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More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:{caption:"IntechOpen Maintains",originalUrl:"/media/original/113"}},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
\n'}],latestNews:[{slug:"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:"10554",leadTitle:null,fullTitle:"Proprioception",title:"Proprioception",subtitle:null,reviewType:"peer-reviewed",abstract:"Proprioception is the sense of body position and movement, with conscious and unconscious components, that determines and conditions the human body’s relationship with the environment. This quality of mechanosensitivity deteriorates in some pathologies and is responsible for some alterations of the locomotor system that appear in elderly persons. In those situations, the failure of proprioception reduces the quality of life of the subjects. The widespread use in developed countries of substitute joint prostheses makes it necessary to rethink the concepts of movement detection and perception. As such, this book examines the basics of proprioception as well as its function in the lower extremities, the head, in children with disabilities, and its connection with virtual reality.",isbn:"978-1-83968-070-0",printIsbn:"978-1-83968-069-4",pdfIsbn:"978-1-83968-074-8",doi:"10.5772/intechopen.92928",price:119,priceEur:129,priceUsd:155,slug:"proprioception",numberOfPages:164,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"e104e615fbd94caa987df3a8d8b3fb8b",bookSignature:"José A. Vega and Juan Cobo",publishedDate:"June 23rd 2021",coverURL:"https://cdn.intechopen.com/books/images_new/10554.jpg",numberOfDownloads:3254,numberOfWosCitations:2,numberOfCrossrefCitations:1,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:1,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:4,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 8th 2020",dateEndSecondStepPublish:"October 6th 2020",dateEndThirdStepPublish:"December 5th 2020",dateEndFourthStepPublish:"February 23rd 2021",dateEndFifthStepPublish:"April 24th 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"59892",title:"Prof.",name:"José A.",middleName:null,surname:"Vega",slug:"jose-a.-vega",fullName:"José A. Vega",profilePictureURL:"https://mts.intechopen.com/storage/users/59892/images/system/59892.jpg",biography:"José A. Vega obtained a Ph.D. in Medicine from the University of Oviedo, Spain. He completed his postdoctoral training at the Universities of Brno and Prague, “La Sapienza” and “Tor Vergara” of Rome, and Harvard University. Currently, Dr. Vega is Professor of Anatomy and Human Embryology, and head of the Sensory Organs and Peripheral Nervous System (SINPOS) research group at the University of Oviedo. He is also an Associated Researcher at the Autonomous University of Chile. He has taught at the Universities of Messina, “Federico II” of Naples, Rome “La Sapienza” and Rome “Tor Vergata,” Sassari, Barí, Buenos Aires, and CEU-San Pablo in Madrid. Dr. Vegas has co-authored more than 350 articles and 50 chapters in books mainly devoted to the peripheral nervous system.",institutionString:"University of Oviedo",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"University of Oviedo",institutionURL:null,country:{name:"Spain"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"100648",title:"Dr.",name:"Juan",middleName:null,surname:"Cobo",slug:"juan-cobo",fullName:"Juan Cobo",profilePictureURL:"https://mts.intechopen.com/storage/users/100648/images/system/100648.jpg",biography:"Juan Cobo graduated in Medicine and Surgery from the University of Zaragoza, Spain, and obtained a Ph.D. from the University of Oviedo, Spain. He completed his postdoctoral training at the University of Chicago, USA. Currently, Dr. Cobo is a Professor of Orthodontics and head of the master’s program in Orthodontic and Dentofacial Orthopedics, University of Oviedo. He has co-authored more than 150 articles, four books, and thirty chapters in books mainly related to orthodontics and the peripheral nervous system.",institutionString:"University of Oviedo",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Oviedo",institutionURL:null,country:{name:"Spain"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"213",title:"Neurobiology",slug:"life-sciences-neuroscience-neurobiology"}],chapters:[{id:"75762",title:"Structural and Biological Basis for Proprioception",doi:"10.5772/intechopen.96787",slug:"structural-and-biological-basis-for-proprioception",totalDownloads:477,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The proprioception is the sense of positioning and movement. It is mediate by proprioceptors, a small subset of mechanosensory neurons localized in the dorsal root ganglia that convey information about the stretch and tension of muscles, tendons, and joints. These neurons supply of afferent innervation to specialized sensory organs in muscles (muscle spindles) and tendons (Golgi tendon organs). Thereafter, the information originated in the proprioceptors travels throughout two main nerve pathways reaching the central nervous system at the level of the spinal cord and the cerebellum (unconscious) and the cerebral cortex (conscious) for processing. On the other hand, since the stimuli for proprioceptors are mechanical (stretch, tension) proprioception can be regarded as a modality of mechanosensitivity and the putative mechanotransducers proprioceptors begins to be known now. The mechanogated ion channels acid-sensing ion channel 2 (ASIC2), transient receptor potential vanilloid 4 (TRPV4) and PIEZO2 are among candidates. Impairment or poor proprioception is proper of aging and some neurological diseases. Future research should focus on treating these defects. This chapter intends provide a comprehensive update an overview of the anatomical, structural and molecular basis of proprioception as well as of the main causes of proprioception impairment, including aging, and possible treatments.",signatures:"José A. Vega and Juan Cobo",downloadPdfUrl:"/chapter/pdf-download/75762",previewPdfUrl:"/chapter/pdf-preview/75762",authors:[{id:"59892",title:"Prof.",name:"José A.",surname:"Vega",slug:"jose-a.-vega",fullName:"José A. Vega"},{id:"100648",title:"Dr.",name:"Juan",surname:"Cobo",slug:"juan-cobo",fullName:"Juan Cobo"}],corrections:null},{id:"75009",title:"Proprioception and Clinical Correlation",doi:"10.5772/intechopen.95866",slug:"proprioception-and-clinical-correlation",totalDownloads:482,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Proprioception is the sense of position or the motion of the limbs and body in the absence of vision. It is a complex system having both conscious and unconscious components involving peripheral and central pathways. The complexity of sensorimotor systems requires deep knowledge of anatomy and physiology to analyze and localize the symptoms and the signs of the patients. Joint sense and vibration sense examination is an important component of physical examination. This chapter consists anatomy, motor control, postural control related to proprioception with neurologic clinical correlation and also the information about the changes of proprioception after orthopedic surgeries and discuss with the available literature.",signatures:"Pinar Gelener, Gözde İyigün and Ramadan Özmanevra",downloadPdfUrl:"/chapter/pdf-download/75009",previewPdfUrl:"/chapter/pdf-preview/75009",authors:[{id:"234748",title:"Dr.",name:"Pinar",surname:"Gelener",slug:"pinar-gelener",fullName:"Pinar Gelener"},{id:"342237",title:"Associate Prof.",name:"Ramadan",surname:"Özmanevra",slug:"ramadan-ozmanevra",fullName:"Ramadan Özmanevra"},{id:"342238",title:"Associate Prof.",name:"Gözde",surname:"Iyigün",slug:"gozde-iyigun",fullName:"Gözde Iyigün"}],corrections:null},{id:"74729",title:"Recording of Proprioceptive Muscle Reflexes in the Lower Extremity",doi:"10.5772/intechopen.95575",slug:"recording-of-proprioceptive-muscle-reflexes-in-the-lower-extremity",totalDownloads:298,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Electromyography (EMG) is routinely used in diagnostics of root syndromes in the lower extremity. By studying signs of axonal damage of different root levels in the corresponding myotomes of the lower extremity and back muscles with needle EMG reveals, which of the motor roots are injured in patients with suspected root compression. But by EMG study only injuries of the anterior motor roots are diagnosed. Routine electroneuromyography does not disclose specific injury of the afferent sensory posterior roots. However, the integrity of some the posterior roots is readily studied with myotatic reflexes. We have routinely measured a proprioceptive reflex, the H-reflex of the soleus muscle with stimulation of the posterior tibial nerve, and found it to be useful in the diagnostics of the S1 root syndrome. It seems to be possible to record H-reflex of the peroneus longus muscle at the L5 level. We discuss the serious problems with volume conduction, when trials to measure proprioceptive reflexes of the L4 and L5 levels are performed. It may also be useful to record the medium latency reflexes in the area of the posterior tibial nerve, which seems to have a different reflex arch (II-afferents – β-efferents) from H-reflex (Ia afferents – α efferents). These measurements are non-invasive and not time consuming, and we hope to be able to add them for the routine ENMG diagnostics, when appropriate.",signatures:"Juhani Partanen, Urho Sompa and Miguel Muñoz-Ruiz",downloadPdfUrl:"/chapter/pdf-download/74729",previewPdfUrl:"/chapter/pdf-preview/74729",authors:[{id:"215350",title:"Dr.",name:"Juhani",surname:"Partanen",slug:"juhani-partanen",fullName:"Juhani Partanen"},{id:"343231",title:"Dr.",name:"Urho",surname:"Sompa",slug:"urho-sompa",fullName:"Urho Sompa"},{id:"343232",title:"Dr.",name:"Miguel",surname:"Muñoz-Ruiz",slug:"miguel-munoz-ruiz",fullName:"Miguel Muñoz-Ruiz"}],corrections:null},{id:"74257",title:"The Knee Proprioception as Patient-Dependent Outcome Measures within Surgical and Non-Surgical Interventions",doi:"10.5772/intechopen.94887",slug:"the-knee-proprioception-as-patient-dependent-outcome-measures-within-surgical-and-non-surgical-inter",totalDownloads:372,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Proprioception considered as the obtaining of information about one’s own action does not necessarily depend on proprioceptors. At the knee joint, perceptual systems are active sets of organs designed to reach equilibrium through synergies. Many surgical procedures, such as ACL reconstruction in personalized medicine, are often based on native anatomy, which may not accurately reflect the proprioception between native musculoskeletal tissues and biomechanical artifacts. Taking an affordance-based approach to this type of “design” brings valuable new insights to bear in advancing the area of “evidence-based medicine (EBM).” EBM has become incorporated into many health care disciplines, including occupational therapy, physiotherapy, nursing, dentistry, and complementary medicine, among many others. The design process can be viewed in terms of action possibilities provided by the (biological) environment. In anterior crucial ligament (ACL) reconstruction, the design goal is to avoid ligament impingement while optimizing the placement of the tibial tunnel. Although in the current rationale for tibial tunnel placement, roof impingement is minimized to avoid a negative affordance, we show that tibial tunnel placement can rather aim to constrain the target bounds with respect to a positive affordance. We describe the steps for identifying the measurable invariants in the knee proprioception system and provide a mathematical framework for the outcome measure within the knee.",signatures:"Wangdo Kim",downloadPdfUrl:"/chapter/pdf-download/74257",previewPdfUrl:"/chapter/pdf-preview/74257",authors:[{id:"216754",title:"Ph.D.",name:"Wangdo",surname:"Kim",slug:"wangdo-kim",fullName:"Wangdo Kim"}],corrections:null},{id:"76398",title:"Proprioceptors in Cephalic Muscles",doi:"10.5772/intechopen.96794",slug:"proprioceptors-in-cephalic-muscles",totalDownloads:274,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The proprioception from the head is mainly mediated via the trigeminal nerve and originates from special sensitive receptors located within muscles called proprioceptors. Only muscles innervated by the trigeminal nerve, and rarely some muscles supplied by the facial nerve, contain typical proprioceptors, i.e. muscle spindles. In the other cephalic muscles (at the exception of the extrinsic muscles of the eye) the muscle spindles are replaced by sensory nerve formations (of different morphologies and in different densities) and isolated nerve fibers expressing mechanproteins (especially PIEZO2) related to proprioception. This chapter examines the cephalic proprioceptors corresponding to the territories of the trigeminal, facial, glossopharyngeal and hypoglossal nerves.",signatures:"Juan L. Cobo, Sonsoles Junquera, José Martín-Cruces, Antonio Solé-Magdalena, Olivia García-Suárez and Teresa Cobo",downloadPdfUrl:"/chapter/pdf-download/76398",previewPdfUrl:"/chapter/pdf-preview/76398",authors:[{id:"270071",title:"Prof.",name:"Juan L.",surname:"Cobo",slug:"juan-l.-cobo",fullName:"Juan L. Cobo"}],corrections:null},{id:"75427",title:"Proprioception Impairment and Treatment Approaches in Pediatrics",doi:"10.5772/intechopen.96382",slug:"proprioception-impairment-and-treatment-approaches-in-pediatrics",totalDownloads:379,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In children problems like trauma and injuries are quite obvious. Other problems related to sensory system dysfunction are identified at the later stages of the child due to lack of awareness of the sensory integration problems which is not obvious. Some children have behavioral problems and some are poor at the school which is related to each other finally cause trouble to perform their daily routine. Early identification and intervention play a major role in improving the ability and development of the proprioceptive senses. Hence this chapter will introduce the new aspect of proprioception sense and its dysfunction. It would enhance you to identify the problems and understand the challenges that the child come across due to increase or decrease in proprioceptive input. We will be able to help them to overcome these challenges and frame a treatment strategy and help them to lead a successful life.",signatures:"Kamatchi Kaviraja",downloadPdfUrl:"/chapter/pdf-download/75427",previewPdfUrl:"/chapter/pdf-preview/75427",authors:[{id:"332439",title:"Dr.",name:"Kaviraja",surname:"Kamatchi",slug:"kaviraja-kamatchi",fullName:"Kaviraja Kamatchi"}],corrections:null},{id:"74677",title:"Proprioceptive Perception: An Emergence of the Interaction of Body and Language",doi:"10.5772/intechopen.95461",slug:"proprioceptive-perception-an-emergence-of-the-interaction-of-body-and-language",totalDownloads:350,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter provides a systemic perspective of human behavior, which reformulates the concept of effective behavior and cognition that derive from the classical vision of neuroscience and psychology based on the Cartesian reductionist functionalist paradigm. This systemic perspective, which is based on the theory of autopoiesis, proposes that the act of perceiving proprioception is decisive in the capacity of the human being to differentiate himself from an external space within which he is situated; a phenomenon that we will denominate “proprioceptive perception”. This complex phenomenon of dynamic character emerges from the relationship between the domains of the body and language in the individual’s relationship with their environment. Furthermore, from this systemic perspective, we will present the emotional states as cognitive states necessary for the conservation of the individual’s living identity and the close relationship they have with the sensorimotor patterns and proprioceptive perception. This chapter answers the question of how proprioceptive perception affects the human being’s experience of being different from others and from the environment in which they find themselves, having the possibility of being aware of themselves and of the world they perceive - in a present - within the environment in which they find themselves. And it explains how this phenomenon modulates its modes of emotion in congruence with what occurs in its present.",signatures:"Alejandra Vasquez-Rosati and Carmen Cordero-Homad",downloadPdfUrl:"/chapter/pdf-download/74677",previewPdfUrl:"/chapter/pdf-preview/74677",authors:[{id:"331407",title:"Ph.D.",name:"Alejandra",surname:"Vasquez-Rosati",slug:"alejandra-vasquez-rosati",fullName:"Alejandra Vasquez-Rosati"},{id:"333809",title:"Prof.",name:"Carmen",surname:"Cordero",slug:"carmen-cordero",fullName:"Carmen Cordero"}],corrections:null},{id:"75834",title:"Nomophobia Kids and Proprioception",doi:"10.5772/intechopen.96236",slug:"nomophobia-kids-and-proprioception",totalDownloads:302,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Proprioception is the sense of self movement and body position. The CNS integrates proprioception and other sensory system such as vision and vestibular system in order to create body position, movement and acceleration. It is developed by movement and works with surroundings. Children using smartphones for a long time result greater impact on the sensorimotor function and their proprioception is affected. In this topic, the write up is going to be regarding the proprioceptional deficit and the problems associated because of that of children using mobile phones for a prolonged period of time. The proprioceptive system has an extensive influence at the protection of human fitness. When the proprioception is dysfunctional, the vital anxious device does no longer recognize the ideal fame of tonicity of the muscular tissues at rest or in motion, does no longer combine effectively the records that comes from sensory receptors, and has issue in modulating multi-sensory integration, with outcomes in motor behavior and cognitive function.",signatures:"Giridharan Vaishnavi",downloadPdfUrl:"/chapter/pdf-download/75834",previewPdfUrl:"/chapter/pdf-preview/75834",authors:[{id:"333944",title:"Dr.",name:"Giridharan",surname:"Vaishnavi",slug:"giridharan-vaishnavi",fullName:"Giridharan Vaishnavi"}],corrections:null},{id:"75326",title:"Proprioception in Immersive Virtual Reality",doi:"10.5772/intechopen.96316",slug:"proprioception-in-immersive-virtual-reality",totalDownloads:321,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Currently, in connection with the advent of virtual reality (VR) technologies, methods that recreate sensory sensations are rapidly developing. Under the conditions of VR, which is an immersive environment, a variety of multimodal sensory experiences can be obtained. It is urgent to create explicit immersive environments that allow maximizing the full potential of VR technology. Activation of the proprioceptive sensory system, coupled with the activation of the visual analyzer system, allows you to achieve sensations of interaction with VR objects, identical to the sensations of the real physical world. Today, the activation of proprioceptive sensations is achieved using various devices, including robotic ones, which are not available for use in routine medical practice. The immersive multisensory environment makes it possible to significantly personalize the rehabilitation process, ensuring its continuity and effectiveness at various stages of the pathological process and varying degrees of severity of physical disorders, while significantly reducing the burden on the healthcare system by automating the rehabilitation process and objectively assessing the effectiveness. Further development and increased availability of VR technologies and devices that allow achieving an increase in immersion due to sensory immersion will be in great demand as a technology that allows teaching patients motor skills.",signatures:"Alexander Vladimirovich Zakharov, Alexander Vladimirovich Kolsanov, Elena Viktorovna Khivintseva, Vasiliy Fedorovich Pyatin and Alexander Vladimirovich Yashkov",downloadPdfUrl:"/chapter/pdf-download/75326",previewPdfUrl:"/chapter/pdf-preview/75326",authors:[{id:"314711",title:"M.D.",name:"Alexander Vladimirovich",surname:"Zakharov",slug:"alexander-vladimirovich-zakharov",fullName:"Alexander Vladimirovich Zakharov"},{id:"314712",title:"Dr.",name:"Elena Viktorovna",surname:"Khivintseva",slug:"elena-viktorovna-khivintseva",fullName:"Elena Viktorovna Khivintseva"},{id:"346435",title:"Prof.",name:"Alexander Vladimirovich",surname:"Kolsanov",slug:"alexander-vladimirovich-kolsanov",fullName:"Alexander Vladimirovich Kolsanov"},{id:"346465",title:"Prof.",name:"Alexander Vladimirovich",surname:"Yashkov",slug:"alexander-vladimirovich-yashkov",fullName:"Alexander Vladimirovich Yashkov"},{id:"346496",title:"Prof.",name:"Vasiliy Fedorovich",surname:"Pyatin",slug:"vasiliy-fedorovich-pyatin",fullName:"Vasiliy Fedorovich Pyatin"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"6899",title:"Chronobiology",subtitle:"The Science of Biological Time Structure",isOpenForSubmission:!1,hash:"521dfb38a216470da6f8f7d02469832c",slug:"chronobiology-the-science-of-biological-time-structure",bookSignature:"Pavol Svorc",coverURL:"https://cdn.intechopen.com/books/images_new/6899.jpg",editedByType:"Edited by",editors:[{id:"169212",title:"Prof.",name:"Pavol",surname:"Svorc",slug:"pavol-svorc",fullName:"Pavol Svorc"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6907",title:"Feed Your Mind",subtitle:"How Does Nutrition Modulate Brain Function throughout Life?",isOpenForSubmission:!1,hash:"91a663d09b6d6e80db3a69fca11e5b68",slug:"feed-your-mind-how-does-nutrition-modulate-brain-function-throughout-life-",bookSignature:"Clémentine Bosch-Bouju, Sophie Layé and Véronique Pallet",coverURL:"https://cdn.intechopen.com/books/images_new/6907.jpg",editedByType:"Edited by",editors:[{id:"265901",title:"Dr.",name:"Clémentine",surname:"Bosch-Bouju",slug:"clementine-bosch-bouju",fullName:"Clémentine Bosch-Bouju"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6808",title:"Autonomic Nervous System",subtitle:null,isOpenForSubmission:!1,hash:"d95e7c43f124d1a6e39b88862a917fc1",slug:"autonomic-nervous-system",bookSignature:"Pavol Svorc",coverURL:"https://cdn.intechopen.com/books/images_new/6808.jpg",editedByType:"Edited by",editors:[{id:"169212",title:"Prof.",name:"Pavol",surname:"Svorc",slug:"pavol-svorc",fullName:"Pavol Svorc"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6991",title:"Neurons",subtitle:"Dendrites and Axons",isOpenForSubmission:!1,hash:"696489f55e1077935f47087fa3829b5f",slug:"neurons-dendrites-and-axons",bookSignature:"Gonzalo Emiliano Aranda Abreu and María Elena Hernández Aguilar",coverURL:"https://cdn.intechopen.com/books/images_new/6991.jpg",editedByType:"Edited by",editors:[{id:"72314",title:"Dr.",name:"Gonzalo Emiliano",surname:"Aranda Abreu",slug:"gonzalo-emiliano-aranda-abreu",fullName:"Gonzalo Emiliano Aranda Abreu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6786",title:"Optic Nerve",subtitle:null,isOpenForSubmission:!1,hash:"b21864e6a0b3b316480d18efda1e18ee",slug:"optic-nerve",bookSignature:"Felicia M. 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\r\n\tDysphagia affects 1 in 25 individuals annually in the United States. Broadly we classify dysphagia into 2 main categories: oropharyngeal dysphagia and esophageal dysphagia. Oropharyngeal dysphagia is generally caused by neuromuscular problems, oropharyngeal tumors, radiation injury, cricopharyngeal achalasia and Zenker’s diverticulum. Esophageal dysphagia is generally due to gastrointestinal reflux disease, eosinophilic esophagitis, foreign body impaction, esophageal dysmotility, benign and malignant esophageal tumors and strictures. The etiology of dysphagia has changed over the years. Nowadays, we are seeing more and more patients with eosinophilic esophagitis presenting as acute dysphagia with food bolus impaction. We are also getting a considerable number of patients with dysphagia secondary to esophagogastric junction outflow obstruction (EGJOO) which could be idiopathic or secondary to prior fundoplication, migrated gastric band or sleeve gastrectomy. More and more patients with achalasia are now being treated by peroral endoscopic myotomy.
\r\n\tI am proposing this book to discuss the different aspects of oropharyngeal and esophageal dysphagia, particularly the current management strategies.
Vitamin D is a secosteroid hormone, which is known to be related to the regulation of the musculoskeletal system. It affects calcium and phosphate metabolism and is related to bone health. Recently, the extraskeletal effects of vitamin D are under intense research and have attracted the interest of the scientific community [1, 2, 3, 4, 5, 6]. In particular, the relationship of vitamin D with the immune system is in the focus of scientific evaluation [7, 8, 9]. In the chapter herein, the effects of vitamin D on the immune system will be discussed, and the relationship of vitamin D deficiency with the development of autoimmune diseases will be reviewed.
\nThe classic function of vitamin D is to enhance intestinal absorption of calcium by regulating several calcium transport proteins in the small intestine [4]. However, various cells express the vitamin D receptor (VDR) and the vitamin D activating enzyme 1-α-hydroxylase. Various cells of the immune system also express the VDR and harbor 1-α-hydroxylase [10, 11]. Thus, cells of the immune system respond to vitamin D and also activate vitamin D in a paracrine or autocrine fashion. The extra-renal 1-α-hydroxylase is not upregulated by PTH, and thus, production of 1,25(OH)2D3 is dependent on concentrations of the substrate 25(OH)D3, and it may be regulated by inflammatory signals, such as lipopolysaccharide and cytokines [12, 13]. Cells of the immune system, which express the VDR and harbor 1-α-hydroxylase, are macrophages, T cells, dendritic cells, monocytes, and B cells (Figure 1) [9]. Vitamin D is involved in the regulation of the innate immunity as it enhances the defense system of the organism against microbes and other pathogenic organisms, and it modulates the adaptive immune system through direct effects on T-cell activation and on the phenotype and function of antigen-presenting cells, particularly dendritic cells.
\nCells of the immune system regulated in part by vitamin D.
The innate immune system is a first line of defense against infection. Vitamin D is a regulator of the innate immune system [1, 14]. The first data on the effect of vitamin D on the innate immune system have been generated on the treatment of diseases caused by mycobacteria, such as tuberculosis and leprosy [15, 16, 17, 18]. Vitamin D has been used as a treatment of infections for more than 150 years. In 1849, Williams reported favorable results with the use of cod-liver-oil, an excellent source of vitamin D, in the treatment of patients with tuberculosis [19]. Fifty years later, Niels Finsen received the third Nobel Prize in Medicine for his description of using UV light, an effective method to increase vitamin D status, to treat lupus vulgaris, a cutaneous form of tuberculosis [20, 21]. Alfred Windaus contributed to the discovery of the chemical structure of vitamin D2 and vitamin D3 found in cod-liver-oil and received the Nobel prize [22, 23, 24]. Thereafter, several groups used vitamin D2 and D3 as a treatment for tuberculosis [22, 25]. Rook et al. [26] demonstrated in the 1980s that 1,25(OH)2D3 inhibited the proliferation of
Data regarding other infections also exist. Thus, children with low vitamin D status may be more prone to urinary tract infections due to low production of cathelicidin and defensin β2 [38, 39]. Also, adults with asthma may be less prone to infection after treatment with vitamin D due to increased production of cathelidicin and modulation of inflammatory cytokines [40, 41]. Low levels of vitamin D may be related to chronic obstructive pulmonary disease severity [42]. Vitamin D may increase resistance to HIV infection. Low levels of vitamin D have been associated with disease progression and mortality [43]. The ability of the immune cells to hydroxylate 25(OH)D3 locally suggests that in patients with infections, it may be better to administer 25(OH)D3 rather than hydroxylated metabolites to allow for local production and the feedback system to function.
\nThe natural history of autoimmunity remains largely unknown. However, the theory is that both genetic susceptibility and environmental factors play a role in the development of clinical autoimmune disease. Vitamin D has known immunomodulatory effects on a wide range of immune cells, including T and dendritic cells [44, 45]. Each of these immune cells expresses VDR and produces the enzymes 1-α-hydroxylase and 24-hydroxylase and is therefore capable of locally producing active 1,25(OH)2D3 [46, 47, 48, 49]. Activation of CD4+ T cells results in a significant increase in VDR expression enabling regulation of many genes responsive to 1,25(OH)2D3 [50]. 1,25(OH)2D3 suppresses T-cell receptor induced T cell proliferation and changes their cytokine expression. The overall shift is away from T helper Th1 phenotype toward a more tolerogenic Th2 response [51, 52, 53]. Vitamin D appears to directly inhibit Th1 cells and may additionally modulate a skewing toward a Th2 response [54]. Th17 cells are a subset of CD4+ T cells involved in organ-specific autoimmunity playing a role in maintaining inflammation, which can lead to tissue damage. 1,25(OH)2D3 suppresses autoimmunity and tissue destruction by inhibiting the Th17 response at several levels [55, 56]. Altogether, the evidence suggests an important role for vitamin D in influencing T-cell responses and in tempering inflammation and tissue damage.
\nVitamin D appears to have a direct effect on B cells and inhibits immunoglobulin production [57]. Additionally, differentiation of B cells is interrupted when exposed to 1,25(OH)2D3. 1,25(OH)2D3 also has effects on dendritic cells. Dendritic cells have important functions in maintaining both protective immunity and self-tolerance [58, 59]. Physiologic levels of 1,25(OH)2D3 inhibit maturation of dendritic cells and maintain an immature and tolerogenic phenotype with inhibition of activation markers such as MHC class II, CD40, and others and upregulation of inhibitory molecules [60, 61]. Thus, it appears that the maturational state of dendritic cells can be modulated by 1,25(OH)2D3, making it possible that the vitamin D status of an individual is likely to have important immunologic consequences.
\nThere are several animal models of autoimmunity, in which disease could either be prevented or ameliorated with the administration of either 1,25(OH)2D3 or one of its analogues. These animal models are models of autoimmune encephalomyelitis, collagen-induced arthritis, type 1 diabetes mellitus, inflammatory bowel disease, autoimmune uveitis, and lupus [44, 56, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76]. These studies show that treatment with active vitamin D is effective in modulating immune function and ameliorating autoimmune disease. Vitamin D deficiency is a risk factor for the development of some autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), diabetes mellitus type 1, multiples sclerosis, inflammatory bowel disease, and Hashimoto’s thyroiditis [49, 69, 74, 77, 78, 79, 80, 81, 82, 83, 84, 85] (Figure 2). Additionally, vitamin D deficiency has been observed in patients with systemic sclerosis [86].
\nAutoimmune diseases related to vitamin D deficiency.
A meta-analysis showed that low vitamin D intake is associated with the development of RA [87]. Thereafter, several studies performed in various areas all over the world showed that vitamin D deficiency is observed in patients with RA and that vitamin D deficiency is associated with disease activity [78, 82, 83, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97]. A meta-analysis of the good quality studies performed regarding the association between vitamin D deficiency and RA showed that vitamin D deficiency is observed in RA patients significantly more than in a control group and that vitamin D levels are inversely correlated with disease activity, meaning that low vitamin D levels are associated with high-disease activity [98]. Moreover, an association has been shown between VDR polymorphism and RA. Specifically, the Fokl F allele of the VDR may be a risk factor for the development of RA [99]. Further studies are needed to unravel the exact association between vitamin D deficiency and RA and to determine the best method of vitamin D supplementation and whether it may be used for the prevention of RA or for the best management of the disease [77, 100]. In addition, it has been proposed that vitamin D may contribute to the management of pain in RA and may be used along with TNF-α inhibitors in RA treatment [77, 101].
\nIn SLE, the inflammatory milieu drives the development of T cells into proinflammatory pathways, defective function of Tregs, and survival and activation of B cells, which produce autoantibodies [78, 81]. Patients with systemic lupus erythematosus have lower 25(OH)D3 levels compared to controls, suggesting that vitamin D deficiency may be a risk factor for SLE [81, 84, 102, 103, 104, 105, 106, 107]. The majority of studies have also found higher SLE disease activity associated with lower levels of 25(OH)D3 [84, 103]. As patients with SLE have often photosensitivity and are advised to avoid direct sun exposure, detecting vitamin D deficiency and replacing 25(OH)D3 with oral supplementation is critical and may impact disease activity [108].
\nType 1 diabetes mellitus is one of the most prevalent chronic diseases with onset in childhood and is the result of immune-mediated destruction of pancreatic insulin producing β cells. There appears to be a geographic variation in incidence following a gradient in latitude, which is the inverse of the global distribution of ultraviolet B irradiation, critical for the production of vitamin D within the skin [109]. Studies have shown higher incidence of vitamin D deficiency in patients with type 1 diabetes [110, 111, 112, 113]. One environmental factor thought to be protective against the development of type 1 diabetes mellitus is early supplementation with vitamin D [114]. A number of large case control studies showed that the risk of type 1 diabetes mellitus was significantly reduced in infants who were supplemented with vitamin D compared to those who were not supplemented [115, 116, 117]. Additionally, a lower incidence of type 1 diabetes was observed in infants born to mothers who were administered cod liver oil during pregnancy [118]. A birth cohort study in Finland, now more than 50 years ago, evaluated the effects of vitamin D supplementation on rickets and the development of type 1 diabetes mellitus [85]. All women due to give birth in 1966 were enrolled. There was an 80% reduction in the risk for type 1 diabetes mellitus in children having received >2000 IU vitamin D/day compared to those receiving less or not receiving supplementation with vitamin D. Evidence from both human and animal studies shows that vitamin D may be protective as far as the development of type 1 diabetes mellitus is concerned [68, 71, 76]. Thus, the administration of vitamin D may prevent diabetes mellitus type 1; however, once the destruction of pancreatic beta cells has taken place, it will not act therapeutically to reverse diabetes mellitus type 1.
\nMultiple sclerosis is characterized by inflammation, demyelination, axonal or neuronal loss, and astrocytic gliosis in the central nervous system, which can result in disability. Epidemiological studies have suggested that vitamin D insufficiency may contribute to the risk of multiple sclerosis [62, 63, 75, 119, 120]. Moreover, several genetic studies in multiple sclerosis patients have shown that diverse abnormalities in vitamin D metabolism are related to the risk of the disease. It appears that vitamin D deficiency may interact with genetic and environmental protective and risk factors, such as the allele HLA BRB1*1501, infections, obesity, smoking, and sexual hormones and may modulate the risk of the disease [63, 74, 80]. Thus, vitamin D deficiency may be a risk modulating factor for the development of multiple sclerosis. Vitamin D acts as an immunomodulatory factor affecting T and B lymphocytes, and it may exert neuroprotector and neurotrophic actions within the central nervous system. Several studies have shown that vitamin D supplementation exerts multiple beneficial immunomodulatory effects in multiple sclerosis [121, 122, 123, 124]. On the contrary, a Cochrane review states that there appears to be no benefit from vitamin D supplementation in patients with multiple sclerosis; however, the level of evidence is very low [125]. Nevertheless, it should be noted that robust statistical models used in association studies have already predicted a favorable vitamin D effect reducing relapses by 50–70% [121]. There is little doubt that vitamin D exerts a beneficial action on multiple sclerosis, the inflammatory component in particular, less so the degenerative. Until more information becomes available, vitamin D supplementation of multiple sclerosis patients, using a moderate physiological dose essentially correcting their vitamin insufficiency, is recommended.
\nVitamin D deficiency has been observed in patients with inflammatory bowel disease, Crohn’s disease, and ulcerative colitis [126]. It was found to be related to disease activity in Crohn’s disease and ulcerative colitis. Vitamin D supports the integrity of the intestinal barrier and is related to microbiota homeostasis in this cohort of patients [127, 128]. Thus, vitamin D may contribute to the prevention of inflammatory bowel disease by supporting the integrity of the intestinal barrier, contributing to bacterial homeostasis and ameliorating disease progression via anti-inflammatory action. Vitamin D deficiency in inflammatory bowel disease is aggravated by decreased absorption of the vitamin via the gastrointestinal tract [128].
\nStudies have observed an association between autoimmune Hashimoto’s thyroiditis and low vitamin D levels [79, 129]. These studies have not observed low vitamin D levels in patients with Graves’ disease. A meta-analysis of 26 observational studies confirmed an association between vitamin D deficiency and autoimmune Hashimoto’s thyroiditis [130]. The aforementioned meta-analysis found that although there was heterogeneity between the results of the various studies performed all over the globe, studies had similar results in populations from different countries and also in populations in different age ranges, in particular pediatric and adult populations.
\nSystemic sclerosis is a chronic, inflammatory, fibrotic disorder thought to be related to autoimmune etiology. Vitamin D deficiency has been observed in patients with systemic sclerosis [86, 131], especially in patients with the diffuse type of the disease [131].
\nThe molecule used to assess vitamin D sufficiency in a population is 25(OH)D3 [9]. It appears that vitamin D has physiologic effects beyond those related to bone physiology and mineral homeostasis. It may be that the alarming prevalence of vitamin D deficiency observed all over the globe may be contributing to the development of autoimmune diseases. Based on bone-related biomarkers such as intact parathyroid hormone, calcium absorption, and bone mineral density, maintaining a 25(OH)D3 level of at least 32 ng/ml appears sufficient.
\nIt appears that vitamin D is a potent immunomodulator. It has multiple and diverse effects on the immune system. In particular, it potentiates the innate immune response enhancing the production of cathelicidin from human macrophages, monocytes, and keratinocytes, thus enhancing and potentiating the immune response against external pathogens. It affects the adaptive immune response shifting the phenotype of the adaptive immune response toward a more tolerogenic phenotype. Vitamin D deficiency is related to various autoimmune disorders. Vitamin D deficiency appears to be related to the development of RA and correlates with disease severity. Vitamin D deficiency is observed in patients with SLE. It was found to be related to disease severity and activity in some but not all studies. Vitamin D deficiency is observed in patients with multiple sclerosis, and vitamin D administration may ameliorate disease severity. Vitamin D deficiency is also observed in patients with inflammatory bowel disease, Crohn’s disease, and ulcerative colitis, and it is related to disease activity. Vitamin D contributes to the integrity of the intestinal barrier and bacterial homeostasis. In addition, vitamin D absorption is decreased making supplementation important. Vitamin D deficiency is also observed in patients with autoimmune Hashimoto’s thyroiditis. Vitamin D deficiency is found in patients with systemic sclerosis, especially the diffuse form of the disease. It appears that optimal levels of vitamin D are important for immune function and for the prevention of autoimmunity in the human organism.
\nThe authors declare no conflict of interest.
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\n\nIf there are supplemental materials to the chapter, these will be published at the time the final book is published online.
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