\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\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:"10707",leadTitle:null,fullTitle:"Primary Health Care",title:"Primary Health Care",subtitle:null,reviewType:"peer-reviewed",abstract:"This book presents examples from various countries about the provision of health services at the primary care level. Chapters examine the role of professionals in primary healthcare services and how they can work to improve the health of individuals and communities. Written by authors from Africa, Asia, America, Europe, and Australia, this book provides up-to-date information on primary health care, including telehealth services in the era of COVID-19.",isbn:"978-1-83969-807-1",printIsbn:"978-1-83969-806-4",pdfIsbn:"978-1-83969-808-8",doi:"10.5772/intechopen.94677",price:139,priceEur:155,priceUsd:179,slug:"primary-health-care",numberOfPages:344,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"c4e637d9f2cbc9ba038719e9c6894f34",bookSignature:"Ayşe Emel Önal",publishedDate:"March 16th 2022",coverURL:"https://cdn.intechopen.com/books/images_new/10707.jpg",numberOfDownloads:1722,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:0,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 19th 2021",dateEndSecondStepPublish:"May 17th 2021",dateEndThirdStepPublish:"July 16th 2021",dateEndFourthStepPublish:"October 4th 2021",dateEndFifthStepPublish:"December 3rd 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"25840",title:"Prof.",name:"Ayse Emel",middleName:null,surname:"Onal",slug:"ayse-emel-onal",fullName:"Ayse Emel Onal",profilePictureURL:"https://mts.intechopen.com/storage/users/25840/images/system/25840.jpg",biography:"Ayşe Emel Önal is a medical doctor, public health specialist, and professor. She graduated from the Faculty of Medicine, Istanbul University in 1985. After experience in public hospital emergency medicine, health center medicine, maternal and child health, and family planning medicine, Dr. Önal became a public health specialist at the Medical Faculty, Department of Public Health, Istanbul University in 1995. She became an associate professor in 2005 and a full professor in 2010. Since 2013, she has been head of the Department of Environmental Health, Department of Public Health, at the Istanbul University Faculty of Medicine. Since 2014, she has been working as the director of the Istanbul University Community Medicine Practice and Research Center. Since 2016, she has been the head of the Department of Public Health, Istanbul University, where she also provides training in environmental health. She is a member of the Association of Public Health Specialists (HASUDER) and Environmental Health Group. She has been the vice-chairman of the Public Health Competence Executive Board since 2021. She has more than 200 research articles in national and international journals and papers in national and international congresses to her credit. She has more than 30 international publications in the Web of Science. Fluent in French and English, Dr. Önal\\'s main research areas are chronic communicable and non-communicable diseases, epidemiology, gerontology, and environmental health.",institutionString:"Istanbul University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Istanbul University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1132",title:"Health Care",slug:"medicine-public-health-health-care"}],chapters:[{id:"80299",title:"Health Promotion",doi:"10.5772/intechopen.101933",slug:"health-promotion",totalDownloads:42,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Health promotion is one the major interventions employed in healthcare delivery generally and primary care in particular. Health promotion enables individuals, families, populations and communities to adopt and/or adapt lifestyles that promote and improve health. It helps the community members to make the right choices that can improve their health. Each individual, population and community have factors that influence their health either positively or negatively. Health promotion enables everyone in their context to identify these factors and increase control over these factors to empower them live a life that improves and promotes their health. This chapter explained health promotion actions, health promotion approaches, health promotion strategies and steps for effective implementation of health promotion programme.",signatures:"Florence Tochukwu Sibeudu",downloadPdfUrl:"/chapter/pdf-download/80299",previewPdfUrl:"/chapter/pdf-preview/80299",authors:[{id:"340301",title:"Dr.",name:"Florence Tochukwu",surname:"Sibeudu",slug:"florence-tochukwu-sibeudu",fullName:"Florence Tochukwu Sibeudu"}],corrections:null},{id:"77582",title:"Primary Care in the USA: The Long Struggle to Build its Foundational Role",doi:"10.5772/intechopen.98792",slug:"primary-care-in-the-usa-the-long-struggle-to-build-its-foundational-role",totalDownloads:100,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Family practice was recognized as the 20th specialty in American medicine in 1969. With the hope that primary care would become the foundation of an improved health care system, vigorous efforts were launched in medical education, research and practice to achieve that goal. This chapter traces the history of that effort, together with negative system changes that have obstructed that goal. Although primary care physicians have been shown to improve access to care, contain costs, decrease inequities, and improve patient outcomes, they are still too few in number to meet national needs for primary care. The COVID-19 pandemic revealed the extent of inadequacy and vulnerability of the system. The U. S. still lacks a system of universal access as has been in place for many years in most other advanced countries around the world. Corporate stakeholders in a largely privatized financing and delivery system continue to challenge the future of primary care. Lessons from the failure of reform initiatives over the last 50 years are discussed, as are current reform alternatives, only one of which would at last bring universal access to health care in this country.",signatures:"John Geyman",downloadPdfUrl:"/chapter/pdf-download/77582",previewPdfUrl:"/chapter/pdf-preview/77582",authors:[{id:"417658",title:"Emeritus Prof.",name:"John",surname:"Geyman",slug:"john-geyman",fullName:"John Geyman"}],corrections:null},{id:"78922",title:"Patient-Centred Point-of-Care Testing: A Life-Changing Technology for Remote Primary Care",doi:"10.5772/intechopen.100375",slug:"patient-centred-point-of-care-testing-a-life-changing-technology-for-remote-primary-care",totalDownloads:99,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Point-of-care (POC) testing has proven to be a life-changing and transformational technology for patients with acute, chronic, and infectious diseases who live in regional and remote Australia. This technology facilitates patient-centred test results, of equivalent laboratory quality, that are rapidly available to inform clinical and public health decisions with immediate impact on case management. Traditionally, POC testing in high-middle income countries has been most widely used in tertiary or acute care settings to provide rapid diagnostic results for emergency departments, intensive care units, operating theatres and outpatient clinics. However, in low-middle income countries, POC tests are commonly used during antenatal and perinatal care for infectious disease detection, such as Human immunodeficiency virus (HIV) or syphilis, where laboratory services are too expensive, inaccessible, or non-existent. Similarly, the application of POC testing in primary care settings in Australia offers improved healthcare benefits to geographically isolated regional and remote communities, where access to laboratory-based pathology testing is poor and the burden of disease is high. Evidence-based data from research in established primary care POC testing networks for acute chronic, and infectious disease is used to describe the clinical, cultural, and economic effectiveness of POC technologies. Innovative solutions to address current barriers to the uptake of POC testing in primary care settings, which include clinical and cultural governance, high staff turnover, operator training and competency, device connectivity, quality testing, sustainable funding strategies, and the need for regulatory requirements are also discussed. POC testing can provide practical and resourceful opportunities to revolutionise the delivery of pathology services in rural and remote primary care sectors, where the clinical and community need for this technology is greatest. However, several barriers to the scale-up and sustainability of POC testing networks in these settings still exist, and the full potential of POC testing cannot be realised until these limitations are addressed and resolved.",signatures:"Brooke Spaeth, Susan Matthews and Mark Shephard",downloadPdfUrl:"/chapter/pdf-download/78922",previewPdfUrl:"/chapter/pdf-preview/78922",authors:[{id:"419830",title:"Dr.",name:"Susan",surname:"Matthews",slug:"susan-matthews",fullName:"Susan Matthews"},{id:"422572",title:"Prof.",name:"Mark",surname:"Shephard",slug:"mark-shephard",fullName:"Mark Shephard"},{id:"435211",title:"Dr.",name:"Brooke",surname:"Spaeth",slug:"brooke-spaeth",fullName:"Brooke Spaeth"}],corrections:null},{id:"78450",title:"The Newborn Baby Check",doi:"10.5772/intechopen.99524",slug:"the-newborn-baby-check",totalDownloads:60,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"The newborn baby check is often the first encounter a General Practitioner (GP) has with an infant and their family. It is an excellent opportunity to review the journey the family has taken antenatally, at the time of delivery and the weeks that have followed. It is also a time to detect and identify conditions that can be managed in their early stages. If untreated, some conditions can result in major morbidity. In this chapter we will look at what makes up a newborn baby check and important considerations to think about when undertaking this assessment. The examination is also performed in a systematic way to maximise the chance of detecting any abnormalities.",signatures:"Harishan Tharmarajah",downloadPdfUrl:"/chapter/pdf-download/78450",previewPdfUrl:"/chapter/pdf-preview/78450",authors:[{id:"418299",title:"Dr.",name:"Harishan",surname:"Tharmarajah",slug:"harishan-tharmarajah",fullName:"Harishan Tharmarajah"}],corrections:null},{id:"77986",title:"COVID-19 Transmission in Children: Implications for Schools",doi:"10.5772/intechopen.99418",slug:"covid-19-transmission-in-children-implications-for-schools",totalDownloads:134,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"The COVID-19 pandemic poses multiple issues of importance to child health including threats to physical health and disruption of in-school learning. This chapter reviews what is currently known about COVID-19 epidemiology, presentation, pathophysiology, case definitions, therapies, and in-school transmission in children. COVID-19 has some unique characteristics in children including the rare yet severe Multisystem Inflammatory Syndrome in Children (MIS-C) that may be related to acquired immune responses. There are limited studies to date to define therapeutic guidelines in children, however consensus recommendations from multiple organizations are summarized including the use of immunomodulatory therapies (intravenous immunoglobulin, steroids, anakinra and tocilizumab), antiplatelet (aspirin) and anti-coagulant (low molecular weight heparin) therapies. Finally, considerations for safe return to the classroom are discussed including strategies for optimized student to teacher ratios, hand washing, social distancing, sibling pairing and staged re-opening strategies.",signatures:"Evelyn Mendoza-Torres, Franklin Torres, Wendy Rosales-Rada, Liliana Encinales, Lil Avendaño, María Fernanda Pérez, Ivana Terán, David Vergara, Estefanie Osorio-Llanes, Paige Fierbaugh, Wendy Villamizar, Aileen Y. Chang and Jairo Castellar-Lopez",downloadPdfUrl:"/chapter/pdf-download/77986",previewPdfUrl:"/chapter/pdf-preview/77986",authors:[{id:"342716",title:"Assistant Prof.",name:"Aileen",surname:"Y. Chang",slug:"aileen-y.-chang",fullName:"Aileen Y. Chang"},{id:"342718",title:"Dr.",name:"Evelyn",surname:"Mendoza-Torres",slug:"evelyn-mendoza-torres",fullName:"Evelyn Mendoza-Torres"},{id:"427633",title:"Dr.",name:"Franklin",surname:"Torres",slug:"franklin-torres",fullName:"Franklin Torres"},{id:"427634",title:"Dr.",name:"Wendy",surname:"Rosales-Rada",slug:"wendy-rosales-rada",fullName:"Wendy Rosales-Rada"},{id:"427635",title:"Dr.",name:"Liliana",surname:"Encinales",slug:"liliana-encinales",fullName:"Liliana Encinales"},{id:"427636",title:"Dr.",name:"Lil",surname:"Avendaño",slug:"lil-avendano",fullName:"Lil Avendaño"},{id:"427637",title:"Dr.",name:"María Fernanda",surname:"Pérez",slug:"maria-fernanda-perez",fullName:"María Fernanda Pérez"},{id:"427638",title:"Dr.",name:"Ivana",surname:"Terán",slug:"ivana-teran",fullName:"Ivana Terán"},{id:"427639",title:"Dr.",name:"David",surname:"Vergara",slug:"david-vergara",fullName:"David Vergara"},{id:"427640",title:"Dr.",name:"Estefanie",surname:"Osorio-Llanes",slug:"estefanie-osorio-llanes",fullName:"Estefanie Osorio-Llanes"},{id:"427641",title:"Dr.",name:"Paige",surname:"Fierbaugh",slug:"paige-fierbaugh",fullName:"Paige Fierbaugh"},{id:"427642",title:"Dr.",name:"Wendy",surname:"Villamizar",slug:"wendy-villamizar",fullName:"Wendy Villamizar"},{id:"457495",title:"Dr.",name:"Jairo",surname:"Castellar-Lopez",slug:"jairo-castellar-lopez",fullName:"Jairo Castellar-Lopez"}],corrections:[{id:"78823",title:"Erratum: COVID-19 Transmission in Children: Implications for Schools",doi:null,slug:"erratum-covid-19-transmission-in-children-implications-for",totalDownloads:null,totalCrossrefCites:null,correctionPdfUrl:null}]},{id:"79824",title:"Sexually Transmitted Infections in Pediatrics",doi:"10.5772/intechopen.101674",slug:"sexually-transmitted-infections-in-pediatrics",totalDownloads:98,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Sexually transmitted diseases (STDs) disproportionately affect young people, with more than half of the infections occurring in 15- to 25-year-olds, although as an age group they constitute only 25% of the sexually active population. Adolescents have been considered as a key and vulnerable population; adolescents are considered as marginalized populations (i.e., poor access to adequate health services, social and parental acceptance, stigmatization, among others. Every year, 87 million new cases of gonorrhea are reported worldwide in the population from 15 to 49 years old. In 2016, the estimated global prevalence of CT in 15-to 49-year-old women was 3.8% and in men 2.7%, with regional values ranging from 1.5 to 7.0% in women and 1.2 to 4.0% in men. The worldwide prevalence of HSV-2 among 15–49-year old is 11.3% and for HSV-1 among 0–49-year-old is 67%. These numbers alert us about the increase in the frequency of these diseases among young populations; more open sexual behavior could be an important factor for this increase; the treatment of these diseases is challenging due to the difficulties with detection and treatment; in the case of gonorrhea, it could become a major public health problem due to the emerging antimicrobial resistance; in the case of Chlamydia, despite the effective treatment, reinfection is still a possibility and for genital herpes, the disease can be controlled but not cured. This chapter will describe the most important aspects of these three diseases for supporting the clinicians and researchers about the management of sexually transmitted diseases in the adolescent population.",signatures:"Diana Coronel-Martínez and Luis Augusto Moya-Barquín",downloadPdfUrl:"/chapter/pdf-download/79824",previewPdfUrl:"/chapter/pdf-preview/79824",authors:[{id:"341814",title:"M.D.",name:"Diana",surname:"Coronel-Martínez",slug:"diana-coronel-martinez",fullName:"Diana Coronel-Martínez"},{id:"445240",title:"Dr.",name:"Luis",surname:"Augusto Moya-Barquín",slug:"luis-augusto-moya-barquin",fullName:"Luis Augusto Moya-Barquín"}],corrections:null},{id:"75767",title:"Chlamydial Infection",doi:"10.5772/intechopen.96501",slug:"chlamydial-infection",totalDownloads:181,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Chlamydial infection is one of the most common sexually transmitted infections worldwide, showing no decreasing trends in the incidence the last years. As a result, it presents a major burden of disease that impacts negatively people’s sexual and reproductive health and may result in adverse perinatal outcomes. The aim of the chapter is to offer today’s practitioners trustworthy guidance on the latest data in chlamydial infection. Thorough, up-to-date content on the epidemiology, pathophysiology, risk factors, clinical manifestations, diagnosis, treatment, prevention, prognosis and outcomes of infected infants, is presented. Data in children and adolescents that differ from infants, are also discussed. The chapter is organized consistently in order to help readers find information quickly and easily and thus, provide direct, optimal and evidence-based care to every pediatric patient.",signatures:"Dimitra Metallinou, Christina Nanou, Antigoni Sarantaki, Eleftheria Lazarou, Anastasia Liagkou and Katerina Lykeridou",downloadPdfUrl:"/chapter/pdf-download/75767",previewPdfUrl:"/chapter/pdf-preview/75767",authors:[{id:"343361",title:"Ph.D.",name:"Dimitra",surname:"Metallinou",slug:"dimitra-metallinou",fullName:"Dimitra Metallinou"},{id:"346832",title:"Prof.",name:"Christina",surname:"Nanou",slug:"christina-nanou",fullName:"Christina Nanou"},{id:"346833",title:"Prof.",name:"Antigoni",surname:"Sarantaki",slug:"antigoni-sarantaki",fullName:"Antigoni Sarantaki"},{id:"346835",title:"M.Sc.",name:"Eleftheria",surname:"Lazarou",slug:"eleftheria-lazarou",fullName:"Eleftheria Lazarou"},{id:"346836",title:"MSc.",name:"Anastasia",surname:"Liagkou",slug:"anastasia-liagkou",fullName:"Anastasia Liagkou"},{id:"346837",title:"Prof.",name:"Katerina",surname:"Lykeridou",slug:"katerina-lykeridou",fullName:"Katerina Lykeridou"}],corrections:null},{id:"77507",title:"The Effects of Multivitamin Use In Pregnancy on Mother and Fetus Health",doi:"10.5772/intechopen.98925",slug:"the-effects-of-multivitamin-use-in-pregnancy-on-mother-and-fetus-health",totalDownloads:48,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Pregnancy and birth method are the key factors to boost healthy new generations. Pregnancy may be a special period during which ladies have lived several process. During this period, for the protection of maternal and fetus health enhanced energy and nutrition demand supply is needed. Sufficient intake of nutrients and correct weight gain has necessary effects on each the mother’s and the developing fetal health. it’s also important to guard against short and long run complications. Nutrition is very important before and once pregnancy yet as throughout pregnancy. During this study, the intake of macro and micro nutrient items moving maternal and ve fetal health issues absolutely during pregnancy is detailed. As macro nutrition items carbohydrate, protein and fat examined. Adequate protein is important during pregnancy. Fats are important nutrients that provide essential fatty acids for the development of the brain and central nervous system of the fetus. Micro nutrition items water soluble and oil soluble as 2 cluster examined. The consequences of minerals during pregnancy were also examined.",signatures:"Neda Taner and Gülden Zehra Omurtag",downloadPdfUrl:"/chapter/pdf-download/77507",previewPdfUrl:"/chapter/pdf-preview/77507",authors:[null],corrections:null},{id:"79058",title:"Anemia during Pregnancy and Its Prevalence",doi:"10.5772/intechopen.99521",slug:"anemia-during-pregnancy-and-its-prevalence",totalDownloads:119,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Anemia is a serious health issue throughout the world affecting both sexes of any age group. This nutritional disease is more common among the pregnant women of developing countries, where it is a major cause of maternal death and negative outcome of pregnancy. Among all anemic types, IDA is most prevalent one and is comprises of about 95% of all anemic cases around the world. In many developing countries it is more common in women of low socio-economic background and with no record of antenatal checkup. There is need for further health educational programs to overcome anemia especially for pregnant females.",signatures:"Sehar Zulkifal, Shumaila Sarwar, Madiha Saddique, Khalida Yaqoob, Arshia Muneer, Aisha Fatima, Ayesha Kabir, Muhammad Asad Mangat, Laiba Mateen, Zeeshan Javed and Maleeha Manzoor",downloadPdfUrl:"/chapter/pdf-download/79058",previewPdfUrl:"/chapter/pdf-preview/79058",authors:[{id:"345826",title:"Dr.",name:"Maleeha",surname:"Manzoor",slug:"maleeha-manzoor",fullName:"Maleeha Manzoor"},{id:"413988",title:"Mr.",name:"Zeeshan",surname:"Javed",slug:"zeeshan-javed",fullName:"Zeeshan Javed"},{id:"425692",title:"Ms.",name:"Shumaila",surname:"Sarwar",slug:"shumaila-sarwar",fullName:"Shumaila Sarwar"},{id:"425693",title:"Ms.",name:"Madiha",surname:"Saddique",slug:"madiha-saddique",fullName:"Madiha Saddique"},{id:"425694",title:"Ms.",name:"Khalida",surname:"Yaqoob",slug:"khalida-yaqoob",fullName:"Khalida Yaqoob"},{id:"425695",title:"Ms.",name:"Arshia",surname:"Muneer",slug:"arshia-muneer",fullName:"Arshia Muneer"},{id:"426832",title:"Ms.",name:"Aisha",surname:"Fatima",slug:"aisha-fatima",fullName:"Aisha Fatima"},{id:"428671",title:"Mr.",name:"Mohammad Asad",surname:"Mangat",slug:"mohammad-asad-mangat",fullName:"Mohammad Asad Mangat"},{id:"428675",title:"Ms.",name:"Ayesha",surname:"Kabir",slug:"ayesha-kabir",fullName:"Ayesha Kabir"},{id:"428678",title:"Ms.",name:"Sehar",surname:"Zulkifal",slug:"sehar-zulkifal",fullName:"Sehar Zulkifal"},{id:"428679",title:"Ms.",name:"Laiba",surname:"Mateen",slug:"laiba-mateen",fullName:"Laiba Mateen"}],corrections:null},{id:"78212",title:"Managing Polypharmacy and Deprescribing in Elderly",doi:"10.5772/intechopen.99637",slug:"managing-polypharmacy-and-deprescribing-in-elderly",totalDownloads:186,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The increase in the number of medications used may result many negative consequences for patients and health system. Elderly patients are more likely to encounter these health problems associated with polypharmacy. Deprescribing, the process of tapering, withdrawing, discontinuing, or stopping medications, is important in reducing polypharmacy, adverse drug effects, inappropriate or ineffective medication use, and costs. Deprescribing in elderly patients in accordance with the evidence based guidelines has many positive outcomes in older people such as decrease in the risk of falls, improvement in cognition, and improvement in patients’ global health status. Therefore, each visit of an elderly patient should be considered as an opportunity to evaluate the unnecessary use or harms of the prescribed or nonprescribed medications. Clinicians should decide to deprescription process by individualized care goals in line with current guidelines. Beers Criteria, STOPP/START and The Medication Appropriateness Index-MAI can be used to assit clinicians to identify unnecessary or potentially inappropriate drugs and reduce the number of medications in older patients. But, a balance is required between over and under prescribing. In conclusion, prevention of polypharmacy and withdrawing unneccesary and inappropriate medications may be the best clinical decision for family physicians who follow the elderly in primary care.",signatures:"Çiğdem Apaydın Kaya",downloadPdfUrl:"/chapter/pdf-download/78212",previewPdfUrl:"/chapter/pdf-preview/78212",authors:[{id:"174121",title:"Associate Prof.",name:"Çiğdem",surname:"Apaydın Kaya",slug:"cigdem-apaydin-kaya",fullName:"Çiğdem Apaydın Kaya"}],corrections:null},{id:"79620",title:"Use of Primary Healthcare Facilities for Care and Support of Chronic Diseases: Hypertension",doi:"10.5772/intechopen.101431",slug:"use-of-primary-healthcare-facilities-for-care-and-support-of-chronic-diseases-hypertension",totalDownloads:24,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Hospitalisation of chronic diseases can be costly and time-consuming to patients with chronic diseases, and success of management of chronic diseases is in the primary care. This chapter gives a detailed description of primary health and its role in the management of chronic diseases. Hypertension as a chronic disease of interest and its management in the primary healthcare (PHC) context are also to be discussed in detail. However, to give this chapter clarity, a brief description of the country Lesotho will be given. The summary of the country will highlight major barriers to health care which mainly include poverty, difficult topography with no or poor infrastructure which hinder access to primary health care. Situational analysis is made with regard to current practice. The potential role of a pharmacist in the care and treatment of hypertension is explored. Best practices, need for policy change, guidelines and implementation plans will be highlighted. The aim of the chapter is to evaluate how chronic diseases are managed at the primary health care. The objectives include: a) to explore primary health care concept, b) to critically evaluate PHC concept in an African country and c) to describe human resource needs to meet the demands of PHC chronic diseases management.",signatures:"Maseabata Ramathebane, Maja Lineo and Sello Molungoa",downloadPdfUrl:"/chapter/pdf-download/79620",previewPdfUrl:"/chapter/pdf-preview/79620",authors:[{id:"319470",title:"Mr.",name:"Sello",surname:"Molungoa",slug:"sello-molungoa",fullName:"Sello Molungoa"},{id:"334836",title:"Dr.",name:"Maseabata",surname:"Ramathebane",slug:"maseabata-ramathebane",fullName:"Maseabata Ramathebane"},{id:"419353",title:"Ms.",name:"Lineo",surname:"Maja",slug:"lineo-maja",fullName:"Lineo Maja"}],corrections:null},{id:"79469",title:"Impact of Cardiovascular Diseases on the Outcome of Patients with COVID-19",doi:"10.5772/intechopen.101121",slug:"impact-of-cardiovascular-diseases-on-the-outcome-of-patients-with-covid-19",totalDownloads:75,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The prevalence of COVID 19 disease cases in India stands too high; this disease is caused by the coronavirus called SARS-CoV-2. Noval coronavirus virus was firstly detected in a group of people suffering from Pneumonia in Wuhan, China. Several studies are conducted to understand the different aspects of novel coronavirus SARS-CoV-2 in causing severe respiratory infections. However, the impact of risk factors on the severity of the symptoms and outcome of COVID 19 is not clearly understood. Similarly, most studies reported that patients who suffer from comorbidities with COVID 19 had a poor prognosis. Most COVID 19 patients who had preexisting medical conditions such as hypertension, diabetes, obesity, smoking habit, etc., required ICU admission and mechanical ventilation. On the other hand, studies reported that COVID 19 infection is responsible for causing the predominant cardiovascular diseases due to myocardial damage, thromboembolism arrhythmias, and ACS.",signatures:"Seeta Devi Akyana and Dipali Dumbre",downloadPdfUrl:"/chapter/pdf-download/79469",previewPdfUrl:"/chapter/pdf-preview/79469",authors:[{id:"338976",title:"Assistant Prof.",name:"Dipali",surname:"Dumbre",slug:"dipali-dumbre",fullName:"Dipali Dumbre"},{id:"417963",title:"Dr.",name:"Seeta Devi",surname:"Akyana",slug:"seeta-devi-akyana",fullName:"Seeta Devi Akyana"}],corrections:null},{id:"77590",title:"Aplication Arterial Oscilography to Study the Adaptive Capacity of Subject with COVID-19 in Primary Care",doi:"10.5772/intechopen.98570",slug:"aplication-arterial-oscilography-to-study-the-adaptive-capacity-of-subject-with-covid-19-in-primary-",totalDownloads:83,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The aim of study is finding complex pathological process markers occurred in COVID-19. Adaptive capacity, cardiovascular features, autonomic, central nervous systems in 67 patients with severe COVID-19 were studied and evaluated using (suggested by authors) temporal, spectral, correlation analysis of arterial oscillograms (AOG). The method is based on mathematical analysis adaptation of electrocardiographic signal heart rate variability to arterial pulsation variability analysis recorded during blood pressure measurement using an electronic tonometer VAT 41–2. Received results were compared with AOG 480 healthy (including 68 people after exercising) and 26 patients in a closed ward at psychoneurological hospital. Study results showed patients with severe COVID-19 have disorders at (four) cardiovascular system (CVS) regulation levels. It’s confirmed by lack of adequate sympathetic-adrenal response to a stressful situation due to severe COVID-19; higher than in healthy, parasympathetic part activity of autonomic nervous system. AOG spectral analysis revealed violation of management centralization, communication and coordination between CVS regulation levels. This leads to functional reserves decrease, low stress resistance of body and finally to a disease severe course and recovery processes. Arterial oscillography can be used to search markers of complex pathological processes occurred in COVID-19 and to improve methods of diagnosis, treatment, control of long-term results in clinical and family medicine.",signatures:"Dmytro Vakulenko, Liudmyla Vakulenko, Leonid Hryshchuk and Lesya Sas",downloadPdfUrl:"/chapter/pdf-download/77590",previewPdfUrl:"/chapter/pdf-preview/77590",authors:[{id:"418269",title:"Prof.",name:"Dmytro",surname:"Vakulenko",slug:"dmytro-vakulenko",fullName:"Dmytro Vakulenko"},{id:"418564",title:"Dr.",name:"Liudmyla",surname:"Vakulenko",slug:"liudmyla-vakulenko",fullName:"Liudmyla Vakulenko"},{id:"418627",title:"Prof.",name:"Leonid",surname:"Hryshchuk",slug:"leonid-hryshchuk",fullName:"Leonid Hryshchuk"},{id:"418628",title:"Dr.",name:"Lesya",surname:"Sas",slug:"lesya-sas",fullName:"Lesya Sas"}],corrections:null},{id:"78257",title:"The Need to Strengthen Primary Health Care Services to Improve Mental Health Care Services in South Africa",doi:"10.5772/intechopen.99781",slug:"the-need-to-strengthen-primary-health-care-services-to-improve-mental-health-care-services-in-south-",totalDownloads:62,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Despite the reported increase in the prevalence of mental disorders, including substance abuse disorders, required services in South Africa have not been improved to meet the demands for these challenges. Although South Africa has invested in a process to conduct a re-engineering of primary health care services to address a range of common health challenges in communities, this process has not demonstrated adequate policy and practice changes toaddress emerging challenges in providing services for mental health disorders at primary health care level. In particular, primary health care services do not include routine screening for common mental disorders, which include depression, anxiety, postnatal depression and substance abuse, although there are easy to use tools for such screening. This has resulted in a failure for early detection of these mental health challenges by the health system. The chapter argues that making moderate changes to the current offerings of primary health care can result in major achievements in offering mental health services, which in turn will benefit the patients and assist health services to address the increasing scourge of mental disorders, which include substance abuse.",signatures:"Kebogile Elizabeth Mokwena and Velaphi Anthony Mokwena",downloadPdfUrl:"/chapter/pdf-download/78257",previewPdfUrl:"/chapter/pdf-preview/78257",authors:[{id:"261452",title:"Prof.",name:"Kebogile",surname:"Elizabeth Mokwena",slug:"kebogile-elizabeth-mokwena",fullName:"Kebogile Elizabeth Mokwena"},{id:"417209",title:"Mr.",name:"Velaphi",surname:"Anthony Mokwena",slug:"velaphi-anthony-mokwena",fullName:"Velaphi Anthony Mokwena"}],corrections:null},{id:"78754",title:"Water, Sanitation, and Hygiene (WASH) and Infection Prevention and Control (IPC) in Primary Healthcare Facilities in Jordan in the Context of COVID-19",doi:"10.5772/intechopen.99523",slug:"water-sanitation-and-hygiene-wash-and-infection-prevention-and-control-ipc-in-primary-healthcare-fac",totalDownloads:24,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Water, Sanitation, and Hygiene (WASH) and Infection prevention and control (IPC) are essential for preventing and containing outbreaks of disease. Nowadays, infection prevention is getting more attention due to the COVID-19 pandemic. The assessment of WASH/IPC indicators in the health sector is a major step in the preparation and management of such a pandemic. A facility-wide WASH and IPC assessment is the cornerstone for designing, developing, and implementing specific WASH and IPC activities at healthcare facilities. This type of assessment helps to identify and prioritize surveillance and prevention activities at the facility and provide healthcare policy makers at all levels with the evidence to strengthen WASH services and infection control policies, practices, and resources in health facilities. Moreover, this helps to motivate facilities to intensify efforts where needed to prevent, respond to, and control the spread of COVID-19. An assessment was conducted in primary healthcare facilities in Jordan to identify the strengths and gaps in the WASH and IPC practices, activities, and resources and to identify areas for quality improvement. This report demonstrates the results of a nationwide assessment of 33 healthcare centres. The assessment included eight domains (areas) pertaining to WASH/IPC with more than 150 indicators. The assessment tools were developed and adapted from the Water and Sanitation for Health Facility Improvement Tool (WASH FIT), the Infection Prevention and Control (IPC) Assessment Framework (IPCAF), Guide to Infection Prevention for Outpatient Settings: Minimum Expectations for Safe Care, the Systems for Improved Access to Pharmaceuticals and Services (SIAPS) tool, and COVID-19 Technical Guidance by WHO. The assessment revealed some deficiencies in basic WASH/IPC indicators such as lack of clear guidelines that support the management of health centres in planning and leadership, shortfalls in the budget needed to strengthen the infrastructure of WASH/IPC, inconsistent or under-provisioned training and education programmes for the development of staff skills to lead, plan, manage, and improve WASH/IPC at their facilities. Moreover, the report identified the unmet WASH/IPC needs at centres that should be addressed by policy makers and stakeholders as soon as possible for further steps of consideration in policy development. The report ends with specific recommendations to improve WASH/IPC services and practices.",signatures:"Yousef Khader, Mohamad Alyahya and Rami Saadeh",downloadPdfUrl:"/chapter/pdf-download/78754",previewPdfUrl:"/chapter/pdf-preview/78754",authors:[{id:"222299",title:"Prof.",name:"Yousef",surname:"Khader",slug:"yousef-khader",fullName:"Yousef Khader"},{id:"426981",title:"Dr.",name:"Mohamad",surname:"Alyahya",slug:"mohamad-alyahya",fullName:"Mohamad Alyahya"},{id:"426982",title:"Dr.",name:"Rami",surname:"Saadeh",slug:"rami-saadeh",fullName:"Rami Saadeh"}],corrections:null},{id:"79015",title:"Strategies to Enhance Compliance to Health and Safety Protocols within the South African Mining Environment",doi:"10.5772/intechopen.100264",slug:"strategies-to-enhance-compliance-to-health-and-safety-protocols-within-the-south-african-mining-envi",totalDownloads:91,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Occupational health focuses on promotive and preventive and curative health. The occupational health practitioners have the responsibility to guide management and employees on the occupational legislative obligations aiming to safeguard legal compliance at the workplace. Additionally, it is the responsibility of the health professionals within the mining industry to provide primary, secondary and tertiary prevention strategies to improve the health and safety of workers. However, the prevalence of work-related diseases such as noise induced hearing loss, silicosis and the occurrence of accidents in the mining industry is an alarming factor. Systematic review method was adopted to identify and screen relevant citations. This book chapter aims to review and discuss existing literature on health and safety strategies to enhance safety compliance within the South African mining industry.",signatures:"Livhuwani Muthelo, Tebogo Maria Mothiba and Rambelani Nancy Malema",downloadPdfUrl:"/chapter/pdf-download/79015",previewPdfUrl:"/chapter/pdf-preview/79015",authors:[{id:"335856",title:"Prof.",name:"Tebogo Maria",surname:"Mothiba",slug:"tebogo-maria-mothiba",fullName:"Tebogo Maria Mothiba"},{id:"416234",title:"Mrs.",name:"Livhuwani",surname:"Muthelo",slug:"livhuwani-muthelo",fullName:"Livhuwani Muthelo"},{id:"425891",title:"Prof.",name:"Rambelani Nancy",surname:"Malema",slug:"rambelani-nancy-malema",fullName:"Rambelani Nancy Malema"}],corrections:null},{id:"80132",title:"Early Occupational Therapy Intervention: Patients’ Occupational Needs",doi:"10.5772/intechopen.102356",slug:"early-occupational-therapy-intervention-patients-occupational-needs",totalDownloads:64,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The occupational therapy management involves the assessment of the individual’s specific needs. This kind of assessment facilitates the therapeutic relationship and boosts the person’s motivation, as he or she feels valued and heard. Early-stage collection of information about meaningful activities for the individual helps them project themselves outside the context of illness. Collecting occupational need at an early stage, permits “Engagement”, which means participating in activities even without actually doing them. An occupational therapy model called “Personal Environment Occupation Model” suggests that already at an early stage we should make the environment and occupations meaningful to the person in order to maximise the patient’s performance. An observational study on stroke patients shows how people have personal occupational needs beyond simple self-care, including productive life and leisure time, already in the subacute phase. A further study is underway to demonstrate the effectiveness of early occupational therapy intervention, including complex patients regardless of diagnosis and taking into account their need for care and disability in order to promote their participation and maximise their autonomy.",signatures:"Margherita Schiavi, Barbara Volta, Gilda Sandri, Erica Keeling and Maria Teresa Mascia",downloadPdfUrl:"/chapter/pdf-download/80132",previewPdfUrl:"/chapter/pdf-preview/80132",authors:[{id:"439048",title:"M.Sc.",name:"Margherita",surname:"Schiavi",slug:"margherita-schiavi",fullName:"Margherita Schiavi"},{id:"439049",title:"Prof.",name:"Maria Teresa",surname:"Mascia",slug:"maria-teresa-mascia",fullName:"Maria Teresa Mascia"},{id:"439050",title:"Dr.",name:"Gilda",surname:"Sandri",slug:"gilda-sandri",fullName:"Gilda Sandri"},{id:"439052",title:"MSc.",name:"Barbara",surname:"Volta",slug:"barbara-volta",fullName:"Barbara Volta"},{id:"446740",title:"Dr.",name:"Erica",surname:"Keeling",slug:"erica-keeling",fullName:"Erica Keeling"}],corrections:null},{id:"77489",title:"Telephone Consultations by Medical Scheme Patients Consulting General Medical Practitioners, South Africa",doi:"10.5772/intechopen.98496",slug:"telephone-consultations-by-medical-scheme-patients-consulting-general-medical-practitioners-south-af",totalDownloads:85,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Background: The COVID-19 climate has seen a shift in the manner that patients seek care. Lockdown measures and COVID-19 regulations, and the fear of contracting the virus at a health care facility has also changed health seeing behaviour among patients. The COVID-19 climate has seen a significant increase in the utilisation of virtual platforms to consult with providers. Objectives: The objective of this chapter was to conduct the descriptive analysis of telephonic consultations by members of medical schemes who consulted general medical practitioners. Methods: The study entailed a descriptive analysis of medical scheme claims data for the 2020 review period. The inclusion criteria were all National Pharmaceutical Product Interface (NAPPI) codes associated with a telephonic consultation consulting general medical practitioners. The ICD-10 code primary diagnosis was used to describe the diagnosis. The study mainly focused on outpatient patients with service dates between March and December 2020. Results: The analysis covered claims data from a total of 12 medical schemes. The schemes analysed accounted for 1,6 million lives. The total number of telephonic consultations was 17 237. The mean (SD) claimed amount for telephone consultation for a general medical practice consult was R2821 (SD = 20). This was slightly lower than the scheme tariff of R2872 (SD = 19). The study found that most telephonic consults were for Acute bronchitis, unspecified; Acute upper respiratory; Emergency use of U07.1 (Confirmed diagnosis); Emergency use of U07.2 (Suspected Diagnosis); Follow-up examination; Special screening. Conclusion: The study found evidence of patients utilising telephonic consultations for general medical practitioner services. The effect of COVID-19 in this respect was seen in the three main primary diagnoses that were associated with the consult, Acute upper respiratory, Emergency use of U07.1 (confirmed diagnosis) and Emergency use of U07.2 (suspected diagnosis). Even though the average telephonic consult was claimed at just under R3003, few general medical practitioners claimed between R4004 and R5005 which were higher than the industry average. There is a need to develop telephone consult guidelines at industry level, these should also address reimbursement rate differentials.",signatures:"Michael Mncedisi Willie, Neo Nonyana and Sipho Kabane",downloadPdfUrl:"/chapter/pdf-download/77489",previewPdfUrl:"/chapter/pdf-preview/77489",authors:[{id:"418229",title:"M.Sc.",name:"Michael",surname:"Willie",slug:"michael-willie",fullName:"Michael Willie"},{id:"418233",title:"Dr.",name:"Sipho",surname:"Kabane",slug:"sipho-kabane",fullName:"Sipho Kabane"},{id:"418240",title:"Mr.",name:"Neo",surname:"Nonyana",slug:"neo-nonyana",fullName:"Neo Nonyana"}],corrections:null},{id:"80349",title:"Utilisation of Digital Health in Early Detection and Treatment of Pre-Eclampsia in Primary Health Care Facilities South Africa: Literature Review",doi:"10.5772/intechopen.101228",slug:"utilisation-of-digital-health-in-early-detection-and-treatment-of-pre-eclampsia-in-primary-health-ca",totalDownloads:63,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Gestational hypertension and pre-eclampsia are the most prevalent in Sub-Saharan Africa leading to undesirable perinatal and maternal outcomes. In South Africa, a high rate of maternal death was noted due to pre-eclampsia. However, the use of digital maternal health in South Africa has become of significance for reinforcement of health care. Digital health initiatives such as mobile health technologies were developed to improve better access to communities in low and middle-income countries. The implementation and practices of digital health seem to be growing expandable to achieve the UHC goals in the provision of care to all globally and nationally. This review aims to review existing literature on the use of digital maternal health to minimise admission of pre-eclampsia and early identification of gravid women who are at risk of developing pre-eclampsia.",signatures:"Mxolisi Welcome Ngwenya, Livhuwani Muthelo, Masenyani Oupa Mbombi, Mamare Adelaide Bopape and Tebogo Maria Mothiba",downloadPdfUrl:"/chapter/pdf-download/80349",previewPdfUrl:"/chapter/pdf-preview/80349",authors:[{id:"416234",title:"Mrs.",name:"Livhuwani",surname:"Muthelo",slug:"livhuwani-muthelo",fullName:"Livhuwani Muthelo"},{id:"440326",title:"M.A.",name:"Mxolisi Welcome",surname:"Ngwenya",slug:"mxolisi-welcome-ngwenya",fullName:"Mxolisi Welcome Ngwenya"},{id:"442074",title:"Dr.",name:"Masenyani",surname:"Oupa Mbombi",slug:"masenyani-oupa-mbombi",fullName:"Masenyani Oupa Mbombi"},{id:"442075",title:"Dr.",name:"Mamare Adelaide",surname:"Bopape",slug:"mamare-adelaide-bopape",fullName:"Mamare Adelaide Bopape"},{id:"442076",title:"Dr.",name:"Tebogo Maria",surname:"Mothiba",slug:"tebogo-maria-mothiba",fullName:"Tebogo Maria Mothiba"}],corrections:null},{id:"80078",title:"Evaluating A Mobile App for Data Collection in Occupational Therapy Practice",doi:"10.5772/intechopen.102084",slug:"evaluating-a-mobile-app-for-data-collection-in-occupational-therapy-practice",totalDownloads:87,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This study investigates the use of a mobile app for data collection in occupational therapy practice. Seven occupational therapists used a mobile app to collect data on housing-adaptation home visits for a period of two months. The occupational therapists documented five home visits on an online diary to document their use of the mobile app. Subsequently, a follow-up focus-group interview was conducted to discuss the diary results and elaborate on the use of the app in occupational therapy practice. The benefits of using the mobile app include the app’s systematic approach, ease of navigation, and the automation of data collection steps. Limitations include the inability to capture the complexity of the practice. Thus, the occupational therapists to some extent experienced that the need to use the mobile app is an added task in therapists’ daily work that did not reflect their current practice. Future transformations of paper-based tools must be conducted in a way that closely reflects the work processes in clinical practice. This study suggests that a digitized tool holds significant potential for developing clinical practice, but digitization does not change the issues or the complexity associated with the tool itself or the existing practice.",signatures:"Tanja Svarre, Marie Bangsgaard Bang and Tine Bieber Lunn",downloadPdfUrl:"/chapter/pdf-download/80078",previewPdfUrl:"/chapter/pdf-preview/80078",authors:[{id:"447103",title:"Mrs.",name:"Marie",surname:"Bangsgaard Bang",slug:"marie-bangsgaard-bang",fullName:"Marie Bangsgaard Bang"},{id:"447104",title:"Mrs.",name:"Tine",surname:"Bieber Lunn",slug:"tine-bieber-lunn",fullName:"Tine Bieber Lunn"},{id:"452106",title:"Associate Prof.",name:"Tanja",surname:"Svarre",slug:"tanja-svarre",fullName:"Tanja Svarre"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"7159",title:"Body-mass Index and Health",subtitle:null,isOpenForSubmission:!1,hash:"bb520e914b9b3d726b9b9f9d047011ce",slug:"body-mass-index-and-health",bookSignature:"Ayşe Emel Önal",coverURL:"https://cdn.intechopen.com/books/images_new/7159.jpg",editedByType:"Edited by",editors:[{id:"25840",title:"Prof.",name:"Ayse Emel",surname:"Onal",slug:"ayse-emel-onal",fullName:"Ayse Emel Onal"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1673",title:"Evidence Based Medicine",subtitle:"Closer to Patients or Scientists?",isOpenForSubmission:!1,hash:"d767dfe22c65317eab3fd9ff465cb877",slug:"evidence-based-medicine-closer-to-patients-or-scientists-",bookSignature:"Nikolaos M. 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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"}}]},chapter:{item:{type:"chapter",id:"65911",title:"Structure-Based Approaches to Antigen-Specific Therapy of Myasthenia Gravis",doi:"10.5772/intechopen.84715",slug:"structure-based-approaches-to-antigen-specific-therapy-of-myasthenia-gravis",body:'
Myasthenia Gravis (MG) is an autoimmune disease that afflicts a significant human population. MG patients suffer from a variable degree of skeletal muscle weakness. The symptoms range from mere lack of muscle strength to life-threatening respiratory failure. MG is a chronic disease that can last many years and negatively impact the quality of living and life expectancy of afflicted individuals. Although MG rate is reported to be 7–20 out 100,000 [1] and the diagnosed MG cases are increasing, probably due to increased awareness of this debilitating disease, the aging population and other intrinsic and extrinsic factors that disturb the human immune system [1].
The majority of MG cases (~85%) are caused by pathological autoantibodies to muscle nicotinic acetylcholine receptors (nAChRs), a ligand-gated ion channel that mediates rapid signal communication between spinal motor neurons and the muscle cells. Autoantibodies against other neuromuscular junction (NMJ) proteins, including muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4), can also cause muscle weakness in a small fraction of patient [2, 3]. The heterogeneous nature of MG autoantibody presents a challenge to both diagnosis and treatment of the disease.
Current treatment regimens for MG include anticholinesterase inhibitors, thymectomy, immunosuppressants, plasmapheresis, or intravenous immunoglobulins [4]. Most MG patients respond favorably to these treatment options to achieve effective symptom relief, and in some cases even clinical remission. Cholinesterase inhibiting drugs can temporarily enhance neuromuscular transmission by delaying the breakdown of acetylcholine (ACh) to compensate for the loss of NMJ nAChRs, but this treatment option only works in a fraction of patients and does not alter the autoimmune response. The more broadly used nonspecific immunosuppressive drugs work by inhibiting lymphocyte activation and proliferation but have little effect on long-lived plasma cells that are terminally differentiated and continue producing pathogenic antibodies [5, 6]. This may explain why treatment with non-specific immunosuppressive drugs takes long time to show clinical improvement.
There are two major limitations in the current MG treatment. First, up to 10% of MG patients do not tolerate or are resistant to the available treatments [7]. Second, all immunosuppressant drugs, which are often used in the long-term control of chronic MG, inevitably carry the serious risks of infection and cancer. As such continued efforts have been put into searching for better MG treatment, as evident by the long list of clinical trials (ClinicalTrials.gov) testing well known immunosuppressive drugs such as methotrexate and azathioprine, as well as new biologics agents such as the anti-CD20 monoclonal antibody rituximab (which depletes B cells) and the anticomplement C5 monoclonal antibody eculizumab.
An ideal therapeutic approach to MG would be to inhibit the pathogenic autoimmune response to nAChR specifically without disrupting other functions of the immune system. Because nAChR is a dominant autoantigen in MG, it has served as the primary target for a wide range of studies attempting to develop antigen-specific therapy to induce immune tolerance to nAChR [8, 9, 10, 11, 12, 13, 14]. While some of these approaches showed promising results in animal model of experimental autoimmune MG (EAMG), translation to human MG treatment is uncertain. Furthermore, introducing an autoantigen like nAChR or its derivative peptides risks to inadvertently enhance the pathogenic autoimmune response.
Here, we will first review structural and molecular features of nAChR and its complexes with autoantibodies. Based on insights derived from structural studies, we will discuss several strategies to specifically inhibit the binding of pathological autoantibodies to nAChR or specifically eliminate nAChR-specific B cells.
As the first isolated neurotransmitter receptor and ion channel, nicotinic acetylcholine receptors (nAChRs) have been the focus of extensive studies to understand the basic mechanisms of neuronal signaling. These receptors are also being targeted for drug development against a variety of diseases, including addiction, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, Alzheimer’s disease, pain and inflammation [15]. nAChRs have been analyzed by a variety of biochemical, biophysical and electrophysiological experiments [16]. Tremendous efforts have been put into pursuing the atomic structure of nAChR. Electron microscopic analyses of nAChR from
Although large quantities of nAChR were available from
All of the three mutations map to the surface of the protein (Figure 1a), with one (V8E) located on the N-terminal helix and the other two (W149R and V155A) located on loop B. The V8E mutation introduces a salt bridge with Lys84 (Figure 1b), whereas the W149R mutation introduces a salt bridge with Asp89 (Figure 1c). These salt bridges apparently contribute to protein stability as evident by the well-defined electron density of these exposed residues with long and charged side chains. Thus, the mutations seem to enhance the protein stability through at least two mechanisms. One is to remove surface exposed hydrophobic residues, including V155A (Figure 1d); the other is to introduce salt bridges on the protein surface. These observations suggest that the ECD of nAChR may be rationally engineered to improve solubility and stability. In principle, one can use homology models to guide the selection of exposed hydrophobic residues and to engineer surface salt bridges, which can increase the stability of recombinant mammalian nAChRs. This insight will be important for the design of stable chimeric nAChR antigen for specific targeting and elimination of nAChR-specific B cells (discussed further below).
Mutations that stabilize nAChR α1 ECD. (a) The three mutations (boxed and indicated by arrow) are mapped on the surface of nAChR α1 ECD (dark green) and away from the binding site of α-bungarotoxin (orange) and the glycan (magenta); (b) the mutation Val8Glu establishes a salt bridge with Lys84. The surrounding structure is well ordered, showing well-defined electron density; (c) the mutation Trp149Arg establishes a salt bridge with Asp89. The side chains of both residues show well-defined electron density; (d) the mutation of Val155Ala removes an exposed hydrophobic residue. The surrounding structure is well ordered (Adapted from Chen [
Most proteins have a densely packed hydrophobic core that is important for stable folding in aqueous solution. However, a hydration pocket was found inside the beta sandwich core of the nAChR α1 ECD [22]. This hydration pocket consists of two buried hydrophilic residues, Thr52 and Ser126, two ordered water molecules, and a few cavities, creating a packing defect near the disulfide that connects the two beta sheets. Both Thr52 and Ser126 are highly conserved in nAChRs but are substituted by large hydrophobic residues (Phe, Leu or Val) in the non-channel homologue AChBPs. This observation suggests that the nAChR ECD has evolved with a non-optimally packed core, hence predisposed to undergo conformational change during ligand-induced gating. Replacing Thr52 and Ser126 with their hydrophobic counterparts in AChBP significantly impaired the gating function of nAChR without affecting the folding of the protein structure [22]. This role of the hydration pocket on the conformation flexibility/dynamics of the nAChR ECD is supported by recent molecular dynamics studies [34]. This model also suggests that the specific location of the hydration cavity is important for a particular class of pentameric LGICs [35]. A practical implication of these observations is that one can design stabilization mutants of LGICs, including nAChR ECD, by structure-guided modifications of such packing defects, which are evolved for intrinsic ion channel functions but may be detrimental to recombinant production of proteins as therapeutic antigen.
Antibodies generated by the immune system may bind various epitopes on nAChR. It is therefore important to know if MG autoantibodies are randomly distributed to various epitopes and if they contribute equally or differently to the disease phenotype. This question is also therapeutically relevant if one wishes to use small molecules or single valent antibody [36] to block the binding of most pathologically relevant autoantibodies to nAChR. Mammalian muscle nAChR has a pentameric structure composed of two α1, one β1, one δ, and one ε (adult form) or γ (fetal form) subunit(s) [18]. Extensive studies suggest that autoantibodies to α1 play a major role in MG pathology [37, 38, 39, 40]. Furthermore, more than half of all autoantibodies in MG and EAMG bind an overlapping region on the nAChR α1 subunit, known as the main immunogenic region (MIR) [41]. The MIR is defined by the ability of a single rat monoclonal antibody (mAb), mAb35, to inhibit the binding of about 65% autoantibodies from MG patients or rats with EAMG [42, 43, 44]. Subsequent studies have mapped MIR to a peptide region that spans residues 67–76 on nAChR α1 [45, 46]. Monoclonal antibodies directed to the MIR can passively transfer EAMG and possess all the key pathological functions of serum autoantibodies from MG patients [37]. Moreover, a recent study showed that titer levels of MIR-competing autoantibodies from MG patients, rather than the total amount of nAChR autoantibodies, correlate with disease severity [47]. These observations suggest that autoantibodies directed to the MIR on nAChR α1 play a major role in the pathogenesis of MG [41]. However, autoantibodies classified as MIR-directed by competition assay may not necessarily have the same binding mechanisms to nAChR: two MIR-competing autoantibodies may share common or overlapping epitopes or may bind different epitopes but compete through steric effect [14].
Given their established myasthenogenic role, extensive efforts have been put into characterizing the interactions between MG autoantibodies and nAChR using biochemical [45, 46, 48, 49, 50, 51, 52, 53], structural [22, 54, 55, 56], and modeling approaches [57]. More recently, the first crystal structures of human (pdb code: 5HBT) and mouse (pdb code: 5HBV) nAChR ECD bound by the Fab fragment of an EAMG autoantibody, Fab35 were determined [58]. Both crystal structures are very similar, so the discussion here will focus mainly on the human complex (pdb code: 5HBT). The crystal structure, which also contains α-Btx that binds and stabilizes nAChR ECD to facilitate crystallization, shows that Fab35 binds to nAChR α1 in an upright orientation, away from the α-Btx (Figure 2). The Fab35 binding sites on nAChR α1 include the MIR and the N-terminal helix. Fab35 has the canonical IgG antibody structure where the complementarity determining regions (CDRs) from the heavy chain, CDR-H2 and CDR-H3, and the light chain, CDR-L3, form the binding site for nAChR α1. Contacting residues from Fab35 and nAChR α1 (defined as being closer than 4.5 Å) can be mapped using the crystal structure. Such contacting analysis revealed several “hotspots” on nAChR α1 that make numerous contacts to Fab35, including Asn68 and Asp71 from the MIR loop and Arg6 and Lys10 from the N-terminal helix. As shown in Figure 3, each of these four “hotspots” anchors an extensive network of interactions that display remarkable chemical complementarities. The importance of these hotspots are supported by extensive mutagenesis studies [50, 51, 53, 59], which showed that Asn68 and Asp71 of the MIR are essential for MG autoantibody binding, while the surrounding Pro69 and Tyr72, when mutated, also affect the interaction between the antibody and the receptor. Mutation of N68D and D71K in the intact receptor also suggested ASn68 and Asp71 are of vital importance for the interaction [49]. On the N-terminal helix of
Crystal structure of the ternary complex of nAChR α1 ECD bound by Fab35 and α-Btx. (a) Ribbon representation of nAChR α1 ECD (α1: cyan) in complex with α-Btx (green) and Fab35 (heavy chain (H, yellow) and light chain (L, magenta)). The variable domains (VH and VL) and the constant domains (CH and CL) of the antibody are indicated accordingly. (b) Surface representation of the ternary complex. (c) Zoomed-in view of the binding interface. The complementarity determining regions of the heavy chain and light chain are indicated as H1, H2, H3, L1, L2, and L3, respectively (Adapted from Noridomi et al. [
Detailed interactions between Fab35 and nAChR α1 ECD at the binding interface. (a) Binding interactions at the vicinity of Asp71 of α1 (located at the MIR). (b) Interactions at the vicinity of Asn68 of α1 (located at the MIR). (c) Interactions involving Arg6 and Lys10 of α1 (located at the N-terminus of α1). (d) Interactions mediated by His3 of α1 (located at the N-terminus of α1) (Adapted from Noridomi et al. [
Although biochemical mapping of antibody-binding residues on nAChR α1 were performed with different antibodies (e.g., mAb210 and mAb132A) [45, 46, 48, 49, 50, 51, 52, 53], it is remarkable that these biochemical data agree so well with the crystal structure. The fact that many MIR residues at the center of the antibody-receptor interface are important for the high affinity binding of a variety of MG antibodies suggests that many MIR-directed autoantibodies share similar binding mechanisms to the core MIR/N-helix region. This is a rather surprising finding given the potential heterogeneity of nAChR antibodies mentioned above. An important implication of this finding is that it may be possible to find small molecule inhibitors to block the binding of a large fraction of pathological MG autoantibodies to nAChR.
To see how various MG/EAMG mAbs may bind nAChR through similar or different mechanisms, we compared the structure of Fab35 with that of two other MG mAbs (Fab198: pdb code 1FN4 and Fab192: pdb code, 1C5D) that have been determined previously [55, 56]. Superposition of the structure of Fab198 and Fab35 from the ternary complex shows that these two Fabs share a similar antigen-binding site (Figure 4a). As such, the MIR loop fits snugly into the pocket formed by the CDR-H2, CDR-H3 and CDR-L3 loops of Fab198, as predicated by previous modeling studies [57]. The CDR-H2 loop of Fab198 is also in a position to interact with the N-terminal α-helix adjacent to the MIR (Figure 4b). Even more remarkably, many key α1-binding residues in Fab35 are also conserved in Fab198 and they appear to have similar contacts to nAChR α1 in the modeled Fab198/nAChR α1 binding interface (Figure 4b). These residues include Trp47 from CDR-H2, Arg50 from CDR-H2, and Tyr95 from CDR-L3 at the center of the MIR-binding pocket, and Trp52 and Asp54 (both from CDR-H2) which interact with the N-terminal α-helix. In contrast to the structural similarities shown above, the CDR-H3 loops between Fab198 and Fab35 differ significantly in length and sequence. The CDR-H3 loop of Fab198 is too short to interact with the surface pocket of nAChR α1, which is occupied by the corresponding CDR-H3 loop of Fab35 in the complex crystal structure (Figure 4b). These structural analyses suggest that mAb35 and mAb198 share a high degree of similarity in binding mechanism to the core MIR/N-terminal helix region but differ in the periphery of the binding interface. On the other hand, superposition of the structure of Fab192 onto that of Fab35 in the ternary complex reveals substantial differences (not shown here). The variable domains (VH and VL) have a significant rotational twist, such that the MIR loop does not fit into the antigen-binding site of Fab192. What is more, the key α1-binding residues of Fab35, like Arg50 and Trp52 of CDR-H2, are not conserved in Fab192. These structural differences suggest that Fab192 may differ significantly from Fab35 in terms of binding mechanisms to nAChR α1, confirming and extending the differences previously recognized between the two [52].
Structural comparisons among MG mAbs. (a) Superposition of Fab198 [
A number of studies showed that the total amount of nAChR antibodies in the serum of MG patients does not seem to correlate with disease severity, suggesting that various nAChR antibodies that bind different regions on nAChR may contribute differently to this disease [41, 60, 61, 62]. As discussed above, the total amount of autoantibody from MG patients directed to the MIR of nAChR α1 subunit did show significant correlation with disease severity [47]. These observations suggest that autoantibodies directed to nAChR α1 MIR play a major role in the pathogenesis of MG [41]. It is now clear that many MIR-directed autoantibodies bind a composite epitope consisting of the original MIR (α1, 67–76) and the N-terminal helix (α1, 2–14) (N-helix) and surrounding regions (α1, 15–32). The structural analyses above and published biochemical data suggest that some MIR-directed autoantibodies (e.g., mAb35 and mAb198) bind epitopes centered around the MIR/N-helix core region while others (e.g., mAb192) seems to require epitopes outside the MIR/N-helix core. Nevertheless, based on crystallography studies and structure-guided analyses of existing biochemical data, it can be concluded that despite the heterogeneity of MG autoantibody repertoire a large fraction of MG autoantibodies share a highly-conserved binding mechanism to a core region on the nAChR, suggesting that it is possible to use a single or a limited set of small molecules to block the binding of a large fraction of MG autoantibodies. Because MG autoantibodies directed to the MIR region on nAChR are most relevant to the MG disease, MIR and its surrounding region are therefore an attractive target site for developing small molecules to block the binding of MG autoantibodies. Blocking the binding of MG autoantibodies to nAChR will likely have a direct impact on the antibody-mediated pathologies and may even alter the long-term immune response to nAChR in MG patient.
Targeting protein-protein interface for drug development is generally more challenging than the enzyme active sites [63]. This is especially true for flat protein interfaces lacking features for small molecule binding. However, successes have been achieved with a number of well-known targets, including the p53/MDM2 complex [64], the Bcl-xL/Bak complex [65] and the IL2/IL2R complex [66, 67]. A common feature of these complexes is that the protein-protein binding interfaces contain concave pockets lined with hydrophobic residues, which may provide favorable anchoring points for small molecules to bind and compete with protein-protein interactions. The crystal structure of the Fab35/nAChR α1 complex revealed that their binding interface is characterized by mutual insertions of loops into the pockets of binding partners. On the receptor side (Figure 5), the MIR loop inserts deeply into a surface pocket between VH and VL, and the N-terminal α-helix sits into a groove on the surface of VH. On the antibody side (Figure 6), the CDR-H3 protrudes into a surface pocket formed by the N-terminal α-helix, the loop following the N-terminal α-helix, the MIR and the loop preceding the MIR (referred to as the CDRH3 pocket here after). Based on these structural features, two MG inhibitor design strategies can be envisioned. One is to find small molecules that bind the surface pockets on Fab35 (Figure 5). But this approach faces the potential issue of antibody heterogeneity in sera of human MG patients because small molecule inhibitors may bind some but not other pathological autoantibodies, as it is highly possible antibodies binding to the same epitope may have subtle differences in their antigen-binding site structures. Another approach is to find small molecules to bind the CDRH3 pocket on nAChR (Figure 6). Small molecules bound to this site will directly interfere with the binding of mAB35 by competing with its CDR-H3. Even for other mAbs with short CDR-H3, such as mAb198, the compounds may also block the binding of CDR-H3 through steric hindrances. Moreover, since the CDRH3 pocket is immediate adjacent (about 6–8 Å) (Figure 6) to the MIR/N-helix core region critical for the binding of a large group of MG autoantibodies, compounds bound to CDRH3 could sterically and/or allosterically inhibit the binding of most pathological MG autoantibodies efficiently. Because of its concaved structure, CDRH3 pocket could serve as the anchoring point to design and/or screen small molecules that bind nAChR α1 and complete with MG autoantibodies directed to MIR and its nearby regions.
Surface pockets on Fab35 bound by the nAChR MIR loop (white dashed circle) and the N-terminal helix (black dashed circle).
The surface pocket (green dashed circle) on nAChR α1 bound by the CDR-H3 loop from Fab35 (indicated as H3 in the figure).
The fact that pathogenic B cell clones can populate for a long time in patients’ body may explain why MG is usually a chronic disease. Ectopic germinal centers are found in the thymus of many MG patients who are diagnosed with thymoma or thymus hyperplasia, where nAChR-specific B lymphocyte are constantly activated, selected and matured to produce the antibody, leading to the disease [68]. This disease model underlies the rationale of thymectomy as a widely adopted treatment of MG, but the result varies depending on the subtype of the disease, with a complete remission rate of 25–53% [69]. These results suggest there are possibly other unknown sites where nAChR specific B cells are activated, selected and matured [13].
Using B cell surface marker CD20 [70, 71, 72] or possibly CD19 [73] as the target, disease-causing B cells can be depleted at the cost of killing normal B cells. For example, an ongoing clinical trial, NCT02110706, is testing if rituximab, which targets CD20 on B cells, can be a safe and beneficial therapeutics for MG. In general, treatment with B cell depletion agent often requires a long recovery time before B cells return to normal level again [71]. Moreover, the treatment has been reported to have a short effective duration time for MuSK-positive MG [74]. Long-term usage of such agent may compromise immunological function with increased risk of infection such as Progressive multifocal leukoencephalopathy (PML) and malignancy [72]. As such, strategies targeting nAChR specific B cells seem to be attractive. Since each B cell expresses B cell Receptors of the same idiotype as its secreted antibody on its surface, one can use such property to specifically target autoreactive B cell as long as the antigenicity of the autoimmune disease is clear. The idea was borrowed from immunotoxins [75] in which an antigen-toxin chimera was constructed. The antigen moiety is used to target the B cells that express the BCR of the same idiotype as the antibody and the toxin moiety is responsible for conveying death signal to the target B cells. In a pioneering study in 1983 the author fused thymoglobulin with ricin to treat an autoimmune disorder-Hashimoto’s thyroiditis [76]. Another attempt was tried a decade later in another autoimmune disease-Pemphigus Vulgaris, in which the authors constructed antigen-toxin fusion protein that can specifically target Dsg3-specific hybridoma cells [77]. Similar strategies have also been attempted in the treatment of MG. In a study of 2006, the author fused the nAChR α1 ECD to a plant toxin and showed its effectiveness in specifically killing of α1-specific B cells [78]. More recently, researchers have developed a variant of such strategy in which nAChR α1 ECD was fused with Fc domain of antibody, which was used to convey the negative signal, since B cells express and only express one kind of Fc receptor, namely FcRγIIB, which transduce negative signal for B cell activation. Consequently, such chimeric protein will specifically target the nAChR α1 specific B cell via the binding to the BCR and deliver negative signal to inhibit α1 specific B cells [79, 80].
The idea of antigen-chimera in the treatment of MG seems attractive but will not be practical unless the chimeric protein is stable enough to be used as a therapeutic agent. As mentioned above, nAChR α1 is just one subunit of the nAChR pentamer and is intrinsically unstable, making the expression of wild type nAChR α1 ECD in stable soluble form very challenging. However, as discussed earlier in this chapter, crystallography studies of nAChR α1 ECD in recent years have accumulated extensive experience and knowledge in designing strategic mutations to improve the stability and expression level of nAChR α1 ECD protein while preserve the binding of MIR-directed MG autoantibodies [22, 31, 58] These progresses will greatly facilitate the approach to using engineered antigen chimera to specially inhibit and eliminate nAChR-specific B cells for MG treatment.
Insights from structural studies and molecular biology/biochemical analyses may ultimately lead to precision medicine and personalized treatment of MG by antigen profiling of patient and the use of corresponding molecular missiles to eliminate antigen specific antibodies or B-cells, induce antigen specific tolerance, or blocking nAChR-autoantibody binding by small molecules. These approaches, once established in the treatment of MG, could be expanded to other autoimmune diseases with well-defined antigen targets.
In the last years the use of mobile devices has increased. The success of mobile devices is due, among other factors, to its moderate cost, the variety of applications that allow being connected to the Internet, and the ease of use for many of its applications [1, 2]. The usability of the applications of the mobile devices is the main characteristic for the acceptance of the users [2]. This implies that the applications are intuitive and easy to use. To achieve this, researchers and developers have proposed design guides, patterns and templates to achieve applications with good features and easy to use. In addition, due to the diversity of sensors that mobile devices have, they can have different interaction modes and gestures that are used to control applications [3, 4].
Despite all the innovative technological elements for a pleasant user experience presented by mobile devices, for the user they have the restriction of the size of the screen, which reduces their area of work. The range of displays for smartphones is between 4 and 7 inches [5]. The sizes of the tablets are between 7 and 18 inches. And the range for smartwatches is between 1.2 and 2 inches. While there are mobile devices with screens larger than 13 inches, most of these devices are below 10 inches [5].
To get the most out of the work area offered by most mobile devices it is needed to take advantage of the work areas of the different mobile devices that the user has, depending on the context in which the user is. To achieve this, it is possible to design applications for mobile devices that can work with DUIs. That is, an application takes advantage other mobile devices carried by the user or other devices such as Smart TV in the area where it is located. Another problem in DUIs design is the quality in order to guarantee the usability and functionality of applications that use DUIs [3].
User interfaces have a time component that allows establishing whether the adaptability of their elements will be done dynamically or statically. Dynamic adaptability refers to the changes that the graphical interface makes when the application detects a change of context. Static adaptability is established when the user chooses how the graphical interface will adapt before doing a task or when starting a session. Therefore, several researches have developed concepts such as DUI and plasticity of user interfaces.
In this work we present concepts of DUIs, plasticity, and mobile computing to establish the specific restrictions for DUIs of mobile applications, and to discuss how the plasticity concepts of user interfaces complement the handling of these restrictions to establish the concept of mobile DUI. We present the design methods that have appeared in the literature and emphasize that both are complementary to a mobile DUI design.
A mobile DUI is a DUI that takes advantage of mobile devices, communication networks and context of use to distribute user interfaces to take advantage of the display restrictions of mobile devices. It should be clear the concepts of DUIs and the characteristics of mobile applications have a complete notion of mobile DUI.
The use of DUIs is very common in multimedia applications such as music players, video players, image galleries, video games, books or interactive learning materials, but there are still few applications that use it for purposes other than entertainment. DUIs can be used in educational contexts [6]and for assistance applications for disabled persons [6, 7]. Also DUIs are required to interaction with smart spaces [8, 9, 10, 11].
One approach to understand the use of DUIs is in [2], where the authors discuss the evolution of trends of computing since main frames to ubiquitous computing (UC). With the arrival of UC, users interact with more computing devices that contain input and output elements. In this section we start with a discussion of the DUIs, then a discussion of the characteristics of the mobile applications, and finally a discussion is presented to define the concept of mobile DUI.
A user interface (UI) is the set of elements that allow the user to interact with computers. These elements can be categorized as input, output and data control. This definition involves all kinds of technology and interaction mechanisms.
Vanderdonckt [12] propose a transversal model to distribute the user interface across users, platforms and environments. In this model, the authors consider the triplet
Transversal model of DUI.
With this model it is possible to determine what elements of the UI would be distributed, to know the interaction modality that will be used when the elements are ported to target platform, to know the tasks that will be performed in a lapse of time, to know the domains involved in the distribution, and to know the platforms that participate in that distribution configuration.
A distributed user interface is a set of UIs that can be implemented in more than one device, or software platform. Some implementations consider the use of two or more devices simultaneously [7, 13]. By authors Penaver, Melchior and Gallud in several papers from 2011 to 2013 [14, 15, 16, 17] we know that any single user interface can be cataloged as a distributed user interface if it has some characteristics like portability, fragmentation (also known as decomposition), simultaneity, and continuity. Being the first two characteristics the most important to satisfied the transformation of a user interface to a distributed one [14, 17, 18].
From 2011 to 2013 several authors make some definitions [14, 15, 16, 17, 18] to formulate the DUI abstract model that allows developers to arrive at an implementation model. In this model, the elements of interaction (input, output and control), functionality, target, user interface, portability, decomposability, sub-user interfaces, platform, distributed user interfaces, simultaneity, requirements function and concurrency restriction stand out.
With these definitions it is possible to have a formal description of the characteristics for distributed user interfaces such as portability, fragmentation, simultaneity and continuity. These characteristics are very important for working with distributed user interfaces. Villanueva et al. [3] propose the use of these characteristics as metrics to determine the quality of DUIs.
A mobile application is an application that runs following the mobile computing paradigm. In this paradigm, the application’s view layer runs on a mobile device, and the business and storage layers may or may not be on or off the device. In addition, the device must have the ability to be always connected (anywhere at any time) taking advantage of the different infrastructures of communication networks and also must consider the mobility of the user [19]. Mobileness means that the use of an application is always under an environment with constant changes, so the application must be able to adapt to changes in the context to remain functional and usable to the end user.
A mobile application is a computer mobile software designed to perform a task or to provide a user experience. The mobile software development presents some special requirements [20]:
Interaction with other applications: most of the mobile devices have many applications from different sources. New applications should be able to interact with the installed applications.
Sensor handling: the applications must be able to use the device sensors in order to improve user experience.
Families of hardware and software platforms: most embedded devices execute code that is custom-built for the properties of that device, but mobile devices may have to support applications that were written for all of the varied devices supporting the operating system, and also for different versions of the operating system.
User interfaces: they must be usable. The design of a user interface must consider the device’s constraint like display size, battery life and processor capacity, and it must take advantage of the device’s capabilities.
Power consumption: many aspects of applications affect the use of the device’s power and thus the battery life of the device. Mobile applications may make extensive use of battery.
Techniques for reconfiguring the components of an application must be used. In addition to these concepts, it should be considered that a user interface in a mobile environment would be affected by changes in the environment, so the term plasticity turns out to be relevant. The plasticity of user interfaces is their ability to adapt to the context of use and to preserve their usability [21, 22]. This concept is useful to handle the adaptation of the elements in a DUI. Due to the mobility and ubiquity inherent in this type of systems, the changes of context are natural in this type of systems [23].
The context deals with the evolution, the structuring and the exchange of information spaces [24], which are designed to fulfill a particular purpose. In plastic user interfaces, the purpose is to support the process of adapting the user interface to preserve usability, i.e., plasticity techniques must handle the context of use. A change of context could be defined as the modification of any element of the contextual information space.
Vanderdonckt et al. [23] define seven dimensions to manage plasticity: adaptation means, UI component granularity, state recovery granularity, UI deployment, context of use, technological space coverage, and plastic meta-UI.
In the literature there are several models to design a DUI and give quality. We can notice that these models complement each other. Vanderdonckt’s transversal model uses three dimensions, Penalver’s, Melchoir’s and Gallud’s model uses four dimensions, and Vanderdonckt’s plastic model considers seven dimensions. The work that has been done with DUIs and their formalization establish that the elements of a UI can be distributed, and the relationship that exists between them. Those works on plasticity of user interfaces establish how adaptability can be made, focusing on the conditions of context.
To handle the context for a mobile DUI, it must be considered that the information spaces are the elements of the UI (elements, sub UI, etc.), and the characteristics of the devices where the DUI will be displayed. The plasticity of the UI must handle the context of use. A change of context is the set of devices where elements of the user interface can be displayed, and in this way it is observed that elements of the information space are modified.
In general, it is possible to distinguish two methods for DUI design. One of these is presented by [12] and the other is presented by [14, 15, 16, 17]. In [12] the way to distribute the GUI elements between users, platforms and environments is emphasized. In [14, 15, 16] the design is considered through a conceptual model based on portability, decomposition, simultaneity, and continuity of the DUI. The formalization of the DUI helps to know what elements are going to be distributed. Plasticity helps to establish when to make the distribution of elements and also raises the problem of how to do it.
We can say that a mobile DUI is a set of DUIs that mainly uses mobile devices sensitive to context, which can be supported by ubiquitous computing. The use of mobile devices allows the use of the different interaction modalities that they include. However, DUIs must consider handling the restrictions of mobile devices, mainly the size associated with the user interface, the high dependence on network connectivity and battery management.
There are several mobile platforms such as Android, iOS or Windows Mobile, among others, that provide tools and frameworks for developing applications. Furthermore, kits and frameworks have been developed to create mobile applications that allow us to share displays among mobile devices of the same family, i.e., their frameworks allow us to build some DUIs. Every platform uses a different strategy because the development paradigm is different for each platform. Another option is to develop rich clients that run on a Web browser.
However, despite the advantages offered by mobile application development platforms, it is necessary to use middleware and frameworks that help to efficiently manage DUIs. Another problem remains the design of the UIs that will be distributed to each platform involved in the DUI.
Work has been done to have models for the design, development and deployment of DUIs in execution time [8, 14, 25, 26, 27, 28]. These works consider software engineering techniques as well as aspects of implemention. These last considerations can be reinforced with the works on plasticity that have been developed [29, 30].
With the elements described in the model of Section 4, we present three examples where the design of the DUI is available in three combinations of computing devices: Tablet-Smart TV, smartphone-smartwhatch, and Tablet-Tablet.
In this example, an application is presented to perform three neuropsychology tests of Luria: Poppelreuter I, Poppelreuter II and Raven [7]. This application is called LuTest, whose architecture allows the user to manage a DUI whose platforms are an iPad tablet and an Apple TV, as shown in Figure 2. The main task of this application is to apply to a user the neuropsychological tests of Poppelreuter I, II and Raven. This example presents two ways to show the elements of the output: one is to duplicate the UI and the other to divide the UI. The final users of these applications are older adults, so the design of the UI is aimed at this population. Applications can only run on the Tablet or they can use the Tablet-Smart-TV combination in order to increase the work area.
Architecture for LuTEST. This application makes a DUI using a Tablet iPad and an Apple TV.
DUIs have a static adaptability. The user determines the tablet orientation and the mode of work: alone or with a Smart TV before starting the test. The designs of the UI, in all cases of adaptability, are oriented to work with older adults. Because a dynamic adaptability could generate confusion in final users, we decide make a static adaptability.
In Poppelreuter I test, the user must indicate the figures presented to them with visual noise. Poppelreuter 1 test begins by showing the user the contour image of an object, later more images containing the original object will be shown, but now the outline is combined with lines that may confuse the patient. The user must indicate the outline of the original object, ignoring the additional lines. The test consists in displaying different images, with different objects and different types of visual noise, as shown in Figure 2. For Poppelreuter II test, the visual noise is generated by overlapping the contours of several forms, Figures 2 and 3. The user must indicate the contour for each of them.
(a) DUI design for Popperreuter 1 test using a tablet in landscape or portrait orientation with a Smart TV and (b) DUI design for Popperreuter II test using a tablet in landscape or portrait orientation with a Smart TV.
The Raven test is used to evaluate visual and cognitive abilities. It works as follows: the patient observes a certain visual structure, which is incomplete. The patient can choose between six or eight possible options, but only one is correct. In some cases, the patient is asked to differentiate their answers from the others, and for that the patient must grasp the principle under which each option was constructed. The complete Raven test is composed of three series, each with 12 different test matrices whose difficulty progresses step by step. The advantage of using Raven to assess cognitive abilities is that a grammatical knowledge or a complex mathematical ability is not required (Figure 4).
DUI design for Raven test using the Tablet in landscape or portrait orientation with the Smart TV.
In this example, a DUI is presented, which allows the communication of smartwatch and smartphone type mobile devices. The objective of this DUI is to show the best walking route that a tourist should follow in the Historic Center of Mexico City to reach a point of interest around it, in a radius no greater than 5 km. The user can execute the application on the smartphone, on the smartwatch or in both devices using a DUI.
The user decides at any time to activate the DUI, from the smartphone or from the smartwatch. If the user activates the DUI from the smartphone and the smartwatch does not have the application active, then the application is activated and the smartphone sends the status of the application, which indicates that it is in some search of a site of interest or that it is displaying geographic information. In this case, the smartphone starts the application. If the user activates the DUI from the smatwatch and the application is not active on the smartphone, then the status of the application is activated and transferred, so that the smartphone knows the activity that it must present on the display.
Figure 5 shows the DUI for the search and guide application of sites of interest. The DUI uses the deployment area of the smartphone and smartwatch. In the case of search by predetermined sites, a list is presented on both devices. To guide the user to the site of interest, the smartphone presents the route on a map and an arrow indicating where to go. To guide the user to a site of interest, the smartwatch presents an arrow indicating the orientation.
DUI design for an application using smartphone and smartwatch.
This example uses a set of tablets or smartphones to increase the working area. The DUI is increased dynamically when the application detects another device with the application. The application is a mental maps editor. The application detects a gesture to add or remove a device from the application, and therefore adjust the DUI dynamically (Figure 6).
DUI design for application using smartphones and tablets.
The trends in DUIs its about the real time system for make the distributions; have software engineering methodologies for the design and implementation of DUIs; have consistent development frameworks and effectively incorporate the context management of applications and users. In this chapter the concept of mobile distributed user interface was made. This concept is based on models of distributed users interfaces, plasticity of user interfaces and mobile applications concepts. The concepts for DUIs help to indicate about elements and sub UIs that can be distributed and define the platforms host. The plasticity of user interface indicates when the applications must fragment de UI, depending on the context state. Now, the main issue in mobile distributed user interface is to decide how to adapt efficiently the sub user interfaces on its platform target. In this work we present some examples of mobile DUIs. We notice that the adaptability of sub user interfaces depends on the user interaction requirements with the application, that include the user group, the device target, and the elements of sub user interfaces, among others, as suggested in [28]. The way to distribute sub user interfaces depends on the application and the devices considers in their use. In some cases it is necessary duplicate elements to others devices but only for output, remaining the input in the original devices, such as the case Tablet-Smart TV, where the Tablet remains the user input, but the output is reply in both devices. In other cases, de GUI is decomposed and then, the input elements remain on the Tablet and the outputs elements are sent to Smart TV. In these cases the input interaction is always on the tablet. For the case of the tourist guide using a smart phone and smart watch, consider several scenarios depending on the user cases.
Authors should like to thank to Cinvestav-IPN and Instituto Politécnico Nacional, SIP project number 20196705 “Diseño de la arquitectura de middleware para protocolos criptográficos en dispositivos restringidos” by the resources provided and the facilities for this work.
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His research interest focuses on computational chemistry and molecular modeling of diverse systems of pharmacological, food, and alternative energy interests by resorting to DFT and Conceptual DFT. He has authored a coauthored more than 255 peer-reviewed papers, 32 book chapters, and 2 edited books. He has delivered speeches at many international and domestic conferences. He serves as a reviewer for more than eighty international journals, books, and research proposals as well as an editor for special issues of renowned scientific journals.",institutionString:"Centro de Investigación en Materiales Avanzados",institution:{name:"Centro de Investigación en Materiales Avanzados",country:{name:"Mexico"}}},{id:"76477",title:"Prof.",name:"Mirza",middleName:null,surname:"Hasanuzzaman",slug:"mirza-hasanuzzaman",fullName:"Mirza Hasanuzzaman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/76477/images/system/76477.png",biography:"Dr. Mirza Hasanuzzaman is a Professor of Agronomy at Sher-e-Bangla Agricultural University, Bangladesh. He received his Ph.D. in Plant Stress Physiology and Antioxidant Metabolism from Ehime University, Japan, with a scholarship from the Japanese Government (MEXT). Later, he completed his postdoctoral research at the Center of Molecular Biosciences, University of the Ryukyus, Japan, as a recipient of the Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship. He was also the recipient of the Australian Government Endeavour Research Fellowship for postdoctoral research as an adjunct senior researcher at the University of Tasmania, Australia. Dr. Hasanuzzaman’s current work is focused on the physiological and molecular mechanisms of environmental stress tolerance. Dr. Hasanuzzaman has published more than 150 articles in peer-reviewed journals. He has edited ten books and written more than forty book chapters on important aspects of plant physiology, plant stress tolerance, and crop production. According to Scopus, Dr. Hasanuzzaman’s publications have received more than 10,500 citations with an h-index of 53. He has been named a Highly Cited Researcher by Clarivate. He is an editor and reviewer for more than fifty peer-reviewed international journals and was a recipient of the “Publons Peer Review Award” in 2017, 2018, and 2019. He has been honored by different authorities for his outstanding performance in various fields like research and education, and he has received the World Academy of Science Young Scientist Award (2014) and the University Grants Commission (UGC) Award 2018. He is a fellow of the Bangladesh Academy of Sciences (BAS) and the Royal Society of Biology.",institutionString:"Sher-e-Bangla Agricultural University",institution:{name:"Sher-e-Bangla Agricultural University",country:{name:"Bangladesh"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",biography:"Kusal K. Das is a Distinguished Chair Professor of Physiology, Shri B. M. Patil Medical College and Director, Centre for Advanced Medical Research (CAMR), BLDE (Deemed to be University), Vijayapur, Karnataka, India. Dr. Das did his M.S. and Ph.D. in Human Physiology from the University of Calcutta, Kolkata. His area of research is focused on understanding of molecular mechanisms of heavy metal activated low oxygen sensing pathways in vascular pathophysiology. He has invented a new method of estimation of serum vitamin E. His expertise in critical experimental protocols on vascular functions in experimental animals was well documented by his quality of publications. He was a Visiting Professor of Medicine at University of Leeds, United Kingdom (2014-2016) and Tulane University, New Orleans, USA (2017). For his immense contribution in medical research Ministry of Science and Technology, Government of India conferred him 'G.P. Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. degree in chemistry in 2000 and Ph.D. degree in physical chemistry in 2007 from the University of Khartoum, Sudan. He moved to School of Chemistry, Faculty of Science, University of Sydney, Australia in 2009 and joined Dr. Ron Clarke as a postdoctoral fellow where he worked on the interaction of ATP with the phosphoenzyme of the Na+/K+-ATPase and dual mechanisms of allosteric acceleration of the Na+/K+-ATPase by ATP; then he went back to Department of Chemistry, University of Khartoum as an assistant professor, and in 2014 he was promoted as an associate professor. In 2011, he joined the staff of Department of Chemistry at Taif University, Saudi Arabia, where he is currently an assistant professor. His research interests include the following: P-Type ATPase enzyme kinetics and mechanisms, kinetics and mechanisms of redox reactions, autocatalytic reactions, computational enzyme kinetics, allosteric acceleration of P-type ATPases by ATP, exploring of allosteric sites of ATPases, and interaction of ATP with ATPases located in cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. His Works are realted to the Green chemistry field, biolubricants, biodiesel, transesterification reactions for biodiesel production and the manipulation of oils for therapeutic purposes.",institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",country:{name:"Argentina"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",biography:"Francisco Javier Martín-Romero (Javier) is a Professor of Biochemistry and Molecular Biology at the University of Extremadura, Spain. He is also a group leader at the Biomarkers Institute of Molecular Pathology. Javier received his Ph.D. in 1998 in Biochemistry and Biophysics. At the National Cancer Institute (National Institute of Health, Bethesda, MD) he worked as a research associate on the molecular biology of selenium and its role in health and disease. After postdoctoral collaborations with Carlos Gutierrez-Merino (University of Extremadura, Spain) and Dario Alessi (University of Dundee, UK), he established his own laboratory in 2008. The interest of Javier's lab is the study of cell signaling with a special focus on Ca2+ signaling, and how Ca2+ transport modulates the cytoskeleton, migration, differentiation, cell death, etc. He is especially interested in the study of Ca2+ channels, and the role of STIM1 in the initiation of pathological events.",institutionString:null,institution:{name:"University of Extremadura",country:{name:"Spain"}}},{id:"217323",title:"Prof.",name:"Guang-Jer",middleName:null,surname:"Wu",slug:"guang-jer-wu",fullName:"Guang-Jer Wu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217323/images/8027_n.jpg",biography:null,institutionString:null,institution:null},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/148546/images/4640_n.jpg",biography:null,institutionString:null,institution:null},{id:"272889",title:"Dr.",name:"Narendra",middleName:null,surname:"Maddu",slug:"narendra-maddu",fullName:"Narendra Maddu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272889/images/10758_n.jpg",biography:null,institutionString:null,institution:null},{id:"242491",title:"Prof.",name:"Angelica",middleName:null,surname:"Rueda",slug:"angelica-rueda",fullName:"Angelica Rueda",position:"Investigador Cinvestav 3B",profilePictureURL:"https://mts.intechopen.com/storage/users/242491/images/6765_n.jpg",biography:null,institutionString:null,institution:null},{id:"88631",title:"Dr.",name:"Ivan",middleName:null,surname:"Petyaev",slug:"ivan-petyaev",fullName:"Ivan Petyaev",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Lycotec (United Kingdom)",country:{name:"United Kingdom"}}},{id:"423869",title:"Ms.",name:"Smita",middleName:null,surname:"Rai",slug:"smita-rai",fullName:"Smita Rai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424024",title:"Prof.",name:"Swati",middleName:null,surname:"Sharma",slug:"swati-sharma",fullName:"Swati Sharma",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"439112",title:"MSc.",name:"Touseef",middleName:null,surname:"Fatima",slug:"touseef-fatima",fullName:"Touseef Fatima",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424836",title:"Dr.",name:"Orsolya",middleName:null,surname:"Borsai",slug:"orsolya-borsai",fullName:"Orsolya Borsai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",country:{name:"Romania"}}},{id:"422262",title:"Ph.D.",name:"Paola Andrea",middleName:null,surname:"Palmeros-Suárez",slug:"paola-andrea-palmeros-suarez",fullName:"Paola Andrea Palmeros-Suárez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Guadalajara",country:{name:"Mexico"}}}]}},subseries:{item:{id:"13",type:"subseries",title:"Plant Physiology",keywords:"Plant Nutrition, Plant Hormone, Photosynthesis, Respiration, Plant Stress, Multi-omics, High-throughput Technology, Genome Editing",scope:"Plant Physiology explores fundamental processes in plants, and it includes subtopics such as plant nutrition, plant hormone, photosynthesis, respiration, and plant stress. In recent years, emerging technologies such as multi-omics, high-throughput technologies, and genome editing tools could assist plant physiologists in unraveling molecular mechanisms in specific critical pathways. The global picture of physiological processes in plants needs to be investigated continually to increase our knowledge, and the resulting technologies will benefit sustainable agriculture.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/13.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11409,editor:{id:"332229",title:"Prof.",name:"Jen-Tsung",middleName:null,surname:"Chen",slug:"jen-tsung-chen",fullName:"Jen-Tsung Chen",profilePictureURL:"https://mts.intechopen.com/storage/users/332229/images/system/332229.png",biography:"Dr. Jen-Tsung Chen is currently a professor at the National University of Kaohsiung, Taiwan. He teaches cell biology, genomics, proteomics, medicinal plant biotechnology, and plant tissue culture. Dr. Chen\\'s research interests include bioactive compounds, chromatography techniques, in vitro culture, medicinal plants, phytochemicals, and plant biotechnology. 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