (MUHO) and is due to deposition of intraabdominal fat.
Hypertrophic stressed adipocytes are unable to take up free fatty acids, which are therefore diverted to other non-fat-storing organs such as muscle, liver, pancreas, and heart, where they are stored as ectopic fat. This results in impaired glucose uptake by muscle cells, decreased glucose utilization by liver and adipose causing hypertriglyceridemia, hyperglycemia, reduced amounts of HDL cholesterol, increased amounts of LDL and VLDL cholesterol, increased proportion of small, dense LDL particles, and insulin resistance. Products of fatty acid metabolism such as long-chain fatty acyl-Co A, diacyl glycerol (DAG), and ceramide are harmful to cells and aggravate insulin resistance by causing phosphorylation of the serine residues on the insulin receptor substrate (IRS) [82]. In skeletal muscle, lipid can be stored in adipocytes between muscle fibers, or as cytosolic triacylglycerols within the muscle cells (intramyocellular lipids, IMCLs). IMCLs are an adaptive response in endurance athletes and are present in close proximity to mitochondria. Increased IMCL stores in insulin resistance or T2DM is a consequence of raised free fatty acid levels in blood and impaired fatty acid oxidation in the muscle [83]. This may also be due to mitochondrial dysfunction.
Recent evidence suggests the role of leptin resistance and hyperleptinemia of obesity causes production of reactive oxygen species (ROS) and increases oxidative stress, promoting the risk of hypertension, heart disease, and cancer [84, 85, 86]. Endoplasmic reticulum stress, protein tyrosine phosphatase 1B, and suppressor of cytokine 3 (SOC3) signaling mediate leptin resistance and are also involved in insulin resistance [87].
Insulin resistance in the liver, adipose, and muscles coupled with ectopic fat in the pancreas contributes to hyperglycemia and T2DM. Deposition of ectopic fat in the pancreas is seen in almost two-thirds of patients with obesity. Most of this is due to adipocyte infiltration into pancreatic tissue rather than accumulation of intracellular lipid. Ectopic pancreatic fat is associated with an increased risk of T2DM and cardiovascular disease (CVD). Increased lipolysis and inflammation caused by ectopic pancreatic fat are also reported to promote acute pancreatitis [88].
Hepatic insulin resistance caused by DAG and ceramide promotes lipotoxicity, ectopic fat deposition, insulin resistance, and steatosis, leading to nonalcoholic fatty liver disease (NAFLD) [89].
Excess free fatty acids reaching the heart can be stored as epicardial adipose tissue (EAT), also called pericardial fat (present between the visceral and parietal pericardia), or surrounding the blood vessels (perivascular adipose tissue or PVAT). Although the cardiac muscle uses free fatty acids for obtaining energy, when delivered in excess these fatty acids are stored as ectopic fat in the cardiac myocyte, disrupting its function. Higher levels of LDL and VLDL receptors are expressed in the epicardial tissue from patients with T2DM. The PVAT produces adipokines and many molecules that affect vascular reactivity: monocyte chemotactic protein-1 (MCP-1)], nitric oxide, prostacyclin, and angiotensin II. PVAT present around the thoracic aorta resembles BAT, while the PVAT around the abdominal aorta resembles WAT [90, 91]. Healthy PVAT is largely anti-inflammatory, while dysfunctional PVAT promotes atherosclerosis.
Different types of cancers associated with obesity include breast, endometrial, prostrate, pancreatic, adenocarcinoma of esophagus, colon cancer, meningioma, and cancers of ovary, kidney, thyroid, liver, etc. [92, 93, 94]. Though different mechanisms have been proposed, chronic inflammation is a major factor for cancer initiation and progression. Excess nutrients activate metabolic signaling pathways such as c-Jun N-terminal kinase (JNK), nuclear factor κ B (NFκB), and protein kinase R that may promote development of neoplasm [95, 96]. Synthesis of IGF-1 is stimulated by insulin. IGF-1 promotes tumor growth via the PI3K/Akt/mTOR and the Ras/Raf/MAPK pathways [96]. IL-6, a pro-inflammatory cytokine produced during adipose tissue inflammation, activates the androgen receptor and promotes cell survival and proliferation in prostate cancer [97]. Aromatase, the rate-limiting enzyme of estrogen synthesis, is also stimulated by inflammatory cytokines and PGE2 [98, 99, 100, 101].
Risk of gallstones is increased in obesity. Chronic gall bladder inflammation from gallstones may predispose to cancer of the gall bladder [102]. Similarly, chronic inflammation of hepatitis may increase the risk of liver cancer [103].
Cancer survivorship, including cancer progression, prognosis, recurrence, and quality of life are reported to be worsened by obesity [104, 105]. Obesity is associated with an increased risk of treatment-related lymphedema in breast cancer survivors and incontinence in prostate cancer survivors (treated with radial prostatectomy) [106, 107]. Risk of local recurrence was higher in obese/overweight male patients with stage II or stage III renal cancer [108]. Similarly, obesity increases the risk of mortality in patients with multiple myeloma [109].
Ocular manifestations of obesity are less known and not well documented. Its association with age-related cataract, glaucoma, age-related maculopathy, and diabetic retinopathy has been reported [110, 111]. Cortical and posterior subcapsular or PSC cataracts have been most consistently associated with obesity. Obesity-induced leptin resistance and hyperlipidemia promote formation of reactive oxygen species, which are involved in cataract formation. Other complications of obesity: insulin resistance, hyperglycemia, diabetes, diabetes, and hypertension (see above) are known to be risk factors for cataract.
Increased retroorbital adipose tissue seen in obesity has been reported to be associated with increased intraocular pressure (IOP) [112, 113]. Raised IOP may be a risk factor for glaucoma. The AREDS (Age-Related Eye Disease Study) Report [114] has reported an association between obesity and age-related macular degeneration. (AMD) Oxidative stress secondary to hyperleptinemia may cause damage to lipids in Bruch membrane and secretion of excessive vascular endothelial growth factor (VEGF), which elicit invasion of neovascularization in Bruch membrane in neovascular AMD [115]. Inflammation may also play a role in AMD development. Diabetic retinopathy, a common complication of T2DM (which is associated with diabetes), can result in loss of vision [116]. Other diseases of the eye that may be associated with obesity include retinal vein occlusion, oculomotor nerve palsy, recurrent lower eyelid entropion, keratoconus, papilledema, floppy eyelid syndrome and benign intracranial hypertension (pseudotumor cerebri) [117, 118, 119, 120, 121].
Besides fatty liver and pancreatitis (discussed above), obesity is associated with increased risk of cholelithiasis (gall bladder stones) and gastroesophageal reflux disease (GERD).
About 90% gallstones are cholesterol stones while the rest are made of calcium bilirubinate, calcium complexes, mucin glycoproteins, or unconjugated bilirubin. Obesity and metabolic syndrome are two risk factors for the development of cholelithiasis, other factors being genetics, age, gender, parity, and presence of hepatitis C virus infection and chronic kidney disease [122]. Recent study by Su et al. [123] shows that obesity reduces the age of onset of gallstone formation. Energy-dense food such as increased consumption of refined carbohydrates and saturated fats with decreased intake of fiber, and medicines such as estrogen and progesterone can promote cholelithiasis [124]. Rapid weight loss of more than 1.5 kg/week can also promote gallstone formation [125].
Heartburn and regurgitation are typical manifestations of GERD. Epidemiologic data show an association of obesity with GERD and Barrett’s esophagus, a condition in which the lower part of the esophagus is damaged by repeated exposure to stomach acid [126, 127].
Obesity has been shown to cause sub-fecundity and infertility in both sexes [128, 129, 130]. Overweight and obesity result in changes in the hypothalamus-pituitary-gonadal (HPG) axis in both men and women, affecting hormone levels and gametogenesis.
Chronic inflammation along with insulin and leptin resistance is associated with increase in adipose tissue (see above), affecting reproductive issues.
Insulin resistance may be responsible for obesity-induced hypogonadism in males. Male obesity secondary hypogonadism or MOSH is caused by hyperestrogenism, metabolic endotoxemia, and hyperleptinemia. Hyperestrogenism decreases pituitary secretion of luteinizing hormone through a negative feedback action that impairs the synthesis and production of testosterone from Leydig cells. Hypercaloric diet with excess lipids causes breakdown of the normal leaky gut, facilitating passage of bacterial endotoxin from gut lumen into the blood stream (metabolic endotoxemia). Some animal studies suggest that bacterial endotoxin (Lipopolysaccharides-LPS) reduces testicular function by binding toll-like receptor 4 (TLR4) on Leydig cells, stimulating production of inflammatory cytokines [131, 132, 133, 134].
Obesity is associated with elevated levels of leptin and leptin resistance. Leptin prevents the neuropeptide Y (NPY) neurons from inhibiting the release of GnRH. Leptin resistance results in reduced release of GnRH, FSH, and LH and impairs spermatogenesis [135].
Kisspeptin, a hypothalamic peptide encoded by the KiSS1 gene, is an important neuromodulator involved in HPG axis and fertility control. Most kisspeptin cells are localized at the hypothalamic level in humans. Kisspeptin and its G-protein-coupled receptor (KISS 1R or GPR-54) increase the delivery of GnRH into portal circulation, resulting in enhanced secretion of LH and FSH from the anterior pituitary. Decreased endogenous kisspeptin secretion is seen in obesity-related hypogonadotropic hypogonadism (HH) [136, 137, 138, 139]. Increased leptin levels are associated with decreased total and free testosterone levels in males.
Hyperinsulinemia results in decreased production of sex hormone binding globulin (SHBG) by the hepatocytes, causing increased availability of free testosterone for reaction by aromatase in the adipose tissue. Aromatase converts testosterone to estradiol [140], further decreasing testosterone level with increase in estrogen level. This may result in pseudo-gynecomastia, with excess adipose deposition in breast area [134]. Sleep apnea associated with obesity disrupts the nocturnal rise in testosterone [134].
High waist circumference is associated with erectile dysfunction due to atherogenic effect on peripheral vasculature [141]. Low ejaculatory volume and oligo-zoospermia have been noted in males with increased BMI and waist circumference [142]. Increased testicular heat, elevated inflammatory mediators, and increased presence of reactive oxygen species in men with obesity affect the quality of sperms [143].
Earlier onset of menarche has been reported in adolescent females with overweight or obesity, compared with their normal-weight counterparts. The association of obesity with menstrual disorders, infertility, and recurrent miscarriages was recognized early [144, 145].
Insulin resistance promotes hyperandrogenemia and decreases the level of steroid hormone binding globulin (SHBG) resulting in elevated levels of free testosterone (discussed above). Aromatization of testosterone to estrogens by aromatase in the adipose tissue suppresses the release of gonadotrophin from the pituitary [140]. Elevated levels of leptin impair follicle development, ovulation, and oocyte maturation in women with obesity [146, 147].
This hormonal disorder is one of the most common endocrine disorder in premenopausal women, is also associated with obesity, metabolic syndrome, and T2DM. Irregular periods, anovulatory cycles, oligo-amenorrhea, excess androgen, hirsutism, and polycystic ovaries are the main characteristics of PCOS [148, 149]. Most women with PCOS have elevated levels of plasma free fatty acids, are insulin resistant, and have compensatory hyperinsulinemia. High levels of free fatty acids induce mitochondrial dysfunction, inflammation, oxidative stress, and immune disorders [150]. High levels of plasma free fatty acids cause increased synthesis of androgens in the ovary as well as in the zona reticularis of the adrenal gland. Insulin stimulates androgenesis by stimulating P450c17 activity in zona reticularis of the adrenal gland to produce DHEA and androstenedione [151]. Hyperinsulinemia causes decreased expression of SHBG by hepatocytes (see above), thus further increasing free testosterone levels. Aromatase (CYP19A1) in adipocytes as well as in the tissue of endometriosis converts androgens to estradiol, which inhibits the secretion of gonadotropin releasing hormone, resulting in decreased release FSH and LH from the pituitary. This affects maturation of follicles, production of estrogen, ovulation, maintenance of function of corpus luteum.
Women with PCOS may have problems in conceiving and increased risk of gestational diabetes and miscarriage or premature birth. Impairment of the hypothalamus-pituitary-gonadal (HPG) axis and follicular environment caused by obesity results in fertility problems, miscarriages, and complications in pregnancy.
Ovulation disorders account for at least 30% cases of infertility. Menstrual cycle without the release of ovum is called anovulatory cycle. Women with obesity have higher rates of anovulatory menstrual cycles [152, 153], the exact mechanism of which is not known. Common causes of anovulation include hyperandrogenism (as in PCOS, congenital adrenal hyperplasia, androgen-producing tumors), hyperprolactinemia, anorexia, excessive strenuous exercise, stress, thyroid dysfunction, primary pituitary dysfunction, premature ovarian failure, and certain medications. Obesity and strenuous exercise are known to alter profiles of insulin and adiponectin, thus impairing fertility in women. Obese women remain sub-fertile even in the absence of ovulatory dysfunction [154, 155].
Obesity affects the quality of sperm, ovum, embryo, placenta, and the uterine environment. The competence of the oocyte is defined in terms of its ability to become fertilized and support embryo development. Oocyte competence may be influenced by obesity. Machtinger et al. [156] have shown that oocytes from women with obesity are smaller in size, have more abnormal spindles and chromosome misalignment than those from women with normal BMI. Negative outcomes for women undergoing in vitro fertilization (IVF) are more common in women with higher BMI, due to the poor oocyte quality, lower preimplantation rate, and uterine receptivity [157]. Decreased rate of conception, infertility, early pregnancy loss, and reduced success of assisted reproductive technology (ART) have been reported in females with obesity [158].
High serum levels of insulin, insulin resistance, high levels of glucose, lactate, triglycerides, and C-reactive protein in the follicular fluid have a negative impact on oocyte maturation.
Mitochondria of the oocyte must be fully functional, as ATP generated by them are required for oocyte maturation and blastocyst formation. High levels of fuel molecules (glucose, free fatty acids, triglycerides, and cholesterol) in environment increase intracellular lipid accumulation and cause damage to the endoplasmic reticulum and mitochondria. Mice fed on high-fat diet have oocytes with accumulated lipid, increased reactive oxygen species (ROS), and have altered structure of mitochondria [159].
Abnormally thickened lining of the uterus due to disordered proliferation of endometrial glands or endometrial hyperplasia is caused by excess androgen with a relative deficiency of progesterone [160]. Untreated endometrial hyperplasia may develop into endometrial cancer [161]. Endogenous estrogen excess may occur in anovulatory cycles (during perimenopause or PCOS), obesity, and estrogen secreting tumors of the ovary. The most common symptom of endometrial hyperplasia is abnormal uterine bleeding.
Women with obesity have a higher risk of miscarriage, gestational diabetes, preeclampsia, premature delivery, cesarean section, and post-partum hemorrhage. Maternal obesity with poor glycemic control may result in fetal macrosomia and associated complications. Twenty percent less detection of fetal anomalies has been reported in women with obesity [162].
A Danish cohort study [163] involving more than 5000 women reported a hazard ratio for miscarriage of 1.23 for women with obesity conceiving spontaneously. Risk of miscarriage is higher in women with obesity who conceive with IVF, even when using donor eggs from women with normal BMI.
Schummers et al. [164] studied 226,000 singleton pregnancies in British Columbia. They have reported an incidence of gestational diabetes of 7.9%. The risk of gestational diabetes was doubled with a BMI > 30, and more than tripled at BMI > 40 kg/m2.
Women with overweight have double the risk of preeclampsia, while women with obesity have triple the risk, compared with women with normal BMI [164, 165]. Increased physical activity during pregnancy may reduce the risk of both gestational diabetes and preeclampsia.
Obesity has been shown to increase the risk of preterm delivery [165, 166]. This may be due to increased levels of circulating cytokines and inflammatory proteins in women with obesity.
The rate of Cesarean section increases with increase in maternal BMI [165, 167]. There is also an increased risk of wound infection, dehiscence, post-partum hemorrhage, and deep vein thrombosis. Duration of labor is longer in women with obesity. There is an increased risk of fetal distress, instrumental delivery, and shoulder dystocia in women with obesity.
Obesity is a risk factor for various diseases (see above). Expenses on medicine, loss of pay due to absence from work caused by illness, reduced job opportunities, etc., lead to constraint on family budget [168].
These include the medical expenses on obesity-related diseases. Expense on medicines for hypertension, type 2 diabetes, dyslipidemia, kidney diseases, stroke; and medical expenses incurred on hospitalization for various conditions affect the family budget as well as the budget of the country [169].
Absence from work due to disease results in decreased pay and early mortality affects the family income. Kjellberg et al. [170] report a 2% decrease in income, 3% increase in social transfer payments, and a 4% increase in healthcare costs per BMI point above 30. Thus, the indirect costs constitute the greatest proportion of total costs associated with obesity. Lee et al. [171] have reported that women with higher BMI are 0.33 times less likely to have service jobs, earn 9% lower monthly wages, and are half as likely to have jobs with bonuses compared with those with normal BMI.
Obesity is considered a social stigma in most societies. People with obesity are considered responsible for their condition and are often the victims of teasing and bullying, at all ages, from preschool through adolescence to adulthood [172, 173, 174, 175, 176].
Bullying is intentional unprovoked aggression that may be physical (hitting, shoving), mental (name calling, spreading rumors, social exclusion, fat shaming on social media) or both, which causes harm to the victim. It involves an imbalance of physical or psychological power. Weight-based victimization is more common at younger age, but may be observed in adults also [177]. It has been noted that pre-adolescent or adolescent boys with overweight or obesity who are stronger than their peer may show bullying behavior, victimizing those who are physically weaker than them [178].
Binge eating disorder (BED) is a type of disordered eating in which the individual consumes a relatively large amount of food in a short span of time, compared with other people of the same age, gender, and weight. BED affects 1–3% of the general population. People with BED are 3–6 times more likely to be overweight or obese than persons without eating disorders [179]. Around 30% persons with BED report a history of childhood obesity [180].
Meta-analysis conducted by Luppino et al. [181] shows a reciprocal link between depression and obesity. Obesity increases the risk of depression, and depression is predictive of developing obesity. Both obesity and depression are common and both are risk factors for cardiovascular diseases [182]. Depression is also an important cause of premature mortality, primarily due to suicide.
Obesity and the associated diseases affect the quality of life and influence the length of life span [183].
Health-related quality of life encompasses physical, mental, and social health and is influenced by factors such as socioeconomic status, culture, and environment of the person concerned. The degree of obesity is inversely proportional with the quality of life, as persons with higher BMI values are more likely to have obesity-associated diseases [184].
At least 2.8 million people die annually as a consequence of being overweight or obese. Many complications of obesity are mentioned above that deteriorate the quality of life and may promote early death. Most of the deaths are a direct consequence of cardiovascular problems or cancer [185].
Obesity is a condition that can compromise health and is closely associated with various medical conditions caused by increased body mass, metabolic derangement, psychological effects, or economic or social aspects. Awareness about the causes and consequences of obesity should be created among the general public so that persons with obesity may receive timely care with empathy.
None.
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It is an oldest, most efficient, and easiest method to apply any surface without modifying the intrinsic properties of materials. Moreover, the initial phase of fire always occurs on the surface by ignition, and hence, it is important to concentrate on the surface protection of a material. Being an organic nature of conventional surface coating will burn easily and generate smoke and toxic fumes, which may not be suitable for application where fire protection or fire prevention is required. Reaction-to-fire and/or resistance-to-fire are to be considered for assessing both flammable and non-flammable material by using fire retardant and fire resistant or fire protective coatings. The degree of fire retardation mainly depends on the coating thickness, substrates, and efficiency of formulations. This chapter explains briefly the fire retardation of wood by using fire retardant coatings.",book:{id:"5827",slug:"new-technologies-in-protective-coatings",title:"New Technologies in Protective Coatings",fullTitle:"New Technologies in Protective Coatings"},signatures:"Thirumal Mariappan",authors:[{id:"198114",title:"Dr.",name:"Thirumal",middleName:null,surname:"Mariappan",slug:"thirumal-mariappan",fullName:"Thirumal Mariappan"}]},{id:"75967",title:"Recent Advances in Ceramic Materials for Dentistry",slug:"recent-advances-in-ceramic-materials-for-dentistry",totalDownloads:804,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Dental ceramics constitute a heterogeneous group of materials with desirable optical and mechanical proprieties combined with chemical stability. They are inorganic non-metallic materials used in several applications. These materials are biocompatible to tissue, highly esthetic, with satisfying resistance to tensile and shear stress. Over the past years, several developments in new ceramic materials in dental restoration were achieved, including processing techniques and high mechanical properties. Thus, concepts on the structure and strengthening mechanisms of dental ceramic materials are also discussed. The dental practitioner requires best knowledge concerning indications, limitations, and correct use of started materials. The purpose of this book chapter is to overview advances in new ceramic materials and processes, which are used in dentistry. The properties of these materials are also discussed.",book:{id:"9894",slug:"advanced-ceramic-materials",title:"Advanced Ceramic Materials",fullTitle:"Advanced Ceramic Materials"},signatures:"Mohsen Mhadhbi, Faïçal Khlissa and Chaker Bouzidi",authors:[{id:"228366",title:"Dr.",name:"Mohsen",middleName:null,surname:"Mhadhbi",slug:"mohsen-mhadhbi",fullName:"Mohsen Mhadhbi"},{id:"324375",title:"Dr.",name:"Faïçal",middleName:null,surname:"Khlissa",slug:"faical-khlissa",fullName:"Faïçal Khlissa"},{id:"324535",title:"Dr.",name:"Chaker",middleName:null,surname:"Bouzidi",slug:"chaker-bouzidi",fullName:"Chaker Bouzidi"}]},{id:"66615",title:"Survey of Bauxite Resources, Alumina Industry and the Prospects of the Production of Geopolymer Composites from the Resulting by-product",slug:"survey-of-bauxite-resources-alumina-industry-and-the-prospects-of-the-production-of-geopolymer-compo",totalDownloads:1222,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Guinea is endowed with huge mineral resources. Several geological surveys have identified bauxite, iron, gold, diamond, and several metal ores. Because of the diversity and the magnitude of its resources, the country is referred to as a geological scandal. Nowadays the aluminum industry is still at the quarrying stage of bauxite, the main raw material that is converted into alumina and further to aluminum. Approximately 35–40% of the processed bauxite ore goes into the waste as alkaline red mud RM slurry which consists of 15–40% solids. RM and other industrial wastes material such as fly ash FA, rice husk ash RHA, that poses environmental hazards can be mixed to make them apt for usage in engineering applications. Geopolymers GP represent a new class of materials consisting of Al2O3▬SiO2-based material suitable for several engineering application. The present chapter presents the bauxitic potential of Guinea, the subsequent developing alumina industry. It reviews the application of RM for the production of geopolymer materials in the perspective of the valorization of the huge bauxite potential of Guinea.",book:{id:"8612",slug:"geopolymers-and-other-geosynthetics",title:"Geopolymers and Other Geosynthetics",fullTitle:"Geopolymers and Other Geosynthetics"},signatures:"Sékou Traoré, A. Diarra, O. Kourouma and D.L. Traoré",authors:[{id:"266484",title:"Prof.",name:"Sekou",middleName:null,surname:"Traore",slug:"sekou-traore",fullName:"Sekou Traore"},{id:"272379",title:"Dr.",name:"Doussou L.",middleName:null,surname:"Traoré",slug:"doussou-l.-traore",fullName:"Doussou L. Traoré"}]},{id:"59550",title:"Introductory Chapter: A Brief Introduction to Porous Ceramic",slug:"introductory-chapter-a-brief-introduction-to-porous-ceramic",totalDownloads:1861,totalCrossrefCites:7,totalDimensionsCites:16,abstract:null,book:{id:"6084",slug:"recent-advances-in-porous-ceramics",title:"Recent Advances in Porous Ceramics",fullTitle:"Recent Advances in Porous Ceramics"},signatures:"Uday M. Basheer Al-Naib",authors:[{id:"182041",title:null,name:"Uday",middleName:"M.",surname:"Basheer",slug:"uday-basheer",fullName:"Uday Basheer"}]}],onlineFirstChaptersFilter:{topicId:"155",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:122,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"July 5th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). 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Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"322007",title:"Dr.",name:"Maria Elizbeth",middleName:null,surname:"Alvarez-Sánchez",slug:"maria-elizbeth-alvarez-sanchez",fullName:"Maria Elizbeth Alvarez-Sánchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",country:{name:"Mexico"}}},{id:"337443",title:"Dr.",name:"Juan",middleName:null,surname:"A. Gonzalez-Sanchez",slug:"juan-a.-gonzalez-sanchez",fullName:"Juan A. Gonzalez-Sanchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico System",country:{name:"United States of America"}}},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}}]}},subseries:{item:{id:"3",type:"subseries",title:"Bacterial Infectious Diseases",keywords:"Antibiotics, Biofilm, Antibiotic Resistance, Host-microbiota Relationship, Treatment, Diagnostic Tools",scope:"