Composition of various silicate-based bioactive glasses [20].
\\n\\n
These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\\n\\n\\n\\n\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\n\n\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"5853",leadTitle:null,fullTitle:"Mycobacterium - Research and Development",title:"Mycobacterium",subtitle:"Research and Development",reviewType:"peer-reviewed",abstract:'This book arose from the combination of diverse areas of knowledge, experience, research, and points of view that try to demonstrate that mycobacteria are a complex science and very relevant to scientific studies that affect the human being in the world. Sophisticated techniques for improving human health do not guarantee that the "battle" against mycobacteria has been won, since tuberculosis, mycobacteriosis, and leprosy are a daily challenge in the world. The book includes contributions made by prestigious experts and research groups in different areas of mycobacteria, and they have contributed new perspectives of their area giving a comprehensive, important, and fascinating emphasis of this field that continues to offer challenges that lead various disciplines to understand their biology and pathogenicity. It is hoped that these chapters will be very useful for learning and discussion.',isbn:"978-1-78923-211-0",printIsbn:"978-1-78923-210-3",pdfIsbn:"978-1-83881-250-8",doi:"10.5772/65613",price:139,priceEur:155,priceUsd:179,slug:"mycobacterium-research-and-development",numberOfPages:374,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"073e7ca9fbfdd31da5499271f17ecdf2",bookSignature:"Wellman Ribón",publishedDate:"June 20th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/5853.jpg",numberOfDownloads:24516,numberOfWosCitations:1,numberOfCrossrefCitations:23,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:52,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:76,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 6th 2016",dateEndSecondStepPublish:"October 27th 2016",dateEndThirdStepPublish:"September 18th 2017",dateEndFourthStepPublish:"October 18th 2017",dateEndFifthStepPublish:"December 18th 2017",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"88491",title:"Dr.",name:"Wellman",middleName:null,surname:"Ribón",slug:"wellman-ribon",fullName:"Wellman Ribón",profilePictureURL:"https://mts.intechopen.com/storage/users/88491/images/system/88491.jpeg",biography:"Wellman Ribón, bacteriologist and clinical laboratory professional of the Industrial University of Santander, Master\\'s degree in Biochemistry from Universidad Javeriana; with more than fifteen years of experience as public health adviser, Colciencias (Departamento Administrativo de Ciencia y Tecnología de Colombia) senior researcher in scientific and technological development. He has worked at the National Health Institute of Colombia as coordinator of the mycobacteria group, manager of research projects and member of Centro Colombiano de Excelencia de Investigación en Tuberculosis (CCITB), EurolabTB Consortium and the SLAMTB. Ribón was the Microbiology School director and is currently a professor in Medicine School and works as professor and researcher at the Industrial University of Santander,.He is also the director of the Mycobacterium Research laboratory. Mr. Ribón has published articles about tuberculosis, leprosy and mycobacteriosis diseases, and has written four book chapters. His major area of interest and research is Mycobacterium tuberculosis complex.",institutionString:"Industrial University of Santander",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"6",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Industrial University of Santander",institutionURL:null,country:{name:"Colombia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"895",title:"Medical Microbiology",slug:"medical-microbiology"}],chapters:[{id:"61262",title:"Introductory Chapter: Scientific Research on Mycobacteria and the Absence of Evaluation Processes",doi:"10.5772/intechopen.76831",slug:"introductory-chapter-scientific-research-on-mycobacteria-and-the-absence-of-evaluation-processes",totalDownloads:955,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Wellman Ribón",downloadPdfUrl:"/chapter/pdf-download/61262",previewPdfUrl:"/chapter/pdf-preview/61262",authors:[{id:"88491",title:"Dr.",name:"Wellman",surname:"Ribón",slug:"wellman-ribon",fullName:"Wellman Ribón"}],corrections:null},{id:"60090",title:"Mycobacterium tuberculosis: Macrophage Takeover and Modulation of Innate Effector Responses",doi:"10.5772/intechopen.75003",slug:"mycobacterium-tuberculosis-macrophage-takeover-and-modulation-of-innate-effector-responses",totalDownloads:2062,totalCrossrefCites:6,totalDimensionsCites:10,hasAltmetrics:0,abstract:"Macrophages mediate the first line of defense in the host against various intracellular pathogens. They are armed with several immune-effector mechanisms to detect and combat pathogens. However, intracellular pathogens have developed strategies to overcome the macrophage protective immune responses and colonize inside the macrophages. Tuberculosis (TB), both pulmonary and extrapulmonary, is an infectious disease of global concern caused by Mycobacterium tuberculosis. M. tuberculosis is a highly successful pathogen and has acquired various strategies to downregulate critical innate-effector immune responses of macrophages such as phagosome-lysosome fusion, antigen presentation, autophagy, and inhibition of reactive oxygen (ROI) and reactive nitrogen (RNI) species to ensure its longer survival inside the macrophages. In addition to these, the bacilli also modulate T cell immune response which can help the bacilli to survive inside the host for a long time. In this chapter, we focus to describe important macrophage innate defense mechanisms and the signaling that can influence T cell adaptive response and the strategies adopted by the bacilli to exploit these signaling cascades to favor its replication and persistence inside the macrophages for establishing a productive infection.",signatures:"Khalid Hussain Bhat and Imtiyaz Yaseen",downloadPdfUrl:"/chapter/pdf-download/60090",previewPdfUrl:"/chapter/pdf-preview/60090",authors:[{id:"162478",title:"Dr.",name:"Khalid Hussain",surname:"Bhat",slug:"khalid-hussain-bhat",fullName:"Khalid Hussain Bhat"},{id:"233902",title:"Dr.",name:"Imtiyaz",surname:"Yaseen",slug:"imtiyaz-yaseen",fullName:"Imtiyaz Yaseen"}],corrections:null},{id:"55940",title:"The Existence of Mycobacterium tuberculosis in Microenvironment of Bone",doi:"10.5772/intechopen.69394",slug:"the-existence-of-mycobacterium-tuberculosis-in-microenvironment-of-bone",totalDownloads:1856,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:1,abstract:"Mycobacterium tuberculosis is an obligate aerobe bacteria requiring oxygen in its metabolism. In normal condition, bones have pH of 6.9–7.4 and temperature of 37°C. With the composition mentioned, bones fall in the group of tissue with less rich oxygen (<35%) which theoretically means, M. tuberculosis is hard to grow in the bone environment. Bone microliving environment is formed by the cells constructing the bone itself and the active cells which periodically interact with the bone cells. Activation of these cells gives impact to the temperature, pH, gas concentration, and liquid concentration, and at the same time triggers calcium, phosphor, and other minerals to be deposited in the bone. In the process of new bone formation, the osteoblast cells produce matrix and release them to the microenvironment that needs a high concentration of calcium and phosphor. The survival of M. tuberculosis in the microenvironment of bone is reflected in interaction of the bacteria and the non-immune cells, the bacteria and the organic environment, and the bacteria and the inorganic environment. In addition, the immune system also threatens the survival of M. tuberculosis. The results of these interactions will affect the lives of bacteria and has an impact on the bone microenvironment.",signatures:"Rahyussalim Ahmad Jabir, Andriansjah Rukmana, Ifran Saleh and\nTri Kurniawati",downloadPdfUrl:"/chapter/pdf-download/55940",previewPdfUrl:"/chapter/pdf-preview/55940",authors:[{id:"198914",title:"Dr.",name:"Ahmad Jabir",surname:"Rahyussalim",slug:"ahmad-jabir-rahyussalim",fullName:"Ahmad Jabir Rahyussalim"},{id:"198916",title:"Dr.",name:"Andriansjah",surname:"Rukmana",slug:"andriansjah-rukmana",fullName:"Andriansjah Rukmana"},{id:"198917",title:"Dr.",name:"Ifran",surname:"Saleh",slug:"ifran-saleh",fullName:"Ifran Saleh"},{id:"198918",title:"Mrs.",name:"Tri",surname:"Kurniawati",slug:"tri-kurniawati",fullName:"Tri Kurniawati"}],corrections:null},{id:"59957",title:"Conventional and Molecular Diagnosis of Drug-Sensitive and Drug-Resistant Pulmonary Tuberculosis",doi:"10.5772/intechopen.75004",slug:"conventional-and-molecular-diagnosis-of-drug-sensitive-and-drug-resistant-pulmonary-tuberculosis",totalDownloads:1388,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Tuberculosis is a transmissible disease, which is primarily caused by the bacteria Mycobacterium tuberculosis and by other Mycobacterium species, forming the Mycobacterium tuberculosis complex. Until the end of the 20th Century, most cases of pulmonary tuberculosis were considered curable. Nevertheless, the rising of tuberculosis resistant to first- and second-line anti-tuberculous drugs is threatening the world’s tuberculosis control programs. Due to this fact, the World Health Organization and other public health institutions recommended applying the conventional methods, affordable by low-incoming countries, to diagnose tuberculosis and to develop faster and more sensitive and specific methods to identify M. tuberculosis and determine their condition of anti-tuberculous drug resistance or drug sensitivity. In this chapter, we mention the most used conventional and molecular methods designed to identify M. tuberculosis and to determine their drug sensitivity or drug resistance. We also briefly describe the fundamentals of methods and its advantages and limitations.",signatures:"Yazmin Berenice Martínez-Martínez, Herminia Guadalupe\nMartínez-Rodríguez and Salvador Luis Said-Fernández",downloadPdfUrl:"/chapter/pdf-download/59957",previewPdfUrl:"/chapter/pdf-preview/59957",authors:[{id:"199705",title:"Dr.",name:"Salvador",surname:"Said-Fernández",slug:"salvador-said-fernandez",fullName:"Salvador Said-Fernández"},{id:"205596",title:"MSc.",name:"Yazmin-Berenice",surname:"Martínez-Martínez",slug:"yazmin-berenice-martinez-martinez",fullName:"Yazmin-Berenice Martínez-Martínez"},{id:"205597",title:"Dr.",name:"Herminia-Guadalupe",surname:"Martínez-Rodríguez",slug:"herminia-guadalupe-martinez-rodriguez",fullName:"Herminia-Guadalupe Martínez-Rodríguez"},{id:"205598",title:"Dr.",name:"Salvador",surname:"Said-Fernández",slug:"salvador-said-fernandez",fullName:"Salvador Said-Fernández"}],corrections:null},{id:"55553",title:"Diagnosis of Tuberculosis among Children and Adolescents",doi:"10.5772/intechopen.69227",slug:"diagnosis-of-tuberculosis-among-children-and-adolescents",totalDownloads:1156,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The authors discuss the challenging aspects of the diagnosis of tuberculosis in children and adolescents, since there is no gold standard for its diagnosis. The different clinical and radiological presentations and the low bacteriological positivity of tuberculosis in childhood are grounds for confrontation to the present. Immunological tests called interferon gamma release assays (IGRAs) failed to overcome the tuberculin skin test in practice. Advances with nucleic acid amplification tests, on the other hand, have contributed to the diagnosis of tuberculosis among adolescents. Standardized systems for diagnosis can be useful as tools for screening or for decision‐making in childhood tuberculosis.",signatures:"Clemax Couto Sant’Anna, Maria de Fátima B. Pombo March and\nRafaela Baroni Aurílio",downloadPdfUrl:"/chapter/pdf-download/55553",previewPdfUrl:"/chapter/pdf-preview/55553",authors:[{id:"202255",title:"Prof.",name:"Clemax",surname:"Sant Anna",slug:"clemax-sant-anna",fullName:"Clemax Sant Anna"},{id:"202586",title:"Prof.",name:"Maria De Fatima",surname:"Pombo March",slug:"maria-de-fatima-pombo-march",fullName:"Maria De Fatima Pombo March"},{id:"202587",title:"Dr.",name:"Rafaela",surname:"Baroni",slug:"rafaela-baroni",fullName:"Rafaela Baroni"}],corrections:null},{id:"57080",title:"Drug Resistance in Mycobacterium tuberculosis",doi:"10.5772/intechopen.69656",slug:"drug-resistance-in-mycobacterium-tuberculosis",totalDownloads:1465,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Tuberculosis (TB) remains to be a serious health problem worldwide. There is an increased transmission of Mycobacterium tuberculosis strains with drug resistance, hence complicating TB control. The deciphering of the M. tuberculosis genome, together with the implementation of new molecular biology tools, has allowed the identification of changes in nucleic acid sequences with a functional impact. These mutations have become important in the design of early‐diagnostic kits to identify the resistance profile of M. tuberculosis. Since the conventional methods to determine the identity of M. tuberculosis strains based in cultures are laborious, time‐consuming and performed by specialized technicians, the result is generated until 4 months after receiving the samples. During this time, patients with TB are not adequately treated, and resistant strains may be transmitted to the rest of the population. In this chapter, we describe the most relevant mutations in genes associated with drug resistance in M. tuberculosis, the analysis of gene expression to identify new markers of drug resistance strains, and the development of new antituberculosis drugs against drug‐resistant strains.",signatures:"Katia Peñuelas-Urquides, Fabiola Castorena-Torres, Beatriz Silva\nRamírez and Mario Bermúdez de León",downloadPdfUrl:"/chapter/pdf-download/57080",previewPdfUrl:"/chapter/pdf-preview/57080",authors:[{id:"188810",title:"Dr.",name:"Mario",surname:"Bermúdez De León",slug:"mario-bermudez-de-leon",fullName:"Mario Bermúdez De León"},{id:"188821",title:"Dr.",name:"Fabiola",surname:"Castorena Torres",slug:"fabiola-castorena-torres",fullName:"Fabiola Castorena Torres"},{id:"198351",title:"Dr.",name:"Katia",surname:"Peñuelas Urquides",slug:"katia-penuelas-urquides",fullName:"Katia Peñuelas Urquides"},{id:"206230",title:"Dr.",name:"Beatriz",surname:"Silva Ramírez",slug:"beatriz-silva-ramirez",fullName:"Beatriz Silva Ramírez"}],corrections:null},{id:"55889",title:"The Physiology of Mycobacterium tuberculosis in the Context of Drug Resistance: A System Biology Perspective",doi:"10.5772/intechopen.69594",slug:"the-physiology-of-mycobacterium-tuberculosis-in-the-context-of-drug-resistance-a-system-biology-pers",totalDownloads:1571,totalCrossrefCites:2,totalDimensionsCites:6,hasAltmetrics:0,abstract:"Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis (Mtb), is the main cause of death due to an infectious disease. After more than 100 years of the discovery of Mtb, clinicians still face difficulties finding an effective treatment for the increasing number of drug-resistant cases. The difficulties in the clinical setting can be related to the slow pace at which the understanding of the physiology of this bacterium has occurred. Mtb is distinct from other microorganisms not only due to its slow growth and difficulties to study in the laboratory, but also due to its inherent physiology such as its complex cell envelope and its metabolic pathways. Understanding the physiology of drug susceptible and resistant Mtb strains is crucial for the design of an effective chemotherapy against TB. This chapter will review the mycobacterial cell envelope and major physiological pathways together with recent discoveries in Mtb drug resistance through different “omics” disciplines.",signatures:"Luisa Maria Nieto, Carolina Mehaffy and Karen M. Dobos",downloadPdfUrl:"/chapter/pdf-download/55889",previewPdfUrl:"/chapter/pdf-preview/55889",authors:[{id:"198240",title:"Dr.",name:"Carolina",surname:"Mehaffy",slug:"carolina-mehaffy",fullName:"Carolina Mehaffy"},{id:"221619",title:"Dr.",name:"Luisa",surname:"Nieto",slug:"luisa-nieto",fullName:"Luisa Nieto"}],corrections:null},{id:"59139",title:"Web Resources on Tuberculosis: Information, Research, and Data Analysis",doi:"10.5772/intechopen.73549",slug:"web-resources-on-tuberculosis-information-research-and-data-analysis",totalDownloads:1062,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Since the first edition of this book in 2013, many new tools and databases have become publicly available, as well as several have been discontinued. Here, we present an updated version of web resources on tuberculosis, providing more detailed information on some key concepts. However, the purpose of this chapter is by no means to offer an exhaustive list of all the resources available on the Internet about TB, the topic of this book. This would be a massive and perhaps futile work since the evolution of the Internet occurs at a very fast pace. Rather, this chapter concentrates on a selection of the most important, relevant and stable websites with relevance to several aspects of TB, such as research, treatment, main institutions, funding, and specialized platforms. We think this should complement all the other information already presented in this book, offering the reader a more integrated view of the disease, as well as access to new platforms and systems specialized in the analysis of data generated by a series of new technologies such as DNA sequencing.",signatures:"Edson Machado, Camillo Cerdeira, Antonio Basílio de Miranda and\nMarcos Catanho",downloadPdfUrl:"/chapter/pdf-download/59139",previewPdfUrl:"/chapter/pdf-preview/59139",authors:[{id:"161917",title:"Dr.",name:"Marcos",surname:"Catanho",slug:"marcos-catanho",fullName:"Marcos Catanho"}],corrections:null},{id:"59262",title:"Patients and Health System-Related Factors Impacting on Tuberculosis Program Implementation in Resource-Constrained Settings: Experience from Multi-TB Facilities in Oyo State, South-West of Nigeria",doi:"10.5772/intechopen.73583",slug:"patients-and-health-system-related-factors-impacting-on-tuberculosis-program-implementation-in-resou",totalDownloads:1155,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Background: Tuberculosis (TB) is one of the most prevalent human infections and is the second leading cause of deaths from infectious diseases worldwide, and Nigeria is the fourth among the 22 high-burden countries in the world for tuberculosis even though the exact burden of TB in Nigeria is not known.",signatures:"Olanrewaju Oladimeji, Joyce Tsoka-Gwegweni, Lungelo Mlangeni,\nLehlogonolo Makola and Olusegun Awolaran",downloadPdfUrl:"/chapter/pdf-download/59262",previewPdfUrl:"/chapter/pdf-preview/59262",authors:[{id:"160349",title:null,name:null,surname:null,slug:"",fullName:null}],corrections:null},{id:"60405",title:"Clients’ Perception of Quality of Multidrug-Resistant Tuberculosis Treatment and Care in Resource-Limited Setting: Experience from Nigeria",doi:"10.5772/intechopen.76001",slug:"clients-perception-of-quality-of-multidrug-resistant-tuberculosis-treatment-and-care-in-resource-lim",totalDownloads:1220,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Background: Quality care is essential to the well-being and survival of people with multidrug-resistant tuberculosis (MDR-TB). The aim of this study is to explore how MDR- TB patients, who were voluntarily hospitalized, perceived care and treatment strategy and to assess the influence of psychosocial factors on their perception of care and treatment strategy in Nigeria. Methods: The study enrolled 98 MDR-TB patients on voluntary confinement in four MDR-TB hospitals in Nigeria. Patients’ perceptions of quality of care and treatment strategy were evaluated with 28-item and 6-item instruments, respectively. Bivariate analysis was used to test for an association and multivariate analysis for factors that might contribute to the perceived quality of care. Results: Seventy-eight per cent (78%) of the participating patients perceived the quality of care to be good. Patients with better psychosocial well-being had five times higher odds to report good quality of care. Conclusion: The majority of MDR-TB patients perceived the quality of inpatient care to be good in Nigerian hospitals; however, their psychological health influenced their perception significantly. Health care providers need to improve treatment strategies to encourage acceptance of care as poor perception to health care service delivery may deter treatment completion and also cause relapse among clients on treatment.",signatures:"Olanrewaju Oladimeji, Daniel Adedayo Adeyinka, Lehlogonolo\nMakola, Kabwebwe Honoré Mitonga, Ekerette Emmanuel Udoh,\nBoniface Ayanbekongshie Ushie, Kelechi Elizabeth Oladimeji,\nJeremiah Chikovore, Musawenkosi Mabaso, Atilola Adeleke, Osman\nEltayeb, Oluwatoyin J. Kuye, Gidado Mustapha, Olusoji Mayowa\nIge, Joyce Nonhlanhla Mbatha, Jacob Creswell, Joyce M. Tsoka-\nGwegweni, Lovett Lawson and Ehimario Uche Igumbor",downloadPdfUrl:"/chapter/pdf-download/60405",previewPdfUrl:"/chapter/pdf-preview/60405",authors:[{id:"160349",title:null,name:null,surname:null,slug:"",fullName:null}],corrections:null},{id:"59732",title:"Mosaic Structure as the Main Feature of Mycobacterium bovis BCG Genomes",doi:"10.5772/intechopen.75005",slug:"mosaic-structure-as-the-main-feature-of-mycobacterium-bovis-bcg-genomes",totalDownloads:1137,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Background: The genome stability of attenuated live BCG vaccine preventing the acute forms of childhood tuberculosis is an important aspect of vaccine production. The purpose of our study was a whole genome comparative analysis of BCG sub-strains and identification of potential triggers of sub-strains’ transition.",signatures:"Voronina Olga Lvovna, Aksenova Ekaterina Ivanovna, Kunda\nMarina Sergeevna, Ryzhova Natalia Nikolaevna, Semenov Andrey\nNikolaevich, Sharapova Natalia Eugenievna and Gintsburg Alexandr\nLeonidovich",downloadPdfUrl:"/chapter/pdf-download/59732",previewPdfUrl:"/chapter/pdf-preview/59732",authors:[{id:"192852",title:"Ph.D.",name:"Olga",surname:"Voronina",slug:"olga-voronina",fullName:"Olga Voronina"},{id:"225483",title:"Dr.",name:"Marina",surname:"Kunda",slug:"marina-kunda",fullName:"Marina Kunda"},{id:"225484",title:"Dr.",name:"Natalia",surname:"Ryzhova",slug:"natalia-ryzhova",fullName:"Natalia Ryzhova"},{id:"225485",title:"Dr.",name:"Ekaterina",surname:"Aksenova",slug:"ekaterina-aksenova",fullName:"Ekaterina Aksenova"},{id:"225486",title:"Mr.",name:"Andrey",surname:"Semenov",slug:"andrey-semenov",fullName:"Andrey Semenov"},{id:"225487",title:"Dr.",name:"Natalia",surname:"Sharapova",slug:"natalia-sharapova",fullName:"Natalia Sharapova"},{id:"225489",title:"Prof.",name:"Alexandr",surname:"Gintsburg",slug:"alexandr-gintsburg",fullName:"Alexandr Gintsburg"}],corrections:null},{id:"57746",title:"Virulence Factors and Pathogenicity of Mycobacterium",doi:"10.5772/intechopen.72027",slug:"virulence-factors-and-pathogenicity-of-mycobacterium",totalDownloads:3031,totalCrossrefCites:6,totalDimensionsCites:16,hasAltmetrics:0,abstract:"Virulence, is referred as the ability of a pathogen to cause disease, and for mycobacteria it depends on their ability to reside within host cells and evade the microbicidal mechanisms of macrophages. The outcome of tuberculosis (TB) infection is highly variable and it seems that the closest relationship between the Mycobacterium genre and humans has shaped the mycobacterial genome to encode bacterial factors that reflects a highly evolved and coordinated program of immune evasion strategies that interfere with both innate and adaptive immunity causing disease even in fully immunocompetent host. Although Mycobacterium tuberculosis (MTB) does not have classical virulence factors, it has described many virulence-associated genes and virulence lifestyle genes from Mycobacterium tuberculosis complex (MTBC). In this chapter, we describe the most important gene/molecule involved in the host defense modulation response, also the plethora of strategies to evade immune mechanisms of macrophage. We review the main genes whose inactivation in the mycobacterial genome leads to a measurable loss in virulence in the different validated TB models.",signatures:"Gabriela Echeverria-Valencia, Susana Flores-Villalva and Clara I.\nEspitia",downloadPdfUrl:"/chapter/pdf-download/57746",previewPdfUrl:"/chapter/pdf-preview/57746",authors:[{id:"81895",title:"Dr.",name:"Clara",surname:"Espitia",slug:"clara-espitia",fullName:"Clara Espitia"},{id:"90043",title:"Ph.D.",name:"Gabriela",surname:"Echeverria-Valencia",slug:"gabriela-echeverria-valencia",fullName:"Gabriela Echeverria-Valencia"},{id:"220022",title:"M.Sc.",name:"Susana",surname:"Flores-Villalva",slug:"susana-flores-villalva",fullName:"Susana Flores-Villalva"}],corrections:null},{id:"59157",title:"Overview of Non Tuberculosis Mycobacterial Lung Diseases",doi:"10.5772/intechopen.73542",slug:"overview-of-non-tuberculosis-mycobacterial-lung-diseases",totalDownloads:1586,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Nontuberculosis mycobacteria (NTM) are ubiquitous in nature and opportunistically infect different animals, including humans. Currently, NTM is emerging as an important cause of pulmonary infection among both immunocompromised and immunocompetent persons worldwide. The clinical relevance of pulmonary NTM varies among species while showing geographical heterogeneity in distribution as well as pathogenicity. The outcome of the respiratory NTM disease is a consequence of a complex interplay between microbial factors and host susceptibility. Furthermore, HIV infection, cystic fibrosis, cancer, underlying chronic lung disease and history of tuberculosis (TB) may be associated as risk factors for active nontuberculosis pulmonary diseases (NTMPD). The diagnosis of NTMPD requires the presence of symptoms, radiographic evidences, microscopic observations and definitive laboratory diagnostics. Lung infections resulted from a clinically significant NTM species should be treated with appropriate antimicrobial regimen.",signatures:"Overview of Non Tuberculosis Mycobacterial Lung\nDiseases",downloadPdfUrl:"/chapter/pdf-download/59157",previewPdfUrl:"/chapter/pdf-preview/59157",authors:[{id:"219525",title:"Dr.",name:"Chamila",surname:"Adikaram",slug:"chamila-adikaram",fullName:"Chamila Adikaram"}],corrections:null},{id:"56790",title:"Unique Biochemical Features of the Cytokinetic Protein FtsZ of Mycobacteria",doi:"10.5772/intechopen.70540",slug:"unique-biochemical-features-of-the-cytokinetic-protein-ftsz-of-mycobacteria",totalDownloads:1409,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"FtsZ, the bacterial cytokinetic protein, a structural homologue of mammalian β-tubulin, is present in bacteria of diverse genera, including mycobacteria. The FtsZ protein of Mycobacterium tuberculosis (M. tuberculosis FtsZ), the causative agent of tuberculosis, is the most studied among the mycobacterial FtsZ proteins as it is a potential anti-tuberculosis drug target. M. tuberculosis FtsZ possesses many unique biochemical features, which include slow polymerisation kinetics, presence of charged amino acids in the C-terminal domain that interacts with a variety of other cell division proteins, and the presence of specific amino acids at unique locations that makes it distinct from the FtsZ of other mycobacterial species and of other bacterial genera. On the other hand, although the FtsZ of Mycobacterium leprae (M. leprae FtsZ), the causative agent of leprosy, shows high level of conservation with M. tuberculosis FtsZ, it has biochemical properties that are very different from those of M. tuberculosis FtsZ due to the difference in specific amino acid residues at critical locations on the protein. The present review focuses on these structural features of M. tuberculosis FtsZ and M. leprae FtsZ, as studied by others and by us, in comparison to those of the FtsZ of other mycobacterial species and of other bacterial genera.",signatures:"Prabuddha Gupta, Atul Pradhan and Parthasarathi Ajitkumar",downloadPdfUrl:"/chapter/pdf-download/56790",previewPdfUrl:"/chapter/pdf-preview/56790",authors:[{id:"198875",title:"Dr.",name:"Parthasarathi",surname:"Ajitkumar",slug:"parthasarathi-ajitkumar",fullName:"Parthasarathi Ajitkumar"},{id:"199664",title:"Dr.",name:"Prabuddha",surname:"Gupta",slug:"prabuddha-gupta",fullName:"Prabuddha Gupta"},{id:"204994",title:"Dr.",name:"Atul",surname:"Pradhan",slug:"atul-pradhan",fullName:"Atul Pradhan"}],corrections:null},{id:"57032",title:"Mycobacteria-Derived Agents for the Treatment of Urological and Renal Cancers",doi:"10.5772/intechopen.69659",slug:"mycobacteria-derived-agents-for-the-treatment-of-urological-and-renal-cancers",totalDownloads:1015,totalCrossrefCites:2,totalDimensionsCites:5,hasAltmetrics:0,abstract:"Mycobacteria are the unique group of bacteria that are currently used in antitumoral immunotherapy. Specifically, intravesical instillation of viable cells of Mycobacterium bovis Bacillus Calmette-Guérin (BCG), after transurethral resection of non-muscle invasive bladder cancer, is the most efficacious treatment for avoiding recurrence and progression of the disease. BCG has been used for the last 35 years for bladder cancer treatment, but other mycobacteria or mycobacteria components are currently under preclinical and clinical studies for the immunotherapeutic treatment of non-invasive bladder cancer and also of other types of tumors located at the urinary system. Those are, for instance, cell wall extracts or heat-killed forms from BCG or other mycobacteria such as Mycobacterium phlei or Mycobacterium indicus pranii (MIP) or even viable cells from non-pathogenic mycobacteria such us Mycobacterium brumae. A review of the literature in which mycobacteria components, non-viable mycobacteria, and viable mycobacteria have been used for these different cancers will be performed. In this chapter, the function of mycobacteria as antitumor agents will be then analyzed, awarding the audience a broad knowledge of one of the beneficial applications of mycobacteria, which are usually introduced as dangerous microorganisms.",signatures:"Estela Noguera-Ortega and Esther Julián",downloadPdfUrl:"/chapter/pdf-download/57032",previewPdfUrl:"/chapter/pdf-preview/57032",authors:[{id:"199657",title:"Dr.",name:"Esther",surname:"Julián",slug:"esther-julian",fullName:"Esther Julián"},{id:"205121",title:"Dr.",name:"Estela",surname:"Noguera-Ortega",slug:"estela-noguera-ortega",fullName:"Estela Noguera-Ortega"}],corrections:null},{id:"55267",title:"Application of Integrated Translational Research as Leprosy Problem Solution in Indonesia",doi:"10.5772/67967",slug:"application-of-integrated-translational-research-as-leprosy-problem-solution-in-indonesia",totalDownloads:1247,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In Indonesia, leprosy remains a health problem because its elimination has not achieved. This shows the high Mycobacterium leprae transmission as a result of difficulties in the early detection, termination of the transmission chain, and management evaluation. Integrated translational research has been carried out as a solution for the problem. Dissemination of the various results of the research is conducted by the educational aspects tiered with a variety of learning methods including a textbook based on research findings, scientific papers at various scientific meetings, and published journals, as well as aspects of community service through electronic media, newspapers, and management and counseling with leprosy patients and their contact person, especially in endemic pockets area.",signatures:"Cita Rosita Sigit Prakoeswa",downloadPdfUrl:"/chapter/pdf-download/55267",previewPdfUrl:"/chapter/pdf-preview/55267",authors:[{id:"198381",title:"Ph.D.",name:"Cita Rosita Sigit",surname:"Prakoeswa",slug:"cita-rosita-sigit-prakoeswa",fullName:"Cita Rosita Sigit Prakoeswa"}],corrections:null},{id:"59150",title:"Mycobacterium as Polycyclic Aromatic Hydrocarbons (PAHs) Degrader",doi:"10.5772/intechopen.73546",slug:"mycobacterium-as-polycyclic-aromatic-hydrocarbons-pahs-degrader",totalDownloads:1201,totalCrossrefCites:5,totalDimensionsCites:9,hasAltmetrics:0,abstract:"The genus Mycobacterium has the ability to degrade various environmental pollutants including polycyclic aromatic hydrocarbons (PAHs). Mycobacterium has an ability to withstand adverse environmental conditions and it has been considered for future bioremediation applications for the removal of PAH contaminants from crude oil–polluted sites. The degradation of PAHs using a cost-effective laboratory microcosm system was discussed. The various conditions such as environmental habitat, degradation behavior, enzymatic mechanisms, and ecological survival are thoroughly discussed in this chapter. Based on the above study, Mycobacterium has proved to be a better candidate in bioremediation of PAH-contaminated sites.",signatures:"Dushyant R. Dudhagara and Bharti P. Dave",downloadPdfUrl:"/chapter/pdf-download/59150",previewPdfUrl:"/chapter/pdf-preview/59150",authors:[{id:"219060",title:"Prof.",name:"Bharti",surname:"Dave",slug:"bharti-dave",fullName:"Bharti Dave"},{id:"225052",title:"Dr.",name:"Dushyant",surname:"Dudhagara",slug:"dushyant-dudhagara",fullName:"Dushyant Dudhagara"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"4567",title:"Tuberculosis",subtitle:"Expanding Knowledge",isOpenForSubmission:!1,hash:"6620343e9ad62f2984bc393701cee6ff",slug:"tuberculosis-expanding-knowledge",bookSignature:"Wellman Ribon",coverURL:"https://cdn.intechopen.com/books/images_new/4567.jpg",editedByType:"Edited by",editors:[{id:"88491",title:"Dr.",name:"Wellman",surname:"Ribón",slug:"wellman-ribon",fullName:"Wellman Ribón"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6178",title:"Hansen's Disease",subtitle:"The Forgotten and Neglected Disease",isOpenForSubmission:!1,hash:"c68f443f518dcee16e6083e7295a2532",slug:"hansen-s-disease-the-forgotten-and-neglected-disease",bookSignature:"Wellman Ribòn",coverURL:"https://cdn.intechopen.com/books/images_new/6178.jpg",editedByType:"Edited by",editors:[{id:"88491",title:"Dr.",name:"Wellman",surname:"Ribón",slug:"wellman-ribon",fullName:"Wellman Ribón"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5197",title:"Microbial Biofilms",subtitle:"Importance and Applications",isOpenForSubmission:!1,hash:"51bccaa7388a26d55298525fd28dd8f1",slug:"microbial-biofilms-importance-and-applications",bookSignature:"Dharumadurai Dhanasekaran and Nooruddin Thajuddin",coverURL:"https://cdn.intechopen.com/books/images_new/5197.jpg",editedByType:"Edited by",editors:[{id:"48914",title:"Dr.",name:"Dharumadurai",surname:"Dhanasekaran",slug:"dharumadurai-dhanasekaran",fullName:"Dharumadurai Dhanasekaran"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"548",title:"Antibiotic Resistant Bacteria",subtitle:"A Continuous Challenge in the New Millennium",isOpenForSubmission:!1,hash:"f8a58b7ebbb9cd01db5c16fbf9f80b44",slug:"antibiotic-resistant-bacteria-a-continuous-challenge-in-the-new-millennium",bookSignature:"Marina Pana",coverURL:"https://cdn.intechopen.com/books/images_new/548.jpg",editedByType:"Edited by",editors:[{id:"77349",title:"Dr.",name:"Marina",surname:"Pana",slug:"marina-pana",fullName:"Marina Pana"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5193",title:"Probiotics and Prebiotics in Human Nutrition and Health",subtitle:null,isOpenForSubmission:!1,hash:"facfb45c80773cd5151d8f53b902be39",slug:"probiotics-and-prebiotics-in-human-nutrition-and-health",bookSignature:"Venketeshwer Rao and Leticia G. 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Henneman",slug:"john-r.-henneman",email:"jrh78@bri.ksu.edu",position:null,institution:null}]}},chapter:{id:"78994",slug:"dry-hydrogen-peroxide-for-viral-inactivation",signatures:"Chris Lee and John R. Henneman",dateSubmitted:"August 18th 2021",dateReviewed:"September 14th 2021",datePrePublished:"October 21st 2021",datePublished:"May 18th 2022",book:{id:"11006",title:"Disinfection of Viruses",subtitle:null,fullTitle:"Disinfection of Viruses",slug:"disinfection-of-viruses",publishedDate:"May 18th 2022",bookSignature:"Raymond W. Nims and M. Khalid Ijaz",coverURL:"https://cdn.intechopen.com/books/images_new/11006.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"104702",title:"Dr.",name:"Raymond W.",middleName:null,surname:"Nims",slug:"raymond-w.-nims",fullName:"Raymond W. Nims"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"414666",title:"M.Sc.",name:"Chris",middleName:null,surname:"Lee",fullName:"Chris Lee",slug:"chris-lee",email:"chris96lee@gmail.com",position:null,institution:null},{id:"415444",title:"MSc.",name:"John R.",middleName:null,surname:"Henneman",fullName:"John R. Henneman",slug:"john-r.-henneman",email:"jrh78@bri.ksu.edu",position:null,institution:null}]},book:{id:"11006",title:"Disinfection of Viruses",subtitle:null,fullTitle:"Disinfection of Viruses",slug:"disinfection-of-viruses",publishedDate:"May 18th 2022",bookSignature:"Raymond W. Nims and M. Khalid Ijaz",coverURL:"https://cdn.intechopen.com/books/images_new/11006.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"104702",title:"Dr.",name:"Raymond W.",middleName:null,surname:"Nims",slug:"raymond-w.-nims",fullName:"Raymond W. 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\r\n\tThe immense benefits of tunnels can be readily recognized and have led to great strides in areas such as transportation, stormwater drainage, waste disposal, and pipeline networking. Requirements for tunnels depend on the intended functions and factors such as size, depth, configuration, and underground conditions. Achieving the desired functionality is usually multifarious and complex due to the range and interrelationships of the myriad of issues that must be taken into account.
\r\n\r\n\tThis book provides further insights into the design and construction processes as well as the performance of tunnels. Areas covered include design considerations, modeling approaches, drilling and excavation techniques, measurement and instrumentation, tunneling in offshore environments, machinery and equipment, ground investigations, cost-benefit evaluations, environmental and social impacts, sustainability, and health and safety. The book aims to provide supplementary information that advances the frontier in tunnel engineering whilst serving as a first recourse for those new in the field of tunneling.
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Hitherto, he was an assistant professor at Prince Mohammad Bin Fahd University, a research fellow at the University of Leeds, a lecturer at the University of Uyo, and a senior consultant at Sustainable Energy Environmental and Educational Development (SEEED), USA. He holds a doctorate in Civil Engineering. His interests include numerical/analytical methods for engineering problems; experimental and numerical modeling of geotechnical systems; site investigation, and laboratory and field geotechnical experimentation; computational fluid dynamics; stochastic and optimization analysis; and structural analysis and design.",institutionString:"University of Wolverhampton",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"University of Wolverhampton",institutionURL:null,country:{name:"United Kingdom"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"11",title:"Engineering",slug:"engineering"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"466997",firstName:"Patricia",lastName:"Kerep",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/466997/images/21565_n.jpg",email:"patricia@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"}},relatedBooks:[{type:"book",id:"7314",title:"Exploitation of Unconventional Oil and Gas Resources",subtitle:"Hydraulic Fracturing and Other Recovery and Assessment Techniques",isOpenForSubmission:!1,hash:"2eba15587cac74206f978e72a0cef2f9",slug:"exploitation-of-unconventional-oil-and-gas-resources-hydraulic-fracturing-and-other-recovery-and-assessment-techniques",bookSignature:"Kenneth Imo-Imo Eshiet",coverURL:"https://cdn.intechopen.com/books/images_new/7314.jpg",editedByType:"Edited by",editors:[{id:"195037",title:"Dr.",name:"Kenneth Imo-Imo Israel",surname:"Eshiet",slug:"kenneth-imo-imo-israel-eshiet",fullName:"Kenneth Imo-Imo Israel Eshiet"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10198",title:"Response Surface Methodology in Engineering Science",subtitle:null,isOpenForSubmission:!1,hash:"1942bec30d40572f519327ca7a6d7aae",slug:"response-surface-methodology-in-engineering-science",bookSignature:"Palanikumar Kayaroganam",coverURL:"https://cdn.intechopen.com/books/images_new/10198.jpg",editedByType:"Edited by",editors:[{id:"321730",title:"Prof.",name:"Palanikumar",surname:"Kayaroganam",slug:"palanikumar-kayaroganam",fullName:"Palanikumar Kayaroganam"}],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:"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:"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:"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:"2270",title:"Fourier Transform",subtitle:"Materials Analysis",isOpenForSubmission:!1,hash:"5e094b066da527193e878e160b4772af",slug:"fourier-transform-materials-analysis",bookSignature:"Salih Mohammed Salih",coverURL:"https://cdn.intechopen.com/books/images_new/2270.jpg",editedByType:"Edited by",editors:[{id:"111691",title:"Dr.Ing.",name:"Salih",surname:"Salih",slug:"salih-salih",fullName:"Salih Salih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"117",title:"Artificial Neural Networks",subtitle:"Methodological Advances and Biomedical Applications",isOpenForSubmission:!1,hash:null,slug:"artificial-neural-networks-methodological-advances-and-biomedical-applications",bookSignature:"Kenji Suzuki",coverURL:"https://cdn.intechopen.com/books/images_new/117.jpg",editedByType:"Edited by",editors:[{id:"3095",title:"Prof.",name:"Kenji",surname:"Suzuki",slug:"kenji-suzuki",fullName:"Kenji Suzuki"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3828",title:"Application of Nanotechnology in Drug Delivery",subtitle:null,isOpenForSubmission:!1,hash:"51a27e7adbfafcfedb6e9683f209cba4",slug:"application-of-nanotechnology-in-drug-delivery",bookSignature:"Ali Demir Sezer",coverURL:"https://cdn.intechopen.com/books/images_new/3828.jpg",editedByType:"Edited by",editors:[{id:"62389",title:"PhD.",name:"Ali Demir",surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"77966",title:"Incorporation of Novel Elements in Bioactive Glass Compositions to Enhance Implant Performance",doi:"10.5772/intechopen.99430",slug:"incorporation-of-novel-elements-in-bioactive-glass-compositions-to-enhance-implant-performance",body:'A bioactive material is one that is able to elicit a specific biological response at the interface of a material that results in bond formation between the body tissues and the material that they surround [1]. Common bioactive materials include bioactive glasses, and from that derived bioactive glass-ceramics and bioactive ceramics.
Bioactive glass was first introduced in the late 1960’s by Dr. Larry Hench after an enlightening conversation with an army officer while attending a scientific conference. During their discussion, they connected on the common tragic injuries that the soldiers were experiencing during the Vietnam War that was occurring at that time. These types of injuries involved those to the limbs, and during that time, the treatment quite often involved amputation due to the absence of a material capable of effectively supporting the hands or the feet. Over the next few years, Hench and his students developed a soda-calcia-phosphate-silicate based glass composition, which was proven to stimulate bone [2]. The result of this development in 1969 was the well-known and copyrighted 45S5 Bioglass. This discovery was the beginning of a new generation of materials, acting as temporary substrates for supporting damaged tissues [3], and since then launched products formed from variations of bioactive glasses and glass-cermaics such as calcium phosphates and synthetic hydroxyapatite [4, 5, 6, 7].
The main purpose of such substrates was to create implants that react to the body’s process unlike the implants that were in use at that time which were inert or unreactive. His continued study focused on revealing the mechanism on why his novel glass composition, 45S5, was able to interact with the body as a result of by-products from the dissolution of the glass components in the body [8, 9].
When a glass is designed to function as a potential implant and possess bioactive features, its behavior is monitored as certain criteria must be achieved before confirming bioactivity. This can be done by determining its surface type. There are five surface type characteristics of silica-based glasses. Type I surfaces undergo only a thin surface layer hydration when exposed to the bodily aqueous environment. In a case like that, the bulk composition is similar to that of the surface composition. Type II surfaces consists of a silica-rich protective film that occurs as a result of selective alkali ion removal. Type III surfaces are known for their ability to form dual surface layers, known to contribute to durability in both acidic and alkali solutions. Type III surface interactions are characteristic of an ideal bioactive glass. Type IV surfaces have the ability to form a silica-rich layer, however, the silica concentration is not high enough to protect the glass from further attack by network dissolution. Therefore, they are known to have poor durability. Glasses that undergo congruent dissolution with equivalent loss of alkali and silica exhibit that of a Type V glass surface [10].
The original purpose for creating a bioactive glass was to form a chemical bond with bone, and this was achieved by Dr. Larry Hench as stated prior. It is important to understand the mechanism of how this interaction became possible. According to Hench, further thermodynamic studies allowed us to understand that there is a formation of an organic structure being derived from an inorganic one. He was able to determine that the stability of Bioglass® came as a direct result of the formation of a Type III surface [10]. This usually occurs as the result of the presence of phosphorus pentoxide P2O5 in its composition or in some cases, aluminum(III) oxide Al2O3, forming an additional surface layer of either alumina-silicate or calcium-phosphate species on the surface of the silica-rich layer. This comes as a result of dealkalization, surface structural modifications or precipitation from solution [9, 10]. Glasses like these tend to be very durable in both acidic and alkaline solutions, which contribute to the formation of a hydroxyapatite layer capable of creating a bond with tissue.
Hench, his students, and his second wife, June Wilson, a clinical biologist, also noted that this mechanism contributed to 45S5 creating strong bonds to living tissue because of the expression of bone-growth genes [2, 11] in the body that was stimulated by the chemical byproducts of the glass components in the body due to Type III surface interaction [10].
The chemical mechanism that occurs once a bioactive glass is successfully introduced into the body as an implant involves a series of ion transfer reactions, as shown in Figure 1, that result in the formation of hydroxyapatite (HA). The HA formation is required for the conformation of bioactivity. When a bioactive glass comes into contact with the bodily environment, a series of reactions occur to confirm bioactivity according to Figure 1 in a 5-stage process:
Cation exchange involving the monovalent and bivalent cations present in the glass with the H+ from the solution, leading to the formation of Si-OH (silanol) bonds on the glass surface and an increase in pH.
The pH continues to increase while Si-O-Si bonds are attacked by hydroxyl ions, causing soluble silica Si(OH)4 to be lost in solution and increases the silanol concentration at the glass surface exposed to the fluid.
Condensation and polymerization of silanol groups occur, resulting in the formation of a silica-rich amorphous layer (silica gel).
Calcium and phosphate ions diffuse through the silica gel, forming and amorphous CaO-P2O5 rich film on the silica gel layer film which later crystalizes.
The crystallization of the CaO-P2O5 amorphous layer leads to the formation of HA.
Illustration of series of ion exchanges involved in the formation of HA [
Following the confirmation of bioactivity in stage 5, adsorption and desorption of growth factors, produced by the surrounding cells, are enhanced by the HA layers. Thereafter, macrophages prepare the implant site for tissue repair by the elimination of dead cells, followed by the attachment of osteoblast stem cells. The following stage involves the differentiation and proliferation of the osteoblast stem cells toward the mature osteoblast phenotype. This typically occurs within hours to weeks depending on the class of the bioactive material. Thereafter, generation of an extracellular matrix occurs as growth factors stimulate cell division and mitosis and the proteins required for the matrix development. The extracellular matrix becomes mineralized followed by the encasement of mature osteocytes in a collagen-HCA matrix, resulting in bone growth [13].
The novel glass composition Bioglass 45S5 was of the Na2O-CaO-SiO2-P2O5 glass system and was known to possess a high calcium concentration with its composition close to a eutectic in the Na2O-CaO-SiO2 phase diagram [4, 5, 14]. Hench’s novel discovery included this glass system in the following mol% concentration: 46.1%SiO2, 24.4%Na2O, 26.9%CaO, 2.6%P2O5. This glass composition was trademarked Bioglass® and since then has only been used in Ref. to the 45S5 composition and not for any other general bioactive glasses [14]. Its ability to create a bond to bone so strong that it could only be removed once the bone was broken.
Figure 2 illustrates a ternary plot in increments of 10 wt% of the three base compounds with the addition on P2O5 for the formation of the novel Bioglass® composition, and for the design of other potential bioactive glasses and glass ceramics based on the wt% of each component. Within it identifies regions of bonding type as it relates to the ability to bond to hard or soft tissue. This is a good tool to predict the bioactive behavior of glass compositions within the SiO2-Na2O-CaO series and other potential series depending on the compounds involved in the desired composition.
Compositional dependence (wt%) of bone bonding and soft tissue bonding of bioactive glass and glass-ceramics. The compositions within region a have a constant 6%P2O5 apart from AW glass ceramic which consists of concentration of P2O5 greater than 6%. Regions S and E both have the ability to interact with and bond to soft tissue and within region E specifically lies the novel bioglass® composition reprinted with permission from [
The index of bioactivity, IB, is used to indicate the measurement of the bioactivity of any material. Introduced by Hench, IB =100/
Since 1994, bioactive materials were classified into Class A and Class B types. Class A bioactive materials were determined to be osteoproductive materials which elicit both intracellular and extracellular responses at its interface. Therefore, Class A bioactive glasses have the ability to bond with both bone and soft tissue. Class B materials are known as osterconductive materials which elicit only an extracellular response at its interface. Therefore, osteoconductive implants provide a biocompatible interface along which bone migrates. Bioglass® is both osteoproductive and osteoconductive and has an IB of 10 [17]. Region D in Figure 2 has an IB of 0 while there is an IB of 2 at region A, and it increases as the composition becomes more central on the ternary plot [18].
Experimental processes known to test for bioactivity include
(a) XRD analysis and identification of HA formation through starred peaks after glass composition S4-Z1 is immersed in SBF solution for 3,7, 14 and 21 days respectively. (b) FTIR analysis of S4-Z1 after immersion in SBF for 3. 7, 14, and 21 days respectively. (c) HA formation identified via SEM analysis after immersion in SBF solution for 21 days. Reprinted with permission [
As Hench’s introduction of the novel 45S5 Bioglass® to the medical and engineering era became popular, it birthed future opportunities and advancements for bioactive glasses as researchers sought to make targeted improvements with it to further their knowledge about their applications. Additionally, toxicity of the glasses and environmental factors such as temperature, pressure, and pH must be considered when designing a particular bioactive glass for medical applications. Throughout the years, bioactive glasses have been used in the following areas: dental fillings and treatment, scaffold production, incorporation into other materials such as polymers and for hard and soft bone tissue engineering [20]. Further exploration and experimentation with bioactive glass compositions, led to the formation of many different compositions intended for specific purposes which were achieved by incorporating other compounds to customize them based of the desired characteristics. A few base compositions that have been created overtime is listed in the following Table 1.
Most of the bioactive glass compositions in Table 1 consists of the following four compounds: SiO2, Na2O, CaO, and P2O5. The original 45S5 composition served to identify which combinations of compounds produced a glass with ideal bioactive properties. While the S53P4 composition comprised of a slight variation of Hench’s original 45S5 composition, the 13-93 and 13-93B1 compositions include compounds not found in Hench’s original composition. Although these deviations from the 45S5 composition reduces their bioactive potential, other benefits are gained. For example, S53P4 bioactive glass is more stable than the 45S5 composition and borate-based bioactive glasses stimulate faster hydroxyapatite (HA) formation rates. Magnesium ions have been shown to increase bioactive glass antibacterial properties and synergize well with host Mg ions in the body during the bone formation process. Furthermore, the “addition of borate ions into the glass matrix has been proven to increase apatite formation rates” on bioactive glass surfaces. This in turn opens the potential for a faster bone remodeling process [21].
The continuous evolution of bioactive glasses is also revealed through their clinical applications. Silica-base bioactive glasses such as the nominal 45S5 and the S53P4 composition were the original accepted standard in the implantation industry. Their rapid surface reaction time and comparatively low softening temperatures allow for optimal conditions for bone remodeling. Recently, though, borate-based bioactive glasses have gained a foothold in the tissue engineering market. Having been approved in 2016 and 2018 respectively, the 13-93B3 and GL1605 compositions represent the newer borate bioactive glass compositions. Borate glasses on average have been shown to release Na and Ca ions at a faster rate than their silica-based counterparts [22]. They are also responsible for slower regional pH increases than silica glasses due to reduced concentrations of alkali ions and the presence of boron. Whether these features are improvements to silica-based glasses or not is up to researchers and their intended applications, but nevertheless, borate glasses have contributed to the expansion of the bioactive glass market.
Like all materials, researchers are continuously testing and expanding the limitations of the base bioactive compositions. For example, some base compositions are more appropriate for environments under constant load while others for those of brief, high load amplitudes. Another factor to consider is the alkalinization of regions introduced to bioactive glasses. While this may not be significant at lower concentrations, it hinders the extent that base bioactive glass compositions can be incorporated into the body since large pH changes can be detrimental to human health. Researchers in response have to determine viable methods of retaining the beneficial effects bioactive glasses present while lessening their control over regional pH. Likewise, the intrinsic brittle nature of bioactive glasses has prompted researchers to consider alternative methods of incorporating them into the body that maintain their biological benefits while increasing their strain to failure nature [23, 24, 25]. Rather than diverting valuable resources toward synthesizing different base bioactive glass compositions for singular uses, researchers are now looking to expand base properties through a variety of methods. The goal is to synthesize inorganic bioactive glasses that feature similar properties to materials found within the human body (Table 2).
Composition (wt%) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
Name | SiO2 | Na2O | CaO | P2O5 | K2O | MgO | B2O3 | ZnO | CuO | Source |
45S5 | 45.0 | 24.5 | 24.5 | 6.0 | • | • | • | • | • | [20] |
S53P4 | 53.0 | 23.0 | 20.0 | 4.0 | • | • | • | • | • | [20] |
13-93 | 53.0 | 6.0 | 20.0 | 4.0 | 12.0 | 5.0 | • | • | • | [20] |
13-93B1 | 34.4 | 5.8 | 19.5 | 3.8 | 11.7 | 4.9 | 19.9 | • | • | [20] |
13-93B3 | • | 6.0 | 20.0 | 4.0 | 12.0 | 5.0 | 53.0 | • | • | [22] |
GL1605 | • | 6.4 | 20.0 | 4.0 | 12.0 | 5.0 | 51.6 | 1.0 | 0.4 | [22] |
Composition of various silicate-based bioactive glasses [20].
Material | Compressive Modulus (GPa) | Bending Strength (MPa) | Compressive Strength (MPa) | Fracture Toughness (MPa m1/2) | Vickers Hardness (MPa) | Structure | Source |
---|---|---|---|---|---|---|---|
HA | 35–120 | 60–120 | 100–150 | 0.8–1.2 | 90–140 | Ceramic | [20] |
Bioglass® 45S5 | 60 | 40 | • | 0.6 | • | Glass | [20] |
Bioglass 52S4.6 | 60 | 40 | • | • | • | Glass | [20] |
Trabecular Bone | 0.05–0.6 | 10–20 | 1.5–7.5 | 0.1–0.8 | 40–60 | • | [20] |
Cortical Bone | 7–30 | 50–150 | 100–135 | 2–12 | 60–75 | • | [20] |
Mechanical properties of various bioactive glasses, ceramics, and human bones [20].
Customization and improvement of bioactive glasses can be achieved through doping. Doping involves the introduction of impurities or other elements into a base composition that would result in the enhancement in properties (mechanical, biological, structural, thermal, electrical, optical) of the particular product. Wetzel
The CaO present in the Bioglass® composition increases its durability. Studies have shown that “when 10 mol% of CaO was substituted with 10 mol% SiO2 to form 20%Na2O-10%CaO-70%SiO2”, it exhibited a slower Na+ dissolution, and a more stabilized SiO2-rich surface film when compared to the binary 20%Na2O-80%SiO2. This is due to the presence of CaO acts as a modifier that increases the coupling reactions between Si-O-Si and NS bonds, stabilizing the SiO2 rich film by filling the micro voids that form as a result of the Na dissolution, satisfies the bond in this film and prevents any further loss of Na ions [10]. The presence of P2O5 allows for the formation of a secondary calcium phosphate film that develops on the side that is in contact with the organic fluid environment.
In some bioactive glass and dopant compositions, low dopant concentrations may not produce the desired properties while high concentrations can. On the other hand, high dopant concentrations may have disadvantages associated with them such as cytotoxic and carcinogenic effects while low concentrations minimize them and provide protection from these drawbacks. Additionally, the application that a bioactive glass will be used for must also be taken into account when doping.
Other functional variables such as load, fatigue, temperature, and the substances that a bioactive glass will experience in its application are essential in the selection of a desired bioactive glass composition. While a doped bioactive glass may function well under minimal stress at room temperature, its properties may not be ideal in its environment of use. Therefore, it is important to consider the dopant material, concentration, and its application to ensure the promotion of ideal properties and the minimization of those that are not wanted.
Transition metals currently make up a large proportion of suitable dopants due to the medical benefits they provide. Elements like iron (Fe), copper (Cu), magnesium (Mg), and zinc (Zn) that already play vital roles within the human body are the focus of these studies [21, 26, 27, 28, 29, 30]. Similar interest has also been directed toward the rare earth elements. Various elements like Gadolinium (Gd), Erbium (Er), and Holmium (Ho) that are extensively used in a wide range of medical treatments are attractive avenues for researchers to explore [31, 32, 33]. While these make up most target dopant materials, much work is needed to understand the effects that doping a bioactive glass with one of these compounds will have and their extent. Figure 4 reveals the cytotoxic effects that various transition element doping oxides have on cell lines. While some compounds may increase desired bioactive glass components, their biocompatibility should also be assessed before wide-spread usage.
Cell viability of various transition metal oxides on A549 cells.
It has been experimentally revealed that borate glass systems exhibit greater hydroxyapatite (HA) formation and dissolution rates than their silicate-based relatives (ex: 45S5, 13-19, S53P4). Furthermore, borate glasses have been used for healing applications by medical professionals due to the borate ions possessing inherent antibacterial capabilities. When bioactive glasses are doped with borate ions, there was a “gradual increase in surface apatite formation rates” with increased concentration. [34] Additionally, the antibacterial properties of borate doped glass composition increased with greater doping concentrations. This trend is repeated microstructurally as the glass transition temperature,
Cu is another metallic ion that researchers have incorporated into bioactive glass matrices and scaffolds to increase biological performance. Researchers are drawn to it because of its positive effects on endothelial cells and blood vessel maturation. Cu is also an essential ion in the human body and plays a pivotal role in angiogenesis, so doping bioactive glasses with it serves to enhance these benefits [28, 29]. This is upheld in Cu-doped calcium phosphates and bioactive glass scaffolds that reveal enhanced angiogenesis and stimulated osteogenesis in Cu-doped bioactive glass scaffolds. The Cu2+ ion also possesses natural antibacterial properties and works in conjunction with the Ca2+ ions in BGs to increase this property. Cu-doped bioactive glasses and scaffolds have also been shown to increase the differentiation levels of mesenchymal stem cells (MSCs) and act as catalyzing agents in endothelial cell proliferation. On the other hand, bioactive glasses and scaffolds doped with Cu are less suitable at elevated temperatures than their non-doped base compositions. This is due to Cu weakening the BG matrix when it is doped which leads to a decreased glass transition temperature,
Bioactive glasses doped with gold nanoparticles (AuNPs) have also garnered interest among researchers. This is because AuNPs possess a wide range of biomedical applications like therapy, hygiene, diagnostics, and prevention. It is important to note that AuNPs with small diameters (1–2 nm) are toxic in the human body because they cause damage to cell structures when absorbed [35]. However, particle diameters from 3 to 100 nm appear to not have any toxic effect on cellular structures. Not only does doping with AuNPs increase a BG’s biocompatibility, but they also increase the rate of the calcium phosphate layer on the surface, bettering its osteoconductive properties. Greater amplitudes in zeta potentials are also positively correlated with increasing dopant concentrations of AuNPs. In other words, increasing the dopant concentration of AuNP corresponds to greater long-term stability for the bioactive glasses. Interestingly, researchers have also discovered that AuNPs have the possibility of being released into nearby organs from the bioactive glasses they were doped with. This has led some to pursue methods of treatment delivery to specific regions of the body.
Iron was one of the initial elements that were incorporated into bioactive glasses to increase their bioactivity and antibacterial properties [28]. Fe ions have been revealed to enhance the bone metabolism process which is why they were considered as potential doping candidates into bioactive glasses. Fe-doped bioactive glasses have characteristically lower crystallization temperatures than their non-doped counterparts and also have greater storage modulus values [27]. This is turn correlates to larger elastic modulus values for Fe-doped bioactive glasses, making them more suitable for implantation applications into the human body [25]. Likewise, scaffolds created from Fe-doped bioactive glasses have much greater degrees of formability than their base compositions. On the other hand, cytotoxic risks must be considered when doping with high concentrations of Fe which can have detrimental effects within patients and their environment. Interestingly, the magnetic properties present in Fe2+ ions are transferred into the base composition they are doped into. Researchers hope to take advantage of this magnetic behavior by expanding upon existing targeted therapeutic treatments.
Magnesium is an important trace element in the human body, which is what makes it an excellent candidate for doping into bioactive glasses. The integral role Mg plays in bone development and maintenance drew researchers to include it among the first wave of transition metals to be considered as a suitable doping agent. Bioactive glasses doped with Mg have shown increased rates of HA formation on their surfaces and enhanced bioactive and antibacterial capabilities in comparison to their base concentrations [21]. Additionally, these bioactive glasses have exhibited superior long-term osteoconductive and biocompatibility properties. This is important because researchers are continuously seeking methods to increase biomedical implant lifespans since the percentage of individuals outliving their implants is increasing. Furthermore, Mg-doped bioactive glasses have promising applications in skeletal tissue regeneration due to their lower ionic release rates which do not affect the cellular environment to the extent of those with elevated rates.
Many REE ions have practical medical applications including but not limited to imaging techniques, cancer treatments, and pain relief [32]. Therefore, it is not surprising that some of these elements are viable options for therapeutic bioactive glasses. REE have been shown to promote bone repair and increase osteogenesis rates [31]. This is due to their ability to mimic calcium’s role in the bone repair process and open the door to bone density disorder treatments. There are concerns about their cytotoxicity to both patients and the environment (Table 3), but that is for researchers to determine what level of risk is acceptable while achieving sought-after results [33]. Furthermore, the sustainability of REE’s use as a whole is in question since demand for these naturally occurring elements will soon outweigh their supply. Solutions ranging from increased research into REE recycling and replacement are viable options to consider. However, one may also decide that the resources spent in developing a solution can be otherwise diverted to additional research into other dopant materials.
Compound | 3 T3 NRU cytotoxicity test | Test | Source | |||
---|---|---|---|---|---|---|
IC50 (μg/ mL) | Calculated LD50 (mg/ kg b.w.) | EC50 (g/ L) | EC50 (mol/ L) | IgEC50 (mol/ L) | [33] | |
Erbium (III) chloride hexahydrate | 613.1 | 1135.2 | 31.6 | 0.0827 | - 1.08 | [33] |
Lanthanum (III) chloride heptahydrate | 379.4 | 962.6 | 28.2 | 0.076 | - 1.12 | [33] |
Praseodymium (III) chloride hydrate | 532.4 | 1085.1 | 18.7 | 0.0755 | - 1.12 | [33] |
Europium (III) chloride hexahydrate | 530.3 | 1078.4 | 26.9 | 0.0734 | - 1.13 | [33] |
Gadolinium (III) chloride hexahydrate | 571.2 | 1120.7 | 27.4 | 0.0736 | - 1.13 | [33] |
Ytterbium (III) chloride hexahydrate | 423.1 | 1001.3 | 31.0 | 0.0801 | - 1.10 | [33] |
Samarium (III) chloride hexahydrate | 575.6 | 1124.0 | 25.1 | 0.0689 | - 1.16 | [33] |
Thulium (III) chloride anhydrous | 440.7 | 1015.0 | 22.7 | 0.0825 | - 1.08 | [33] |
Dysprosium (III) chloride hexahydrate | 931.8 | 1264.0 | 31.5 | 0.0836 | - 1.08 | [33] |
Terbium (III) chloride hexahydrate | 397.4 | 979.2 | 31.6 | 0.0846 | - 1.07 | [33] |
Holmium (III) chloride hexahydrate | 963.6 | 1205.3 | 27.1 | 0.0714 | - 1.15 | [33] |
Lutetium (III) chloride hexahydrate | 580.2 | 1066.5 | 34.3 | 0.088 | - 1.06 | [33] |
Yttrium (III) chloride hexahydrate | 377.0 | 959.6 | 31.0 | 0.0801 | - 1.10 | [33] |
Neodymium (III) chloride hexahydrate | 418.5 | 966.2 | 25.8 | 0.072 | - 1.14 | [33] |
Cerium (III) chloride heptahydrate | 501.9 | 1067.1 | 31.7 | 0.0852 | - 1.07 | [33] |
Barium Chloride | 661.5 | 1184.0 | 15.6 | 0.075 | - 1.12 | [33] |
Cadmium chloride | 0.252 | 62.7 | 16.5 | 0.09 | - 1.05 | [33] |
Cytotoxicity and Ecotoxicity of rare earth compounds [33].
Greater quantities of bone tissue around bioactive glasses have been observed with Si3N4-doped BGs [23]. This compound’s high strength, fracture toughness, low friction wear, and biocompatibility make it an ideal doping substance for bioactive glasses designed for load-bearing purposes. It is also important to note that Si3N4 is an osteoconductive biomaterial with the potential to catalyze osteogenesis. In other words, this compound increases the rate of bone formation by reducing the time it takes bone-forming cells to reach their target regions. Like other viable dopants, Si3N4 promotes MSC differentiation into osteoblasts and improves their adhesion to organic material. This in turn leads to an increased production of collagen and mineralization, enhancing the bone formation process. The increased bone formation also corresponds with an increase in environment pH. This is due to the Na+ and Ca2+ ions being released during bone formation that create hydroxides which contribute to an increase in regional pH. This phenomenon is shared among most bioactive glass compositions, and there are a multitude of methods to negate potential detrimental effects to patients.
Silver was one of the first transition metals that researchers attempted to dope bioactive glasses with. This is due to its inherent antibacterial capability that covers a wide array of diseases. Medical professionals have enjoyed its benefits in surgical applications and researchers sought to expand upon their success. It has been observed that Ag-doped bioactive glasses have greater bioactive and antibacterial capabilities than their non-doped bioactive glass counterparts [28]. Furthermore, Ag particles are able to diffuse uniformly throughout the bioactive glasses in which they are doped. The feature of not forming a separate Ag layer at the glass surface is important because some unintended and potentially dangerous cellular responses can occur [36]. Likewise, the antibacterial and bioactive benefits Ag particles present are countered by their possible cytotoxic effects in the human body at high concentrations. Therefore, researchers’ margin of error and the specific application of these bioactive glasses play key roles in determining the extent they are doped with Ag particles.
Zinc and Strontium have been doped separately and together into bioactive glass compositions to optimize their properties. Zn is responsible for promoting bone formation while Sr. has been found to limit bone resorption and promote bone remodeling [30]. Bioactive glasses, MSC proliferation and differentiation processes are also increased by the doping of Zn and Sr. When Zn is doped into the glass matrix, it is distributed uniformly, and the surface matrix experiences an accelerated growth of its apatite layer. This in turn corresponds to an overall increase in bioactivity. It is important to note that doping the bioactive glass with too much Zn will increase the potential of cytotoxic effects and a create a lower degradation profile. Additionally, solely doping a bioactive glass with Sr. has been found to limit the formation of the apatite layer on the glass surface. Furthermore, the Sr-glass network is looser than the base glass and Zn-glass networks due to Sr’s ionic radius being larger than those of Ca, the element being substituted with the dopant material, and Zn. Although extensive research has been done regarding these differences in glass networks, there do not seem to be any significant effects in BG properties when low doping concentrations are used. Likewise, it has been experimentally determined that small molar concentrations of Zn (~2%) and Sr. (~5%) produce optimum cell proliferation and differentiation properties, minimizing negative effects associated with elevated doping concentrations. Co-doping the bioactive glass composition with both Zn and Sr. results in a combination of the two dopant effects. The (Zn + Sr)-glass network promotes cell proliferation and differentiation while also limiting the formation of the glass’s surface apatite formation and bone resorption. These represent a few of the various elements and their effects that are considered throughout the glass doping process.
Over the past few decades, since the discovery of Bioglass® in 1969, hundreds of other bioactive glass compositions have been derived or attempted, all with the hopes of either improving properties of existing applications such as metal implants, or to personalize a specific composition for a unique application. For instance, using a bioactive glass composition to coat a particular metal alloy for implantation. Over the years, researchers have introduced elements in the form of compounds into base compositions with the aim of achieving distinct properties such as increased bioactivity, anti-bacterial behavior, bone proliferation, etc. Therefore, they have since seen promising outcome when incorporating elements such as magnesium, copper, zinc, boron, and strontium, just to name a few. The evolution of bioactive glasses has already shown promising progress and is expected to be become a staple prat in medical devices and applications within the near future. However, this journey has yet to continue. It is important to evaluate the biological response to the newly developed bioactive glass compositions to fully understand their risks and benefits. We are curious to see where this field is leading us in the next years.
A special thanks is directed toward Dr. Vijay Vaidyanathan, Founding Chair of the Biomedical Engineering department at the University of North Texas in Denton, TX, through which all of this is possible.
The authors declare no conflict of interest.
Every year, thousands of people come from the lowlands to high altitude such as the Qinghai-Tibetan plateau, the Andes, and the Alps, for sight-seeing and mountaineering. Although identification on high altitude is controversial [1, 2] (see Table 1), altitude illnesses do not generally occur until 2500 m altitude or greater [2]. Currently, there are hundreds of thousands of non-native people working and living in these areas at altitudes ranging from 4000 to 5072 m including mountaineers, search and rescue personnel, and military personnel.
Davis et al. [1] | Rolan [2] | |
---|---|---|
High altitude | Beyond 2400 m | 2500 m–3500 m |
Very high altitude | Beyond 4000 m | 3500 m–5800 m |
Extremely high altitude | Beyond 5500 m | Beyond 5800 m |
Identification of high altitude.
Poor sleep quality is a common experience for new arrivals at high altitude in the days to weeks following acute ascent. They often encounter with increased awakenings, frequent brief arousals, a sense of suffocation relieved by a few deep breaths, and resumption of sleep, which is now known as periodic breathing (PB). Upon arising from sleep, the impression is one of greatly restless sleep. Poor sleep quality at high altitude is one of the serious complaints in people with mountain sickness and influences physical and mental well-being, which can manifest as impaired cognitive abilities [3, 4] and poor daytime performance [5]. Up to now, there are no acceptable diagnostic criteria for sleep disorder at high altitude. It is recognized as a symptom of mountain sickness rather than an altitude disease.
Here we discuss the features of sleep at high altitude with focus on the role and causes of PB in altitude sleep disturbance, subjective changes in sleep quality, objective variations in sleep architecture, and management of sleep disorder at high altitude. We also discuss whether it is appropriate to name it high-altitude sleep disorder (HASD) as one of the altitude-related illness in accordance with the nomenclature of other high-altitude diseases.
One of the most important characteristics of sleep disorder at high altitude is PB, which usually occurs at altitudes above 2000 m [6]. PB during sleep was first recorded in 1886 by Mosso [7] and further observed by Douglas and Haldane in 1909 [8]. It is considered that under high altitude hypoxic circumstances, breathing was stimulated by hypoxia, leading to hypocapnia and lessening of hypoxia, which triggers apnea during sleep. Apnea, in turn, restores ventilatory by raising PCO2 and increasing hypoxia, generating the periodic respiratory cycle. This cyclical crescendo-decrescendo pattern periodicity usually consists of 2–4 breaths, separated by an apnea of 5–15 s in duration from the next burst of 2–4 breaths. Therefore, unstable breathing is the main characteristic of PB.
The extent of PB increased progressively as the altitude increased [9]. There is a strong positive correlation between PB and severity of acute mountain sickness (AMS) as assessed by Lake Louise (LL) score. With the increasing of altitude, normal values for partial pressure of arterial (PaO2) decreased compared to sea level, pH changing to respiratory alkalosis with concomitant hypocapnia [10]. Above 4000 m altitude, PB exists in most people, but this phenomenon may be beneficial, because with the worsening of PB, a higher arterial oxygen saturation (SaO2) was observed during sleep [10, 11]. After 3 months of acclimatization at 3800 altitude, PB could also be observed in lowlanders. Although acclimatized lowlanders experienced PB more frequently than native Tibetans at 89–85% of SaO2 stage, there is no significant difference in total PB events occurring either in non-rapid eye movement (NREM) or rapid eye movement (REM) stage [12]. See details in Figure 1, periodic breathing during sleep between native Tibetans and acclimatized Han lowlanders at 3800 m altitude. Even for a longer time (13 months) of camp in the Antarctic base Concordia (3800 m), PB prevailed for the major part of sleeping time [13]. These findings from a cross-sectional and a longitudinal study support our current understanding which assumes PB would not be largely relieved after acclimatization.
Periodic breathing during sleep between native Tibetans and acclimatized Han lowlanders at 3800 altitude. Modified from Kong et al. [
The mechanism underlying this respiratory pattern for apnea and PB during sleep in hypoxic environments is believed to be a reduction in the PaO2 and acid-base adjustments. The procedure of PB may be summarized as conflicting dynamics between hypoxic stimulation of ventilation and suppression of respiratory output from ensuing hypocapnia. These changes lead to alterations in chemoreflex control and cerebrovascular responses to changes in arterial O2 which finally result in hyperventilation. For lowlanders, acclimatization to high altitude magnifies these changes. Briefly, an elevated chemosensitivity causes a more vigorous response to the rise in PaCO2 while the apnea outweighs the improvements in the effectiveness of ventilation in changing the arterial O2 caused by the chronic hypocapnia leading to the occurrence of PB [14].
The severity of PB is determined to be aggravated by an increasing neural respiratory drive (NRD), which can be measured by the electromyogram of the diaphragm. A sleep study in four healthy mountaineers performed at 3380, 4370, and 5570 m in the Andes, Argentina, confirmed this hypothesis [15]. A high NRD at altitude leads to a higher ventilation to maintain oxygenation, which results in more significant hypocapnia. This triggers apneas and O2 desaturations, as indicated by the positive correlation between the EMG of the diaphragm and the O2 desaturation index.
PB is considered to contribute to and/or be a result of sleep fragmentation by frequent arousals which may be responsible for poor sleep quality following altitude ascent. Sleep and arousals lead to greater breathing instability. Apnea is in correspondence to an increase in PaCO2 and decrease in PaO2 and consequently unstable ventilation. These changes in blood gases also lead to marked alterations in cerebral blood flow (CBF) which, in turn, may result in a sudden elevation (with reduced CBF) or reduction (with increased CBF) in brain stem pH.
Therefore, the uncomfortable sensation of sleep at high altitude is largely due to respiratory disturbance arising from the physiologic ventilatory dilemma of acute ascent, where stimulation by hypoxia alternates with inhibition by hypocapnic alkalosis.
Subjective sleep quality at high altitude is usually evaluated by a questionnaire, e.g., sleep log questions, Pittsburgh Sleep Quality Index (PSQI), and Athens Insomnia Score (AIS). The prevalence of sleep disorder may differ considerably at altitude from observational studies. At a 3500 m hotel, 46% of 100 Iranian ski tourists reported frequent awakenings and other subjective sleep disturbances [16]. At an altitude of 3700 m in Lhasa, Tibet, 36.8% of 180 Chinese stationed soldiers reported poor sleep quality as measured by PSQI [17]. Data analysis from the same sample also indicated that poor sleepers (defined as PSQI > 5) were 1.45 times greater in those with polycythemia than those without polycythemia [95% (confidence interval) CI 1.82–2.56] [4]. Report from early pharmacologic treatment trials in acute mountain sickness (AMS) suggested that 53–71% of participants reported difficulty sleeping [18, 19]. Of note, despite the 3 months of acclimatization, a greater proportion of poor sleepers were still observed in lowlanders stationed at 3800 altitude than the native Tibetans (90.91 vs. 45.45%, P = 0.004) [12].
Poor sleep quality at high altitude was one of the most frequently reported symptoms in mountain sickness as assessed by the Lake Louise Symptom Questionnaire and the Qinghai Chronis Mountain Score [12], which are used to diagnose AMS [20] and evaluate severity of chronic mountain sickness(CMS) [21], respectively. This was confirmed by a study using PSQI and AIS which reports decreased subjective sleep quality at high altitude, especially reduced general sleep quality and prolonged sleep induction [22]. For workers rapidly transported from sea level to high altitude, there are no statistically significant differences in polysomnographic parameters between subjects with AMS and those without AMS [23].
For people with CMS stationed at Tibet, the proportion of poor sleepers (defined as PSQI > 5) with severe CMS was 12.54-fold higher than that of good sleepers. See Figure 2, CMS severity comparison between “good” and “poor” sleepers at 3996 m altitude. Subjects with CMS had higher scores in each sleep component of the PSQI score, except the use of sleep medication. After adjusted for CMS score, age, and education, poor sleep quality was determined to be an independent predictor of impaired intelligence quotient [odds ratio (OR) 1.59, 95% CI 1.30–1.95] and short-term memory (OR 1.18, 95% CI 1.07–1.31). Therefore, for people with CMS, the poorer the sleep quality, the worse was the cognitive function [4].
Sleep quality comparison among different CMS severity at 3996 altitude. Modified from Kong et al. [
Polysomnography (PSG) is the gold standard for investigating sleep architecture. However, the technical complexity and logistic demands had brought restriction on its utilization during altitude studies. Although there are several studies that suggest wrist actigraphy-derived data on total sleep time, sleep efficiency and sleep onset latency were similar to those of PSG [24]; actigraphy is insufficient in detecting sleep stage and breathing events.
Objective assessment of sleep architecture at altitude by electroencephalogram was first reported by Joern et al. in 1970 [25]. They found a near absence of stages 3 and 4 and a 50% reduction in rapid eye movement (REM) sleep and reported PB and arousals in one subject. A later study in 1975 confirmed a decrease in deeper sleep and increase in lighter sleep stages and brief arousals after ascending to an altitude of 4300 m at the Pikes Peak when compared to subjects at low altitude [26]. Subsequent studies have generally confirmed the shift at altitude toward lighter sleep stages, with a variable change in duration of REM sleep and increased awakenings associated with PB [27, 28, 29, 30].
Alterations in objective sleep parameters have also been observed during acclimatization. A recent literature review on high-altitude sleep concludes that during rapid ascent to high altitude, there is a reduction in total sleep time, sleep efficiency, and deep sleep (stages 3 and 4) (in new nomenclature N3) and a significant increase in arousals and PB [31]. These variations are possibly high altitude dependent, and the effects tend to moderate with acclimatization [6]. Hypnograms of a partially acclimatized lowlander sleeping and a native Tibetan sleeping at high altitude are shown in Figures 3 and 4.
Hypnogram of a 27-year-old young man sleeping acclimatized for 11 months at altitude of 3800 m. Frequent awake, less proportion of stage 4 and REM sleep might be observed.
Hypnogram of a 25-year-old native Tibetan sleeping at altitude of 3800 m. There is sufficient time in stage 4 sleep and scarce REM sleep.
Although subjective sleep quality is impaired at high altitude, attempts to find a correlation between objective and subjective measures have failed to find a connection [24]. One study investigated 63 participants who completed a 3-hour flight from sea level to the South Pole (3200 m) and discovered no association between self-reported sleep quality and sleep efficiency, nocturnal oxygen saturation, and apnea/hypopnea index (AHI) obtained from PSG [32]. When assessed by LL score, there was no significant correlation of the subjective sleep measurement compared to sleep efficiency derived from PSG and actigraphy [24]. Another study investigated 165 young male soldiers stationed in Tibet Plateau (3800 m) for at least 3 months. In a multiple regression model adjusted for age, service time, body mass index, Epworth Sleepiness Scale, anxiety, and depression, sleep onset latency (b = 0.08, 95% CI: 0.01–0.15) and NREM latency (b = 0.011, 95% CI: 0.001–0.02) obtained from PSG were slightly positively correlated with global PSQI, while mean nocturnal SpO2 (b = −0.79, 95% CI: −1.35 to −0.23) and time in stage 3 + 4 sleep (b = −0.014, 95% CI: −0.001 to −0.028) was slightly negatively associated with global PSQI [12].
Tibetans and Andeans are the native populations to the Tibetan and Andean Plateaus descending from colonizers. Both populations have been exposed to the hypoxic environmental stress of lifelong exposure to high altitude. But native Tibetans and Andean highlanders exhibit different ways of adaptation to chronic hypoxia [33]. Andean highlanders have blunted hypoxia ventilatory response compared to Tibetans which is thought to be acquired and developed in adolescence [34]. Native Tibetans were reported to have higher maximal oxygen uptake, greater ventilation, and brisker hypoxic ventilatory responses to adapt to the hypoxic environment at high altitude and, therefore, to have a better-quality sleep than Han lowlanders [35] which may largely be attributed to genetic adaptations [36].
Few studies had compared sleep architecture between high-altitude dwellers and non-native highlanders. An elder study investigated the Sherpa highlanders dwelling above 3500 m. The Sherpas exhibited few PB with apnea due to low ventilatory sensitivity to hypoxia at 5300 m altitude [37]. A later study reported the sleep pattern of Peruvian Andeans situated at 4330 m altitude. Sleep architecture is closely resembling to normal of people at sea level with significant amount of NREM sleep and unimpaired REM sleep [38]. Contrary to the previous reports, a recent study surveyed sleep architecture of Peruvian highlanders living in Puno at 3825 m. The highlanders had a longer time in total sleep time and increased wake-after-sleep onset and arousal index but decreased sleep efficiency, which suggest greater disturbances in sleep in highlanders compared with lowlanders [39].
As we mentioned above, acclimatization would help lowlanders to relieve sleep disturbance after ascending to high altitude. This could be supported by an earlier study which claimed over 3 days of acclimatization over 4559 m resulted in a partial recovery of sleep structure with increases in slow wave sleep and REM sleep and a reduction in the arousal index [40].
But little is known whether prolonged hypoxia may help to improve sleep architecture at high altitude. Animal studies showed that there was a 50% reduction in the proportion of slow wave sleep and loss of REM sleep when rats were chronically exposed to hypoxia environment simulating an altitude of 5000 m [41, 42]. A clinical study conducted in Shangri-La, which has an altitude of 3800 m, surveyed the differences in sleep architecture between native Tibetans’ and Han lowlanders’ stations for at least 3 months. After adjusted for the length of stay at altitude, significant differences in lower mean nocturnal SpO2 and shorter time in NREM sleep were determined in acclimatized lowlanders than the native Tibetans [12]. Figure 5 indicates a decreased nocturnal artery oxygen of a 3-month acclimatized lowlander. So, it is reasonable to conclude that the effect of prolonged acclimatization to hypoxia is limited in relieving hypoxemia and improving deep sleep which might be an explanation for the impaired cognition brought about by poor sleep.
Decreasing in artery oxygen during sleep of a 24-year lowlander acclimatized for 3 months at 3800 altitude. The lowest SaO2 is 83% and the mean SaO2 is 92%.
Studies on sleep disorder at high altitude from the above reviewed scientific literature confirm the assumption that altitude-related illness including AMS and HAPE may deteriorate sleep quality either directly or indirectly through complaints of headache, hard breathing, cough, etc. It is widely accepted that HAPE usually develops within 2–4 days after quickly ascending to high altitude, but sleep in the first night at altitude may have been affected. Both susceptible HAPE subjects and healthy mountaineers without HAPE revealed a major reduction in sleep efficiency and in NREM stage 3 and 4 sleep (in new nomenclature N3) in the first night after the ascent to 4559 m within 1 day [43]. The deteriorated ventilation and intermittent hypoxia associated with PB in the first 1–2 nights at high altitude with the associated elevation of pulmonary artery pressure may promote the subsequent development of HAPE in susceptible subjects. Thus, the occurrence of sleep disorder is prior to and/or independent of HAPE but may worsen due to HAPE.
Literature reports also provide empirical evidence that sleep disturbance was discordant from other AMS symptoms and absent in 40% of cases with severe headache, long considered a symptom of AMS. Since sleep disorder correlated poorly with other symptoms of AMS, the sleep component had been removed from the 2018 Lake Louise Acute Mountain Sickness Score [44].
Therefore, it is conceivable that sleep disorder should be viewed as an independent altitude-related illness rather than a symptom of AMS despite the fact that it may overlap other mountain sicknesses. In accordance with the nomenclature of other high-altitude diseases [e.g., high altitude cerebral edema (HACE), high altitude pulmonary edema (HAPE), etc.], high-altitude sleep disorder (HASD) might be an appropriate name.
Hypoxemia is the main reason and one of the primary independent contributors to poor sleep quality at high altitudes [12]. In theory, correction of hypoxemia by supplemental oxygen or pharmacological suppression of ventilation may have the potential in treating sleep disorder at high altitude.
A case report tested the treatment effect of a nasal demand oxygen delivery device on hypoxemia during sleep at high altitude in a 46-year-old male healthy participant at an altitude of 4600 and 5700 m [45]. The participant received a volume of oxygen delivery dose for 0, 16.7, 33.3, and 50 ml/s at random per pulse for every 2 h during sleep period. Results of the study indicated an increase in arterial blood oxygen saturation and decreases in tidal volume and AHI.
Another controlled trial employed a noninvasive ventilation mode named adaptive servo ventilation (ASV) to stabilize periodic breathing due to hypobaric hypoxemia at an altitude of 3800 m, but it failed to affirm its efficacy in controlling central sleep apnea during sleep. However, in their controlled group, supplemental oxygen improved oxygen desaturation index and oxygen saturation, whereas it reduced the arousal index and NREM stage 1 sleep. But neither ASV nor supplemental oxygen could improve subjective quality as measured by the Stanford Sleep Questionnaire and LL score [46].
In summary, based on current limited studies, supplemental oxygen does improve arterial blood oxygen saturation but could not result to a better sleep quality.
Dietary nitrate (NO3−), which is found in beetroot and other vegetables, and inorganic NO3− salts have been shown to have vasodilatory properties [47] and also to reduce oxygen uptake during exercise [48], suggesting NO3− supplementation might play a physiological role during sleep at high altitude. A single-blind placebo-controlled trial examined the effects of dietary NO3− supplementation on the degree of sleep-related hypoxemia in healthy subjects at an altitude from 3700 to 4900 m. Each subject received two 70 ml shots of either beetroot juice (∼5.0 mmol NO3− per shot) or placebo (∼0.003 mmol NO3− per shot) over two consecutive nights at altitude. Results of the study favored dietary nitrate in increasing fluctuations in arterial O2 saturation during sleep at altitude in native lowlanders, but it does not improve AHI or oxygenation [49].
Previous reports suggested that only a few medications may be helpful at high altitudes [50, 51], including theophylline, acetazolamide, zolpidem, zaleplon, temazepam, and integripetal rhodiola herb, a traditional Chinese herb. However, there are often several limitations on pharmacological selection at high altitudes in clinical practice, as current sleeping medications prescribed for sleep disturbances at sea level are not suggested to be used at altitude. For example, it is widely accepted that benzodiazepines (BZDs) may cause hypoventilation, triggering respiratory abnormalities during sleep [52, 53, 54]. Therefore, an ideal choice for medication use at high altitude should neither deteriorate ventilation and oxygen saturation nor affect sleep architecture.
Acetazolamide is considered to increase ventilation and oxygenation, effectively reducing PB by approximately 50% [55]. A meta-analysis of randomized controlled trials determined that acetazolamide improves sleep apnea at high altitude by decreasing AHI and percentage of PB time and increasing nocturnal oxygenation. Results from clinic trials also suggested that a 250 mg daily dose may be as effective as higher daily doses for healthy trekkers [56].
The efficacy and safety of zolpidem and zaleplon in treating sleep disturbances at high altitude had been confirmed by several well-designed clinic trials [57, 58, 59, 60]. A recent meta-analysis of randomized placebo-controlled trials revealed that zaleplon and zolpidem improved the total sleep time, sleep efficiency, and stage 4 sleep duration, whereas they decreased the wake-after-sleep onset without impairing ventilation [61] (data are shown in Figure 6).
Summary of non-benzodiazepines in improving sleep architecture at high altitude. Modified from Kong et al. [
There was no significant difference in ventilation as measured by SpO2 and PB between participants administered with zaleplon or zolpidem and placebo [58, 59, 60]. Furthermore, participants who were administered with zaleplon or zolpidem expressed a significant improvement in the subjective sleep quality, which was measured by sleep log question [59, 60] and PSQI (4.15 ± 2.76 in zolpidem group vs. 6.58 ± 3.98 in placebo group, P = 0.047) [60].
Benzodiazepine use in this environment is controversial. Early studies showed that 1 mg of oral loprazolam did not worsen either slow wave sleep depression or apnea and allowed normal sleep reappearance after acclimatization [28, 62]. Later, a randomized, double-blind, placebo-controlled trial conducted at 3000 m altitude validated PaO2 decreasing and PaCO2 increasing significantly 1 hour after 5 mg of oral diazepam [63], which suggests that it may cause hypoventilation.
On the contrary, temazepam, a short-acting benzodiazepine, was recommended to be safely used by the International Climbing and Mountaineering Federation MedCom Consensus Guide [51]. However, the effect of temazepam on the objective sleep parameters was inconsistent. Nicholson et al. [64] reported that temazepam significantly shortened the mean sleep onset latency and increased the amount of the REM sleep, whereas Nickol et al. [65] reported no differences in the actigraphy-derived sleep parameters. Results on oxygen saturation and PB from the aforementioned studies were also inconsistent. When compared to the placebo, temazepam showed no significant effect on mean oxygen saturation, yet PB significantly decreased [66]. Although Nickol et al. [65] reported that temazepam could decrease median oxygen saturation, it did not significantly reduce PB during sleep. Because of the inconsistencies in the reported variables, no confirming conclusions can be drawn from available evidence.
To sum up, the use of benzodiazepines should be discouraged at high altitude due to the nocturnal hypoventilation nature of these agents. The efficacy and safety of temazepam need further confirmation by well-designed placebo-controlled trials.
Additional drugs that may be helpful reported by case series include theophylline and the integripetal rhodiola herb, which is a widely used traditional Chinese herb in Tibetan areas. However, strong clinical evidence from randomized controlled trials supporting the effectiveness and safety of these agents has not been demonstrated.
Evidence from current available studies support the routing use of supplemental oxygen during sleep to increase arterial blood oxygen saturation. Acute dietary NO3− supplementation reduces flow limitation and induces more pronounced SaO2 desaturations during sleep at high altitude. Acetazolamide at 250 mg daily dose is effective in reducing sleep apnea, decreasing AHI and PB, and increasing nocturnal oxygenation. Both zaleplon and zolpidem improved the objective sleep architecture without impairing ventilation.
Our understanding on sleep disorder at high altitude is still limited. Mountain tourists commonly complain about subjective sleep disturbances with difficulty in onset of sleep and frequent awakenings in the first few nights at altitude. But those subjective sensations of poor sleep neither are associated with severity of mountain sickness nor tend to disappear after long exposure to high altitude. And consequently, cognitive function was impaired.
There is no reliable evidence that support the consistency between self-report sleep quality and sleep parameters obtained from PSG. The most frequently reported changes in sleep architecture at high altitude are detected by PSG including a decrease in NREM sleep and occurrence of PB. Different patterns of adoption to hypoxic environment exist among native highlanders. For lowlanders ascending to high altitude, acclimatization would be beneficial in relieving hypoxemia and improving deep sleep; however, PB would not be largely relieved after acclimatization.
The occurrence of HASD is prior to most altitude-related diseases and would last for a longer time. We strongly suggest future study to consider it as an independent high-altitude illness as it had been removed from the diagnosing and managing of AMS by the International Society of Mountain Medicine World Congress Committee.
The treatment principle of HASD should not deteriorate nocturnal ventilation and SaO2 or affect sleep architecture. The following evidence-based choices are recommended. Effective treatments for altitude-related nocturnal hypoxemia include dietary NO3− supplementation before sleep and supplemental oxygen during sleep. Medication for respiratory disturbance is 250 mg daily dose of oral acetazolamide, which is beneficial in relieving sleep apnea, decreasing AHI and PB, and promoting nocturnal oxygenation. Both zaleplon and zolpidem are optional agents in improving the objective sleep architecture and subjective sleep quality without impairing ventilation.
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On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. 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Besides, these parts are not only about cutting-edge technologies, but also related with conventional methods and their new applications in colored wastewater treatment area briefly.",book:{id:"5086",slug:"textile-wastewater-treatment",title:"Textile Wastewater Treatment",fullTitle:"Textile Wastewater Treatment"},signatures:"Serkan Arslan, Murat Eyvaz, Ercan Gürbulak and Ebubekir Yüksel",authors:[{id:"170083",title:"Associate Prof.",name:"Murat",middleName:null,surname:"Eyvaz",slug:"murat-eyvaz",fullName:"Murat Eyvaz"},{id:"176699",title:"Dr.",name:"Ercan",middleName:null,surname:"Gürbulak",slug:"ercan-gurbulak",fullName:"Ercan Gürbulak"},{id:"176700",title:"MSc.",name:"Serkan",middleName:null,surname:"Arslan",slug:"serkan-arslan",fullName:"Serkan Arslan"},{id:"176701",title:"Prof.",name:"Ebubekir",middleName:null,surname:"Yüksel",slug:"ebubekir-yuksel",fullName:"Ebubekir Yüksel"}]},{id:"42001",doi:"10.5772/53777",title:"Cyclodextrins in Textile Finishing",slug:"cyclodextrins-in-textile-finishing",totalDownloads:5486,totalCrossrefCites:19,totalDimensionsCites:39,abstract:null,book:{id:"3137",slug:"eco-friendly-textile-dyeing-and-finishing",title:"Eco-Friendly Textile Dyeing and Finishing",fullTitle:"Eco-Friendly Textile Dyeing and Finishing"},signatures:"Bojana Voncina and Vera Vivod",authors:[{id:"33838",title:"Prof.",name:"Bojana",middleName:null,surname:"Voncina",slug:"bojana-voncina",fullName:"Bojana Voncina"}]},{id:"41409",doi:"10.5772/53911",title:"Surface Modification Methods for Improving the Dyeability of Textile Fabrics",slug:"surface-modification-methods-for-improving-the-dyeability-of-textile-fabrics",totalDownloads:7061,totalCrossrefCites:13,totalDimensionsCites:36,abstract:null,book:{id:"3137",slug:"eco-friendly-textile-dyeing-and-finishing",title:"Eco-Friendly Textile Dyeing and Finishing",fullTitle:"Eco-Friendly Textile Dyeing and Finishing"},signatures:"Sheila Shahidi, Jakub Wiener and Mahmood Ghoranneviss",authors:[{id:"58854",title:"Dr.",name:null,middleName:null,surname:"Shahidi",slug:"shahidi",fullName:"Shahidi"}]},{id:"68157",doi:"10.5772/intechopen.87968",title:"Introductory Chapter: Textile Manufacturing Processes",slug:"introductory-chapter-textile-manufacturing-processes",totalDownloads:4473,totalCrossrefCites:14,totalDimensionsCites:26,abstract:null,book:{id:"8892",slug:"textile-manufacturing-processes",title:"Textile Manufacturing Processes",fullTitle:"Textile Manufacturing Processes"},signatures:"Faheem Uddin",authors:[{id:"228107",title:"Prof.",name:"Faheem",middleName:null,surname:"Uddin",slug:"faheem-uddin",fullName:"Faheem Uddin"}]}],mostDownloadedChaptersLast30Days:[{id:"68157",title:"Introductory Chapter: Textile Manufacturing Processes",slug:"introductory-chapter-textile-manufacturing-processes",totalDownloads:4488,totalCrossrefCites:16,totalDimensionsCites:27,abstract:null,book:{id:"8892",slug:"textile-manufacturing-processes",title:"Textile Manufacturing Processes",fullTitle:"Textile Manufacturing Processes"},signatures:"Faheem Uddin",authors:[{id:"228107",title:"Prof.",name:"Faheem",middleName:null,surname:"Uddin",slug:"faheem-uddin",fullName:"Faheem Uddin"}]},{id:"41411",title:"Textile Dyes: Dyeing Process and Environmental Impact",slug:"textile-dyes-dyeing-process-and-environmental-impact",totalDownloads:20676,totalCrossrefCites:101,totalDimensionsCites:320,abstract:null,book:{id:"3137",slug:"eco-friendly-textile-dyeing-and-finishing",title:"Eco-Friendly Textile Dyeing and Finishing",fullTitle:"Eco-Friendly Textile Dyeing and Finishing"},signatures:"Farah Maria Drumond Chequer, Gisele Augusto Rodrigues de Oliveira, Elisa Raquel Anastácio Ferraz, Juliano Carvalho Cardoso, Maria Valnice Boldrin Zanoni and Danielle Palma de Oliveira",authors:[{id:"49040",title:"Prof.",name:"Danielle",middleName:null,surname:"Palma De Oliveira",slug:"danielle-palma-de-oliveira",fullName:"Danielle Palma De Oliveira"},{id:"149074",title:"Prof.",name:"Maria Valnice",middleName:null,surname:"Zanoni",slug:"maria-valnice-zanoni",fullName:"Maria Valnice Zanoni"},{id:"153502",title:"Ph.D.",name:"Farah",middleName:null,surname:"Chequer",slug:"farah-chequer",fullName:"Farah Chequer"},{id:"153504",title:"MSc.",name:"Gisele",middleName:null,surname:"Oliveira",slug:"gisele-oliveira",fullName:"Gisele Oliveira"},{id:"163377",title:"Dr.",name:"Juliano",middleName:null,surname:"Cardoso",slug:"juliano-cardoso",fullName:"Juliano Cardoso"},{id:"163393",title:"Dr.",name:"Elisa",middleName:null,surname:"Ferraz",slug:"elisa-ferraz",fullName:"Elisa Ferraz"}]},{id:"49647",title:"Fiber Selection for the Production of Nonwovens",slug:"fiber-selection-for-the-production-of-nonwovens",totalDownloads:10568,totalCrossrefCites:9,totalDimensionsCites:17,abstract:"The most significant feature of nonwoven fabric is made directly from fibers in a continuous production line. While manufacturing nonwovens, some conventional textile operations, such as carding, drawing, roving, spinning, weaving or knitting, are partially or completely eliminated. For this reason the choice of fiber is very important for nonwoven manufacturers. The commonly used fibers include natural fibers (cotton, jute, flax, wool), synthetic fibers (polyester (PES), polypropylene (PP), polyamide, rayon), special fibers (glass, carbon, nanofiber, bi-component, superabsorbent fibers). Raw materials have not only delivered significant product improvements but also benefited people using these products by providing hygiene and comfort.",book:{id:"5062",slug:"non-woven-fabrics",title:"Non-woven Fabrics",fullTitle:"Non-woven Fabrics"},signatures:"Nazan Avcioglu Kalebek and Osman Babaarslan",authors:[{id:"119775",title:"Prof.",name:"Osman",middleName:null,surname:"Babaarslan",slug:"osman-babaarslan",fullName:"Osman Babaarslan"},{id:"175829",title:"Dr.",name:"Nazan",middleName:null,surname:"Kalebek",slug:"nazan-kalebek",fullName:"Nazan Kalebek"}]},{id:"41409",title:"Surface Modification Methods for Improving the Dyeability of Textile Fabrics",slug:"surface-modification-methods-for-improving-the-dyeability-of-textile-fabrics",totalDownloads:7063,totalCrossrefCites:13,totalDimensionsCites:36,abstract:null,book:{id:"3137",slug:"eco-friendly-textile-dyeing-and-finishing",title:"Eco-Friendly Textile Dyeing and Finishing",fullTitle:"Eco-Friendly Textile Dyeing and Finishing"},signatures:"Sheila Shahidi, Jakub Wiener and Mahmood Ghoranneviss",authors:[{id:"58854",title:"Dr.",name:null,middleName:null,surname:"Shahidi",slug:"shahidi",fullName:"Shahidi"}]},{id:"55424",title:"Textile Reinforced Structural Composites for Advanced Applications",slug:"textile-reinforced-structural-composites-for-advanced-applications",totalDownloads:3876,totalCrossrefCites:9,totalDimensionsCites:16,abstract:"Textile-reinforced composites are increasingly used in various industries such as aerospace, construction, automotive, medicine, and sports due to their distinctive advantages over traditional materials such as metals and ceramics. Fiber-reinforced composite materials are lightweight, stiff, and strong. They have good fatigue and impact resistance. Their directional and overall properties can be tailored to fulfill specific needs of different end uses by changing constituent material types and fabrication parameters such as fiber volume fraction and fiber architecture. A variety of fiber architectures can be obtained by using two- (2D) and three-dimensional (3D) fabric production techniques such as weaving, knitting, braiding, stitching, and nonwoven methods. Each fiber architecture/textile form results in a specific configuration of mechanical and performance properties of the resulting composites and determines the end-use possibilities and product range. This chapter highlights the constituent materials, fabric formation techniques, production methods, as well as application areas of textile-reinforced composites. Fiber and matrix materials used for the production of composite materials are outlined. Various textile production methods used for the formation of textile preforms are explained. Composite fabrication methods are introduced. Engineering properties of textile composites are reviewed with regard to specific application areas. The latest developments and future challenges for textile-reinforced composites are presented.",book:{id:"5921",slug:"textiles-for-advanced-applications",title:"Textiles for Advanced Applications",fullTitle:"Textiles for Advanced Applications"},signatures:"Nesrin Sahbaz Karaduman, Yekta Karaduman, Huseyin Ozdemir\nand Gokce Ozdemir",authors:[{id:"175839",title:"Ph.D.",name:"Nesrin",middleName:null,surname:"Sahbaz Karaduman",slug:"nesrin-sahbaz-karaduman",fullName:"Nesrin Sahbaz Karaduman"},{id:"201620",title:"Dr.",name:"Yekta",middleName:null,surname:"Karaduman",slug:"yekta-karaduman",fullName:"Yekta Karaduman"},{id:"201621",title:"Dr.",name:"Hüseyin",middleName:null,surname:"Özdemir",slug:"huseyin-ozdemir",fullName:"Hüseyin Özdemir"},{id:"201622",title:"Dr.",name:"Gökce",middleName:null,surname:"Özdemir",slug:"gokce-ozdemir",fullName:"Gökce Özdemir"}]}],onlineFirstChaptersFilter:{topicId:"1376",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:122,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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