Data from the Prostate Cancer Prevention Trial [2]. This cohort of men were biopsied as part of the trial design and were on a placebo. Men with a PSA > 4.0 would have been biopsied earlier “for cause”.
\\n\\n
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{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"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"11196",leadTitle:null,fullTitle:"New Updates in E-Learning",title:"New Updates in E-Learning",subtitle:null,reviewType:"peer-reviewed",abstract:"This book presents state-of-the-art educational technologies and teaching methodologies and discusses future educational philosophies in support of the global academic society. New Updates in E-Learning is a collection of chapters addressing important issues related to effective utilization of the Internet and Cloud Computing, virtual robotics, and real-life application of hybrid educational environments to enhance student learning regardless of geographical location or other constraints. Over ten chapters, the book discusses the current and future evolution of educational technologies and methodologies and the best academic practices in support of providing high-quality education at all academic levels.",isbn:"978-1-80355-418-1",printIsbn:"978-1-80355-417-4",pdfIsbn:"978-1-80355-419-8",doi:"10.5772/intechopen.97987",price:119,priceEur:129,priceUsd:155,slug:"new-updates-in-e-learning",numberOfPages:190,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"6afaadf68e2a0a4b370ac5ceb5ca89c6",bookSignature:"Eduard Babulak",publishedDate:"May 18th 2022",coverURL:"https://cdn.intechopen.com/books/images_new/11196.jpg",numberOfDownloads:475,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:0,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 9th 2021",dateEndSecondStepPublish:"October 7th 2021",dateEndThirdStepPublish:"December 6th 2021",dateEndFourthStepPublish:"February 24th 2022",dateEndFifthStepPublish:"April 25th 2022",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"10086",title:"Prof.",name:"Eduard",middleName:null,surname:"Babulak",slug:"eduard-babulak",fullName:"Eduard Babulak",profilePictureURL:"https://mts.intechopen.com/storage/users/10086/images/system/10086.jpg",biography:"Professor Eduard Babulak is an accomplished international scholar, researcher, consultant, educator, professional engineer, and polyglot with more than thirty years of experience. He has published research that has been cited by scholars worldwide. He has been an invited speaker at the University of Cambridge, England; Massachusetts Institute of Technology (MIT); Purdue University, Indiana; Yokohama National University, Japan; University of Electro-Communications, Japan; Sungkyunkwan University, Korea; Shanghai Jiao Tong University, China; Graz University of Technology, Austria; and other prestigious academic institutions worldwide. He serves as editor in chief, associate editor in chief, co-editor, and guest editor for numerous journals. He communicates in sixteen languages and his biography was cited in the Cambridge Blue Book, Cambridge Index of Biographies, Stanford Who’s Who, and several issues of Who’s Who in the World and America.",institutionString:"National Science Foundation (NSF)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"National Science Foundation",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1318",title:"Virtual Learning",slug:"virtual-learning"}],chapters:[{id:"81000",title:"Technology Integration on Teaching Writing in the Foundation Phase Classrooms in the Eastern Cape Province, South Africa",doi:"10.5772/intechopen.103666",slug:"technology-integration-on-teaching-writing-in-the-foundation-phase-classrooms-in-the-eastern-cape-pr",totalDownloads:26,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Teachers play a significant role in developing writing. They are responsible for teaching the younger generations exposed to technology through various gadgets. This study aims to better integrate technology in teaching writing in the Foundation Phase (FP). The premise for this study is the need to integrate technology in the Foundation Phase in order to attain educational goals. A qualitative case study was conducted that involved semi-structured interviews and the draw and talk/write method to gain in-depth knowledge of integrating technology to develop writing skills. For this study, the cognitive theory of multimedia learning (CTML) and sociocultural theory of learning were used as a theoretical framework. The participants were four Grade 3 teachers and 12 learners from two primary schools. This study indicated the importance of integrating technology in teaching writing, which subsequently led to more positive learning experiences for the FP learners. The study’s key finding is that FP teachers are technologically illiterate. As a result, it is suggested that a set of curriculum guidelines based on the interests of this generation of learners be produced to enable teachers and students in successfully integrate teaching and technology in the FP.",signatures:"Pretty Thandiswa Mpiti and Bulelwa Makena",downloadPdfUrl:"/chapter/pdf-download/81000",previewPdfUrl:"/chapter/pdf-preview/81000",authors:[{id:"451956",title:"Dr.",name:"Pretty Thandiswa",surname:"Mpiti",slug:"pretty-thandiswa-mpiti",fullName:"Pretty Thandiswa Mpiti"},{id:"452016",title:"Dr.",name:"Bulelwa",surname:"Makena",slug:"bulelwa-makena",fullName:"Bulelwa Makena"}],corrections:null},{id:"80627",title:"New Updates in Online Learning",doi:"10.5772/intechopen.102576",slug:"new-updates-in-online-learning",totalDownloads:54,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"During the COVID-19 pandemic, a rapid transformation happened overnight in the teaching-learning strategy in primary, secondary and tertiary education. All educators started using web-conferencing tools as principal element of online learning. However, in spite of health concerns among the pandemic situation, strong student preferences towards returning back to face-to-face or hybrid mode brought challenges to the effectiveness of online learning. Students cite many reasons for dropping out of online courses. Increased workload and poor organization of remote learning have been found to be the principal reason for the students’ dissatisfaction. The orientation of online learning needs alignment towards the principle of course design along with the flexibility to attain the instructional goals, objectives, and outcomes. Sophisticated technology often makes online and even hybrid course design to change track from well-designed pedagogy leading to loss of functional relevance for the students. Instructors should be flexible and employ multiple strategies to improve online learning experiences in both asynchronous and synchronous learning environment. Studies have proved that using the best practice of the alignment of learning outcome, online learning activities and repeated online knowledge-checks foster student motivation towards the completion of online courses.",signatures:"Nilesh Kumar Mitra",downloadPdfUrl:"/chapter/pdf-download/80627",previewPdfUrl:"/chapter/pdf-preview/80627",authors:[{id:"439978",title:"Prof.",name:"Dr. Nilesh Kumar",surname:"Mitra",slug:"dr.-nilesh-kumar-mitra",fullName:"Dr. Nilesh Kumar Mitra"}],corrections:null},{id:"80356",title:"Training Framework to Enhance Digital Skills and Pedagogy of Chemistry Teachers to Use IMFUNDO",doi:"10.5772/intechopen.102003",slug:"training-framework-to-enhance-digital-skills-and-pedagogy-of-chemistry-teachers-to-use-imfundo",totalDownloads:51,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The purpose of this study was to develop a training framework to enhance digital skills, practice and pedagogy of Chemistry teachers to effectively use a learning management system (LMS). The Department of Chemistry has been unsuccessful in adopting and integrating technology in teaching since 2011 due to the lack of a framework for training teachers in skills and competencies required to successfully implement digitalization pedagogy, engage students and improve student success. The challenge was that Chemistry teachers used LMS as a repository. This observation was not in line with the newly approved study University’s Teaching, Learning and Technology Strategy and did not support student-centered learning. Action research was employed. It was found that the teacher-training framework and the remote training of Chemistry teachers were developed and implemented. After training, the design and development of online modules significantly improved. COVID-19 lockdown accelerated the transition to fully online teaching.",signatures:"Sibongile Simelane-Mnisi and Ntebogeng Mokgala-Fleischmann",downloadPdfUrl:"/chapter/pdf-download/80356",previewPdfUrl:"/chapter/pdf-preview/80356",authors:[{id:"355471",title:"Dr.",name:"Sibongile",surname:"Simelane-Mnisi",slug:"sibongile-simelane-mnisi",fullName:"Sibongile Simelane-Mnisi"},{id:"449056",title:"Prof.",name:"Ntebogeng",surname:"Mokgalaka-Fleischmann",slug:"ntebogeng-mokgalaka-fleischmann",fullName:"Ntebogeng Mokgalaka-Fleischmann"}],corrections:null},{id:"80271",title:"The Impact of Academic Discipline on Student’s Engagement in Online Learning: An Extension of the Technology Acceptance Model",doi:"10.5772/intechopen.102071",slug:"the-impact-of-academic-discipline-on-student-s-engagement-in-online-learning-an-extension-of-the-tec",totalDownloads:58,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Tertiary education has dramatically changed after the outbreak of COVID-19. The use of the Learning Management System (LMS) in online learning has become popular. Many researchers are trying to investigate its features that influence the degree of acceptance and usage of learners among those techniques. However, some of their acceptance is not behavioral, but more on mental and abstract, which would be considered as engagement. In addition, academic disciplines would have a different focus on the integration of technology into their teaching and learning, thus, it would influence students\\' acceptance of the technology. This research addressed this gap by studying university students in Hong Kong about the Technology Acceptance Model (TAM), and behavioral, agentic, cognitive, and emotional engagement. The findings extended the previous literature of TAM by adding engagement and academic discipline into the model. The current study demonstrates that LMS displays the potential of delivering learning and teaching materials amid the pandemic.",signatures:"Ka Long Chan, Roy Kam and Man Sing Wong",downloadPdfUrl:"/chapter/pdf-download/80271",previewPdfUrl:"/chapter/pdf-preview/80271",authors:[{id:"438312",title:"Mr.",name:"Ka Long",surname:"Chan",slug:"ka-long-chan",fullName:"Ka Long Chan"},{id:"439874",title:"Mr.",name:"Roy",surname:"Kam",slug:"roy-kam",fullName:"Roy Kam"},{id:"439875",title:"Prof.",name:"Man Sing",surname:"Wong",slug:"man-sing-wong",fullName:"Man Sing Wong"}],corrections:null},{id:"80472",title:"Strategy as Plan for Technology Integration to Reposition Lecturers for the New Normal in Higher Education",doi:"10.5772/intechopen.102078",slug:"strategy-as-plan-for-technology-integration-to-reposition-lecturers-for-the-new-normal-in-higher-edu",totalDownloads:26,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter reports on the strategy as plan using ICT policy that could impact on repositioning the lecturers for the integration of technology for the new normal in education. Global, the COVID-19 pandemic distinctly exposed the unpreparedness of lecturers to integrate technology in teaching and learning when the shutdown of the higher institutions was announced. The participants consisted of 37 lecturers from four departments in the School of Education at a university of technology in South Africa. A qualitative case study method was used. An open-ended questionnaire, individual interviews and document analysis were used to collect data. Atlas.ti was used to analyse data. The findings revealed that the study University does not have the eLearning policy to enforce technology integration. Hence the unpreparedness of lecturers to integrate was discovered during Covid-19. It is recommended the study university develops an ICT policy, involving lecturers as stakeholders to promote ownership and conformability.",signatures:"Sibongile R. Ngcapu, Sibongile Simelane-Mnisi and Andile Mji",downloadPdfUrl:"/chapter/pdf-download/80472",previewPdfUrl:"/chapter/pdf-preview/80472",authors:[{id:"355471",title:"Dr.",name:"Sibongile",surname:"Simelane-Mnisi",slug:"sibongile-simelane-mnisi",fullName:"Sibongile Simelane-Mnisi"},{id:"122407",title:"Prof.",name:"Andile",surname:"Mji",slug:"andile-mji",fullName:"Andile Mji"},{id:"448504",title:"Mrs.",name:"Sibongile R.",surname:"Ngcapu",slug:"sibongile-r.-ngcapu",fullName:"Sibongile R. Ngcapu"}],corrections:null},{id:"80566",title:"Lessons Learned in a Hybrid Environment",doi:"10.5772/intechopen.102575",slug:"lessons-learned-in-a-hybrid-environment",totalDownloads:42,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In the last two years in isolation, the hybrid environment for education becomes the most normal way to deliver education. The well-known design techniques are not enough for new learners from distance. The common practice from face-to-face training is neither. A lot of lessons are learned. The new combined approach is based on e-learning in combination with nugget education. The design considers learning and personal users’ styles. The learning experience design takes a significant role in rethinking the course/training design in the hybrid environment. Nowadays, understanding learners’ needs is most important for training design and to motivate them.",signatures:"Eugenia Kovatcheva",downloadPdfUrl:"/chapter/pdf-download/80566",previewPdfUrl:"/chapter/pdf-preview/80566",authors:[{id:"174963",title:"Associate Prof.",name:"Eugenia",surname:"Kovatcheva",slug:"eugenia-kovatcheva",fullName:"Eugenia Kovatcheva"}],corrections:null},{id:"80165",title:"Improving Accessibility of e-Learning Templates for Students with Disabilities",doi:"10.5772/intechopen.101931",slug:"improving-accessibility-of-e-learning-templates-for-students-with-disabilities",totalDownloads:87,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Because of the effective development of contemporary technologies, also during the recent COVID-19 pandemic, students with disabilities have been increasingly integrated into the society, work, and academic environment. Accordingly, the question of how to provide accessible graphical design of e-learning materials for various categories of students with disabilities and how to comply with international accessibility standards is becoming more and more prominent. The purpose of the study was to propose recommendations for the design of e-learning materials to achieve the preparation of effective study materials for students with hearing and visual loss, as well as autism spectrum disorders. According to their needs and requirements, recommendations for the graphic design of accessible e-learning materials have been designed, developed, implemented, and evaluated. The findings revealed a higher level of acceptance of adapted material for all experimental groups and can be helpful for teachers and other professionals educating students with disabilities.",signatures:"Peter Čakš, Monika Ferk, Matjaž Debevc, Julija Bele Lapuh and Ines Kožuh",downloadPdfUrl:"/chapter/pdf-download/80165",previewPdfUrl:"/chapter/pdf-preview/80165",authors:[{id:"201794",title:"Associate Prof.",name:"Matjaž",surname:"Debevc",slug:"matjaz-debevc",fullName:"Matjaž Debevc"},{id:"201798",title:"Dr.",name:"Ines",surname:"Kožuh",slug:"ines-kozuh",fullName:"Ines Kožuh"},{id:"439304",title:"MSc.",name:"Peter",surname:"Čakš",slug:"peter-caks",fullName:"Peter Čakš"},{id:"439308",title:"MSc.",name:"Monika",surname:"Ferk",slug:"monika-ferk",fullName:"Monika Ferk"},{id:"439310",title:"Dr.",name:"Julija",surname:"Bele Lapuh",slug:"julija-bele-lapuh",fullName:"Julija Bele Lapuh"}],corrections:null},{id:"80569",title:"Workers’ Education from the Cloud: Maximising Latest Technologies for Human Resource Development in Africa",doi:"10.5772/intechopen.102793",slug:"workers-education-from-the-cloud-maximising-latest-technologies-for-human-resource-development-in-af",totalDownloads:12,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"As the world is getting increasingly globalised as occasioned by rapid advancements in technology, so is the need for continuous skills enhancement on the part of the working population. What it takes to cope with the demands of the ever dynamic workplace in today’s tech-driven world has kept changing. Therefore, a worker who refuses to up-skill in line with the changing demands of the workplace will soon become obsolete. This has an implication for workers’ training and re-training towards skills enhancement which has some elements of digital skills acquisition. Meanwhile, cloud-based technology is increasingly being used in the education sector, and it is also considered to hold much promise for workers’ education. Cloud computing systems provide a variety of opportunities for content delivery, as well as providing limitless access to information over the internet. This chapter, therefore, explores the workability of workers’ education through the use of cloud computing systems, particularly in Africa in the face of her obvious challenges relating to a high level of poverty, epileptic power supply and poor internet connectivity, among others.",signatures:"Kehinde O. Kester and Solomon O. Ojedeji",downloadPdfUrl:"/chapter/pdf-download/80569",previewPdfUrl:"/chapter/pdf-preview/80569",authors:[{id:"110666",title:"Dr.",name:"Kehinde O.",surname:"Kester",slug:"kehinde-o.-kester",fullName:"Kehinde O. Kester"},{id:"440034",title:"Ph.D. Student",name:"Solomon O.",surname:"Ojedeji",slug:"solomon-o.-ojedeji",fullName:"Solomon O. Ojedeji"}],corrections:null},{id:"80166",title:"Virtual Robotics in Hybrid Teaching and Learning",doi:"10.5772/intechopen.102038",slug:"virtual-robotics-in-hybrid-teaching-and-learning",totalDownloads:85,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Traditional robotics instruction in face-to-face classrooms, after-school clubs, and independent competition environments align with expensive, physical robot kits shared by students. Students or parent groups often elect themselves because of previous experience, expertise, or perceived technical ability to dominate the physical robotic platforms’ planning, engineering, building, and subsequent programming. This self-elected grabbing of control leaves students who are not regarded as well-positioned to contribute sidelined to observe the self-appointed experts of the group. Virtual robotics platforms provide educators and coaches with the unique opportunity to give every student access to a robot. Each student learns programming, math, and scientific forces that impact robots through simulated physics algorithms. With their customizable virtual environments, virtual robotics platforms such as Vex VR and Robot Virtual Worlds level the playing field. All students can learn, practice, and subsequently contribute to robotics-centered group projects or competitive teams in meaningful ways. This book chapter delineates the strategies to implement virtual robotics in hybrid classroom environments supported by the Technological Pedagogical Content Knowledge (TPACK) framework. Additionally, this chapter reviews how computer-aided design and augmented reality platforms provide students with the opportunity to incorporate 3D objects into virtual worlds.",signatures:"Sharon Mistretta",downloadPdfUrl:"/chapter/pdf-download/80166",previewPdfUrl:"/chapter/pdf-preview/80166",authors:[{id:"437279",title:"Dr.",name:"Sharon",surname:"Mistretta",slug:"sharon-mistretta",fullName:"Sharon Mistretta"}],corrections:null},{id:"80568",title:"Emergency Remote Education Amid COVID-19 Pandemic",doi:"10.5772/intechopen.102822",slug:"emergency-remote-education-amid-covid-19-pandemic",totalDownloads:38,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The COVID-19 health emergency has created an unprecedented crisis in many areas. In education, it caused the suspension of face-to-face classes at all educational levels to prevent the spread of the virus and mitigate its impact. In extraordinary circumstances, such as those faced since 2020, the governments and the corresponding educational authorities found it necessary to apply strategies that would allow continuity to the learning processes remotely, causing a series of changes. The teacher, for example, required a transformation in his/her role as part of the social isolation demanded by the pandemic, for which it should be noted, he/she was not prepared; compelling him/her to act mainly as a mediator in the teaching-learning processes, and rely on the use of technology as an educational resource. Therefore, given the particularities of the current context and the conditions required for students to adapt themselves to the challenges to come, the education needs to be structured according to the four pillars raised by Jaques Delors at the end of the last century; but from a different approach; which will be addressed through the next chapter.",signatures:"María de Jesús Araiza-Vasquez and Mariel García-Leal",downloadPdfUrl:"/chapter/pdf-download/80568",previewPdfUrl:"/chapter/pdf-preview/80568",authors:[{id:"443390",title:"Ph.D. Student",name:"Mariel",surname:"García Leal",slug:"mariel-garcia-leal",fullName:"Mariel García Leal"},{id:"443392",title:"Dr.",name:"María De Jesús",surname:"Araiza-Vasquez",slug:"maria-de-jesus-araiza-vasquez",fullName:"María De Jesús Araiza-Vasquez"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,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. 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The male disease process “prostate cancer” is a heterogeneous entity at multiple subtopics including epidemiology, screening, diagnosis, treatment options, side effects, and cancer control results. It is common to introduce a peer-reviewed article or text chapter focused on any aspect of prostate cancer with the observation that the disease is common but a much smaller subset result in a disease-specific mortality—almost to the point of useless repetition. The heterogeneity of prostate cancer extends well beyond population statistics, and in this chapter, we will focus on one aspect of heterogeneity—diagnosis. The key paradigm in contemporary practice is a male screened for prostate cancer with serum prostate specific antigen (PSA) and digital rectal examination (DRE). The alternate/related paradigm is the male with lower urinary tract or other pelvic symptoms who is evaluated for prostate cancer with serum PSA/DRE as a differential diagnosis. Performing a biopsy and subsequent treatment has certainly altered key statistics in prostate cancer compared to pure clinical detection. The incidence has increased as well as treatment numbers. Recently, Welch et al. demonstrated with SEER/Medicare data that the incidence of metastatic disease at diagnosis significantly declined with the introduction of PSA, compared with the relatively flat effect of mammography screening to breast cancer staging [1].
\nThe problem faced from this paradigm is that the results of a prostate biopsy are frustrating for a growing list of reasons:
Too many negative or indeterminate biopsies.
Too many negative or indeterminate biopsies that are found to be falsely negative with future evaluations.
Too many positive biopsies for low grade disease—leads to overtreatment.
Too many positive biopsies for low grade disease that with future radical prostatectomy or repeat biopsies are found to have missed higher grade disease.
Cost, discomfort, and an occasional septic infection as the side effects of this effort to make the
The concepts can be illustrated in the following case vignettes:
A patient with Gleason Score 3+3 on biopsy has a radical prostatectomy, and the final pathology showed Gleason 4+4.
A patient with three negative biopsies has a continuous rising PSA—should he have a 4th biopsy or accept the cause as benign?
A patient with a negative biopsy and stable PSA—should he continue screening? What age to stop?
An elderly patient with Gleason 7 prostate cancer is unsure of overall longevity—does he need curative therapy or just watchful waiting based on symptoms?
Physicians managing patients at risk for prostate cancer can certainly use clinical features to frame many questions. In the asymptomatic patient who might have clinically localized disease, a life expectancy of less than 10 years would be treated differently than a life expectancy greater than 10 years. Family history of prostate cancer (father, brothers, uncles) and African American race are well-known adverse risk features for prostate cancer. The PSA has its statistical problems with specificity (related to false positives), but does have sensitivity (related to true positives) related to its value—higher PSAs have more risk of cancer, but hard to determine a clear line to draw where you call the test clearly normal versus abnormal. Translating these narrated elements into summary numerical estimates (noncited as widely available):\n
For the common case with elevated PSA between 2.5 and 6.0, and leading to a prostate biopsy, the overall cancer detection rate can be 30%, ±10% depending upon region. Of all positive biopsies, 10–25% may have high grade elements. This means that the majority of prostate biopsies are free of cancer, and an even higher number are free of clinically significant cancer.
For men with a previous negative biopsy, a repeat biopsy for continued rise is often positive in 10–20%. Subsequent repeat biopsies lower the rate further but not to something approaching zero.
For men placed on active surveillance for low grade cancer, approximately 30% will be upgraded at some point with repeat testing.
Moving forward, the unmet needs in prostate cancer evaluation are to increase the detection of clinically significant disease when it is present, and to effectively rule out significant disease when it is not present, such that subsequent monitoring can be reduced or eliminated.
In a state-of-the-art lecture at the 2015 American Urological Association Annual Meeting, Stacy Loeb (New York, USA) made the key analogy that the first 10 or more years of use of PSA was analogous to a pregnancy test—in search of when to call the test positive or negative. The initial cut-point was 4.0, and many labs still flag a result in red at >4.0, and subsequent proposals were for >2.5. Clinical experience clearly showed the fallacy of this version of laboratory medicine—a man’s risk of prostate cancer does not go from zero at PSA 3.9 to 100% at PSA of 4.1. The point was well illustrated by a follow-up report from the Prostate Cancer Prevention Trial that showed the biopsy results of men with different PSA cut-points who were all biopsied and on a placebo medication—sample size of 2950 participants and 449 cancers [2]. Table 1 shows a sample of their report. Note that the pregnancy illustration was carried forward in this trial, as men with a PSA > 4.0 were biopsied “for cause” and the data represent the men followed for the 7-year duration of the trial who were considered clinically “normal range”. Prior to this publication, there was very limited data available on the results of a prostate biopsy in men with a normal DRE and PSA < 4.0.
\nWith this data, you can certainly counsel a man on the concept of a relative range of prostate cancer risk rather than oversimplify it to a positive/negative result. This same dataset was refined further into an online calculator tool where you can input multiple clinical variables and receive an estimate on overall cancer detection and high grade (Gleason 7 or higher) cancer. The web link is: http://deb.uthscsa.edu/URORiskCalc/Pages/uroriskcalc.jsp.
\nHere are two example cases:
Race Caucasian, age 59, PSA 2.1, no family history, abnormal DRE, no prior biopsy. Result: 3% high-grade cancer, 14%, low-grade cancer, and 83% negative biopsy.
Race African American, age 59, PSA 9.8, positive family history for prostate cancer, DRE abnormal, no prior biopsy. Result: 35% high-grade cancer, 20% low-grade cancer, 45% negative biopsy.
PSA level | \nPercentage positive biopsy | \nPercentage of positive biopsies with high grade | \n
---|---|---|
≤0.5 | \n6.6 | \n12.5 | \n
0.6–1.0 | \n10.1 | \n10.0 | \n
1.1–2.0 | \n17.0 | \n11.8 | \n
2.1–3.0 | \n23.9 | \n19.1 | \n
3.1–4.0 | \n26.9 | \n25.0 | \n
Data from the Prostate Cancer Prevention Trial [2]. This cohort of men were biopsied as part of the trial design and were on a placebo. Men with a PSA > 4.0 would have been biopsied earlier “for cause”.
The results also remind you that regardless of the biopsy result, there may be a 2–4% chance of an infection requiring hospitalization. Thus, the absolute risks of cancer and side effects can be discussed and a personalized choice made. We should not forget why we are considering these efforts. The third update to the Bill-Axelson trial of radical prostatectomy versus watchful waiting reminds us that the treatment arm had a 12.7% absolute difference in overall mortality, with a relative risk of 0.71 in favor of surgery and number needed to treat to avoid a death of 1:8 [3]. Additional benefits were observed in palliation, metastatic progression, and androgen deprivation utilization.
\nAs established thus far, PSA is the gold standard for prostate cancer detection. Many experts have voiced the opinion that this might change in the next generation [4]. First, we should review key biomarker nomenclature recognized by the FDA—whether a biomarker is serum, urine, or tissue base. Table 2 shows four key distinctions and a biomarker such as PSA has elements of all four.
\nData on biomarkers is a separate and vast topic and we will not review it. But the key headings would be whether a study is in preclinical exploratory trials, assay development, assay validation, retrospective use/repositories, prospective screening, or randomized controlled. Biomarkers can be described based on their validity with a number of statistical expression and eventually need to be described based upon clinical utility, i.e., strength of ability to alter key clinical decisions and add value to health care.
\nBiomarker type | \nWhen | \nIndications | \n
---|---|---|
Prognostic | \nPrior to treatment | \nRisk of a specific outcome | \n
Predictive | \nPrior to treatment | \nIdentify which patients benefit from a treatment | \n
Response indicator | \nDuring or after treatment | \nResponse to treatment (pharmacology, physiology) | \n
Efficacy-response (surrogate) | \nAfter treatment | \nEarly/accurate prediction of a clinical endpoint | \n
FDA biomarker classification based on context of use.
As stated, there are many statistical advantages to PSA screening compared to using prostatic acid phosphatase (PAP) [5], or clinical exam [6]. However, there is significant room to improve accuracy and especially specificity. Early efforts to make progress were numerous such as adding the percent-free PSA to PSA ratio [7], age adjustment [8], PSA velocity of ≥0.75 ng/mL/year [9], and PSA density of 0.15 [10]. These methods all made incremental practice, but perhaps the most significant is in making decisions about a repeat biopsy versus a primary biopsy. Another useful contribution to PSA screening interval questions came from Lilja et al., who showed that a single PSA before age 50 could be predictive of lifetime prostate cancer incidence [11].
\nSimilar themes in advancing future prostate cancer screening have come from focusing on “isomers” or molecular variants of the PSA molecule. Another variant of PSA is called Pro-PSA and can be more prevalent in the free-fraction within cancer versus noncancer [12]. In a validation study of Pro-PSA versus percent-free PSA, the area under the curve (AUC) was 0.68 for %ProPSA and 0.567 for %free PSA. At sensitivity of 75%, the %ProPSA would eliminate 59% of negative biopsies versus 33% with %fPSA [13]. Catalona et al. [14] also did a serum bank study on biopsied patients with elevated PSA and found the %proPSA can eliminate 19–33% of biopsies while holding 90% sensitivity.
\nThe next iteration came from the discovery of an isoform p2PSA, and the concept of combining the information with free PSA and total PSA into an equation: ([−2]pPSA/fPSA)/√(tPSA). This is now the Prostate Health Index and licensed by Beckman Coulter laboratories. Jansen et al. [15] reported a multisite study showing that prostate cancer patients had higher PHI levels and %p2PSA. A U.S. validation study of 829 patients holding sensitivity at 95% had specificity of 16% for PHI and 8.5% for %fPSA [16]. Relevant to our case vignettes in the introductory narrative, the higher PHI values were also correlating with
A PHI score is currently reported in four “brackets” of results: 0–24.9, 25.0–34.9, 35.0–54.9, and >55. The PHI, as stated will include a total PSA, the free PSA, and the Pro-PSA. The PHI result is then translated into a percentage risk of prostate cancer. The source reference [16] includes the high grade numbers, but an actual test result for some reason does not. Table 3 shows a commercial report range. The study listed ranges for Gleason ≥7 were PHI 0–24.9 = 26.1%, PHI 25.0–34.9 of 28.2%, PHI 35.0–54.9 of 30.1%, and PHI >55.0 of 42.1%. Thus, the trends are strongest comparing the lowest versus highest PHI brackets.
\nBiomarker | \nSample result | \nReference interval | \n||||
---|---|---|---|---|---|---|
Total PSA | \n7.8 | \nNormal < 2.0 At risk ≥ 2.0 | \n||||
Free PSA | \n1.16 | \nSee below | \n||||
Pro2PSA | \n20.78 | \nSee PHI | \n||||
%free PSA | \n15 | \n% Free PSA prostate cancer probability by age | \n||||
\n | \n | \n | \n\n | \n\n | \n\n | \n|
\n | \n | <7 | \n85% | \n95% | \n96% | \n|
\n | \n | 7–15 | \n25% | \n50% | \n60% | \n|
\n | \n | 16–25 | \n11% | \n27% | \n35% | \n|
\n | \n | >25 | \n2% | \n6% | \n10% | \n|
PHI | \n49.9 | \n\n | ||||
\n | \n | 0–24.9 | \n11.0% | \n\n | ||
\n | \n | 25.0–34.9 | \n18.1% | \n\n | ||
\n | \n | 35.0–54.9 | \n32.7% | \n\n | \n | |
\n | \n | >55.0 | \n52.1% | \n\n | \n |
PHI result reporting as of 2015.
A European cohort was published by Lazzeri et al. [17] and showed an AUC of 0.67 for PHI as well as %proPSA—both superior to total PSA and %free PSA. At a PHI cutoff of 27.6, biopsies could have been avoided in 15.5%. The Gleason ≥7 trend was also observed in their statistical analyses.
\nAnother research direction developing in parallel has been human glandular kallikrein 2—hK2. It is also part of the serine protease family along with PSA. Nam et al. [18], for example, looked at hK2 and hK2 to %free PSA ratios could find trends elevated in PCa. Vickers et al. then expanded the concept as a panel of Kallikrein markers: total PSA, free PSA, intact PSA, and hK2. This coined the phrase 4 K score [19]. The process developed a nomogram that includes the four markers, age, DRE, and determines a probability of cancer. The model adds to a clinical base model and increases prediction for high grade prostate cancer. The AUC for the full model was 0.832 and high-grade cancer was 0.870, and a decision curve analysis is presented to propose a threshold value of 20% as a biopsy trigger that would spare a significant number of biopsies and only miss 3% high-grade cancers. Parekh et al. [20] then published a U.S. prospective trial that used the PCPT risk calculator above as a control. Again, the full model had an AUC of 0.821 and higher AUC for Gleason ≥7, as well as decision curve benefit. As an illustration, a 4 K score cutoff of 9% led to 43% of biopsies avoided and 2.4% risk of delay in Gleason ≥7 diagnosis.
\nFor the clinician, the question then becomes which test to use? PHI had a slight advantage in being earlier in regulatory approval. Nordstrom et al. presented a comparison study of PHI versus 4 K [21]. The PHI and 4 K both had improved prediction for overall and high grade prostate cancer. The AUC for 4 K was 0.69 and for PHI was 0.704, and for high-grade prostate cancer was 0.718 and 0.711, respectively. Comparable metrics were observed with a 4 K cutoff of 10% and PHI of 39.
\n\n | \n | \n\n | \n\n | \n
---|---|---|---|
\n | \nSerum ([−2]pPSA/fPSA)/√(tPSA) | \nSerum tPSA, fPSA, intact PSA, hk2, age Clinical model (add DRE results) | \nUrine; (mRNA PCA3/mRNA PSA) × 1000 | \n
\n | \n>50 y/o, PSA 4–10 ng/mL, normal DRE | \nAny patient referred for TRUS Bx | \n>50 y/o; prior negative Bx | \n
\n | \n2012 | \nn/a | \n2012 | \n
\n | \nPCa | \nHigh risk PCa (GS ≥ 7) | \nPCa | \n
\n | \n0–29 = low risk; 8.7% risk PCa 21–39.9 = mod risk; 20.6% risk PCa >40 = high risk; 43.8% risk PCa | \n≥9%, eliminates 43% of unnecessary Bx, w/2.4% risk of delayed dx of HG PCa | \n>35 sensitivity = 58%, and specificity = 72% for PCa | \n
\n | \n\n | Not currently covered by private insurances/Medicaid/ Medicare | \nRequires prostate message | \n
\n | \nComparable diagnostic accuracy to both 4 K and PCA3, and both their recommended indications | \nNo comparison to PCA3; comparable accuracy and utility to 4 K | \nNo comparison to 4 K; comparable diagnostic accuracy to PCA3 for initial & repeat Bx | \n
\n | \n$71–80 | \n$395 | \n$385 | \n
Comparison of serum biomarkers PHI, 4K, and urine biomarker PCA3.
Another biomarker with a little more clinical experience and validation data is the PCA3 score—different in being a urinary marker rather than serum as for PHI and 4 K. The assay uses a ratio of messenger RNA for the PCA3 molecule with a PSA ratio built in. The AUCs for PCA3 are generally in the 0.0.68–75 range [22]. In the validation study for repeat biopsy patients, Marks et al. showed an AUC of 0.68 for PCA3 versus 0.52 for PSA [23]. The cutoffs recommended are in the 25–35 range. In the Marks study, a PCA3 cutoff of 35 showed 58% sensitivity and 72% specificity. A particular advantage of PCA3 has been that it is not affected by prostate volume and performed well across multiple PSA levels [24].
\nBack to comparative studies, Ferro et al. compared PCA3 to PHI in a prospective observational study [25]. The diagnostic accuracy was similar at 90% sensitivity: PHI specificity of 40% and PCA3 of 40% with 31.6 and 22 cutoffs, respectively. In a decision curve analysis, PHI had slightly higher benefit at probability of 25%. The Scattoni study [26] looked at these markers in initial and repeat biopsy populations and found a slight benefit to PHI but not significant. A comparison of AUC for initial biopsy showed PSA of 0.54, %fPSA of 0.67, PCA3 of 0.57, and PHI of 0.69. In repeat biopsy, it showed PSA of 0.60, %fPSA of 0.52, PCA3 of 0.63, and PHI of 0.72.
\nIn Table 4, we consolidate these statistics into a final comparison with existing data.
\n\nThe cost comparison certainly favors PHI, although the PCA3 test has more clinical experience and strong metrics in repeat biopsy decisions. It remains to be determined whether the 4 K cost is justified; however, when this test is up and running and through regulation, it may give a more objective reporting of specific high grade prostate cancer risk that clinicians may prefer.
\nIn this chapter, we have outlined the PSA problem with emphasis on triggers for a biopsy. A separate but related topic is the technique of biopsy. The gold standard for all of these biomarker studies has been the 10–12 core transrectal ultrasound-guided biopsy. Emerging data, however, demonstrate that a transperineal template biopsy may sample the apex and anterior zones better. Other areas of research are looking at improvements in multiparametric MRI staging, and commercial software platforms that fuse the images such that an ultrasound biopsy now has a more accurate target to sample rather than random sampling by anatomic region. The endpoints are the same—ability to improve Gleason score ≥7 and the ability to trust that a negative test is actually negative. For diagnosed patients, commercial genetic profiling products can then look at specific grades of prostate cancer and offer additional prognostic information such as risk of upgrading/upstaging at surgery, mortality rates untreated, biochemical relapse after surgery, or metastatic relapse after surgery [27]. These topics can be separate chapters, but the themes are consistent—solving heterogeneity in prostate cancer diagnosis such that the downstream monitoring and treatment decisions are optimized.
\nParasitism is a relationship among species, in which one organism, the parasite, sustains on the host organism. Parasitic diseases can affect almost all living organisms. Parasites are dependent on the host organisms for their own survival. Not all parasites are harmful but some cause severe pathology to the host, such as
IFNs are the key soluble immune molecules belonging to the IFN family with specific structural and functional characteristics. They are divided into three main groups based on the structural details and functional contribution toward modulating the immune response during parasitic infections: IFN-I, II and III. The IFN-I family includes IFN-α and IFN-β. IFN-I signaling is mediated through a common cell surface receptor, (IFNAR). IFN-I production by a wide variety of cells mediates autocrine and paracrine signaling pathways upon viral infections. The IFN-II family represents IFN-γ. Its response is mediated by IFN-γ receptor (IFNGR). IFN-II plays a role in defense against intracellular pathogens by modulating diverse cellular functions. The third IFN-III family, or IFN-λ, comprises four different subtypes: IFN-λ1, λ2, λ3 and λ4. IFN-III is not well studied but has a role similar to IFN-I. The expression of IFN-λR receptor is mainly restricted to cells of epithelial origin [3].
Protozoan parasitic infections are among the most common life-threatening infectious diseases. They can enter into the human body generally by a bite from an insect vector or through fecal-oral route. Protozoan parasites are responsible for serious infections.
Chagas disease or American trypanosomiasis is caused by the parasite
Transmission of
Chagas disease has two phases of infection: an acute and a chronic phase. Acute form is mild. The parasite remains in the blood circulation for a long time (few weeks to months). Acute phase is followed by prolonged asymptomatic “chronic phase,” marked by very few or negligible parasite in blood. Chronic Chagas disease symptoms include dilated colon or esophagus and different heart rhythm abnormalities. Diagnosis of acute phase of infection is marked by the presence of parasite in peripheral blood circulation and can be observed by microscopic examination of stained blood smear. Diagnosis of chronic Chagas disease is generally made by testing blood for parasite-specific antibodies [4].
Chagas disease is associated with several immunological alterations due to change in the expression pattern of cytokines that play a fundamental role in regulating the functionality of almost all cell types.
IFN-I has an important role in inhibiting the parasite multiplication. Induction/production of IFN-I in response to
IFN-γ has a central role in Chagas disease cardiomyopathy. The disease is characterized by increased production of IFN-γ in the periphery [13]. Several cytokines, including IFN-γ, IL-1-α, IL-6 and TNF-α, modulate the expression of immune cells and contribute to the inflammatory process by recruiting the T cells into the inflammatory sites. Conversely, IL-4, TGF-β and IL-10 negatively regulate NO production and downregulate the intracellular control of
Type III IFNs serve as regulatory cytokines by reducing the damage caused by pro-inflammatory cytokines or by retaining the more potent IFN-I for times when immune responses are inadequate [21]. This subtype is poorly recognized and has not been studied in Chagas disease.
Circulation of T cells in response to parasitic infection is securely controlled as various cytokines and chemokines influence the disease outcome. It has been reported that in
Peripheral and thymic changes induced in host organism (mice and/or human) upon
Malaria is a deadly disease caused by
Malaria is generally transmitted through the bite of
Malaria can be fatal if not treated. Disease outcome is determined by the parasite species and host immunity. Complications may arise in the form of cerebral malaria (CM) wherein the parasite infects the brain and leads to serious damage including seizures and coma accompanied with breathing problems, organ failure and low blood sugar. Early detection and disease treatment are important to reduce the risk of disease severity. Staining-based microscopic parasite diagnosis methods or malaria rapid diagnostic tests (RDTs) are widely used for preliminary diagnosis of the disease. RDTs detect specific antigen produced by malaria parasite in human blood using a dye-labeled capture antibodies providing an evidence of malaria infection [33].
Host immune response against
IFN-γ is the most widely studied in malaria and has a versatile effect on the host. It may exert a protective or destructive effect, depending on the stage of the infection or the species of
IFN-γ regulates various components of the host immune system such as defense against intracellular pathogens by antigen presentation, antimicrobial mechanism, leukocyte development and immune cell trafficking. The protective role of IFN-γ is evident from the
Type I and type II interferons [IFNs] are critical to govern the disease outcome; however, reports on the involvement of recently identified IFN-III humans during malaria infection are scarce [3].
Malarial infection results in increased levels of IFN-γ and TNF-α in human serum. Both these cytokines have been shown to be involved in double positive T-cell death [52, 53, 54]. However, neutralizing the effect of IFN-γ and TNF-α did not alter the apoptosis-inducing capacity of the serum [28]. Conversely, TNF-α neutralization helps in the reduction of DP T-cell count due to increased apoptosis, stating that TNF-α exerts a protective rather than a destructive role in malaria-induced thymic atrophy [28]. Studies done on BALB/c mice model show a high level of apoptosis and premature migration of thymocytes in mice upon
Peripheral and thymic changes induced in host organism (mice or human) upon
Female phlebotomine sandflies transmit the Leishmania parasite during blood meal. Disease transmission is dependent on the parasite or sandfly species, environmental conditions, host immunity and animal reservoir [62].
There are three main clinical forms of leishmaniasis: Visceral leishmaniasis (VL) or kala-azar is characterized by hepatosplenomegaly, fever and anemia. Cutaneous leishmaniasis (CL) is the most common form of the disease, characterized by skin lesions on exposed body parts, scars on the body and societal stigma. Mucocutaneous leishmaniasis (MCL) manifestation involves mucous membranes of the nose, mouth and throat. Diagnosis is generally based on microscopic examinations of
There is a mixed Th1 and Th2 immune response during
IFN-II is considered the main player in cell-mediated immune responses against infections, but recently, IFN-I is also being reported to play a role in Leishmaniasis pathology outcome. Activated macrophages initiate the parasite elimination via the production of iNOS. Deficiency of this enzyme in mice promotes susceptibility to
Thymus is the least studied in context of
Peripheral and thymic changes induced in host organism (mice or human) upon
In conclusion, the role of IFN family in both immune-protective and immune-pathogenic processes in parasitic infections makes it a key set of molecules to be studied in depth (Figure 4). Modulatory effect of IFNs on T cells and downstream effector function of T cells along with their complex cross-network functionality in other circulating blood and tissue-resident immune cells warrant further understanding on their role in disease manifestation and outcome. IFNs as the modulators of thymic structure and function are an interesting dimension of the immune-regulatory capabilities of these soluble immune molecules in infectious diseases. IFNs work as double-edged sword to modulate immune effector mechanisms determined by parasite and host components. This family of important cytokines can be tailored to be used as immunomodulators and/or immunotherapeutic molecules.
Mechanistic of IFNs (IFN-I and IFN-γ) upon parasitic invasion in host organism. IFNs play a dual role in disease progression and/or protection, depending on the type and expression levels in relation to other secretory molecules and cytokines (Th1/Th2/Treg) and cause-effect cross talk between different IFN producers and effector immune cells.
Aklank Jain and Manju Jain would like to acknowledge Central University of Punjab, Bathinda, India, for providing Research Seed Money Grant.
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The Gram-positive pathogen is armed with battery of virulence factors that facilitate to establish infections in the hosts. The organism is well known for its ability to acquire resistance to various antibiotic classes. The emergence and spread of methicillin-resistant S. aureus (MRSA) strains which are often multi-drug resistant in hospitals and subsequently in community resulted in significant mortality and morbidity. The epidemiology of MRSA has been evolving since its initial outbreak which necessitates a comprehensive medical approach to tackle this pathogen. Vancomycin has been the drug of choice for years but its utility was challenged by the emergence of resistance. In the last 10 years or so, newer anti-MRSA antibiotics were approved for clinical use. However, being notorious for developing antibiotic resistance, there is a continuous need for exploring novel anti-MRSA agents from various sources including plants and evaluation of non-antibiotic approaches.",book:{id:"5471",slug:"frontiers-in-i-staphylococcus-aureus-i-",title:"Frontiers in Staphylococcus aureus",fullTitle:"Frontiers in Staphylococcus aureus"},signatures:"Arumugam Gnanamani, Periasamy Hariharan and Maneesh Paul-\nSatyaseela",authors:[{id:"192829",title:"Dr.",name:"Arumugam",middleName:null,surname:"Gnanamani",slug:"arumugam-gnanamani",fullName:"Arumugam Gnanamani"},{id:"204388",title:"Dr.",name:"Periasamy",middleName:null,surname:"Hariharan",slug:"periasamy-hariharan",fullName:"Periasamy Hariharan"},{id:"204389",title:"Dr.",name:"Maneesh",middleName:null,surname:"Paul-Satyaseela",slug:"maneesh-paul-satyaseela",fullName:"Maneesh Paul-Satyaseela"}]},{id:"32282",doi:"10.5772/33983",title:"Bacteriophages of Ralstonia solanacearum: Their Diversity and Utilization as Biocontrol Agents in Agriculture",slug:"bacteriophages-of-ralstonia-solanacearum-their-diversity-and-utilization-as-biocontrol-agents-in-agr",totalDownloads:3730,totalCrossrefCites:7,totalDimensionsCites:23,abstract:null,book:{id:"555",slug:"bacteriophages",title:"Bacteriophages",fullTitle:"Bacteriophages"},signatures:"Takashi Yamada",authors:[{id:"98151",title:"Dr.",name:"Takashi",middleName:null,surname:"Yamada",slug:"takashi-yamada",fullName:"Takashi Yamada"}]},{id:"32276",doi:"10.5772/34642",title:"Bacteriophages and Their Structural Organisation",slug:"bacteriophages-and-their-structural-organisation-",totalDownloads:12391,totalCrossrefCites:9,totalDimensionsCites:17,abstract:null,book:{id:"555",slug:"bacteriophages",title:"Bacteriophages",fullTitle:"Bacteriophages"},signatures:"E.V. 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Clonal complex 398 (CC398), a predominant clonal lineage of livestock-associated-MRSA in domestic animals and retail meat, is capable of infecting humans. In order to monitor and prevent MRSA contamination, it is critical to understand its source and transmission dynamics. In this review, we describe MRSA in food-producing animals (pig, cattle, chicken), horses, pet animals (dogs, cats), and food products (pork, beef, chicken, milk, and fish).",book:{id:"5471",slug:"frontiers-in-i-staphylococcus-aureus-i-",title:"Frontiers in Staphylococcus aureus",fullTitle:"Frontiers in Staphylococcus aureus"},signatures:"Jungwhan Chon, Kidon Sung and Saeed Khan",authors:[{id:"189634",title:"Dr.",name:"Kidon",middleName:null,surname:"Sung",slug:"kidon-sung",fullName:"Kidon Sung"},{id:"190400",title:"Dr.",name:"Jungwhan",middleName:null,surname:"Chon",slug:"jungwhan-chon",fullName:"Jungwhan Chon"},{id:"190401",title:"Dr.",name:"Saeed",middleName:null,surname:"Khan",slug:"saeed-khan",fullName:"Saeed Khan"}]}],mostDownloadedChaptersLast30Days:[{id:"69731",title:"Isolation and Purification of Sulfate-Reducing Bacteria",slug:"isolation-and-purification-of-sulfate-reducing-bacteria",totalDownloads:1501,totalCrossrefCites:1,totalDimensionsCites:6,abstract:"Sulfate-reducing bacteria (SRB) are a widespread group of microorganisms that are often isolated from the anoxygenic environments (lake depths, soil, or swamps), and they are also present in the human and animal intestines. This group is often detected in patients with inflammatory bowel disease, including ulcerative colitis. That is why new rapid methods for their isolation, purification, and identification are important and necessary. In this chapter, the methods of mesophilic SRB isolation from various environments are described. Particular attention is paid to the purification of mesophilic SRB since they can be in close interaction with other microorganisms (Clostridium, Bacteroides, Pseudomonas, etc.), which are their frequent satellites. Moreover, the main methods of mesophilic SRB identification based on their morphological, physiological, biochemical, and genetical characteristics are presented.",book:{id:"8997",slug:"microorganisms",title:"Microorganisms",fullTitle:"Microorganisms"},signatures:"Ivan Kushkevych",authors:[{id:"252191",title:"Associate Prof.",name:"Ivan",middleName:null,surname:"Kushkevych",slug:"ivan-kushkevych",fullName:"Ivan Kushkevych"}]},{id:"65773",title:"Life Cycle of Trypanosoma cruzi in the Invertebrate and the Vertebrate Hosts",slug:"life-cycle-of-em-trypanosoma-cruzi-em-in-the-invertebrate-and-the-vertebrate-hosts",totalDownloads:1393,totalCrossrefCites:4,totalDimensionsCites:7,abstract:"Trypanosoma cruzi (T. cruzi) is a protozoan parasite that causes Chagas disease, a zoonotic disease that can be transmitted to humans by blood-sucking triatomine bugs. T. cruzi is a single-celled eukaryote with a complex life cycle alternating between reduviid bug invertebrate vectors and vertebrate hosts. This article will look at the developmental stages of T. cruzi in the invertebrate vector and the vertebrate hosts, the different surface membrane proteins involved in different life cycle stages of T. cruzi, roles of different amino acids in the life cycle, carbon and energy sources and gene expression in the life cycle of T. cruzi. The author will also look at extracellular vesicles (EV) and its role in the dissemination and survival of T. cruzi in mammalian host.",book:{id:"8806",slug:"biology-of-em-trypanosoma-cruzi-em-",title:"Biology of Trypanosoma cruzi",fullTitle:"Biology of Trypanosoma cruzi"},signatures:"Kenechukwu C. Onyekwelu",authors:[{id:"245368",title:"Dr.",name:"Kenechukwu C.",middleName:null,surname:"Onyekwelu",slug:"kenechukwu-c.-onyekwelu",fullName:"Kenechukwu C. Onyekwelu"}]},{id:"54154",title:"Staphylococcus aureus: Overview of Bacteriology, Clinical Diseases, Epidemiology, Antibiotic Resistance and Therapeutic Approach",slug:"staphylococcus-aureus-overview-of-bacteriology-clinical-diseases-epidemiology-antibiotic-resistance-",totalDownloads:7096,totalCrossrefCites:14,totalDimensionsCites:25,abstract:"Staphylococcus aureus is an important human pathogen that causes wide range of infectious conditions both in nosocomial and community settings. The Gram-positive pathogen is armed with battery of virulence factors that facilitate to establish infections in the hosts. The organism is well known for its ability to acquire resistance to various antibiotic classes. The emergence and spread of methicillin-resistant S. aureus (MRSA) strains which are often multi-drug resistant in hospitals and subsequently in community resulted in significant mortality and morbidity. The epidemiology of MRSA has been evolving since its initial outbreak which necessitates a comprehensive medical approach to tackle this pathogen. Vancomycin has been the drug of choice for years but its utility was challenged by the emergence of resistance. In the last 10 years or so, newer anti-MRSA antibiotics were approved for clinical use. However, being notorious for developing antibiotic resistance, there is a continuous need for exploring novel anti-MRSA agents from various sources including plants and evaluation of non-antibiotic approaches.",book:{id:"5471",slug:"frontiers-in-i-staphylococcus-aureus-i-",title:"Frontiers in Staphylococcus aureus",fullTitle:"Frontiers in Staphylococcus aureus"},signatures:"Arumugam Gnanamani, Periasamy Hariharan and Maneesh Paul-\nSatyaseela",authors:[{id:"192829",title:"Dr.",name:"Arumugam",middleName:null,surname:"Gnanamani",slug:"arumugam-gnanamani",fullName:"Arumugam Gnanamani"},{id:"204388",title:"Dr.",name:"Periasamy",middleName:null,surname:"Hariharan",slug:"periasamy-hariharan",fullName:"Periasamy Hariharan"},{id:"204389",title:"Dr.",name:"Maneesh",middleName:null,surname:"Paul-Satyaseela",slug:"maneesh-paul-satyaseela",fullName:"Maneesh Paul-Satyaseela"}]},{id:"55437",title:"Biological Control of Parasites",slug:"biological-control-of-parasites-2017-07",totalDownloads:4229,totalCrossrefCites:7,totalDimensionsCites:7,abstract:"Parasites (ectoparasites or endoparasites) are a major cause of diseases in man, his livestock and crops, leading to poor yield and great economic loss. To overcome some of the major limitations of chemical control methods such as rising resistance, environmental and health risks, and the adverse effect on non‐target organisms, biological control (biocontrol) is now at the forefront of parasite (pests) control. Biocontrol is now a core component of the integrated pest management. Biocontrol is defined as “the study and uses of parasites, predators and pathogens for the regulation of host (pest) densities”. Considerable successes have been achieved in the implementation of biocontrol strategies in the past. This chapter presents a review of the history of biocontrol, its advantages and disadvantages; the different types of biological control agents (BCAs) including predators, parasites (parasitoids) and pathogens (fungi, bacteria, viruses and virus‐like particles, protozoa and nematodes); the effect of biocontrol on native biodiversity; a few case studies of the successful implementation of biocontrol methods and the challenges encountered with the implementation of biocontrol and future perspectives.",book:{id:"5527",slug:"natural-remedies-in-the-fight-against-parasites",title:"Natural Remedies in the Fight Against Parasites",fullTitle:"Natural Remedies in the Fight Against Parasites"},signatures:"Tebit Emmanuel Kwenti",authors:[{id:"191763",title:"Dr.",name:"Tebit Emmanuel",middleName:null,surname:"Kwenti",slug:"tebit-emmanuel-kwenti",fullName:"Tebit Emmanuel Kwenti"}]},{id:"70336",title:"Plastics Polymers Degradation by Fungi",slug:"plastics-polymers-degradation-by-fungi",totalDownloads:1383,totalCrossrefCites:3,totalDimensionsCites:5,abstract:"The studies on plastic degradation are very important for the development of biodegradable plastics, and for reduction of pollution, since plastic waste can remain in the environment for decades or centuries. We have showed the degradation of oxo-biodegradable plastic bags and green polyethylene by Pleurotus ostreatus. This fungus can also produce mushrooms using these plastics. The plastic degradation was possibly by three reasons: (a) presence of pro-oxidant ions or plant polymer, (b) low specificity of the lignocellulolytic enzymes, and (c) the presence of endomycotic nitrogen-fixing microorganisms. In this chapter, the plastic bags’ degradation by abiotic and microbial process using the exposure to sunlight and the use of a white-rot fungus will described. The physical, chemical, and biological alterations of plastic were analyzed after each process of degradation. The degradation of plastic bags was more effective when the abiotic and biotic degradations were combined.",book:{id:"8997",slug:"microorganisms",title:"Microorganisms",fullTitle:"Microorganisms"},signatures:"José Maria Rodrigues da Luz, Marliane de Cássia Soares da Silva, Leonardo Ferreira dos Santos and Maria Catarina Megumi Kasuya",authors:[{id:"217699",title:"Dr.",name:"Jose Maria",middleName:null,surname:"Da Luz",slug:"jose-maria-da-luz",fullName:"Jose Maria Da Luz"}]}],onlineFirstChaptersFilter:{topicId:"151",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"79935",title:"Salmonellosis and Campylobacteriosis, Emerging Zoonosis in the World and Current Situation in Mexico",slug:"salmonellosis-and-campylobacteriosis-emerging-zoonosis-in-the-world-and-current-situation-in-mexico",totalDownloads:14,totalDimensionsCites:0,doi:"10.5772/intechopen.101875",abstract:"Salmonellosis and campylobacteriosis are the furthermost common zoonotic infections around the world that are transferred. The spread of Salmonella enterica serotypes Enteritidis (SE) and Typhimurium (ST) has increased dramatically in the last 50 years due to the consumption of food contaminated and the emergence of SE and ST infections with multiple antibiotic resistance. Retrospective investigations imply an epidemiological link between people and poultry. It has been argued that farm modernization and global exports of progenitor birds have had a vital role in spreading SE and ST. On the other hand, campylobacteriosis is more common than salmonellosis in affluent countries. Campylobacter jejuni has been identified as the primary cause of acute diarrheal illnesses, frequently associated with animal-derived foods, particularly poultry meat. The current review examines immunological and molecular biological techniques that allow for the quick detection of asymptomatic animal carriers, as well as recent characterizations of relevant taxonomic and pathogenic characteristics of these organisms. We further urge epidemiological research to evaluate the incidence of human diseases arising from poultry eating, based on preliminary non-publisher findings implying a prevalence of salmonellosis and campylobacteriosis in Mexican poultry farms comparable to other nations.",book:{id:"10536",title:"Campylobacter",coverURL:"https://cdn.intechopen.com/books/images_new/10536.jpg"},signatures:"Adriana del Carmen Gutiérrez-Castillo, Leopoldo Henri Paasch-Martínez and Norma Leticia Calderón-Apodaca"},{id:"76534",title:"Health Care Associated Infections (HCAIs) a New Threat for World; U-Turn from Recovery to Death",slug:"health-care-associated-infections-hcais-a-new-threat-for-world-u-turn-from-recovery-to-death",totalDownloads:224,totalDimensionsCites:0,doi:"10.5772/intechopen.97193",abstract:"Health care associated infections also termed as nosocomial infections are notable cause of morbidity and mortality especially in resource limited countries like Pakistan. Newborns and aged people have more probability of being infected by Health care associated infections because of immunosuppressant. Central line associated blood stream infections (CLABSI) are considered as one of the promising negotiator associated with Health Care associated infections. Improper health care setting and unaware medical staff play a championship protagonist in prevalence of health care associated infections. Standard hygienic measures should be adopted to reduce risk of Health care associated infections. So, there is a pressing need to take on control policies by Government to handle this dilemma. This chapter gives new intuition to healthcare associated microbes, infections and provides comprehensive detailed on ironic precaution to scientific community.",book:{id:"10536",title:"Campylobacter",coverURL:"https://cdn.intechopen.com/books/images_new/10536.jpg"},signatures:"Ayesha Noor, Ali Raza Ishaq, Laila Jafri, Faiza Jabeen, Rehana Rani, Bushra Hafeez Kiani, Nosheen Akhtar, Zeeshan Javed, Tahira Younis and Fatima Jalal"},{id:"75880",title:"Conventional and Molecular Detection Methods of the Opportunistic Bacterial Pathogen Campylobacter concisus",slug:"conventional-and-molecular-detection-methods-of-the-opportunistic-bacterial-pathogen-campylobacter-c",totalDownloads:148,totalDimensionsCites:0,doi:"10.5772/intechopen.97004",abstract:"Campylobacter concisus is an emerging pathogen that causes gastroenteritis and is a suspected cause of inflammatory bowel diseases. Its importance is enhanced by the chronic sequela that results from acute infection. This bacterium has been under-diagnosed in intestinal infectious diseases, and its clinical importance has not been determined yet. In order to establish the implication of this emerging bacterial species in human gastroenteritis and other infections, different approaches and procedure have been performed, where molecular typing methods have played a central role. The chapter provides a comprehensive past and recent updates on the detection of C. concisus by biochemical and molecular methods.",book:{id:"10536",title:"Campylobacter",coverURL:"https://cdn.intechopen.com/books/images_new/10536.jpg"},signatures:"Mohsina Huq and Taghrid Istivan"},{id:"75751",title:"The Role of Immune Response and Microbiota on Campylobacteriosis",slug:"the-role-of-immune-response-and-microbiota-on-campylobacteriosis",totalDownloads:229,totalDimensionsCites:1,doi:"10.5772/intechopen.96755",abstract:"Million cases of campylobacteriosis and complications of post-Campylobacter jejuni infection occur every year around the world with huge life losses and economic burdens of billions of dollars. Few therapy options, such as antibiotics, are available to relieve severe cases of the enteritis. The slow progression on new intervention discovery and application is partially resulted from limited mechanistic understanding on campylobacteriosis pathogenesis. As a type of intestinal disorders, campylobacteriosis shares many common features with other intestinal diseases such as inflammatory bowel diseases (IBD) and Clostridium difficile infection. In pace with the advancement of the gastroenterology field, a large body of knowledge is accumulating on the factors influencing campylobacteriosis onset, development, and outcomes, including host immune response, intestinal microbiota, and its metabolites. In this chapter, we review the intestinal immune system, intestinal microbiome, and microbiome modulation of inflammation in the development of campylobacteriosis. The interplay between immunity, microbiota, and its metabolites may play essential roles on campylobacteriosis pathogenesis and the finding on the interaction may lead to new prevention and treatment options. 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Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. 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He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. 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