Drugs used in therapy of CMV disease.
\r\n\tGlobalization does not represent a pure and generous process for humanity or other species, but rather it implies social exclusion and also provokes situations of vulnerability in groups of people, forced exclusion, and apartheid: poor job opportunities, lack of access to education, worse socio-sanitary conditions. Specifically, it can be said that social segregation entails the apartheid of social groups of different ages, genders, and ethnicities; these groups live a reality manifested through the deepening of poverty, in terms of increased vulnerability of the poor and groups with little economic, social, cultural, labor and health stability.
\r\n\r\n\tThis book aims to talk about some topics that are neglected in the discourses of academic communities and political elites. The inequality process is deeply rooted among humans and is part of many people's lives in the form of modern apartheid, gender segregation, lack of health access, and cultural gap. All those structural inequality processes are the product of the biopower perpetuated and produced in the macrosystem, exosystem, mesosystem, and microsystem. For many people from the academy, the information-consuming public, and the society in general, it is a problem to talk about these processes, since they have either lost interest or have normalized the structural and social inequity. For this reason, we see it as transcendental to explain how this situation occurs from the most internal fibers to the most evident processes, intending to make it more visible and thus expose the situation for possible solutions.
",isbn:"978-1-83768-406-9",printIsbn:"978-1-83768-405-2",pdfIsbn:"978-1-83768-407-6",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"cefab077e403fd1695fb2946e7914942",bookSignature:"Ph.D. Yaroslava Robles-Bykbaev",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11473.jpg",keywords:"Wage Gap, Gender Segregation, Fundamental Human Rights, Health Access, Social Inequity Processes, Modern Apartheid, Resilience, Cultural Gaps, Globalization, Geopolitics of Social Inequality, Public Policies, Social Vulnerability",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 15th 2022",dateEndSecondStepPublish:"July 13th 2022",dateEndThirdStepPublish:"September 11th 2022",dateEndFourthStepPublish:"November 30th 2022",dateEndFifthStepPublish:"January 29th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"13 days",secondStepPassed:!1,areRegistrationsClosed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"Dr. Bykbaev is a member of the UNESCO Chair of Politecnica Salesiana University. She has contributed as co-author and author to approximately thirty scientific publications in the field of statistics, inclusive education, and social and cultural anthropology. These publications focus on the visibility of problems in the field of public health and focus on the creation of proposals to improve community health. Dr. Bykbaev is an active member of the NODO Ecuadorian Network of Women Scientists (REMCI).",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"313341",title:"Ph.D.",name:"Yaroslava",middleName:null,surname:"Robles-Bykbaev",slug:"yaroslava-robles-bykbaev",fullName:"Yaroslava Robles-Bykbaev",profilePictureURL:"https://mts.intechopen.com/storage/users/313341/images/system/313341.jpg",biography:null,institutionString:"Politecnica Salesiana University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Politecnica Salesiana University",institutionURL:null,country:{name:"Ecuador"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"23",title:"Social Sciences",slug:"social-sciences"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"444316",firstName:"Blanka",lastName:"Gugic",middleName:null,title:"Mrs.",imageUrl:"https://mts.intechopen.com/storage/users/444316/images/20016_n.jpg",email:"blanka@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"6926",title:"Biological Anthropology",subtitle:"Applications and Case Studies",isOpenForSubmission:!1,hash:"5bbb192dffd37a257febf4acfde73bb8",slug:"biological-anthropology-applications-and-case-studies",bookSignature:"Alessio Vovlas",coverURL:"https://cdn.intechopen.com/books/images_new/6926.jpg",editedByType:"Edited by",editors:[{id:"313084",title:"Dr.",name:"Alessio",surname:"Vovlas",slug:"alessio-vovlas",fullName:"Alessio Vovlas"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6942",title:"Global Social Work",subtitle:"Cutting Edge Issues and Critical Reflections",isOpenForSubmission:!1,hash:"222c8a66edfc7a4a6537af7565bcb3de",slug:"global-social-work-cutting-edge-issues-and-critical-reflections",bookSignature:"Bala Raju Nikku",coverURL:"https://cdn.intechopen.com/books/images_new/6942.jpg",editedByType:"Edited by",editors:[{id:"263576",title:"Dr.",name:"Bala",surname:"Nikku",slug:"bala-nikku",fullName:"Bala Nikku"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"66962",title:"Viral Infections after Kidney Transplantation: CMV and BK",doi:"10.5772/intechopen.86043",slug:"viral-infections-after-kidney-transplantation-cmv-and-bk",body:'\nCMV and polyomavirus infection is common in the human population and mainly remains asymptomatic through the life of healthy individuals. However, in immunocompromised individuals, such as kidney transplant recipients (KTRs), it can be associated with various complications, including direct systemic effects of viral infection, bacterial or fungal superinfection, viral infection of the transplanted kidney, and acute and chronic rejection, which consequently diminish patient and graft survival. Current preventive strategies in KTRs include preemptive therapy with valganciclovir or intravenous ganciclovir and universal prophylaxis with antivirals after kidney transplantation and for 1–3 months after treatment with antilymphocyte antibodies. Strategies to control established virus infection include decreasing immunosuppression, adding antivirals, and a combination of both [1, 2, 3].
\nBK virus nephropathy is the most common manifestation of BKV reactivation after renal transplantation, leading to loss of renal grafts in approximately 43% of patients. BKV viruria and viremia can be seen without renal injury and viral nephropathy, so renal biopsy remains the gold standard for definite BKN diagnosis. Therapeutic strategies of BKN management are still very limited, so screening protocols in order to detect early BK reactivation are important. BKN might be successfully managed with a reduction of baseline immunosuppression but is potentially harmful since it may be associated with increased risk of rejection [4, 5, 6].
\nCMV is a double-DNA virus of the herpesvirus family transmitted via saliva, body fluids, or tissue. There are various, species-specific strains of cytomegalovirus [7]. Seroprevalence ranges between 30 and 70% in Europe and North America. Following primary infection, CMV establishes latency in myeloid progenitor cells and can be transiently reactivated in a healthy host without causing disease, similar to polyomaviruses. However, CMV reactivates frequently and causes disease in KTRs in the setting of immunocompromised, typically in the first 2–3 months after transplantation [8, 9]. CMV viremia in the 1–6 months after transplantation is significantly more frequent in KTRs older than 65 years.
\nReinfection (primary infection with a different human strain) can also occur [10].
\nCMV infection is the most common infectious disease following solid organ transplantation, including kidney [1, 3].
\nIn addition to the direct effects of viral infection, CMV infection and disease have been associated with acute and chronic rejection and diminished patient and graft survival [2]. The transplanted kidney itself is only rarely affected by CMV reactivation.
\nThe greatest recognized risk factor for CMV disease is a serological mismatch between the donor and the recipient (the recipient is CMV IgG seronegative and the donor is CMV IgG seropositive: D+/R−). Furthermore, CMV D+/R+ and CMV D−/R+ transplantations are of intermediate risk for the development of disease, and CMV D−/R− transplantation is considered as low risk (<5% incidence) [11, 12].
\nAfter the resolution of primary infection, CMV establishes latent infection. CMV can present in KTRs as either active CMV infection or CMV disease [9, 13].
\nFor a determination of CMV syndrome, CMV in plasma (quantitative PCR CMV DNA (PCR)) and the presence of at least one of the following symptoms and signs of disease are necessary: fever ≥38°C, general signs (malaise, myalgia, arthralgias), leukopenia (≤3.5 × 109/L), atypical lymphocytosis (≥5%), and thrombocytopenia (≤100 × 109/L). In a case of suspected CMV nephritis in KTRs, kidney graft rejection should always be ruled out [3].
\nIn a case of tissue-invasive CMV disease, evidence of particular tissue/organ involvement (hepatitis, colitis, pancreatitis, pneumonitis, nephritis, cystitis, etc.) is based on clinical symptoms and signs associated with a particular organ, positive quantitative PCR CMV DNA in plasma, and, in particular, on the presence of CMV in a given organ or tissue (detected by methods of isolation, histopathology, immunohistochemistry, or hybridization in situ). CMV invasive disease can be most frequently detected in the intestine (40%) followed by the liver (20%), lungs (10%), kidneys (5%), and eyes/brain (1%) [8]. For CMV encephalitis, it is sufficient to prove the presence of CMV in the liquor (PCR) and for CMV pneumonitis in bronchoalveolar flushing (PCR).
\nIn suspected CMV retinitis, ophthalmological examination is sufficient for the diagnosis. In patients with tissue-invasive disease (particularly in CMV infection of the central nervous system, chorioretinitis, and in CMV infection of the gut), CMV viremia may be absent, so some more invasive diagnostics (lumbar puncture, sigmoidoscopy/colonoscopy) must be proceeded in case of clinical suspicion [14].
\nIn KTRs who present with signs and symptoms suspicious for CMV disease, laboratory confirmation is required to establish the diagnosis. A biopsy with histopathologic examination of tissue is occasionally necessary to diagnose tissue-invasive CMV disease.
\nA diagnosis of CMV infection is most often confirmed with nucleic acid testing using polymerase chain reaction (PCR) for the detection of CMV DNA. PCR is primarily used to evaluate blood, cerebrospinal fluid, and ocular or vitreous fluid, although various clinical specimens can be subjected to this assay.
\nAmong other tests to detect CMV, the demonstration of CMV p65 antigen in circulating polymorphonuclear leukocytes in the buffy coat has been used both to monitor response to therapy and as a guide to starting treatment in some centers. Traditional viral cultures are rarely used to diagnose CMV [15].
\nThe most common serologic tests that detect CMV antibodies (IgM and IgG antibody to CMV) are based on enzyme-linked immunosorbent assay (ELISA). A positive test for CMV IgG indicates that a person was infected with CMV at some time during their life. The presence of CMV IgM cannot be used by itself to diagnose primary CMV infection because IgM can persist for months after primary infection and because IgM can be positive in reactivated CMV infections [16].
\nOn occasion histopathological confirmation of CMV disease is necessary to prove CMV organ-specific dysfunction.
\nProductive CMV infection in the tissue is characterized by a cytopathic viral effect in the biopsy specimen of parenchymal organs and the presence of CMV-positive cells by immunohistochemistry or by in situ hybridization with antibody directed against the immediate early antigen. Additionally, CMV virions may be detected by electron microscopy [17].
\nIn daily practice, CMV reactivation is most frequently detected in GIT biopsies, including the colon and stomach (Figure 1). In contrast to polyomaviruses, CMV invasive disease is only sporadically detected in transplanted kidney [18, 19]. Histological features of CMV replication-related lesions in native kidneys are similar to those in renal transplants [20, 21].
\nCMV gastritis with focal active and chronic inflammation (A, Trichrome stain, 100x). Immunohistochemical stain against CMV antigen shows numerous CMV-positive cells (B, CMV, 100x).
CMV nephritis is characterized by virally induced direct tissue injury and by biopsy-proven cytopathic changes. Cytopathic changes are typically focal and detected in tubular epithelial cells or endothelial cells (Figure 2).
\nCMV nephritis in transplanted kidney: focal interstitial inflammation and cytopathic changes in scarce tubular epithelial cells (A, hematoxylin eosin (HE), 200x). CMV inclusions are confirmed by immunohistochemistry (B, CMV, 400x). Courtesy of Danica Galešič Ljubanović and Petar Šenjug.
Three patterns have been observed: pattern I with large intranuclear inclusions in tubular epithelial cells with interstitial nephritis, pattern II with central large eosinophilic intranuclear inclusions in endothelial cells, and rarely, CMV infection may occur as acute glomerulonephritis (pattern III) [18]. CMV infection may also affect podocytes.
\nIn the predominant tubular involvement, tubular CMV infection is usually accompanied by variable interstitial inflammation. In addition, monocyte inclusions in the interstitial infiltrate may be observed. Occasionally, a dense nodular mononuclear and plasma cell infiltrate is present in the interstitium, sometimes reminiscent of granuloma. Focal necrosis and microabscesses are rarely observed. Prominent tubulitis reminiscent of T-cell-mediated rejection characteristic in BKN is absent.
\nThe involvement of endothelial cells is characterized by a central large eosinophilic intranuclear inclusions surrounded by a circumferential halo resembling a typical owl’s eye. Glomerular and peritubular capillary endothelial cells may be infected. In some nuclei, a smudgy-appearing intranuclear inclusion can be detected. In the cytoplasm of viral-infected cells, there are sometimes small basophilic cytoplasmic viral inclusions. When endothelial cells are predominantly CMV-infected cells, tubular epithelium tends to be spared. In such cases, interstitial inflammation is not prominent [18].
\nImmunofluorescence with a standard panel of antibodies is usually unremarkable, only rarely are scarce glomerular IgG deposits detected [20, 21, 22].
\nCMV nephritis may be associated with concurrent antibody- and T-cell-mediated rejection in 30% of cases [22]. In contrast to polyomavirus, CMV often replicates in endothelial and inflammatory cells. Distinction between infection-driven inflammation and rejection may be difficult.
\nImmunomodulation of the immune response might be the most important indirect effect of CMV infection on kidney graft, rather than direct CMV nephritis. It is considered to promote rejection episodes by stimulating a T-cell-mediated response. Reinke reported that 85% of patients with late-acute renal allograft rejection with otherwise symptomless CMV infection responded to ganciclovir therapy, which emphasized the indirect role of CMV infection on graft function [23]. CMV infection does not activate classic complement pathway nor trigger the deposition of complement factor C4d along peritubular capillaries; in the case of positive C4d deposition, concurrent ABMR should be considered.
\nCytomegalovirus infection of the gastrointestinal tract is the most common manifestation of tissue-invasive CMV disease and is a significant cause of morbidity and mortality in the solid organ transplantation recipients. Patients usually present with esophagitis, colitis, and hepatitis; however, infection can occur anywhere in the gastrointestinal tract [17, 24, 25].
\nMucosal ulceration was the most common endoscopic finding present in 75% of cases (Figure 3). Other endoscopic features include mucosal edema, hyperemia, and nodularity. In a renal transplant patient, cytomegalovirus infection may rarely present as a localized disease, such as inflammatory polyps [26].
\nMucosal ulcerations in CMV colitis of kidney transplant recipient are common endoscopic findings.
Two histologic patterns of GIT tissue injury have been described. In the first form, viral inclusions are typically found in the glandular epithelium with little associated tissue reaction (Figure 4). In the second form, CMV inclusions are found in swollen endothelial and stromal cells, especially in areas of ulceration. Typically, mucosal erosion, ulceration, hemorrhage, necrosis, perforation, and/or fistula formation can be detected. CMV colitis is characterized by uneven inflammation in the lamina propria, with active changes and ulcers with abundant purulent exudate (Figures 3 and 5) [24].
\nCMV gastritis. Intranuclear inclusion (arrow) in foveolar gastric cell (A) and in endothelial cell (arrow) of a capillary in the lamina propria (both Thricrome stain, 600x). CMV positive Intranuclear inclusions by immunohistochemistry (C, CMV, 600x). Scarce mucosal ulcerations seen on gastroscopy (D).
CMV colitis in kidney transplant recipient. Focal active colitis with erosions (A, Trichrome stain, 100x). There was only one positive CMV cell by immunohistochemistry (CMV, 400x).
In contrast to other organs, CMV infection in the colon does not always produce the diagnostic large cells with viral inclusions with owl’s eye appearance. Rather, the infected cells can be smaller, up to twice as big as their normal counterparts, and have small basophilic inclusions, often with no characteristic clear halo. They have been called “atypical inclusions” [27].
\nDiagnosis is usually by histopathology with immunohistochemistry or viral culture of tissue specimens; molecular assays such as quantitative PCR also often have a role (Figures 4 and 5).
\nHowever, there is little consensus on the specificity of PCR [28, 29, 30]. Since CMV typically produces latent infection residing in leukocytes, concern has been raised that positive PCR might therefore not necessarily reflect active disease in the colon but only latent infection. The use of colon tissue alone was therefore not widely considered to provide definitive proof of CMV colitis [13]. Zidar et al. observed good correlation among the density of positive cells by immunohistochemistry, the morphology, and the number of viral copies by qPCR in IBD patients. Both immunohistochemistry and qPCR can therefore be successfully used for diagnosing CMV reactivation, at least in CMV reactivation in patients with IBD. The optimal sites for endoscopic biopsies to obtain specimens with the highest values of CMV are the base and the edge of ulcers [28, 31].
\nCMV can be prevented in two ways: by prophylaxis and by preemptive treatment. Both options are effective for preventing CMV disease [32, 33, 34].
\nCMV prophylaxis is widely used in the transplantation setting and has been associated with reductions in CMV disease, mortality, and graft rejection. Prophylaxis refers to the administration of antiviral drugs to all patients (universal prophylaxis) or to a subgroup of patients at higher risk of viral replication (specific prophylaxis) for a predetermined period of time. In KTRs, prophylaxis therapy aims to prevent CMV infection and, consequently, CMV-associated disease. According to current guidelines, universal prophylaxis is recommended in patients with high risk (i.e., those who have D+/R− CMV IgG or who have received T-cell depletion for induction prior to transplantation). Antiviral drug treatment should begin immediately after transplantation or after the use of antilymphocyte antibodies. Patients with low to intermediate risk can undergo preemptive treatment instead of prophylaxis [35].
\nUntil recently, the emphasis on prophylaxis with prophylactic agents focused on early disease occurring in high-risk patients, with the duration of prophylaxis typically no longer than 3 months. Although early-onset CMV infection was usually sufficiently controlled, the reported incidence of delayed-onset CMV infection following the completion of a 3-month course of preventive therapy was high, and, consequently, prophylactic therapy in most centers was extended to 6 months in the group of KTRs at most risk (D+/R−) [36, 37].
\nSeveral medications are available: acyclovir, valacyclovir, intravenous ganciclovir, oral ganciclovir, and valganciclovir. Ganciclovir takes precedence over acyclovir. In a clinical setting, the most commonly used medication for prophylaxis is oral valganciclovir with dose adjustment according to kidney function [38].
\nThe prophylaxis should be initiated immediately after transplantation. The decision on the duration of prophylaxis depends on the CMV serostatus of the donor (D) and recipient (R), of the organ transplant, and the degree of immune deficiency in the transplant recipient.
\nIn D+/R−, prophylaxis should last for 3–6 months. According to recent research, many transplant centers are opting for a 6-month prophylaxis, which has been associated with a significant decrease in the incidence of late CMV disease, compared to 3-month prophylaxis. Valganciclovir at a dosage of 900 mg orally once daily with the dose adjusted for renal function is used in most centers for a period of 6 months following transplantation.
\nIn D+/R+ or D−/R+, prophylaxis should last for 3 months. Extension to 6 months is suggested for KTRs who have received antilymphocyte antibody induction. Valganciclovir at 900 mg orally once daily for 3 months following transplantation, with the dose adjusted for renal function, is the standard prophylactic therapy in most centers.
\nThere is little risk of CMV infection in these patients. Precautions for transfusion of blood and blood products of CMV-positive donors are required [35].
\nTheoretically, a method of minimizing the risk of CMV infection would be to avoid transplantation of a seropositive organ into a seronegative recipient. Historically, before the advent of antiviral prophylaxis, many units avoided transplanting CMV-positive solid organs into CMV-negative recipients. However, given the shortage of donor organs, such an approach is difficult to practice in these settings.
\nOne area in which CMV matching remains relevant is in the elective use of blood products. Where it is known that both donor and recipient are seronegative for CMV, leukodepleted blood and blood products are available and should be used to minimize the risk of primary infection [39].
\nPassive immunoprophylaxis has been explored in solid organ transplantation in a number of randomized trials, whereby hyperimmune globulin provided significant overall protection from severe disease, with a reduced rate of CMV disease to approximately half of that seen in the placebo groups. Intravenous treatment is generally less convenient for the patient and health-care provider and carries the theoretical risk of transmitting blood-borne viruses [39].
\nWith quantitative monitoring of CMV DNA in plasma (viral load, viremia) once a week (sometimes twice a week), CMV viremia can be detected before the occurrence of symptomatic infection. However, the exact cutoff point of plasma CMV concentration to initiate preemptive treatment (from a few hundred to several thousand copies of CMV DNA in 1 ml of plasma) is not known. The decision to initiate preemptive treatment is therefore individual and depends mainly on the degree and duration of immunosuppression [40].
\nThe benefits of this type of strategy are that fewer patients are exposed to antivirals and for a shorter period of time (fewer side effects, fewer interactions with other medicines, lower costs).
\nIntravenous ganciclovir (5 mg/kg every 12 h or a dose adjusted to creatinine clearance) is used for preemptive treatment in a patient with a high viral load (>50,000 copies of CMV DNA in 1 ml of plasma), in severe renal impairment, and in pediatric patients; otherwise, valganciclovir (900 mg every 12 h, or a dose adjusted to creatinine clearance) is recommended. If there is no CMV disease, the CMV viremia is checked for the first time after 7–10 days of preemptive treatment, afterward being monitored every 7–10 days. It is recommended to continue with preemptive therapy until two negative results of quantitative plasma PCR CMV DNA tests performed in a space of 7 days [40].
\nThe activity and concentration of CMV-specific lymphocytes in the blood have a decisive role in controlling CMV infection, especially in situations of increased risk of CMV reactivation or primary infection, such as after therapeutic use of antilymphocyte antibodies. The count of CMV-specific T lymphocytes allows a decision on preemptive treatment in a period when the viral load is still not critically increased.
\nAmong the available methods, the most reliable predictor of viremia and disease is measurement of the blood concentration of T lymphocytes, which, after in vitro stimulation with CMV peptides, increasingly produce cytokines such as interferon gamma and interleukin 2. CMV-specific lymphocytes CD4 and CD8 are analyzed by the flow cytometry method (one of the most commonly used is a whole blood interferon gamma release assay QuantiFERON-CMV test marketed by an Australian company, Cellestis Inc., which measures the production of interferon gamma after stimulating the patient’s lymphocytes with CMV peptides) [41].
\nTreatment is always indicated in case of active CMV infection (CMV viral syndrome) or in the presence of tissue-invasive CMV disease [42].
\nIntravenous ganciclovir is a gold standard for the treatment of CMV disease. In mild to moderate cases of the disease, oral valganciclovir was found to be non-inferior to intravenous ganciclovir. However, due to limited evidence, severe disease should be treated with intravenous ganciclovir. Acyclovir and valacyclovir are not indicated for treatment. The use of foscarnet as a first-line therapy is limited by its toxicity (mainly nephrotoxicity) (Table 1).
\nDrugs used in therapy of CMV disease.
i.v., intravenous; p.o., peroral; eGF, estimated glomerular filtration.
Drug resistance should be suspected in patients with persistent viral replication and/or clinical progression after 2–3 weeks of treatment. Ganciclovir-resistant CMV infection has been observed in 1–2% of kidney transplant recipients and is a result of the widespread use of antiviral prophylaxis and preemptive therapy. Drug resistance typically develops in CMV D+/R− patients and is also associated with high viral load, prolonged antiviral therapy, high level of immunosuppression (i.e., use of antilymphocyte antibodies), and suboptimal serum drug concentrations. Genotypic tests reveal characteristic viral mutants (UL97) associated with resistance [43].
\nDrug-resistant or refractory CMV disease occasionally responds to an increased dose of ganciclovir. In cases of genotypic resistance of CMV to ganciclovir, it is necessary to introduce combined treatment with ganciclovir and foscarnet (half or standard doses) or treat with foscarnet only [44].
\nThe treatment should be continuous until viral eradication is achieved in two assays after a minimum of 2 weeks of induction treatment. Initial treatment with intravenous ganciclovir can be later replaced with oral valganciclovir. During the course of treatment, renal function must be promptly monitored. In most cases (especially in high viremia, a moderate to severe clinical course, ganciclovir resistance), it is necessary to reduce immunosuppressive therapy (especially antimetabolites, i.e., azathioprine or mycophenolate). The same applies in cases of recurrent CMV infection/disease [35].
\nIn the case of high-risk patients, some authors recommend secondary prophylaxis after completion of treatment, although no consensus has so far been achieved on this approach [35, 45].
\nPolyomaviruses are non-enveloped, double-stranded ubiquitous DNA viruses living in birds and mammals as natural hosts. The name indicates their ability to produce tumors (Greek poly- many, multiple; -oma, tumors), particularly in rodents and experimental models [46].
\nSeroprevalence in humans ranges from 20 to 90%, depending on the viral strain and patient age. It generally remains asymptomatic in the renourinary tract of healthy individuals, although may undergo periods of self-limiting transient asymptomatic activation with viruria and viremia, without causing disease [46]. However, in immunocompromised individuals, such as renal transplant recipients, it can be associated with various patterns of tissue injury, of which BK virus nephropathy is the most common.
\nAmong approximately 18 polyomavirus strains, BK virus, JC virus, and simian virus (SV-40) have been considered to be pathogenic in humans. Infections with SV-40 were detected following the administration of contaminated polio vaccines in the late 1950s, without known clinical manifestation in humans [46].
\nBK virus was isolated in 1971 from a patient with ureteral stenosis after kidney transplantation and was named after the initials of the infected patient. Similarly, JC virus was named after a patient with progressive multifocal leukoencephalopathy. Both strains are characterized by productive viral infection with tissue injury, showing specific tropism for the renourinary tract or central nervous system [46, 47].
\nRecent studies have indicated that BK virus may be involved in the tumorigenesis of bladder carcinoma in renal transplant recipients and salivary gland inflammation and sclerosis in HIV patients [48, 49]. Trichodysplasia spinulosa-associated polyomavirus and Merkel cell carcinoma polyomavirus, recently detected new strains, may be related to proliferative lesions and neoplasms without productive viral replication [50].
\nPVN is a major causative agent in nephropathy after renal transplantation, affecting 1–10% of patients [51].
\nIn the past, when immunosuppressive therapy was based mainly on cyclosporine, only sporadic PVN cases were reported. Although modern immunosuppressive drugs introduced after 1990 have enabled less rejection and improved allograft survival, they have been responsible for the occurrence of previously uncommon side effects, including PVN and hemorrhagic cystitis [47].
\nBefore screening protocols for PV reactivation in renal transplant recipients were routinely used, PVN was usually diagnosed late after transplantation, in an advanced histologic stage, with chronic renal changes leading to allograft loss within 1 year in 50–90% of cases [4, 50]. Potential misdiagnosis of concurrent rejection resulting in increased immunosuppression might contribute to accelerated allograft failure.
\nPVN is typically caused by the BK strain and only rarely by simultaneous activation of BK and JC viruses. The specific viral activation mechanisms remain unknown [47]. The transplant microenvironment may promote viral reactivation, because only sporadic detection of PV in native kidney of patients with other organ transplants or in immunodeficient patients has been reported [52, 53]. PVN also commonly occurs in patients with posttransplantation complications, including delayed graft function and acute rejection. Other risk factors are male gender, older recipient age, diabetes, prolonged ureteral stent placement, smoldering subclinical graft inflammation, and/or abnormalities of dendritic cell and NK cell/T-cell activation. Relative over-immunosuppression by modern immunosuppressive drugs, though, is considered the main risk factor [47, 51, 54].
\nPolyomavirus infection represents serological or virological evidence of virus exposure without distinguishing among replicating, latent, and transforming patterns. Manifest viral disease is, however, defined as histological evidence of polyomavirus-mediated organ pathology and is mainly limited to immunocompromised patients, such as transplant recipients [47, 55, 56].
\nRecognition of BKN is critical, since the proper therapy is reduction, rather than enhanced immunosuppression.
\nIn order to confirm intrarenal BKV replication, renal biopsy remains the gold standard for a definitive diagnosis of BKN [51]. A minimum of two cores including the medulla are recommended to make a correct diagnosis, since in the early stage, viral inclusions may be present only in the medulla [5, 51, 57]. However, characteristic viral inclusion and tubular injury might be focally observed in the biopsy specimens, so PVN can be missed due to sampling error (Figure 6).
\nDiagnosis of BK nephropathy: intranuclear viral inclusion bodies in tubular epithelial cells (A, HE, 200x), intracellular virions of 40–50 nm in diameter by electron microscopy (B, electron micrograph), intranuclear expression of SV-40 antigen in tubular epithelial cells (C) and/or epithelial cells of Bowman’s capsule (D, both SV-40, 400x).
BKN is morphologically characterized by intrarenal viral replication, mainly in tubular epithelial cell nuclei (intranuclear inclusions), causing tubular injury, shedding of tubular epithelial cells, and cell lysis (Figures 7 and 8). On immunofluorescence, focal immune complex-type granular deposition of IG along the tubular basement membrane is sometimes found, indicating BK infection (Figure 9), although the biologic and clinical significance of this finding needs further evaluation [5].
\nBK virus nephropathy. Virally induced tubular epithelial cell injury and lysis in cortex (A, HE, 200x) and medulla (B, HE, 100x). Intranuclear viral inclusion bodies are observed (arrow).
Virally induced tubular epithelial cells with intranuclear inclusions, shedding of infected cells, tubular injury, and lysis (A,HE, 400x and B, HE, 200x).
On immunofluorescence, focal immune complex-type granular deposition of IgG along the tubular basement membrane is sometimes found.
Viral replication in tubular epithelial cells can induce various nuclear changes: an amorphous ground-glass inclusion body (type 1), a central irregular inclusion body surrounded by a halo (type 2), finely granular nuclear alterations (type 3), and vesicular changes with coarsely clumped viral inclusions (type 4) (Figure 10). In rare cases, the ascending PV infection can affect the parietal epithelial cells of Bowmanʼs capsule, mainly detected by immunohistochemistry (Figure 6).
\nVarious nuclear changes induced by viral replication: type 1, an amorphous ground-glass inclusion body (A); type 2, a central irregular inclusion body surrounded by nuclear halo (B); type 3, finely granular nuclear alteration (C); type 4, vesicular nuclear changes with coarsely clumped viral inclusions (D, all HE, 600x).
Diagnostic confirmation can easily be achieved by immunohistochemistry (Figure 6) or immunofluorescence, with antibodies directed against the polyomavirus T antigen, VP capsid proteins, or detection of intracellular virions of 40–50 nm in diameter by electron microscopy (Figure 11) [5, 57].
\nIntranuclear viral inclusions in a tubular epithelial cell (A). Intranuclear virions measuring 40–50 nm in diameter (B, electron micrographs).
In early stages of PVN with focal and minimal tubular changes without tubular injury and characteristic intranuclear inclusions, a diagnosis can only be established by immunohistochemistry with antibody directed against SV-40-T antigen (Figure 12). Later in the course of the disease, many cases of PVN may show numerous infected cells and an inflammatory lymphocytic infiltrate with tubulitis mimicking acute T-cell-mediated rejection (Figure 13). Advanced disease, detected late after transplantation, often shows marked interstitial fibrosis/tubular atrophy, while interstitial inflammation and viral replication may be variable (Figure 14).
\nBKN grade 1. Early phase with only focal tubular injury.(A, HE, 100x) and few SV-40 positive cells on immunohistochemistry (B, SV-40, 100x).
BKN grade 2. Florid phase with severe interstitial inflammation and tubulitis in BK nephropathy, indistinguishable from acute rejection. There was no endarteritis (A, PAS, 200x). Numerous BK-positive cells on immunohistochemistry were detected. (SV-40, 200×).
BKN grade 3. Moderate interstitial fibrosis/tubular atrophy and interstitial inflammation composed of CD3 positive lymphocytes in areas of fibrosis (A, CD3 and PAS, 100x). Many tubules show viral replication (B, SV-40 antigen, 200x).
PVN must be differentiated from other rare viral infections, including CMV, herpes simplex virus, and adenovirus. CMV disease in transplant recipients is more frequent than BKN and usually affects the intestine, liver, or lungs but only rarely manifests as CMV reactivation in renal graft. Since the histological features of BKN may overlap with other viral infections, specific immunohistochemical staining is a sensitive tool for differentiating among BK, CMV, adenovirus, or herpes simplex viral infection. The main histological features of common transplant kidney viral infection are shown in Table 2.
\n\n | Polyomavirus | \nCytomegalovirus | \n
---|---|---|
Viral inclusions | \nType 1: an amorphous ground-glass inclusion body Type 2: a central irregular inclusion body surrounded by nuclear halo Type 3: finely granular nuclear alteration Type 4: finely granular nuclear alteration | \nSmudgy/ground-glass nuclear inclusions surrounded by typical halo-owl eye | \n
Viral replication tubules | \nYes | \nYes | \n
Endothelial cells | \nNo | \nYes | \n
Inflammatory cells | \nNo | \nYes | \n
Acute tubular injury | \nRarely | \nRarely | \n
Interstitial inflammation | \nFocal to diffuse | \nFocal | \n
Tubulitis | \nMild to severe | \nMild | \n
Histologic features of CMV and polyoma BK viral lesions in transplanted kidney.
However, the most important differential diagnosis, particularly in PVN after reduction of immunosuppression, remains T-cell-mediated acute rejection [6]. Careful correlations with clinical data, such as the presence of donor-specific antibodies, recent immunosuppression reduction, DNA viral load in the serum, and presence of decoy cells in the urine, provide additional information in order to make a correct diagnosis. Glomeruli and vessels must be carefully examined in order to exclude glomerulitis and vasculitis, which would strongly suggest concomitant rejection. C4d positivity and diffuse peritubular capillaritis outside the area of extensive interstitial inflammation, together with positive donor-specific antibodies (DSA), are consistent with concomitant antibody-mediated rejection.
\nA diagnosis of PVN and concomitant T-cell-mediated rejection after immunosuppression reduction is challenging and needs careful correlation of biopsy findings with the dynamics of BK viremia. Focal interstitial inflammation in the context of stable graft function and recently cleared BK viremia should be interpreted as residual BKN, but the same histology findings detected beyond 3 months after BK clearance, accompanied by a rise in serum creatinine, might rather point toward acute rejection.
\nThe natural course of BKN remains to be elucidated. Some authors have reported that biopsies obtained after reduction of immunosuppression during decrease of the plasma viral load may show severe interstitial infiltrate and tubulitis reminiscent of T-cell-mediated acute rejection, but the outcome of renal grafts was good despite prolonged reduction of immunosuppression without corticosteroid administration [4, 6, 58, 59]. Such patients typically presented with a transient increase in serum creatinine, accompanied by a decrease in plasma viral load, which finally disappeared [59]. Moreover, serum creatinine returned to the baseline level after a few months. In subsequent biopsies, the virus was cleared from renal tissue, and inflammation resolved without the presence of marked interstitial fibrosis. These authors have suggested that such tubulointerstitial nephritis might be immune reconstitution-associated graft inflammation, enabling the resolution of PVN.
\nThe challenging concepts of immune reconstitution injury and extensive inflammation in resolving BKN after reducing immunosuppression need further investigation [6].
\nVarious studies have indicated that different extents of BKN in the transplant may predict the clinical presentation and outcome of the disease [58, 60, 61].
\nIn order to provide optimal diagnostic and prognostic information of BKN, the Banff working group on BKN proposed three clinically significant disease grades based on the severity of polyomavirus replication and the degree of interstitial fibrosis [47, 62, 63]. BK virus replication was defined as the histologic viral load, estimated by the % of virally infected epithelial cells detected by immunohistochemistry. It ranged from scattered SV-40-positive cells in BKN grade 1 to numerous in grades 2 and 3 (Figures 12
Disease grade may reflect the time of the diagnosis: BKN grade 1 was generally diagnosed in the first 5 months after transplantation, usually presenting with normal renal function and associated with a favorable outcome in 85–90% of cases. In contrast, grade 2 BKN was detected 6–12 months posttransplantation, characterized by elevated serum creatinine or acute graft injury leading to graft failure in 25% of cases. Finally, BKN grade 3 was usually detected more than 12 months after transplantation, also associated with worsening of kidney function and graft failure in 50% of cases (Table 3).
\nPVN disease grade | \nViral load | \nInterstitial fibrosis | \nRenal function | \nTime of diagnosis after TX (months) | \nFavorable outcome (%) | \n
---|---|---|---|---|---|
Grade 1 | \nScattered SV-40-positive cells | \nNo | \nNormal | \n4–5 | \n85–90 | \n
Grade 2 | \nNumerous | \nLess than 25% | \nIncreased serum creatinine, renal failure | \n6–12 | \n75 | \n
Grade 3 | \nNumerous | \nMore than 25% | \nIncreased serum creatinine, acute renal failure | \n12 | \n50 | \n
Characteristics of different BKN grades regarding viral load, chronic tissue injury-interstitial fibrosis, renal function, time of diagnosis after transplantation, and outcome.
Since BKN has limited treatment options, the early detection of PVN has a major impact on the prognosis of the disease and therefore on allograft survival. Early diagnosis of PVN is difficult, because early BKN stage does not show any signs of systemic infection, proteinuria, or hematuria. Renal function may remain normal transiently, particularly when only the medulla is involved [5].
\nTo date, reduction of baseline immunosuppression remains the only potentially effective therapeutic strategy of BKN, but it is associated with an increased risk of rejection. It is considered that preemptive reduction of immunosuppression prior to the development of overt nephropathy might be beneficial [6, 51, 59]. Since unrecognized BKN diagnosed late after transplantation causes chronic tissue injury and graft failure, the goal of screening protocols and classification schemes of BKN is to characterize early disease grades that respond to therapeutic intervention and may heal without progressing to chronic graft injury.
\nThe first step of viral reactivation shown in almost all patients is characterized by the detection of characteristic polyomavirus inclusion-bearing cells in the urine—decoy cells (Figure 15). Initial viruria may be followed by detection of BK virus in plasma and onset of BKN after a 6–12-week window in some patients but only in a minority (Figure 16) [51].
\nDecoy cells in urine screening test.
Type and prevalence of BK virus (BKV) infections in kidney transplant recipients.
Current guidelines recommend a urinary cytology test in order to detect urinary decoy cells initially and then a plasma test by PCR if urinary decoy cells are consistently present [51]. While PVN is most commonly diagnosed in the first year after transplantation, urine screening at least every 3 months during the first 2 years and after antirejection treatment seems appropriate to cover the majority of PVN cases [51]. The cytology urine test is characterized by a high negative predictive value to rule out a diagnosis of BKN and reduce costs. In addition, a window between viral reactivation and BKN enables urine samples to be screened in time.
\nHowever, several studies have shown that only a variable number of patients with urinary shedding of virus progressed to BKN. Notably, BK viruria and even viremia may represent transient asymptomatic BK activation or may originate from extrarenal sites, usually along the lower urinary tract. In patients without biopsy-proven BKN, preemptive long-lasting reduction of immunosuppression could be potentially harmful due to increased risk of acute rejection [64].
\nA plasma test by PCR detecting BK copies is currently the accepted biomarker for clinical application, although the exact range of viral load that would predict BKN cannot be defined. The majority of patients with more than 10,000 copies per ml DNA in 1 ml of plasma show BKN on renal biopsy, but some patients with hardly detectable BK virus copy numbers may have manifest BKN. Several studies have indicated that PCR-based BK viremia correlates only moderately well with the presence of BKN and severity of the intrarenal disease, ranging between 25 and 75% (Figure 15) [6, 57].
\nSeveral biomarkers had been proposed in order to enable noninvasive diagnosis of definitive BKN without the risk of renal biopsy; these include heat shock protein 90alfa, CXCL9, neutrophil gelatinase-associated lipocalin, urinary exosomal biomarkers, urinary VP1, and urinary Haufen [65, 66, 67].
\nPolyomavirus-Haufen are tight cast-like three-dimensional viral aggregates, detected by negative staining electron microscopy of a voided urine sample. Since polyomavirus-Haufen admixed with uromodulin is formed in the tubular lumens, they might specifically predict intrarenal disease, comparable to renal biopsy [68]. Recent studies have indicated that the titer of polyomavirus-Haufen tightly correlates with the degree of intrarenal polyomavirus replication, providing additional information on the severity of PVN [64]. The urinary polyomavirus-Haufen test may emerge as a sensitive and specific biomarker for intrarenal viral disease, with positive and negative predictive value higher than 90%. The limitations of this investigation include the relatively high cost, time-consuming procedure, and limited availability of electron microscopy in transplant centers.
\nBK virus VP1 mRNA and urinary exosomal miRNA biomarkers have been described as potential surrogate markers for the diagnosis of PVN, with high sensitivity and specificity for BKN [66, 67]. Detection of additional urine biomarkers not only offers additional strategies for noninvasive PVN diagnosis but might also predict graft outcome.
\nManagement of PVN is still very limited. Reduction of the baseline immunosuppression, as the common therapeutic strategy, may be risky due to the possibility of acute rejection and may not be successful in all patients. Namely, some patients with BK viremia subsequently develop definitive BKN despite preemptive reduction of immunosuppression [4]. On the other hand, prolonged reduction of immunosuppression may be associated with clinical acute rejection rates of 8–14% [5, 69]. Renal biopsy, although considered to be an invasive procedure, may provide additional information in order to diagnose concomitant vascular rejection.
\nData concerning the frequency of concurrent PVN and rejection vary. Some authors consider inflammation to be part of immune reconstitution injury, with a very low risk of concomitant rejection, whereas others have diagnosed concurrent acute rejection in 10–15% of cases at the time of initial PVN diagnosis [6, 47, 63]. Additional corticosteroid treatment in patients with PVN and severe tubulointerstitial inflammation at the time of PVN diagnosis also remains controversial. Some authors believe that corticosteroid treatment interferes with efficient BK clearance from the graft although, on the other hand, it might decrease interstitial inflammation and subsequent interstitial fibrosis [59].
\nBiopsy-proven diagnosis of concurrent BKN and rejection reveals the therapeutic dilemma concerning treatment strategy. In some individual cases, concomitant biopsy-proven T-cell-mediated rejection and PVN on low immunosuppression have been efficiently treated with transient pulse immunosuppressive therapy [70]. On surveillance kidney biopsy, BK was cleared from the tissue, interstitial inflammation disappeared, and serum creatinine returned to the baseline level.
\nMany of the therapeutic agents, including leflunomide, quinolone, and cidofovir, have been involved in BKN treatment with undetermined antipolyomavirus effect. It was recently shown that intravenous immunoglobulins’ (IV IGs) administration may be effective in the treatment of BK viremia and PVN in patients who have failed to respond to immunosuppression reduction and leflunomide therapy [71].
\nSuccessful resolution of BKN and BK clearance may be associated with the recipient’s antiviral cell-mediated immune response. Recently, novel laboratory-based methods based on BK-directed cellular immunity and anti-BK T-cell phenotype have been introduced, such as ELISPOT assays, which might provide additional information in relation to the resolution of PVN [72, 73, 74].
\nKTRs receiving immunosuppressive regimes to prevent transplant rejection are at increased risk of opportunistic infections such as CMV and polyoma BK virus. In both viruses, reactivation of latent infection is the principal mechanism rather than de novo infection.
\nWhile reactivation of CMV infection is usually present with systemic infection, including fever, leukopenia, organ dysfunction, and viremia without invading renal graft, the most harmful presentation of BK infection reactivation includes BKN directly affecting the transplanted kidney.
\nBoth CMV and BK infections commonly appear in the first year after transplantation, so screening protocols are very important in order to detect patients with increased risk of virus reactivation and early disease, and this should be started immediately after transplantation.
\nWith systematically quantitative monitoring of CMV DNA in plasma, CMV viremia can be detected before the occurrence of symptomatic infection. Ganciclovir and valganciclovir are generally used to prevent or treat CMV.
\nFor BKN screening, current guidelines recommend a urinary cytology test initially and then plasma DNA test by PCR if urinary decoy cells are consistently found.
\nThe reduction of baseline immunosuppression is considered to be the common therapeutic strategy of BKN but is associated with increased risk of rejection. Since polyomavirus viruria and viremia can be observed without renal injury and BKN, a definite diagnosis of PVN must be confirmed by renal biopsy. In order to prevent BKN in viremic patients, preemptive reduction of immunosuppression prior to the development of overt nephropathy might be beneficial.
\nCareful detection and management of opportunistic infection enable better graft survival and quality of life in KTRs.
\nThe authors would like to acknowledge Jerica Pleško, Karmen Wechtersbach, Živa Pipan Tkalec, Špela Borštnar, MD, and Matic Bošnjak, MD for their valuable help with providing figure material for this chapter. Professor Danica Galešić Ljubanović, MD PhD and Petar Šenjug, MD provided figures of CMV nephritis.
\nAuthors declare no conflict of interest.
Undoubtedly, plastics play a major role in our everyday life, since plastic parts are used in numerous applications, such as packaging (for instance, food containers), automotive industry, electric and electronic equipment (EEE), etc., due to their unique properties [1]. Some of their most important characteristics that necessitate their use in these applications are lightness, ease of processing, resistance to corrosion, transparency, and others. Nevertheless, their wide use in various applications in combination with the short life span of many plastic products leads to large amounts of end-of-life plastics. Taking all these into account, along with plastic nonbiodegradability, research has focused on exploring environmentally friendly approaches for their safe disposal [2]. Plastic handling involves collection, treatment, and afterward recycling. Unfortunately, finding environmentally friendly approaches for their disposal is no mean feat (Figure 1); due to the variation in types of plastics, which are often of unknown composition, the existence of polymer blends, or composites, multilayer structures with other materials apart from polymers, as well as the wide range of additives (such as UV and thermal stabilizers, antistatic agents, (brominated) flame retardants, colorants, plasticizers, etc.) they may contain [3, 4].
Difficulties encountered during end-of-life plastic handling.
The disposal of post-consumer plastics occurs via landfilling, primary recycling, energy recovery, mechanical recycling, and chemical recycling [2]. Although landfilling is an undesirable, non-recycling method, since it results in serious environmental problems, such as soil and groundwater contamination, until now large amounts of end-of-life plastics still end up in landfilling [5, 6]. With a view to eliminating plastic landfilling, research has focused on recycling methods (Figure 2) that can be applied, which are primary recycling, recycling without quality losses, energy recovery-quaternary, mechanical or secondary recycling-downcycling into lower qualities and chemical or tertiary recycling-recovery of chemical constituents [7]:
In primary recycling (re-extrusion), the plastic scrap is reinserted in the heating cycle of the processing line in order to increase the production [8]. It remains a very popular method, because of its simplicity and low cost. However, it can be applied only in case of clean, uncontaminated single-type waste [2].
Mechanical recycling involves reprocessing and modification of plastic waste using mechanical-physical means with the aim of forming similar, plastic products, at nearly the same or lower performance level when compared with the original products [6]. Since mechanical recycling can be used only in case of homogeneous plastics, heterogeneous plastics require sorting and separation before their recycling. In mechanical recycling, the presence of brominated flame retardant (BFR) incorporated in plastics must be identified before its application, in order to avoid the possible formation of toxic substances, such as polybrominated dibenzo-p-dioxins/furans (PBDD/Fs) [9, 10]. Its main drawback is the fact that product’s properties are deteriorated during every cycle [2]; and it should be underlined that each polymer can endure only a limited number of reprocessing cycles [11]. An additional challenge is the existence of mixed plastic waste (polymer blends), since different polymer types have different melting points and processing temperatures. In such cases, the processing temperature is usually set to the highest melting component. Nevertheless, this may result in overheating and possible degradation of the lower melting components and so, in reduced final properties [12].
In chemical or feedstock recycling, plastic wastes are converted into lower-molecular-weight products, such as: fuels, monomers, or secondary valuable products that can be used as feedstock for refineries. Conversion takes place through chemical reactions in the presence of solvents and reagents [10]. It is an environmentally friendly method, since, as mentioned previously, it results in the formation of valuable products or monomers [9].
During energy recovery, plastics are incinerated in a boiler or in other industrial equipment, taking advantage of their high energy value; for energy production in the form of heat and electricity. Nevertheless, if incomplete incineration takes place, then toxic substances, such as dioxins, furans, and others, may be formed and released into the atmosphere, resulting in environmental issues [2, 8, 9, 10].
Recycling methods for post-consumer plastics.
In conclusion, during chemical recycling, plastics are converted into smaller molecules (mainly liquids and gases), which can be used for the production of new, valuable products; and that is why it is considered as an environmentally friendly and economically feasible technique. Furthermore, chemical recycling seems to be more advantageous than the other existing methods; taking into account, for instance, the fact that during chemical recycling, both heterogeneous and contaminated polymers can be treated, only with a limited pretreatment. Moreover, the energy consumption of the process is very low, if compared with that of mechanical recycling or energy recovery [6].
Chemical recycling comprises two processes: solvolysis and thermolysis. During solvolysis, polymers are dissolved in a solvent and treated with or without catalysts and initiators.
Chemical recycling routes.
Generally, it should be underlined that pyrolysis can be considered as one of the best options for plastics recycling, since its advantages are aplenty. Specifically, pyrolysis enables material and energy recovery from polymer waste, as a very small amount of the energy content of waste is consumed for its conversion into valuable hydrocarbons. Furthermore, pyrolysis products are valuable, since they can be used as fuels or chemical feedstock. Last but not least, in case that flame retardants are present in plastic waste, via pyrolysis the formation of toxic substances may be restricted, due to the fact that it takes place in the absence of oxygen [17]. Of course, catalyst’s presence, as mentioned previously, plays a vital role. Apart from catalysts, various other parameters, including temperature, heating rate, residence time, operating pressure, etc., can strongly affect the quality and distribution of pyrolysis products [6].
As mentioned previously, many obstacles can be found during the end-of-life plastic recycling. In this unit there are presented in detail three case studies, including: polymeric blends (difficulties due to the coexistence of mixed plastic wastes), plastics originating in multilayer packaging (challenging because of the coexistence of different materials, such as plastics, paper, and metals), and brominated flame-retarded plastics from WEEE (possible formation of undesirable, toxic substances due to the BFR’s presence), along with suggestions on how to overcome these difficulties.
Polymer blends are mixtures of two or more polymers in concentration greater than 2%wt. The blends can be miscible or immiscible, a parameter that depends on the thermodynamics of the system and molecular structure, weight, and polymer concentration. More information on the complicated thermodynamics that govern polymer blend miscibility can be found in the Polymer Blends Handbook [18, 19]. Miscible polymer blends are also known as homogeneous blends and are monophasic while immiscible blends with morphologies that differ such as, spheres, cylinders, fibers, or sheets (Figure 4) [12].
(a) and (b) are a visual representation of the differences between miscible and immiscible Polymer Blends. Images (c), (d), and (e) show the spherical, fibrous, and cylindrical morphologies of immiscible Polymer Blends, respectively. Image inspired by Ragaert et al. [
Subject to polymer compatibility, polymer blends can exhibit synergistic, antagonistic, or additive behavior. A common method used to assuage the immiscibility of polymers blends is the inclusion of compatibilizers—a polymeric surface tension reduction agent that promotes interfacial adherence—in the blend. The three most common types of compatibilizers are reactive functionalized polymers, nonreactive polymers containing polar groups, and block or graft polymers [12, 19, 20].
The difficulty during polymer blend recycling lies in the different properties presented by its component parts such as melting points and processing temperatures between polymers [12]. Most recycling efforts are concentrated on the procedure of pyrolysis to extract energy through the oils, wax, char, and gasses produced. Furthermore, research in recent years has focused on the use of various, different catalysts in order to lower the energy consumption of the whole process and increase the exploitable yield. Along with those some novel methods of polymer blend recycling will be explored.
Polymer composites are made up of two or more elements resulting in a multiphase, multicomponent system that exhibits superior properties compared with the constituent materials due to a synergistic effect. It comprises two parts:
A polymeric matrix that can be either thermoplastic polymers such as polypropylene (PP), polycarbonate (PC), acrylonitrile-butadiene-styrene (ABS) and poly(ethylene terephthalate) (PET) or thermoset polymers such as epoxy, vinyl ester, and polyester.
A reinforcing filler such as glass, carbon, and aramid [21].
One way that polymer blend can be recycled is by acting as the matrix for secondary elements creating composite materials. In this way it is possible to unite the two components in a form that reinforces the secondary materials and reuses the polymer blends. This method can be adapted to use natural fillers or fibers as the reinforcing fillers. Those can be added along with a coupling agent to optimize the interaction of the fillers with the matrix further and have the positive side effect of making the whole process environmentally friendly. It is important, however, that these fillers have the capacity to be chemically treated.
In a research conducted by Choudory et al., [22], Low-density polyethylene (LDPE)/Linear low-density polyethylene (LLDPE) blend extracted from milk pouches was used as a matrix for coir fibers. The result was composites with properties only slightly lacking from the virgin material ones. In case a maleated styrene pretreatment was applied, the mechanical properties and thermooxidative stability were drastically increased [23].
In another research conducted by Lou et al., [24], PET/PP blend and bamboo charcoal were used to create extruded or injection-molded composite materials. A great increase in mechanical properties was observed in the injection-molded composites, which maintained their mechanical properties even after three rounds of processing. The percentage of total mass of PET in the blend plays a particularly significant role in the product’s final behavior [23].
Pyrolysis is a promising choice as regards the recycling of polymer blends. With pyrolysis, high levels of conversion of the polymer blend into oil and gas with high calorific values can be attained. These can be used afterward to either fuel the process, or they can be utilized elsewhere [25]. This can be an invaluable asset to the petrochemical industry and a green way for the recycling of plastic waste [26].
Another advantage of pyrolysis is that a sorting process is not needed in contrast to other recycling methods that are extremely susceptible to contamination. This can of course save money and time when recycling polymer blends. Lastly, with the use of the pyrolysis procedure, waste management becomes easier as it is a cheap and environmentally friendly method. In the meanwhile, it allows for minimization of landfill capacity—a serious contemporary difficulty [5]. As the combination of polymers that make up polymer blends is wide, with every blend presenting different properties and pyrolysis behavior, it would be impractical to analyze each one of them. Instead, this chapter will focus on the pyrolysis route taken for the most common polymer blends by examining the research conducted by scientists in the field.
In general, the pyrolysis process can be either thermal or catalytic. In practice, however, the latter is widely preferred by the industry as it demands lower operating temperatures—and thus cost is minimized—that produce a more satisfactory yield of pyrolytic oils, if the correct catalyst has been elected [5].
In a study conducted by Vasile et al., [26], a blend with a composition similar to that originating in municipal waste—24%wt high-density polyethylene (HDPE), 39%wt LDPE, 21.5%wt isotactic polypropylene (IPP), 10%wt PS, 4%wt ABS, and 1.5%wt PET—was investigated. The blend underwent the process of catalytic pyrolysis two separate times each with a different catalyst—HZSM-5 in the first batch and PZSM-5 zeolite catalyst in the second batch, in order to find which catalyst led to better results. It was concluded that the PZSM zeolitic catalyst was characterized by higher selectivity and stability. The optimal temperature for the pyrolysis was found to be 450–480°C, and the gas produced increased sixfold in comparison to the non-catalytic process. Furthermore, the liquid products were found to contain high concentrations of aromatic hydrocarbons. As such, both the liquid and the gas phase can be utilized by the petrochemical industry. Lastly, the pyrolysis oil could be useful as petrochemical feedstock [26].
A novel research conducted by Bober et al. [27] proposed a way to produce hydrogen gas from the catalytic pyrolysis of different consistency HDPE/ poly(methyl methacrylate) PMMA polymer blends. After trial and error, the optimal temperature for maximum hydrogen production was found to be 815°C, a temperature where the catalyst used, Ni/Co, operated the best for hydrogen production. It was also found that, the higher the HDPE content in the blend, the bigger the hydrogen output. In contrast, when PMMA was the dominant polymer in the blend, CO was produced at a greater rate than the previous procedure. The research team proposed that the best ratio for HDPE/PMMA in the blend is 4:1 [27].
It must also be noted that concerning the production of hydrogen from pyrolysis of polymer blends, a popular option is the co-pyrolysis of the polymer blends with biomass [28].
A largely untapped potential of Polymer Blends is their recycling as feedstock for the chemical industry. A study presented by Plastics Europe [29], displays that only 2–3% of the collected plastic waste in Europe is utilized as feedstock (Figure 5).
The fate of the European collected plastic waste. Image inspired by Donaj et al. [
A possible procedure for the creation of feedstock from pyrolysis of Polymer Blends on the group of polyolefins was suggested by Donaj et al., [30]. For the purposes of the process, the researchers used a blend of polyolefins—46% LDPE, 30% HDPE, 24% PP- taken from MSW/plastic waste. The collected material was firstly reduced in size to about 3 mm pieces and then pyrolysis ensued under temperatures of 600–700°C in a fluidized bed reactor and with the use of steam and a catalyst if that was deemed feasible as the latter materials increase the yield of olefines. To optimize the procedure, Ziegler-Natta catalyst was used.
The research noted that after the procedure’s conclusion, plastic pyrolysis had directly yielded 15–30% gaseous olefins that can then be channeled directly into a polymerization plant. The residue produced consists of a naphtha-like consistency. To be used, this residue must undergo reformation via petrochemical technologies to be upgraded into olefins. Also, as in the previous cases of pyrolysis, the products of the process can be used to fuel the procedure itself. However, work still needs to be done on this field as the process described is not as cost-effective as desired [30].
A last noteworthy method for the utilization of immiscible Polymer Blends is their direct melting processing into fibers with good mechanical properties proposed by Shi et al. [31]. The blend used in this research was PS/PP while fibers were chosen due to two distinct reasons: (a) The fiber spinning technique is known to endow improved properties to polymer blends. (b) Fibers from polymer blends may display new properties in comparison to pure polymers. This method is widely cost-effective for preparing strong fibers for the industry, and it is expected to see great development in the coming years [31].
In this age of climate change and overall pollution, it has been the priority of policymakers to ensure the viable and sustainable future of human development. An example of this is the EU with the European Plastic Strategy dictating that all packaging used should be reusable or recyclable by 2030 [32].
A prime example of the challenges the industry faces to reach this standard is Tetra Pak, a multilayer packaging used mostly in the food, medicine, chemical, and commodities industry. Tetra Pak most usually consists of three elements: paper cardboard, aluminum, and LDPE.
As stated by the Tetra Pak company, its composition is as follows: (a) 71% paperboard, (b) 24% plastics, and (c) 5% aluminum foil (Figures 6 and 7).
Raw materials used to produce Tetra Pak. Image inspired by the Tetra Pak site information.
The layers of Tetra Pak. Image inspired by Georgiopoulou et al. [
These three make up the six layers that combined make Tetra Pak. Each layer has a particular use elaborated on below:
However, this is not an absolute rule. For example, certain products with a short shelf life have no need for the protection given by the aluminum layer. On the other hand, when the aforementioned shelf life needs to be extended, the LDPE layers can be substituted by PP providing a chance for further heat treatment of the product. HDPE, PET, and PA are also possible options for replacing the LDPE layers. Lastly, polyurethanes and EMAA are often utilized as adhesives between layers [34] while the Tetra Pak carton may also contain various chemical additives such as plasticizers, stabilizers, lubricants, fillers, foaming agents, colorants, flame retardants, and antistatic agents [35].
As Tetra Pak cartons are composed of mainly paper, the removal and recycling of the carboard layer are of much significance. As such there are two main processing routes: recycling without hydropulping and recycling with hydropulping. The initial procedure processes the cartons as a whole, while the latter uses the technique of hydropulping to first separate the cellulosic fibers from the Al-LDPE laminate.
The main aim of those following this route is energy recovery or downcycling. Energy recovery is attained in combination with solid municipal waste through means of pyrolysis, gasification, or incineration. However, this method comes with many downsides. Paper—the main ingredient of Tetra Pak cartons—has a low heat combustion (16 MJ/Kg), high moisture content, and a significantly high ash value. This makes the entire process inefficient, and thus it is in general not widely used [34].
Before proceeding with the options in this category, it would be useful to briefly go over the hydropulping process. When the soon-to-be recycled material first arrives into the recycle unit, the hydropulper breaks apart the paper with rotating blades that use high pressure water and a slurry of fibers is produced. Further processing ensues in centrifugal cleaners that remove heavy materials such as sand, adhesives, staples, etc. [36]. The end result of this procedure is a pulp of cellulosic fibers and can be used as a substitute for wood pulp, in the production of brown paper and pulp board [37]. What remains after the process is the external LDPE layer and the Al-LDPE laminates. However, residual cellulosic fibers can account for up to 5% of the finished products (Figure 8).
The main recycling routes.
The appeal of this method lies in its simplicity and cost-effectiveness. The pyrolysis procedure has two steps: (a) the degradation of paper (200–400°C) and (b) the devolatilization of LDPE (420–515°C) [38, 39, 40]. It should be noted that the temperature plays an important role in the composition of the final products. For example, the production of char is minimized with higher temperatures, and the opposite is true for wax.
The solid products that follow the process are aluminum, char caused by paper degradation, wax from LDPE degradation and tar. A great deal of gaseous products are also formed that mainly consist of CO2, CO, H2, CH4, C2–6 hydrocarbons, and volatile matter. Lastly, there is an aqueous phase consisting of water and phenols.
Many uses have been proposed for those pyrolytic products. The produced gases could be used to sustain the pyrolysis procedure itself or used elsewhere entirely, the char and tar can be exploited as a solid and oil fuel, respectively, while char can also act as a primal resource for the production of carbon-based materials. Lastly, the wax and aqueous phase can readily be utilized as a raw material for the chemical industry [39, 40].
A novel approach has been taken by researchers in Mexico and Spain who have used the char and the aluminum from the pyrolysis to have them act as absorbents of mercury in aqueous solutions. By means of trial and error and using thermodynamical analyses, they did conclude that char obtained from pyrolysis at 600°C at a 3 h procedure demonstrated the most promising mercury adsorption capacity at 21.0 mg/g. The field of char absorbents is still expanding with hopes of Tetra Pak pyrolysis chars acting as major absorbents for industry in the future [41].
The basic principle of this approach is the immersion of the Al-PE laminate in a carefully selected solvent and under specific temperature conditions with the aim of the dissolution of the LDPE in the solvent. What follows is the removal by means of filtration of additives and impurities. Lastly an antisolvent is added, and as a result precipitation of the dissolved polymer follows. To maximize LDPE and pure aluminum recovery, the SDP process is repeated three times.
The LDPE produced is of quality that matches that of the virgin product while the aluminum collected is also of high purity. Along with the hydropulping process, this is a very promising option for Tetra Pak recycling. However, the procedure is not without drawbacks: firstly, because of the cost-effective energy consumption needed to separate the solvent-antisolvent mixture and secondly, due to its high environmental impact. The economic viability of this technique rests upon whether the solvent-antisolvent mixture can be separated cheaply (Figure 9) [33].
The SDP process. Image inspired by Georgiopoulou et al. [
This technique has been developed by researchers in China and focuses on the separation of LDPE and aluminum by means of a separation reagent, mostly aqueous solutions of organic acids or even mixtures of acids. The procedure works by breaking the mechanical bonds holding the laminate together and as such allows for recovery of the products.
The yield of the process is highly dependent on the conditions of the reaction. In the process some of the aluminum is dissolved by the acid—which is also consumed—and thus losses are to be expected. However, this depends on many factors such as acid used, temperature, etc. Product purity is also correlated with those factors.
After trial and error, it has been found that methanoic acid is the best separation reagent for Tetra Pak. Lastly, there seems to be a high correlation between the separation rate, the temperature the reaction is taking place at, and the concentration of the reagent. More specifically, reaction time decreases with the rise of reagent concentration and temperature (Figure 10) [37].
The acid-based delamination process. Image inspired by Zhang Ji-fei et al. [
Thanks to the high heating value of the Al-LDPE laminate (40 MJ/Kg), it can be used as a sufficient fuel source. This has taken precedent especially in Europe. Although the laminate can be used directly after the hydropulping process, it is most usually used in conjunction with other fuel sources. This recycling route can be considered environmentally friendly as the LDPE of Tetra Pak burns cleanly without producing fumes containing elements such as sulfur, nitrogen, or halogens.
Also, the Al2O3 produced during pyrolysis, by the reaction between Al and moisture in high heat conditions, is in big part exploited by the cement industry, which uses it as a desired component of cement production [36]. Lastly there is the choice of forming finished products directly by using the laminates in roof tile production, injection and rotational molding, and PE-Al agglomeration and pulverization [42, 43].
In these times that society demands a more environmental way of thinking from the industry, recycling of multilayer packaging becomes a priority for many scientists. They have developed a plethora of ways to recycle such packaging, from using it as a fuel to using its pyrolysis products as a mercury absorbent. It is most likely that this field will keep on expanding with ever more innovative and cost-effective ways to fully exploit, reuse, and transform the Tetra Pak multilayer packaging as human development is going into the future.
The rapid technological advances along with people’s need for better living conditions resulted in a global rise in the consumption of EEE over the last years and so in huge amounts of WEEE [44]. Plastics in WEEE account for ~30% of WEEE and in most cases contain BFR that necessitates careful handling [9], since BFR’s presence in plastics leads to the formation of various, toxic brominated substances in the liquid fraction obtained after pyrolysis, inhibiting its further use. In such cases a pretreatment step before or during the recycling is necessary in order to receive bromine-free products. So, due to the fact that
One very common pretreatment method for the removal of BFR applied before pyrolysis is
Apart from the typical soxhlet extraction, many advanced solvent extraction techniques have been explored over the years, including supercritical fluid extraction (SFE), pressurized liquid extraction (PLE), ultrasonic-assisted extraction (UAE), and microwave-assisted extraction (MAE). These techniques require less time and volumes of solvents than those during soxhlet extraction [47]. Vilaplana et al. applied MAE for the removal of TBBPA and decabromodiphenyl ether (Deca-BDE) from virgin high-impact polystyrene (HIPS) and standard samples from real WEEE. They found that complete extraction of TBBPA took place when they used a combination of polar/nonpolar solvent system (isopropanol/n-hexane) and high extraction temperatures (130°C). On the other hand, in case of Deca-BDE, there were obtained lower extraction yields due to its high molecular weight and its nonpolar nature [47].
In another study [48], UAE and MAE were investigated for the recovery of TBBPA from real WEEE samples that consisted of ABS, polypropylene (PP), polycarbonate (PC), and blends of ABS/PC. From the results obtained it was proved that MAE was more efficient in extracting TBBPA than UAE, especially in case of ABS polymers. The optimal solvent media was isopropanol: n-hexane (1:1), which is a binary mixture of a polar –nonpolar solvent, whereas pure isopropanol, as a solvent, could not result in complete extraction of TBBPA [48].
As mentioned previously, SFE has also attracted a lot of attention as regards the degradation of brominated flame-retarded plastics from WEEE, because of the supercritical fluids’ unique properties, such as high density, low viscosity, varied permittivity related to pressure, and high mass transfer, as well as the fact that their viscosity, density, and diffusion coefficient are very sensitive to changes in temperature and pressure. Supercritical fluids appear at temperature and pressure higher than their critical state. Supercritical CO2 is the most widely used fluid in SFE, since it presents remarkable advantages, including: low critical point, low cost, ease of availability, non-toxicity, recyclability, and simplicity as regards its operation. Water is also, a cheap, nontoxic, and easily available fluid, but it has a relatively high supercritical point [49].
Onwudili and Williams [50] studied supercritical water (T > 374°C and P > 22.1 MPa) due to the fact that it presents different characteristics in comparison with organic solvents. They focused on ABS and HIPS, since they are some of the most representative brominated plastics in WEEE and degraded them in supercritical water (up to 450°C and 31 MPa) in a batch reactor. Furthermore, they investigated the effect of alkaline additives, NaOH and Ca(OH)2, by treating the plastics both in the absence and in the presence of them. They noticed that oils, which were the main reaction products, had almost zero bromine and antimony content in the presence of NaOH additive [50]. In another work, [51] there was used subcritical water for the debromination of printed circuit boards (PCB) that contained BFR in a high-pressure batch reactor. They applied three different temperatures, 225, 250, and 275°C, and noticed that debromination increased with increase in temperature. After the debromination of the samples, they applied recycling methods, such as pyrolysis.
Apart from water, organic solvents such as acetone, methanol, and ethanol can also be used as supercritical fluids in chemical recycling of plastics from WEEE [52]. For instance, Wang and Zhang [52] used various supercritical fluids: acetone, methanol, isopropanol, and water with a view to studying the degradation of waste computer housing plastics that contained BFR. They came to the conclusion that supercritical fluid process was efficient for the debromination and decomposition of brominated flame-retarded plastics enabling the recycling of bromine-free oil. As for solvent’s efficiency in debromination, the order was the following: water > methanol > isopropanol > acetone.
It should be highlighted here that although SFE technology is considered as a green choice for resource recovery, it has some important drawbacks as well. One of the main obstacles in such technology is the fact that only equipment able to withstand high pressures and temperatures and very resistant to corrosion can be used. These demands, however, increase the cost a lot, and along with the large amount of energy that is required, prevent its industrial implementation [49].
To avoid the latter difficulties, there are other approaches that can be applied in case of flame-retarded plastics. One such approach is that of
As described above, during co-pyrolysis, the end-of-life brominated plastics along with other (plastic) waste are pyrolyzed together and result in bromine reduction in the derived pyrolysis oil, without any kind of pretreatment before the pyrolysis process. Another idea, in order to reduce bromine while avoiding the extra pretreatment step, is that of the
During
In another study [59], there was investigated activated Al2O3 for catalytic pyrolysis of waste PCB examining three different temperatures: 400, 500, and 600°C, as well as different ratios of PCB: Al2O3. They noticed that higher temperatures improved the oil production; and the optimal results as regards the production of light oil and the debromination were obtained at 600°C. The catalyst’s presence increased the formation of light hydrocarbons and in the meantime the debromination. Wu et al. [60] carried out catalytic pyrolysis of brominated HIPS that also contained Sb2O3, in the presence of red mud, limestone, and natural zeolite, with a view to eliminating bromine and antimony from the pyrolysis oil. They found that in their presence, the total amount of bromine (and antimony) in the oil was reduced. Nevertheless, red mud was the most efficient catalyst in reducing bromine, since Fe2O3 present in red mud reacted with HBr that was formed during the degradation of the BFR and hindered the formation of the volatile SbBr3; in the meanwhile, its zeolite property catalytically destroyed the organobromine compounds [60].
Co-pyrolysis can also take place in the presence of catalysts, known as
An example that belongs in the first category is [63], in which they examined a small-scale two-stage pyrolysis and catalytic reforming of brominated flame-retarded HIPS at 500°C using four zeolites: natural zeolite (NZ), iron oxide–loaded natural zeolite (Fe-NZ), HY zeolite (YZ), and iron oxide–loaded HY zeolite (Fe-YZ). They observed that the bromine content in the oil was reduced in the presence of catalysts; however, Fe-NZ and Fe-YZ showed better debromination results, due to the reactions between the iron oxide that was loaded and the derived HBr. Compared with Fe-YZ, Fe-NZ did not greatly change the pyrolysis products and so preserved the valuable single-ring aromatic compounds. As a result, Fe-NZ was more effective and feasible for the feedstock recycling of brominated HIPS via the pyrolysis process.
Areeprasert and Khaobang [64] studied pyrolysis and catalytic reforming of a polymer blend (ABS/PC) and PCB, at 500°C, using some conventional catalysts: Y-zeolite (YZ), ZSM-5, iron oxide–loaded Y-zeolite (Fe/YZ), and iron oxide–loaded ZSM-5 (Fe/ZSM-5), as well as some alternative, green catalysts: biochar (BC), electronic waste char (EWC), iron oxide–loaded biochar (Fe/BC), and iron oxide–loaded electronic waste char (Fe/EWC). They found that all catalysts increased the single-ring hydrocarbon products of the liquid fraction. As for the debromination, it was noticed that in case of ABS/PC, the most effective catalyst was Fe/BC, whereas in case of PCB, it was Fe/EWC. Also, they concluded that the green-renewable catalysts could be a promising choice for removing bromine from the liquid fraction [64]. Ma et al. [65] investigated pyrolysis-catalytic upgrading of brominated flame-retarded ABS. The process took place in a two-stage fixed bed reactor; and the second stage included the catalytic upgrading of the vapor intermediates that were obtained from pyrolysis (first stage). The examined catalysts were: HZSM-5 and Fe/ZSM-5. Both catalysts had high catalytic cracking activities that led to an increased yield of oil and to a reduction of the bromine in the liquid fraction.
This chapter briefly presents all methods that are used nowadays for plastic recycling, including primary recycling, energy recovery, mechanical recycling, and chemical recycling. The advantages and disadvantages of each method are discussed. Emphasis though is given on chemical recycling and mainly, pyrolysis, due to its many benefits, which are fully described. Furthermore, three case studies that involve some difficulties in plastic recycling are thoroughly investigated. The first one includes the case of polymeric blends, where the coexistence of different plastic materials makes their recycling more difficult. The second one is focused on the recycling of plastics that come from multilayer packaging. The main obstacle in this case lies in the fact that multilayer packaging comprises various, different materials, such as paper and metals, apart from the plastics, so extra attention is required for their separation and recycling. The last case study that is presented here is that of brominated flame-retarded plastics from WEEE, since in such cases direct recycling is not that easy due to the formation of undesirable brominated compounds and more often than not a pretreatment step prior to their recycling is necessary. Taking into account the mentioned difficulties, the aim of this chapter is to present and analyze various recent literature data along with suggestions on how to overcome the mentioned problems.
The research work was supported by the Hellenic Foundation for Research and Innovation (HFRI) under the HFRI PhD Fellowship grant (Fellowship Number: 853).
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Besides its wide and promiscuous tropism, AAV infection does not result in considerable toxicity or pathogenicity and is capable of achieving adequate and long-term levels of gene transfer, especially following generation of the AAV recombinant variant: rAAV. Due to these properties, rAAV has gained special attention as a viral vector for gene therapy in the last decade. Currently, there are 130 clinical trials taking place worldwide for several diseases testing the safety and efficacy profiles of rAAV. During preclinical and clinical studies, several challenges have arisen in terms of reaching the full therapeutic potential of rAAV, such as efficient delivery of the virus in a targeted and specific manner to a desired tissue. Importantly, the development of immune responses towards the viral capsids poses an obstacle to rAAV applicability in the clinical setting. 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Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:229,paginationItems:[{id:"318170",title:"Dr.",name:"Aneesa",middleName:null,surname:"Moolla",slug:"aneesa-moolla",fullName:"Aneesa Moolla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/318170/images/system/318170.png",biography:"Dr. Aneesa Moolla has extensive experience in the diverse fields of health care having previously worked in dental private practice, at the Red Cross Flying Doctors association, and in healthcare corporate settings. She is now a lecturer at the University of Witwatersrand, South Africa, and a principal researcher at the Health Economics and Epidemiology Research Office (HE2RO), South Africa. Dr. Moolla holds a Ph.D. in Psychology with her research being focused on mental health and resilience. In her professional work capacity, her research has further expanded into the fields of early childhood development, mental health, the HIV and TB care cascades, as well as COVID. She is also a UNESCO-trained International Bioethics Facilitator.",institutionString:"University of the Witwatersrand",institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419588",title:"Ph.D.",name:"Sergio",middleName:"Alexandre",surname:"Gehrke",slug:"sergio-gehrke",fullName:"Sergio Gehrke",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038WgMKQA0/Profile_Picture_2022-06-02T11:44:20.jpg",biography:"Dr. Sergio Alexandre Gehrke is a doctorate holder in two fields. The first is a Ph.D. in Cellular and Molecular Biology from the Pontificia Catholic University, Porto Alegre, Brazil, in 2010 and the other is an International Ph.D. in Bioengineering from the Universidad Miguel Hernandez, Elche/Alicante, Spain, obtained in 2020. In 2018, he completed a postdoctoral fellowship in Materials Engineering in the NUCLEMAT of the Pontificia Catholic University, Porto Alegre, Brazil. He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,institution:{name:"Universidad Católica San Antonio de Murcia",country:{name:"Spain"}}},{id:"342152",title:"Dr.",name:"Santo",middleName:null,surname:"Grace Umesh",slug:"santo-grace-umesh",fullName:"Santo Grace Umesh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/342152/images/16311_n.jpg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"333647",title:"Dr.",name:"Shreya",middleName:null,surname:"Kishore",slug:"shreya-kishore",fullName:"Shreya Kishore",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333647/images/14701_n.jpg",biography:"Dr. Shreya Kishore completed her Bachelor in Dental Surgery in Chettinad Dental College and Research Institute, Chennai, and her Master of Dental Surgery (Orthodontics) in Saveetha Dental College, Chennai. She is also Invisalign certified. She’s working as a Senior Lecturer in the Department of Orthodontics, SRM Dental College since November 2019. She is actively involved in teaching orthodontics to the undergraduates and the postgraduates. Her clinical research topics include new orthodontic brackets, fixed appliances and TADs. She’s published 4 articles in well renowned indexed journals and has a published patency of her own. Her private practice is currently limited to orthodontics and works as a consultant in various clinics.",institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"323731",title:"Prof.",name:"Deepak M.",middleName:"Macchindra",surname:"Vikhe",slug:"deepak-m.-vikhe",fullName:"Deepak M. Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Univeristy of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:null},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:null},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. Her knowledge of English is at an advanced level.",institutionString:null,institution:null},{id:"332914",title:"Dr.",name:"Muhammad Saad",middleName:null,surname:"Shaikh",slug:"muhammad-saad-shaikh",fullName:"Muhammad Saad Shaikh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jinnah Sindh Medical University",country:{name:"Pakistan"}}},{id:"315775",title:"Dr.",name:"Feng",middleName:null,surname:"Luo",slug:"feng-luo",fullName:"Feng Luo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sichuan University",country:{name:"China"}}},{id:"423519",title:"Dr.",name:"Sizakele",middleName:null,surname:"Ngwenya",slug:"sizakele-ngwenya",fullName:"Sizakele Ngwenya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419270",title:"Dr.",name:"Ann",middleName:null,surname:"Chianchitlert",slug:"ann-chianchitlert",fullName:"Ann Chianchitlert",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419271",title:"Dr.",name:"Diane",middleName:null,surname:"Selvido",slug:"diane-selvido",fullName:"Diane Selvido",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419272",title:"Dr.",name:"Irin",middleName:null,surname:"Sirisoontorn",slug:"irin-sirisoontorn",fullName:"Irin Sirisoontorn",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"355660",title:"Dr.",name:"Anitha",middleName:null,surname:"Mani",slug:"anitha-mani",fullName:"Anitha Mani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"355612",title:"Dr.",name:"Janani",middleName:null,surname:"Karthikeyan",slug:"janani-karthikeyan",fullName:"Janani Karthikeyan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"334400",title:"Dr.",name:"Suvetha",middleName:null,surname:"Siva",slug:"suvetha-siva",fullName:"Suvetha Siva",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}}]}},subseries:{item:{id:"94",type:"subseries",title:"Climate Change and Environmental Sustainability",keywords:"Environmental protection, Socio-economic development, Resource exploitation, Environmental degradation, Climate change, Degraded ecosystems, Biodiversity loss",scope:"\r\n\tSustainable development focuses on linking economic development with environmental protection and social development to ensure future prosperity for people and the planet. To tackle global challenges of development and environment, the United Nations General Assembly in 2015 adopted the 17 Sustainable Development Goals. SDGs emphasize that environmental sustainability should be strongly linked to socio-economic development, which should be decoupled from escalating resource use and environmental degradation for the purpose of reducing environmental stress, enhancing human welfare, and improving regional equity. Moreover, sustainable development seeks a balance between human development and decrease in ecological/environmental marginal benefits. Under the increasing stress of climate change, many environmental problems have emerged causing severe impacts at both global and local scales, driving ecosystem service reduction and biodiversity loss. Humanity’s relationship with resource exploitation and environment protection is a major global concern, as new threats to human and environmental security emerge in the Anthropocene. Currently, the world is facing significant challenges in environmental sustainability to protect global environments and to restore degraded ecosystems, while maintaining human development with regional equality. Thus, environmental sustainability with healthy natural ecosystems is critical to maintaining human prosperity in our warming planet.
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