Hazardous characteristics: extracted from UN listing [2].
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"8720",leadTitle:null,fullTitle:"Topics in Local Anesthetics",title:"Topics in Local Anesthetics",subtitle:null,reviewType:"peer-reviewed",abstract:"The fascinating history of local anesthetics was born in the Andean Mountains with the use of Erythroxylum coca and has gradually evolved into a group of safe drugs in anesthesiology and pain medicine. Their mechanism of action on the cell membrane produces anesthesia, analgesia, and side effects that can be catastrophic. Other effects such as antimicrobial, anti-inflammatory, antineoplastic, and other therapeutic results have also been found and are still under investigation. Pharmacological advances in local anesthetics, the use of adjuvant drugs, and new regional anesthesia techniques have resulted in greater efficacy and safety for patients.Written by authors from around the world, this book examines selected topics on local anesthetics and their current use in clinical practice.",isbn:"978-1-78984-944-8",printIsbn:"978-1-78984-943-1",pdfIsbn:"978-1-83968-820-1",doi:"10.5772/intechopen.80137",price:119,priceEur:129,priceUsd:155,slug:"topics-in-local-anesthetics",numberOfPages:192,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"593b219700438225954cb0905332ae9f",bookSignature:"Víctor M. Whizar-Lugo and Enrique Hernández-Cortez",publishedDate:"September 30th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/8720.jpg",numberOfDownloads:11060,numberOfWosCitations:0,numberOfCrossrefCitations:2,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:7,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:9,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"December 10th 2018",dateEndSecondStepPublish:"February 26th 2019",dateEndThirdStepPublish:"April 27th 2019",dateEndFourthStepPublish:"July 16th 2019",dateEndFifthStepPublish:"September 14th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"169249",title:"Prof.",name:"Víctor M.",middleName:null,surname:"Whizar-Lugo",slug:"victor-m.-whizar-lugo",fullName:"Víctor M. Whizar-Lugo",profilePictureURL:"https://mts.intechopen.com/storage/users/169249/images/system/169249.jpg",biography:"Dr. Víctor M. Whizar-Lugo graduated from Universidad Nacional Autónoma de México. He completed a residency in Internal Medicine at Hospital General de México, and a residency in Anesthesiology and Critical Care Medicine at Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City. He also completed a fellowship in the Anesthesia Department, Pain Clinic, University of California, Los Angeles, USA. Currently, Dr. Whizar-Lugo works as an anesthesiologist at Lotus Med Group. He is also a researcher at the National Institutes of Health. He has many publications on anesthesia, pain, internal medicine, and critical care to his credit. He has edited four books and given countless conferences at congresses and meetings around the world. He has been a member of various editorial committees in anesthesiology journals, past chief editor of the journal Anestesia en México, and is currently the editor-in-chief of the Journal of Anesthesia and Critical Care: Open Access. He is the founding director and current president of Anestesiología y Medicina del Dolor (www.anestesiologia-dolor.org), a free medical education program.",institutionString:"Institutos Nacionales de Salud",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"7",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"Cairo University",institutionURL:null,country:{name:"Egypt"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"288453",title:"Dr.",name:"Enrique",middleName:null,surname:"Hernández-Cortez",slug:"enrique-hernandez-cortez",fullName:"Enrique Hernández-Cortez",profilePictureURL:"https://mts.intechopen.com/storage/users/288453/images/system/288453.jpg",biography:"Enrique Hernández-Cortez graduated from the Faculty of Medicine of the Universidad Michoacana de San Nicolás de Hidalgo, México. He completed his residency in Anesthesiology at the Anesthesia Department Hospital de Alta Especialidad, Instituto Mexicano del Seguro Social in León Guanajuato. He is past head of the Anesthesia Department at the Hospital de Alta especialidad de Gineco-Pediatría No. 48, Instituto Mexicano del Seguro Social, León Guanajuato, México. Dr. Hernández-Cortez is editor-in-chief of the journal Anestesia en México and vice president of the Federación Mexicana de Colegios de Anestesiología, A.C. He is editor of the book Complications of Pediatric Anesthesia, has published a variety of articles on pediatric anesthesia, and has lectured at countless conferences and meetings around the world.",institutionString:"Instituto Mexicano del Seguro Social, León",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1192",title:"Anesthesiology",slug:"pharmacology-toxicology-and-pharmaceutical-science-pharmacology-anesthesiology"}],chapters:[{id:"73160",title:"Local Anesthetics",doi:"10.5772/intechopen.93643",slug:"local-anesthetics",totalDownloads:916,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The fascinating history of local anesthetics (LAs) began in South America with the herbal and traditional use of cocaine leaves by the indigenous peoples of Peru and Bolivia, the sacred plant of the Incas Erythroxylum coca. The use for anesthetic purposes dates back to 1884. Since then, the evolution of LAs has been closely related to research motivated by its efficacy and safety versus toxicity. According to their chemical structure, these drugs are classified into two main groups: esters and amino amides; however, there are three LAs with different characteristics: articaine, sameridine, and centbucridine. The pharmacological and toxic mode of action is primarily in the voltage-dependent sodium channels located in the cell membrane, which clinically produces analgesia, anesthesia, seizures, arrhythmias, and cardiac arrest. The quality of anesthesia and analgesia depends on the type of LA, dose, and application technique, while the deleterious effects are secondary to its plasma concentration. Nonanesthetic properties of LAs such as their antimicrobial, antineoplastic, antiarrhythmics, antitussive, and antiasthmatics effects have been described and are briefly reviewed.",signatures:"Víctor M. Whizar-Lugo, Karen L. Íñiguez-López, Ana C. Cárdenas-Maytorena and Cristian D. Ramírez-Puerta",downloadPdfUrl:"/chapter/pdf-download/73160",previewPdfUrl:"/chapter/pdf-preview/73160",authors:[{id:"169249",title:"Prof.",name:"Víctor M.",surname:"Whizar-Lugo",slug:"victor-m.-whizar-lugo",fullName:"Víctor M. Whizar-Lugo"},{id:"329178",title:"Dr.",name:"Karen L.",surname:"Íñiguez-López",slug:"karen-l.-iniguez-lopez",fullName:"Karen L. Íñiguez-López"},{id:"329179",title:"Dr.",name:"Ana C.",surname:"Cárdenas-Maytorena",slug:"ana-c.-cardenas-maytorena",fullName:"Ana C. Cárdenas-Maytorena"},{id:"329180",title:"Dr.",name:"Cristian D.",surname:"Ramírez-Puerta",slug:"cristian-d.-ramirez-puerta",fullName:"Cristian D. Ramírez-Puerta"}],corrections:null},{id:"71920",title:"Pharmacokinetics and Pharmacodynamics of Local Anesthetics",doi:"10.5772/intechopen.91700",slug:"pharmacokinetics-and-pharmacodynamics-of-local-anesthetics",totalDownloads:1063,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Local anesthetics are basically weak bases whose structure consists of an aromatic half connected to a substituted amine through an ester amide linkage. The pKa values of local anesthetics are close to physiological pH, both protonated and unprotonated forms are present. The individual structures confer different physiochemical and clinical characteristics. Potency is correlated to lipid solubility in vitro, but less so in vivo. The duration of action is associated with the extent of protein binding. The onset of action is related to pKa. The intrinsic vasodilator activity varies between drugs and influences potency and duration of action. Local anesthetics block nerve conduction and interact directly with specific receptor on the Na+ channel, inhibiting Na+ ion influx and impairing Propagation of the action potential in axons. There are some characteristics in the blocking of nerve conduction and are related to size and function of the peripheral nerves, and to the fact that a specific concentration of local anesthetics may produce a different intensity of block. Some pathological states like decreased cardiac output, severe hepatic disease, renal disease, cholinesterase activity, fetal acidosis, sepsis, etc. altered the pharmacokinetics and pharmacodynamics of local anesthetics.",signatures:"Javier Marcos Michel-Levy",downloadPdfUrl:"/chapter/pdf-download/71920",previewPdfUrl:"/chapter/pdf-preview/71920",authors:[{id:"294496",title:"M.D.",name:"Javier Marcos",surname:"Michel Levy",slug:"javier-marcos-michel-levy",fullName:"Javier Marcos Michel Levy"}],corrections:null},{id:"67934",title:"Bupivacaine Pharmacokinetics in Pregnant Women",doi:"10.5772/intechopen.87184",slug:"bupivacaine-pharmacokinetics-in-pregnant-women",totalDownloads:726,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Pregnancy, labor, and delivery are accompanied by physiological changes that impact on the use of the drugs to which they are exposed. The anesthesiologist needs to understand the principal differences in management of this particular population. The study of the main pharmacokinetic changes associated with pregnancy is relevant for the proper management of drugs to avoid adverse effects. The objective of this chapter is to review the physiological changes that impact on the pharmacokinetics of the pregnant woman with a focus on local anesthetics of the amide type, specifically bupivacaine, and the main studies that have led to a deeper understanding.",signatures:"Yazmín Guillén-Dolores",downloadPdfUrl:"/chapter/pdf-download/67934",previewPdfUrl:"/chapter/pdf-preview/67934",authors:[{id:"290491",title:"M.D.",name:"Yazmin",surname:"Guillen Dolores",slug:"yazmin-guillen-dolores",fullName:"Yazmin Guillen Dolores"}],corrections:null},{id:"71663",title:"Adjuvant Drugs to Local Anesthetics",doi:"10.5772/intechopen.91980",slug:"adjuvant-drugs-to-local-anesthetics",totalDownloads:1160,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Local anesthetics have a potential to be used in a wide variety of situations including central neuraxial blocks, peripheral nerve blocks, intravenous, and local infiltration both for surgeries and acute and chronic pain management. Their use can be limited by their duration of action and the dose-dependent adverse effects on the cardiac and central nervous system. Adjuvants are drugs which, when co-administered along with local anesthetic agents, improve the latency of onset and duration of analgesia and counteract disadvantageous effects of local anesthetics. There is a wide armamentarium of adjuvant drugs to choose to be added in neuraxial and peripheral nerve blocks. They can be broadly divided into non-opioids and opioids, with non-opioids being vasoconstrictors, α2-adrenoceptor agonists, anti-inflammatory agents, acetylcholine esterase inhibitors (neostigmine), adenosine, ketorolac, midazolam, magnesium, and sodium bicarbonate and opioids being lipophilic (fentanyl and sufentanil) and hydrophilic (morphine).",signatures:"Nandita Mehta and Sayyidah Aasima tu Nisa Qazi",downloadPdfUrl:"/chapter/pdf-download/71663",previewPdfUrl:"/chapter/pdf-preview/71663",authors:[{id:"235758",title:"Prof.",name:"Nandita",surname:"Mehta",slug:"nandita-mehta",fullName:"Nandita Mehta"},{id:"263407",title:"Dr.",name:"Sayyidah Aasima Tu Nisa",surname:"Qazi",slug:"sayyidah-aasima-tu-nisa-qazi",fullName:"Sayyidah Aasima Tu Nisa Qazi"}],corrections:null},{id:"68517",title:"Current Local Anesthetic Applications in Regional Anesthesia",doi:"10.5772/intechopen.88528",slug:"current-local-anesthetic-applications-in-regional-anesthesia",totalDownloads:962,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Complete anesthesia is often described using terminology that pertains to the pharmacodynamic effects of the medications administered. This vocabulary often includes akinesia, analgesia, amnesia and hypnosis. Local anesthesia is more specific and represents the administration of an amide or ester local anesthetic, to affect analgesia, at or around the site of administration. Anesthesiologists employ a breadth of different clinical techniques that utilize local anesthetic medications. These techniques include topical, mucosal, endotracheal, intravenous, peripheral nerve block, epidural, and intrathecal (spinal) administration. Unique to the fields of anesthesiology and pain medicine, however, is the administration of epidural and intrathecal local anesthetic. Together, these routes are jointly referred to as neuraxial anesthesia and are often utilized to facilitate surgical intervention, labor analgesia, or pain therapy. The history of neuraxial local anesthetic administration is rich and intriguing. The anatomy of the spinal cord and surrounding structures is complex and pertinent to the pharmacologic discussion of neuraxial local anesthetic administration. The pharmacodynamic and pharmacokinetic interactions of local anesthetics, when administered via the neuraxial route, are unique and worthy of continued investigation. Much has been studied, but there is still more to be discovered. These topics will be the focus of our discussion.",signatures:"Jeffrey M. Carness and Mark J. Lenart",downloadPdfUrl:"/chapter/pdf-download/68517",previewPdfUrl:"/chapter/pdf-preview/68517",authors:[{id:"296917",title:"M.D.",name:"Jeffrey",surname:"Carness",slug:"jeffrey-carness",fullName:"Jeffrey Carness"},{id:"304903",title:"Dr.",name:"Mark",surname:"Lenart",slug:"mark-lenart",fullName:"Mark Lenart"}],corrections:null},{id:"68872",title:"Local Anaesthetics for Spinal Anaesthesia in Day-Case Surgery",doi:"10.5772/intechopen.89018",slug:"local-anaesthetics-for-spinal-anaesthesia-in-day-case-surgery",totalDownloads:967,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Day-case procedures require a high turnover, high quality and low costs. Lidocaine has long been the gold standard for ambulatory spinal anaesthesia. However, the risk of transient neurological symptoms (TNS) limits its use. The perfect local anaesthetic for spinal anaesthesia in day-case surgery should have fast recovery, fast voiding time and a low risk on TNS and urinary retention. Urinary retention is a result of prolonged sensory blockade of the pelvic nerves and is local anaesthetic dose and potency dependent. As a substitute for lidocaine, several local anaesthetics have been suggested in various doses or combinations with or without additives. However, not all are registered for spinal use or have a short-acting profile. The use of additives has been subject of debate because of possible delay in the recovery of bladder. Recently, the old local anaesthetics chloroprocaine and prilocaine were reintroduced in the market. They provide rapid recovery after spinal anaesthesia in day-case surgery. This chapter gives an overview of the local anaesthetics suitable for spinal anaesthesia in day-case surgery, the advantages and disadvantages and the influence on discharge time and recovery of bladder function.",signatures:"Margaretha Barbara Breebaart",downloadPdfUrl:"/chapter/pdf-download/68872",previewPdfUrl:"/chapter/pdf-preview/68872",authors:[{id:"290846",title:"Ph.D.",name:"Margaretha",surname:"Breebaart",slug:"margaretha-breebaart",fullName:"Margaretha Breebaart"}],corrections:null},{id:"69061",title:"Local Anesthetics Infiltration and Wound Healing Process",doi:"10.5772/intechopen.89278",slug:"local-anesthetics-infiltration-and-wound-healing-process",totalDownloads:869,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"It is a good practice, nowadays, to infiltrate local anesthetics along the incision to prevent postoperative pain. This can reduce the use of opioids and the side effects they cause. It is known clearly that the surgical trauma causes inflammatory reaction, and this can be the beginning of a bad cicatrization or even a scar. The use of local anesthetics preventing the acute pain is a very simple technique and has proved to be useful. Nevertheless, the reaction that various anesthetics have over the tissues and the cicatrization process is yet controversial and deserves to be investigated deeply. The use of different formulations of these drugs has been stimulated. The duration and secureness have been the goals of many researches. Levobupivacaine, ropivacaine, and bupivacaine for their long action; lidocaine for less toxicity; and liposomal formulation for the longest duration ever seen, all of them have been indicated in the postoperative pain management. The aim of this chapter is to evaluate the role of long duration local anesthetics on the inflammatory reaction and consequently the collagen production and resistance of the tissue to traction.",signatures:"João Abrão, Marcelo Antunes and Luis Vicente Garcia",downloadPdfUrl:"/chapter/pdf-download/69061",previewPdfUrl:"/chapter/pdf-preview/69061",authors:[{id:"290823",title:"Associate Prof.",name:"Joao",surname:"Abrao",slug:"joao-abrao",fullName:"Joao Abrao"},{id:"298726",title:"Dr.",name:"Marcelo",surname:"Antunes",slug:"marcelo-antunes",fullName:"Marcelo Antunes"},{id:"298727",title:"Prof.",name:"Luis Vicente",surname:"Garcia",slug:"luis-vicente-garcia",fullName:"Luis Vicente Garcia"}],corrections:null},{id:"72876",title:"Local Anesthetics in Odontology",doi:"10.5772/intechopen.91738",slug:"local-anesthetics-in-odontology",totalDownloads:867,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Pain has been a faithful companion of human beings and is a result of most of the dental procedures and illness; therefore a good control of dental pain is inevitable and feasible. The administration of local anesthetics has come to be the standard of care of dental profession. All local anesthetics are effective and high safety margin in all patients including childhood. The choice of using a local anesthetic depends on time of the surgical procedure, patient’s medical history, and the interaction between local anesthetics and patient usual medications. The use of vasoconstrictors is priority in surgical/dental bleeding, but it must be used with caution in patients with cardiovascular disease to avoid a dental catastrophe. Dentists should be experts in dental-anesthetic techniques and in pharmacology of local anesthetics, since they are the most used medications in odontology. The accidental injection or a high absorption of local anesthetics in blood results in systemic toxicity. In such situation sedation, stunning, diplopia, sensory disturbances, disorientation, muscles spasm, respiratory depression, seizures, or cardiac arrest may be present; the dentist must immediately recognize this clinical complication to stablish an early treatment.",signatures:"Enrique Hernández-Cortez, Cecilia G. Sandoval Larios and Juan Carlos Flores-Carrillo",downloadPdfUrl:"/chapter/pdf-download/72876",previewPdfUrl:"/chapter/pdf-preview/72876",authors:[{id:"288453",title:"Dr.",name:"Enrique",surname:"Hernández-Cortez",slug:"enrique-hernandez-cortez",fullName:"Enrique Hernández-Cortez"}],corrections:null},{id:"67979",title:"Complications Associated with Local Anesthesia in Oral and Maxillofacial Surgery",doi:"10.5772/intechopen.87172",slug:"complications-associated-with-local-anesthesia-in-oral-and-maxillofacial-surgery",totalDownloads:2825,totalCrossrefCites:2,totalDimensionsCites:6,hasAltmetrics:1,abstract:"One of the important attempts in clinical oral surgery practice is to maintain safe and effective local anesthesia. Dental procedures are frequently performed under local anesthesia; thus, drug-related complications are often encountered. It is mandatory to have a preoperative evaluation of the patient and choosing the proper local anesthetic agent. Various complications including hypersensitivity, allergy, overdosage, toxicity, hematoma, trismus, paresthesia, or neuralgia can be observed during practice. Therefore, the practitioner should be aware of the possible complications and management methods. The aim of this chapter is to review the preoperative and postoperative complications associated with the local anesthetic in oral and maxillofacial surgery practice. The prevention of measures and treatment of the complications is also emphasized.",signatures:"Basak Keskin Yalcin",downloadPdfUrl:"/chapter/pdf-download/67979",previewPdfUrl:"/chapter/pdf-preview/67979",authors:[{id:"298628",title:"Dr.",name:"Basak",surname:"Keskin Yalcin",slug:"basak-keskin-yalcin",fullName:"Basak Keskin Yalcin"}],corrections:null},{id:"70582",title:"Local Anesthetic Systemic Toxicity",doi:"10.5772/intechopen.90605",slug:"local-anesthetic-systemic-toxicity",totalDownloads:709,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Local anesthetics are used very often in medicine and dentistry. They have few adverse effects, but the increased use of these drugs has resulted in a higher incidence of local and systemic anesthetic toxicity (LAST). From the initial symptoms to the deleterious effects on cardiac and the central nervous system, LAST is an important consequence of which we should be aware. LAST is known since the introduction and use of local anesthetics; it was originally associated with seizures and respiratory failure. However, in the 1970s, side effects on the heart were also identified, as the fatal cardiac toxicity associated with bupivacaine was discovered in healthy patients. Prevention and safe administration of regional anesthesia remains primary factors in the avoidance of the toxicity of these drugs. When a patient has LAST, treatment should be started immediately to reduce seizures. If there is cardiac arrest, follow ACLS guidelines. Intravenous lipids improve cardiac conduction, contractility and coronary perfusion by removing liposoluble local anesthetic from cardiac tissue.",signatures:"Divya Garg, Shikha Soni and Rakesh Karnawat",downloadPdfUrl:"/chapter/pdf-download/70582",previewPdfUrl:"/chapter/pdf-preview/70582",authors:[{id:"302381",title:"M.D.",name:"Rakesh",surname:"Karnawat",slug:"rakesh-karnawat",fullName:"Rakesh Karnawat"},{id:"302385",title:"Dr.",name:"Divya",surname:"Garg",slug:"divya-garg",fullName:"Divya Garg"},{id:"304900",title:"Dr.",name:"Shikha",surname:"Soni",slug:"shikha-soni",fullName:"Shikha Soni"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"3819",title:"Topics in Spinal Anaesthesia",subtitle:null,isOpenForSubmission:!1,hash:"d7bf34d33972bf5002ed97828eb508ad",slug:"topics-in-spinal-anaesthesia",bookSignature:"Victor M. 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Investigation of new and effective active substances against pathogenic Candida spp. and a better understanding of the role of molecular mechanisms involved in the formation of antifungal resistance will help prevent Candida infection among individuals with immunological deficiency and will make the antifungal therapy much more effective and improved. 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",isbn:"978-1-80356-870-6",printIsbn:"978-1-80356-869-0",pdfIsbn:"978-1-80356-871-3",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"862074d07a4355fe3035ae1d14f3e2e6",bookSignature:"Dr. Tulin Askun",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11608.jpg",keywords:"Candida, Candidiasis, Drug Resistance, Antifungal Drug, Invasion Biology, Immune Response, Oropharyngeal Candidiasis, Vulvovaginal Candidiasis, Intestinal Candidiasis, Oesophageal Candidiasis, Candidal Gingivostomatitis, Invasive Candidiasis",numberOfDownloads:3,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 31st 2022",dateEndSecondStepPublish:"June 10th 2022",dateEndThirdStepPublish:"August 9th 2022",dateEndFourthStepPublish:"October 28th 2022",dateEndFifthStepPublish:"December 27th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Prof. Dr. Tulin Askun works as the Head of the Molecular Biology Department at Balıkesir University, Turkey. 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People have to manage the produced waste. Disposal of waste into the surrounding locality has to date been the usual practice with little concern for the environment. Waste has to be managed properly to preserve the planet for the coming generations.
\nWaste generally generated accordingly with life continuity and related proportionally with the human activities such as agricultural, industrial, residential, institutional, municipal, commercial, mining, recreational, and others. This issue is strongly increasing and becomes a potential trouble in the community. The main focus of this study is on hazardous and radioactive wastes accompanying with their Different technologies developed for management.
\nRapid trend of industry and high‐technological progress are the main sources of the accumulation of hazardous materials. Nuclear applications have been rapidly developed recently, and several nuclear power plants have been started to work throughout the world. The potential impact of released radioactive contaminants into the environment has received growing attention due to nuclear accidents, which pose serious problems to biological systems.
\nHazardous wastes are those that may contain toxic substances generated from industrial, hospital, some types of household wastes. These wastes could be corrosive, inflammable, explosive, or react when exposed to other materials. Some hazardous wastes are highly toxic to environment including humans, animals, and plants.
\nRadioactive waste was generated from use of radioactivity, in many but not all cases. Scientific society has approached the management of radioactive waste differently from the management of other waste types. Radioactive waste is defined as the material that contains or is contaminated with radionuclides at concentrations or activities greater than clearance levels as established by regulatory authorities. The higher the concentration of radionuclides above the established levels, the greater the hazard the waste possesses. The hazard of radioactive waste also depends on the nature of the radionuclides, and, at the same concentration, different radionuclides have different levels of hazard.
\nThe management of extremely increasing volumes of these wastes became a very important accordingly. Inadequate management of waste led to contamination of environment: water, soil, and atmosphere and to a serious impact on public health. Direct health impacts of mismanagement of waste are well known and can be observed obviously in developing countries.
\nSaving of the environment and human health from the detrimental effects of hazardous and radioactive wastes is achieved by the effective improvement of waste management programs.
\nIn the scope of this study, the development in waste management planning and implementation of hazardous and radioactive wastes was presented.
\nWith increasing manufacturing processes, solid, liquid, and/or gaseous emissions generate as by‐products. Some of these wastes are potentially harmful to human health and environment and thus need special techniques of management.
\nWastes are classified as hazardous if they exhibit one or more of ignitability, corrosivity, reactivity, or toxicity. According to Resource Conservation and Recovery Act (RCRA), hazardous wastes are defined as any waste or combination of wastes which pose a substantial present or potential hazard to human health or living organisms because such wastes are non‐degradable or persistent in nature or because they can be biologically magnified, or because they can be lethal, or because they may otherwise cause or tend to cause detrimental cumulative effects [1].
\nThe management of hazardous wastes has become a specialized discipline because of the complex nature of the problem and the solutions available to humanity. The mismanagement examples of hazardous wastes causing disastrous human and environmental consequences are numerous. The management process is based on the definition and classification of the different wastes, and their toxic effects on human and taking in consideration the application of risk management to control human health and environmental impacts of hazardous waste. Hazardous waste management, therefore, deals with minimizing harmful effects on humans and environment by applying special techniques of handling, storage, transportation, treatment, and disposal of hazardous wastes.
\nA useful listing of hazardous characteristics is that provided by the United Nations [2] as part of recommendations relating to the transport of dangerous goods as illustrated in Table 1.
\nUN class number | \nHazardous characteristic | \n
---|---|
1 | \nExplosive | \n
3, 4 | \nFlammable | \n
5 | \nOxidizing | \n
6 | \nPoisonous/infectious | \n
7 | \nRadioactive | \n
8 | \nCorrosive | \n
9 | \nToxic (delayed or chronic)/ecotoxic | \n
Hazardous characteristics: extracted from UN listing [2].
Waste generated from industrial sources can have non‐hazardous and hazardous components, with non‐hazardous waste usually representing the greater part of the volume. The hazardous component of this waste is relatively small in volume [3].
\nThis type of waste was identified as hazardous waste when proceeds toxicity test, corrosively test, ignitability test, and some special character test. As a hazardous pollutant, it may impose serious impacts on surrounding environment and such impacts should be quantitatively examined to assess the influence on human health [4].
\nHouseholds generate small quantities of hazardous wastes such as oil‐based paints, paint thinners, wood preservatives, pesticides, insecticides, household cleaners, used motor oil, antifreeze, and batteries. It has been estimated that household hazardous waste in industrialized countries such as the United States accounts for a total of about 0.5% (by weight) of all waste generated at home, while in most developing countries, the percentage probably is even lower [3].
\nThere are some of hazardous medical and dental wastes that, when disposed improperly, could cause harm to the environment. It also presents an occupational health hazards to the healthcare personnel who handle these wastes at the point of generation and those involved with their management, that is, segregation, storage, transport, treatment, and disposal.
\nHealthcare waste that is capable of producing injury or disease including many sorts of hazardous wastes such as:\n
Infectious waste: Which contain pathogens namely bacteria, viruses, fungi, or parasites in concentrations sufficient to cause disease in susceptible hosts. Cultures and stocks of infectious agents from laboratory work; tissues and dressing generated from autopsies, surgeries, and treatment of infected patients and animals; materials or equipment in contact with blood and infected body fluids.
Pathological waste: Including tissue, organs, body parts, human fetuses, and animal carcasses, blood and body fluids.
Sharps: It comprise syringes, needles, scalpels, saws, infusion sets, knives, blades, broken glass, or other items that can cause cut or puncture wounds.
Pharmaceutical waste: It covers expired, unused, spilt, and contaminated pharmaceutical products, drugs, vaccines, and sera that are no longer required and need to be disposed of in appropriate manner.
Genotoxic waste: This type combines cytostatic drugs, vomit, urine, or feces from the patients treated with cytotoxic drugs, chemicals, and radioactive materials. Genotoxic waste has mutagenic, teratogenic, and carcinogenic properties.
Chemical waste: Discarded solid, liquid, or gaseous chemicals should be considered as hazardous if it is toxic, corrosive, inflammable, or reactive.
Waste with high content of heavy metals: Mercury (thermometers, blood pressure gauges, amalgam), cadmium (discarded batteries), and lead (reinforced wood panels for radiation proofing in radiology department) generated from hospitals could be represented as a subcategory of hazardous chemical waste.
Radioactive waste: The use of radioisotopes in vitro analysis of body tissues and fluids, in vivo organ imaging, tumor localization, and treatment and various clinical studies involving certain radionuclides need to be specially managed in a centralized treatment facility for radioactive wastes.
Nuclear applications have been rapidly developed recently, and several nuclear power plants started to work throughout the world. The potential impact of released radioactive contaminants into the environment has received growing attention due to nuclear accidents. Contamination of soil and water by radionuclides due to natural processes, global fallout from nuclear weapon testing, discharges from nuclear installations, disposal of nuclear waste, and occasional nuclear accidents (i.e., Chernobyl in 1986 and Fukushima in 2011) poses serious problems to biological systems. Radioactive waste includes a variety of radionuclides and occurs in a variety of physical and chemical forms. It can be generally classified as low‐/intermediate‐level radioactive waste and high‐level radioactive waste [6].
\nRadioactive waste, arising from civilian nuclear activities as well as from weapon activities, poses a potential problem for handling and saving the environment for coming generations.
\nRadioactive waste includes a variety of radionuclides and occurs in a variety of physical and chemical forms. It can be generally classified as low‐/intermediate‐level radioactive waste and high‐level radioactive waste. Nuclear research establishments include, for example, waste containing different organic components, toxic or chemically aggressive constituents, radionuclides with specific properties (high mobility, high chemical activity, volatile elements, etc.), waste difficult for treatment and not appropriate for direct immobilization (e.g., spent organic ion exchange resins and spent liquid scintillation cocktails). For such waste, application of conventional treatment and conditioning options may not be efficient and appropriate in terms of economy, safety, and performance characteristics. In many cases, such wastes are stored awaiting an appropriate treatment and conditioning solution [7].
\nThe primary sources of radioactive wastes in a country without nuclear fuel cycle activities are nuclear research, production of radioisotopes, application of radioisotopes, and decontamination and decommission of nuclear installations.
\nWaste management is an important component of environmental policy all over the world. Priority of hazardous solid waste for environmental protection is formulated on source reduction and reuse, recycling, treatment, and landfilling [8].
\nMinimization program for low‐ and intermediate‐level radioactive wastes [
The objective of radioactive waste management is to deal with those wastes that in a manner that protects human health and the environment now and in the future without imposing undue burden on future generations [9]. Radioactive waste management involves many steps keeping the position of radioactivity clean. As nuclear power and arsenal grow, continuous monitoring and immobilization of waste over several decades and centuries and deposition in safe repositories assume great relevance and importance. The overall waste management generally includes the following steps: segregation and sorting of the radioactive wastes, treatment, conditioning, storage, transport, and final disposal. To achieve a satisfactory overall waste management strategy, component steps must be complementary and compatible with each other [10]. Consequently, for every nuclear activity, there should be a waste minimization program that aims to reduce the amount of generated wastes. Such programs should cover the organizational, technological, and economic aspects of the performed waste minimization processes. The key considerations of the minimization program for low‐ and intermediate‐level radioactive wastes are illustrated in Figure 1, based on the effectiveness and cost of processing [11].
\nWaste minimization is a process aimed to reduce the amount and activity of waste to a level as low as reasonably achievable. This process is now applied at all stages of nuclear processing from power plant design through operation to decommissioning. It consists of reducing waste generation as well as recycling, reuse, and treatment, with due consideration for both primary wastes from the original nuclear cycle and secondary wastes generated by reprocessing and clean‐up operations [12].
\nSome wastes may require treatment for safety, handling, or stability for interim storage reasons. Treatment methods can be generally classified as chemical, physical, and/or biological. For new wastes, there is an opportunity to influence the process design so that wastes generated will require little or no treatment. If treatment is required, it is usually easier to obtain most of the characterization, while the waste is in raw form and characterization requirements may be directed toward treatment process control. For historic wastes, many situations are possible. Wastes may have already undergone some degree of treatment with little or no precharacterization. In such a case, further characterization will be required both before and during treatment to obtain a sufficient degree of detailed information. Waste streams may have been inadvertently combined, leading to a much larger volume of material that must be checked for certain properties. Previously treated wastes need to be examined to determine the compatibility of the prior treatment process with the waste acceptance criteria for the conditioning and disposal phases [13].
\nHowever, the seeking of inexpensive methods has led to develop new technologies based on the utilization of plant in biosorption of hazardous elements such as radioisotopes. Phytoremediation is the using of plants to remove hazardous contaminants from the environment. This trend is a growing application in remediation studies due to its numerous advantages, such as environmental friendliness, cost‐effectiveness, and high abundance [6, 14]. Phytoremediation like other traditional treatment processes has to follow the subsequent step called immobilization process, and it could be done to solidify and stabilize the resulting secondary solid waste in an inert matrix [15]. The efficiency of contamination removal by phytoremediation can be greatly enhanced by a proper selection of the species suitable for the nature of pollutant and according to its geographic location, the microclimate, hydrological conditions, soil properties, and accumulation capacity of the plant species.
\nProcessing of radioactive waste includes any operation that changes its characteristics such as pretreatment, treatment, and conditioning. Solidification/stabilization (s/s) of hazardous and radioactive wastes is an attractive technology to reduce their risks and facilitate their handling prior to disposal. The long‐term safe landing of the solidified hazardous waste is an important request for keeping the surrounding environment more secure for the coming generations [16, 17]. Immobilization reduces the potential for migration or dispersion of contaminants including radionuclides. The International Atomic Energy Agency (IAEA) defines immobilization as the conversion of a waste into a waste form by solidification, embedding, or encapsulation. It facilitates handling, transportation, storage, and disposal of radioactive wastes. Conditioning means those operations that produce a waste package suitable for handling, transportation, storage, and disposal. Conditioning may include the conversion of waste to a solid waste form and enclosure of waste in containers [12].
\nSolidification/stabilization is typically a process that involves the mixing of a waste with a binder to reduce the contaminant leachability by both physical and chemical means and to convert the hazardous waste into an environmentally acceptable waste form for land disposal. Moreover, it provides the waste form acceptable mechanical performance to withstand transport and handling. Inorganic binders such as cement are effective in immobilizing heavy metals through chemical and physical containment mechanisms, but are not as effective in immobilizing most organic contaminants. Many substances in the wastes significantly affect the setting and hardening characteristics of binders, especially cement‐based cementing systems [18].
\nThe requirements for the waste form are to provide physical, chemical, and thermal stabilities of the solidified radioactive materials. Moreover, the immobilized final waste forms resist leaching, powdering, cracking, and other modes of degradation. Portland cement is the most widely inorganic‐based system used for solidification/stabilization of hazardous, low‐ and intermediate‐level radioactive wastes [19–21].
\nWaste disposal is the final step of waste management and ideally comprises placing hazardous waste in a dedicated disposal facility, although discharging of effluents into the environment within permitted limits is also a disposal option. Concepts for radioactive waste disposal have, however, developed considerably since that time and great consideration is now given to the necessary retention times and retention capacities for different types of waste, resulting in much‐improved repositories and planned disposal facilities [12].
\nAccording to IAEA, the disposal of radioactive waste is defined as the emplacement of waste in an approved specific facility that is intended to isolate the waste from human and environment and to prevent or limit a release of potentially harmful substances such that human health and the environment are protected. However, the safe disposal of radioactive wastes is one of the main concerns for those who oppose the nuclear technology. Therefore, disposal plays an important role in public acceptance of civilian applications of nuclear technology in different nations [10].
\nThe effect of climatic conditions, for example, flooding and freezing/thaw accidents on the solidified wastes, is one of the most issues taken into consideration to evaluate the performance of this immobilized hazardous and radioactive wastes under the worst climatic conditions during the disposal process. Flooding accidents, one of the main dangerous problems that could face the solidified waste at the disposal site, should deserve special attention. Water is the primary agent of both creation and destruction of many natural materials, happens to be central of most durability problems in solidified waste materials [22, 23]. The rate of chemical deterioration is dependent on whether the chemical attack is confined on the surface of solidified waste material or also happening inside the material. The rate of deterioration is affected by the type and the concentration of ions present in water and by the chemical composition of the solid matrix.
\nSafety strategy for radioactive waste containment and isolation for the proposed storage and transportation focuses on two objectives: (1) to provide stabilization of the radioactive waste within the including package and (2) to limit the radiation exposure dose of the public during the transportation or other handling processes [24].
\nVitamin D plays an important role in calcium and phosphorus metabolism, which are essential for bone health and various biological functions. In vitamin D deficiency, clinical and biochemical rickets characterized by hypocalcemia (irritability, fatigue, muscle cramps, seizures), hypophosphatemia and skeletal manifestations (delayed closure of fontanelles, craniotabes, frontal bossing, bowed legs, enlarged wrists, bone pain, and short stature) in children and adolescents or osteomalacia in adults may occur. Over the past several decades, it has been reported that the efficiency of vitamin D is not limited only to maintaining bone health by managing the calcium homeostasis, but also seems to have anti-inflamatory, immune-modulating and pro-apopitothic properties [1]. There are two different precursor molecules of vitamin D. The first is vitamin D3, or cholecalciferol, which is the main source of vitamin D in the body and is synthesized from the skin by exposure to sun. Vitamin D3 can also be obtained from dietary animal foods (fish, egg yolks) or medicines (vitamin supplements). The second precursor is vitamin D2, or ergocalciferol, which can be used as a source of vitamin D via oral medication or through enriched foods. Vitamin D3 differs in molecular structure from vitamin D2 in that it has a double bond between the 22nd and 23rd carbon atoms and a methyl group on the 24th carbon atom [2]. These structural differences in vitamin D2 affect its catabolism. Compared to vitamin D3, vitamin D2 has a lower affinity for vitamin D-binding protein (VDBP), which leads to its easy removal from the circulation, a reduced formation of 25-hydroxy vitamin D2 (25OHD2) by the 25-hydroxylase enzyme, and increased inactivation by the action of 24-hydroxylase [3, 4, 5]. Although both vitamin D2 and D3 are used as drugs, studies have shown that a higher serum 25OHD2 vitamin level is obtained when vitamin D3 is used in treatment compared to vitamin D2 [6]. In addition, it has been shown that active vitamin D obtained from vitamin D3 has a higher affinity for the vitamin D receptor (VDR) [4]. Despite these differences, vitamins D2 and D3 are both metabolized in substantially the same way and are commonly referred to as vitamin D. Vitamin D is a prohormone and inactive, and to be activated, it must go through a series of enzymatic and non-enzymatic steps.
Formation of vitamin D3, which is the first step of vitamin D synthesis, takes place in the epidermis by a non-enzymatic process (Figure 1). Vitamin D3 is the most important source of vitamin D in the body. 90–95% of vitamin D3 in the human body is produced from the skin with the effect of sunlight. Therefore, sunlight is the main source of vitamin D synthesis, and if there is sufficient exposure to sunlight, there is no need to take additional vitamin D. The mechanism of non-enzymatic photolysis of vitamin D by ultraviolet B (UVB) rays with wavelengths in the range of 290–315 nm involves the breaking of a bond in the B ring of 7-dehydrocholesterol (pro-vitamin D3), resulting in pre-vitamin D3 formation in the epidermis. Subsequently, two different double bonds are formed between the broken carbon atoms in the B ring by thermo-sensitive non-enzymatic process, and the formation of vitamin D3 from pre-vitamin D3 is completed (Figure 2) [7].
Vitamin D metabolism.
Vitamin D3 synthesis from 7-dehydrocholesterol in the epidermis.
The synthesis of vitamin D3 from pro-vitamin D3 in the skin is adjusted according to the needs of the organism. In a period of just fifteen minutes, pre-vitamin D3 is synthesized from pro-vitamin D3 with the effect of ultraviolet light. Conversion from pre-vitamin D3 to vitamin D3 occurs by isomerization in a rather slow and thermo-sensitive manner. In the case of exposure to UV rays or solar radiation for a long period, pre-vitamin D3 converts to a number of photolyzed inactive by-products, such as lumisterol (irreversible) or tachysterol (which can be converted back to pre-vitamin D3). These by-products have no biological effects (Figure 2). In other words, once pre-vitamin D3 is formed in the skin, it turns into either vitamin D3 or inactive metabolites. This is a physiological control mechanism that protects the body from vitamin D intoxication by preventing unnecessary vitamin D synthesis [8, 9].
Some conditions that prevent UVB rays from reaching the skin cause a decrease in vitamin D production. One of these reasons is the ozone (O3) layer surrounding the atmosphere, which reflects some of the sun’s rays, preventing them from reaching the Earth and their harmful carcinogenic effects on the skin. The peak UVB wavelength required for optimal vitamin D synthesis from the skin is 297 (290–315) nm [1, 8]. In addition, air pollution, aerosols, water vapors, and increased nitrogens in the air also play a role in preventing sunlight reaching the Earth, and consequently result in a potential reduced synthesis of vitamin D [8]. Another factor affecting the effectiveness of UVB rays in the synthesis of vitamin D in the skin is the solar zenith angle, which affects how UVB rays reach the world quantifiably. When the sun moves in a path closer to the horizon, which occurs in the northern latitudes in the winter season, vitamin D synthesis is more adversely affected (or reduced). In the summer time in the northern latitudes, a normal biosynthesis is more propitious or favorable. The narrowing of this angle indicates that the sun rays reach the Earth more steeply and intensely. The solar zenith angle is closely related to sunbathing time during the day, the seasons and the geographic region (latitude). Sunlight reaches the Earth most intensely in the “mid-day” when it is summer in the northern latitudes and the weather is clear. Finally, it is thought that sunlight exposure is sufficient for vitamin D synthesis in all geographic regions below 35 degrees north or south latitude all year round. In regions beyond this latitude toward the poles, especially in winter, sunlight is not sufficient for vitamin D synthesis. For example, UVB rays are not sufficient for vitamin D synthesis between October and April in Rome, which is located on 41.9 degrees north latitude, and between November and February in Berlin and Amsterdam, which are located on 52 degrees north latitude. For the reasons mentioned above, it is difficult to predict how much UVB rays reach the skin and how much of this increases serum vitamin D levels. In experimental studies, it has been reported that UVB rays that will cause minimal erythema in 25% of the skin are equivalent to 1000 units of oral vitamin D intake [2, 3, 8].
UVB rays are also affected by the individual’s clothing style, use of sunscreen, and skin colour determined by pigmentation with melanin. In dressing style, especially the type of the clothing fabric used is of great importance [10]. Non-synthetic, light-colored, and linen garments play a less preventive role in UV rays reaching the skin than do garments made of silk, nylon, polyester, and wools. For example, black-dyed cotton clothing prevents 98.6% of UVB rays from reaching the skin compared to white (undyed) cotton clothing, which blocks 47.7% of UVB. Topical sunscreens also prevent UVB rays from reaching the skin by absorbing, reflecting or dispersing them. Topical creams with a sun protection factor of 8 or higher block vitamin D synthesis above 95% [11]. Melanin is a large, opaque polymer synthesized by melanocytes in the skin through the stimulus of exposure to UVB rays. Melanin competes with dehydrocholesterol 7 in the skin to absorb UVB photons and thus inhibits vitamin D synthesis [12]. Individuals with dark skin colour have more melanin pigment in their epidermis than light-skinned individuals and require higher concentrations of sunlight for the same amount of vitamin D synthesis [12]. In addition, the 7-dehydrocholesterol level (provitamin D) in the epidermis can also affect the serum vitamin D concentration. For example, 7-dehydrocholesterol levels in scar tissue caused by the burn are reduced by 42.5% of normal. In these cases, progressive vitamin D deficiency develops, especially if supplemental dietary vitamin D is not provided. Moreover, the content of provitamin D in the skin decreases with age. Skin temperature is also important for vitamin D synthesis. Vitamin D from pre-vitamin D by isomerization whose rate of formation is temperature- dependent. The rate decreases as the skin temperature decreases. In a healthy person, the skin temperature is lower than the central body temperature and varies between 29 and 35 degrees Celcius. When the skin temperature is 37 degrees Celcius, the isomerization of vitamin D from pre-vitamin D occurs within 2.5 hours [13, 14].
Vitamin D3 synthesized in the skin is released into the systemic circulation and all forms are transported by binding to VDBP in serum. A portion of vitamin D, a fat-soluble vitamin, is stored in adipose tissue for use when necessary. The ability of vitamin D to be stored in adipose tissue extends its total half-life in the body up to approximately 2 months. When vitamin D3 is transported to the liver, it is first converted into 25OHD3 by the cytochrome P450 25-hydroxylase enzyme. 25OHD3 is the main circulating form of vitamin D, and it is the parameter that provides the best estimation about the body’s vitamin D pool [15]. Various enzymes that show 25-hydroxylase properties have been described in the body. Among these, the first one is CYP27A1 located in mitochondria, and the second is microsomally located CYP2R1 [1, 6, 16]. CYP27A1 also exerts 27-hydroxylase effect and is involved in bile acid synthesis. Although CYP27A1 is expressed in different tissues of the body, the tissues where it is most commonly found are liver and skeletal muscle tissues [1, 2]. In experimental studies, it was reported that the serum 25OHD3 levels were increased in mice which possess an inactivated CYP27A1 gene, and that rickets did not occur in these mice [17]. Interestingly, in this study, it was shown that CYP2R1 expression increased after CYP27A1 gene inactivation, and consequently 25-hydroxylation activity increased [17]. In addition, individuals with a CYP27A1-inactivating mutation develop a cerebrotendinous xanthomatosis disease with bile and cholesterol synthesis disorders, but without rickets manifestation [18]. Besides CYP27A1, different CYP-450 enzymes with 25-hydroxylase activity (CYP2D25, CYP2J2, CYP2J3, and CYP2C11) have been identified in humans and animals, with the most important one in human being CYP2R1. It is assumed that enzymes other than CYP2R1 have effects only on serum 25OHD3 levels [2].
Studies have suggested that CYP2R1 is the major enzyme responsible for 25-hydroxylation in the human body. This enzyme is expressed in many tissues, mainly liver, skin, and testis [1, 2, 17]. The 25-hydroxylase encoded by the CYP2R1 gene was first described by Cheng et al. [19]. It was first reported by Chen et al. [20] that homozygous inactivating mutations of this gene lead to clinically observed rickets (vitamin D-dependent rickets type IB) in Nigerian families. It has been reported that these cases gave suboptimal response to standard vitamin D (inactive vitamin D2 or D3 forms) treatment [21]. The CYP2R1 enzyme has equal affinity for the different forms of vitamin D precursors (D2 or D3) [19]. Studies have shown that 25-hydroxylase effect increased in male rats given estrogen, whereas this activity decreased in female rats given testosterone [21]. Despite experimental studies, the effect of sex steroids on 25-hydroxylase enzyme activity in humans is unknown. It has been shown that in CYP2R1-null mice, the level of 25OHD3 decreases by 50%, when both CYP2R1 and CYP27A1 are inactivated, and that serum 25OHD3 levels decrease by 70%, and serum 25OHD3 level remains at a measurable level in both cases [2, 17]. This supports the view that serum vitamin D level is compensated by other enzymes with recruitable 25-hydroxylase enzyme activity.
The final step of active vitamin D formation takes place in the proximal tubules of the kidney, led by the enzyme 1-alpha hydroxylase. 25OHD3, which is bound to VDBP, is taken into tubule cells and metabolized (1-alpha hydroxylation) through megalin and cubilin, which are transmembrane proteins located in renal tubules and act as surface receptors for VDBP in tubules. 25OHD3, which then undergoes 1-alpha hydroxylation [1, 2]. The 1-alpha hydroxylase enzyme hydroxylates the first carbon atom in the A ring of 25OHD3, resulting in the formation of 1,25 (OH) 2D3 [1]. CYP27B1 is the only enzyme that has 1-alpha hydroxylase activity. This enzyme, which belongs to the cytochrome P-450 enzyme system, is located in the inner mitochondrial membrane and carries out electron transport to NADPH via ferrodoxin-ferrodoxin reductase [1, 2]. The gene for the enzyme consists of nine exons and is located 12q14.1 chromosomal region. Four different groups reported the cloning and sequencing of the gene from rats, mice and humans [22, 23, 24, 25, 26]. In biallelic inactivating mutations of this enzyme, which is highly homologous to some mitochondria located cytochrome P-450 enzymes (CYP27A1 and CYP24A1), 25OHD3 cannot be converted to 1.25 (OH) 2D3, which is the active vitamin D form. In this case, the clinical picture of vitamin D-dependent rickets type 1A (also called pseudo-vitamin D deficiency rickets) occurs [23]. This disease is typically characterized by rickets, with clinically observed very low 1.25 (OH) 2D3, low serum calcium/phosphorus, and high parathyroid hormone (PTH) levels. CYP27B1 is expressed mainly in the renal proximal tubules and in the placenta during pregnancy [27]. While the expression of the gene encoding this enzyme increases with the effect of PTH, it decreases with FGF23 (fibroblast growth factor 23) and 1.25 (OH) 2D3. CYP27B1 gene is also expressed in lung, brain, breast and intestinal system epithelial cells, immune system cells (macrophage, T/B lymphocytes and dendritic cells), osteoblasts, chondrocytes, and some tumor cell types [1, 2]. The regulation of the extra-renal localized 1-alpha hydroxylase enzyme differs. In some granulomatous diseases where monocyte/macrophage cells play an important role (sarcoidosis, tuberculosis, Chron’s disease, etc.), with the effect of IL-1, TNF-α, IFN-γ, 1-alpha hydroxylase enzyme activity increases and 1,25 (OH) 2D3 is synthesized in greater quantities than normal, and consequently, hypercalcemia and hypercalciuria emerge [28, 29, 30]. Additionally, since cells in these tissues do not have PTH receptors, it is not yet understood how PTH exerts its enhancing effect on the 1-alpha hydroxylase enzyme activity in these cells. In one study, it has been suggested that this enhancing effect of PTH may have occurred through post-transcriptional effects [31]. Moreover, 1-alpha hydroxylase enzyme in these cells is not inhibited by 1,25 (OH) 2D3 or hypercalcemia, unlike the renal tubules.
The 24-hydroxylase enzyme is located in the mitochondrial inner membrane of the cells located in the proximal kidney and, like CYP27B1, uses the electron transport system that enables electron transport to NADPH via ferrodoxine-ferrodoxin reductase. It is known that CYP24A1, which is the only enzyme showing 24-hydroxylase enzyme activity in humans, can also exhibit 23-hydroxylase enzyme activity [2]. Which enzyme will be more prominent varies according to the species [32]. The 23-hydroxylase, another enzyme that degrades vitamin D, is the first step activity in the conversion of 1,25 (OH) 2D3 to 1,25 (OH) 2D3-23,26-lactone.
The CYP24A1 enzyme, encoded in 20q13 chromosomal region and having 24-hydroxylase enzyme activity, initiates catabolic processes that lead to the inactivation of vitamin D by hydroxylating the 24th carbon atom. This enzyme can use both 25OHD3 and 1.25 (OH) 2D3 as substrates, but has a higher affinity for 1.25 (OH) 2D3. As a result of a series of enzymatic reactions, calcitroic acid is formed, which becomes biologically inactive. On the other hand, it has been suggested that the 1,25 (OH) 2D3-23,26-lactone, which is formed in the 23-hydroxylase pathway, lowers serum calcium level, inhibits bone resorption induced by 1.25 (OH) 2D3, and stimulates the formation of collagen tissue in bone tissue [33]. In addition, it has been suggested that 24,25 (OH) 2D3 is not only a degradation product, but has an important role in bone metabolism, especially in endochondral bone formation [34].
There are two vitamin D response elements (VDRE) in the promoter region of the CYP24A1 gene [35]. When active vitamin D is bound to the these one of VDRE after heterodimerization with various molecules, thus initiates the inactivation process of vitamin D. In addition, it has been shown that CYP24A1 gene expression decreases with the effect of PTH, whereas it increases with increased FGF23 concentrations [1, 32, 36, 37]. Inactivating mutations in CYP24A1 lead to an idiopathic infantile hypercalcemia clinic characterized by hypercalcemia, hypercalciuria, nephrocalcinosis, low PTH, low 24.25 (OH) 2D3 and high 1.25 (OH) 2D3 levels [37]. As a result, CYP24A1 is a critical enzyme that protects the body from excessive accumulation and possible intoxication of vitamin D.
3-epimerase activity was first demonstrated in 2001, with the detection of the 3-epi form of 1,25 (OH) 2D3 in keratinocytes [38]. In the following years, epimer forms of 25OHD3 and other vitamin D metabolites were discovered. However, the enzyme or enzymes involved in epimerization has not yet been identifiedpurified or cloned. This enzyme changes the hydroxyl group in the 3rd carbon of the A ring from the alpha orientation to the beta orientation, causing the three-dimensional structure to change and consequently alter the activity of CYP27B1 and CYP24A1 enzymes on vitamin D metabolism. These epimers can be detected by special liquid chromatography-mass spectroscopy (LC-MC) measurement methods [2]. C-3 epimer forms of 25OHD3 and 1,25 (OH) 2D3 have been shown to have lower affinity for VDR and VDBP compared to non-epimer forms [38]. The C-3 epimer form of 1,25 (OH) 2D3 has been shown to cause PTH suppression similar to the non-epimer form, but its effects on bone tissue are not clear. In addition, epimer forms have also been shown to have non-calcium effects (anti-proliferative effect, surfactant synthesis) [39]. It has been shown that the serum levels of vitamin C-3 epimer forms are found to be 60% higher in the period between the neonatal period and one year old, and decrease after one year of age and decrease to very low levels in adulthood [2, 38]. The reason why epimer forms with limited biological activity are important is that they cause interference and false high results in serum 25OHD3 and 25OHD2 measurement. Therefore, it is important to prefer the method (especially LC–MS / MS) that can exclude this effect of epimer forms that cause serum vitamin D measurement interference. However, the use of LC–MS/MS method in the measurement of vitamin D has not become widespread in the world, and the use of this method is only recommended in selected cases.
The largest part of the circulating vitamin D is in the form of 25OHD3, and its serum concentration is in equilibrium with the level of vitamin D stored in muscle and adipose tissues. The parameter that gives the best information about the whole vitamin D pool in the body is 25OHD3 and its known half-life of 15–20 days. Most of all forms of vitamin D in circulation (85–88%) are transported by binding to VDBP and the remaining part (12–15%) to albumin [2, 40]. The serum concentration of VDBP is 4–8 nM and only 2% of it is bound with vitamin D metabolites [2]. Moreover, the affinity of VDBP to 25OHD3 is 20 times higher than 1.25 (OH) 2D3 [3]. 0.03% of 25OHD3 and 0.4% of 1.25 (OH) 2D3 are in free form [2]. In chronic liver disease or nephrotic syndrome, VDBP and albumin levels and thus total serum 25OHD3 and 1.25 (OH) 2D3 levels decrease, but the levels of free forms are not affected [41]. Likewise, since the VDBP level may decrease during the acute disease period, evaluating the body’s vitamin D pool by measuring the serum 25OHD3 level with standard immunoassays may lead to misinterpretations [42]. In conclusion, while the total levels of vitamin D forms are affected by the VDBP level, there is no relationship between VDBP and free vitamin D forms, which are essential for biological activity. It was shown that both 25OHD3 and 1.25 (OH) 2D3 levels in VDBP-null mice were lower than wild type mice, but serum PTH and calcium levels were similarly normal in both groups [43]. This supports the view that serum vitamin D level measured by the standard method may not be an indicator of biologically active vitamin D pool. In addition, the predisposition of VDBP-null mice to the development of osteomalacia after a vitamin D-restricted diet suggests that VDBP may play a role in maintaining the existing vitamin D pool [44]. In addition, some single nucleotide polymorphisms (GC1F, GC1S, GC2) in the
Vitamin D provides its biological effect in two different ways. The first is by directly affecting gene transcription (genomic effect) as other steroid hormones. This effect is relatively slow and usually occurs within hours or days. The second is the non-genomic pathway whose biological effect is relatively faster (within minutes). Vitamin D exerts its non-genomic effect by directly altering the trans-membrane passage of some ions (Ca, Cl) or by affecting intracellular signaling pathway activities (cAMP, PKA, PLC, PI-3 kinase and MAP kinase) [1, 2]. Genetic studies on vitamin D support that active vitamin D directly or indirectly regulates 0.8–5% of the total genome, suggesting the role of active vitamin D in many actions such as regulation of cellular growth, DNA repair, differentiation, apoptosis, membrane transport, cellular metabolism, adhesion and oxidative stress [1, 2, 3, 47].
The active form of vitamin D displays this effect through the vitamin D receptor (VDR). VDR is a member of the nuclear hormone receptor superfamily, which includes steroid, thyroid hormone, and retinoic acid receptors [48]. The VDR gene located on chromosome 12 consists of 427 amino acids encoded by. The structure of the VDR consists of a relatively short N-terminal domain compared to other nuclear receptors, two zinc-fingers that allow the receptor to bind to DNA, and a highly variable C-terminal region, and the hinge region connecting binding these domains (Figure 3) [2]. The DNA-binding region of the receptor is rich in cysteine, and the sequence of this region is largely conserved between species. The zinc-finger structure close to the C-terminal part of VDR determines the specificity for the VDRE (vitamin D response element), which is the binding site on the DNA. The other zinc-finger structure is involved in the heterodimerization of VDR with RXR (retinoid X receptor) [1, 2]. The ligand-binding part of the receptor consists of 12 α-helix structures (H1-12; the H12 part is also called AF2) and 3 β-sheet structures (S1-3) [49]. The AF-2 region located at the end of the C-terminal is the binding site of co-activator complex structures such as SRC (steroid receptor coactivator) and DRIP (vitamin D receptor interacting protein). Transcription is initiated by binding co-activators to this region [50]. Apart from these functional domains, there are NLS (nuclear localization signal) regions within the DNA binding region of VDR, which are necessary for maintaining transcriptional activity [2]. In addition, there is a hinge region between the ligand-binding and DNA-binding domains of the VDR that ensures molecule stabilization.
The structure of the Vitamin D receptor (VDR).
After active vitamin D crosses the target cell membrane, it interacts with the ligand-binding domain of its own receptor (VDR) in the cytoplasm of the cell. Vitamin D is embedded in the ligand-binding domain, and subsequently, in the H12 alpha-helix H12 (AF-2) region, which is located at the end of the ligand binding part [51]. This critical conformational change of AF-2 facilitates the binding of co-activators in later stages [52]. In the next step, vitamin D-bound VDR binds to RXRα to form a VDR/RXR heterodimer structure that binds to cognate VDR elements (VDRE) in the promoter region in the target genes with a high affinity to initiate gene activation or inhibition. There are many gene-specific VDREs associated with bone metabolism, xenobiotic detoxification, drug resistance, cell growth and differentiation, angiogenesis, mammalian hair growth cycle, lipid synthesis regulation, apoptosis, and immune functions, suggesting that vitamin D has numerous regulatory roles in various organs or tissues in the body [53].
After active vitamin D-VDR-RXR-VDRE interaction, the progression of transcription is controlled by co-activator and co-repressors. The best known co-activators are the p160 co-activator family (eg CBP/p300 and p/CAF) and SRC 1,2,3. Both bind to the AF-2 part and have histone acetyl transferase (HAT) activity, which enables the opening of the histone structure and thus facilitates gene expression [54]. The SRC complex has three NR regions that facilitate binding and contain LxxLL (L, leucine; x, any amino acid) motifs. Likewise, the DRIP complex (Mediator) also has NR regions with LxxLL motifs consisting of 15 or more amino acids [55]. Unlike SRC, DRIP complex does not have HAT activity. This suggests the fact that both protein complexes play a complementary role in the initiation of transcription. The mediator multi-protein complex DRIP205/MED1 (also known as MED1) accumulates around RNA polymerase 2of the initiation complex. This complex then interacts with the TATA region in the promoter region and enables transcription to be initiated [56]. Co-repressors (eg SMRT and NCoR) have histone de-acetylase activity and inhibit transcription by preventing unfolding of the histone core.
Some of the hormones that act on the nuclear hormone receptor can also exert their biological effects on the membrane receptor without the need for additional gene regulation [2]. The non-genomic effect occurs through messenger-mediated pathways. Estrogen, progesterone, testosterone, corticosteroids and thyroid hormones have been reported to exert their effects by using both genomic and non-genomic pathways [2]. Vitamin D has been shown to directly regulate the activation or distribution of various ion-transport channel proteins (for calcium and chloride) and of enzymes (protein kinase C and phospholipase C) through the membrane receptor in osteoblast, liver, muscle, and intestinal cells (Figure 4) [57, 58, 59, 60, 61, 62]. In order to demonstrate the non-genomic effect of vitamin D, many studies have been conducted on intestinal calcium absorption. Rapid vesicular calcium absorption (also called transcaltachia) has been shown in the chick intestinal tract [63]. Further experimental studies have shown that intestinal calcium transport cannot be blocked by the administration of actinomycin D (which inhibits the genomic effect) [64], whereas calcium absorption can be blocked by inhibition of voltage-gated L-type calcium channel proteins [65] or by protein kinase C [66].
Representation of the signal transduction pathways where Vitamin D has its non-genomic effect (2). After vitamin D binds to the membrane receptor, GDP in the G protein α-subunit turns into GTP and activation occurs. The α-subunit of the G protein is separated from other subunits and binds to phospholipase C (PLC). The PLC is then activated to convert phosphoinositol bisphosphate (PIP2) to inositol triphosphate (IP3) and diacylglycerol (DAG). Calcium release from the endoplasmic reticulum via the IP3 receptor (IP3R); DAG activates PKC. PKC, on the other hand, provides calcium entry into the cell via the L-type calcium channel in the membrane.
Apart from the intestinal system, it has been suggested that the non-genomic effect also occurs in chondrocytes in the growth plate and keratinocytes in the skin [67, 68]. Vitamin D is believed to exert its non-genomic effects through VDR analog and MARRS (also known as ERp57/GRp58/ERp60) receptors located on the cell membrane [69, 70]. These membrane receptors are located within the caveolar lipid layer [71]. In addition, research findings indicate that VDR is also necessary for the expression of membrane receptors that involve in the emergence of non-genomic effect [1, 2]. In studies evaluating the effects of vitamin D analogs (6-s-cis or 6-s-trans conformations), the 6-s-cis form can activate intestinal rapid calcium entry even though the VDR affinity is very low, whereas the 6-s-trans form has been shown to be ineffective in calcium metabolism [67].
One of the most important functions of vitamin D is to increase calcium absorption from the intestines. Calcium absorption from the intestinal tract occurs trans-cellular and para-cellular processes mediated through genomic and non-genomic effects. Among these, the trans-cellular pathway largely utilized by the intestinal system, which is regulated by vitamin D [2]. The absorption effect of vitamin D with non-genomic effect of calcium occurs directly on the membrane (transcaltachia). The channel-mediated calcium absorption effect of vitamin D occurs more slowly [2].
Calcium enters the epithelian cell by the effect of an electrical and chemical gradient via calcium channel protein TRPV6 (which has significant sequence homology to TRPV5 in the kidney), the transmembrane protein at the lumenal brush border edge of the intestinal epithelial cell. The expression of TRPV6 is activated by vitamin D [72]. Reduced intestinal calcium transport is observed in TRPV6 null mice [73]. Calcium entering the cell binds to calmodulin (CaM), which is bound with myosin 1A (also known as brush border myosin I). This formed complex allows calcium to be transported across the microvilli. Subsequently, the transport of calcium up to the basolateral membrane occurs inside the vesicle via calbindin-D9k (CaBP). The affinity of calcium for calbindinin is greater than for calmodulin, and better facilitates calcium transport inside the cell [74]. The calcium reaching the basolateral membrane is pumped out of the cell to systemic circulation via the Ca-ATPase (PMCA1b) pump located on the membrane [1, 2]. In addition, although it is less important, NCX (sodium/calcium exchanger), located in the basolateral region, also plays a role in excretion of calcium [2, 75]. Vitamin D shows its increasing effect on intestinal calcium absorption by inducing expression of TRPV6, CaBP and PMCAb and increasing the binding affinity of CaM to myosin 1A [1, 2].
Intestinal calcium absorption, serum calcium level and bone mineral content in Kalbindin D9k null mice (regardless of dietary calcium level) have been shown to be similar to normal mice [76]. Intestinal calcium absorption was found to be normal in calbindin D9k and TRPV6 null mice when a diet containing the daily requirement for calcium was given [77]. These findings indicate there is a mechanism other than the genomic effect through which vitamin D exerts its action (a non-genomic effect) in calcium absorption in the intestines when the amount of calcium in the diet is sufficient.
While trans-cellular calcium absorption is effective in compensating for a low-calcium diet, para-cellular calcium transport becomes important with the increase in calcium content in the diet [1]. Paracellular transport occurs through the extracellular space between the layer of the epithelial cells in the intestine. Although it was previously thought that vitamin D does not affect para-cellular calcium absorption, studies conducted in recent years indicate otherwise, with vitamin D still affecting calcium absorption by increasing levels of various transmembrane and adhesion proteins that control the extracellular space between cells [78, 79]. However, it is not clear at what stage of the paracellular pathway these proteins are involved.
Phosphate, another important molecule for bone mineralization, is actively absorbed mostly in the jejunum, with absorption influenced by vitamin D [2]. This absorption is provided by sodium-phosphate co-transporter IIb (NaPi IIb). In experimental studies, it has been shown that phosphate absorption is blocked when cycloheximide, which inhibits protein synthesis, is given [80]. This situation supports that phosphate absorption occurs by genomic effect. Vitamin D increases NaPi-IIb expression and thus phosphate absorption [2].
Most of the calcium that reaches the kidney tubules is absorbed from the proximal and distal tubules and approximately 1–2% of it is excreted through urine. Approximately 65% of calcium absorption in the kidney is passively absorbed para-cellularly from the proximal tubules with the sodium gradient and independent of vitamin D direct action [1]. The rest of the calcium is absorbed from the ascending limb of the loop of Henle (20%), the distal tubules (15–20%), and the collecting ducts (5%) [81]. Vitamin D plays an important role in calcium absorption in the distal tubules and provides active calcium absorption via the trans-cellular pathway with the help of an electrochemical gradient [1]. Calcium is taken into the cell by TRPV5 channel on the surface of the tubular cell and is transported inside the cell by calbindin-D9k and D28k. Transported to the basolateral part of the cell, calcium is released into the systemic circulation by NCX1 (sodium/calcium exchanger) and PMCA1b. This mechanism is similar to that in the intestinal tract. Vitamin D increases the expression of TRPV5, calbindin, NCX and PMCA1b.
Phosphate is reabsorbed by sodium-dependent phosphate carrier proteins (NaPi-IIa and NaPi-IIc) in proximal tubular cells under vitamin D control. In addition, for phosphate reabsorption, a Na/K-ATPase channel located in the basolateral membrane is also needed [1, 2]. The impact of vitamin D on transport channels is not clearly known. While PTH increases the lysosomal degradation of phosphate transport channels, FGF23 causes a decrease in the expression of these channels [1, 2, 82].
Calcium, phosphorus and vitamin D are important molecules for bone metabolism and health. Calcium is one of the most abundant minerals in the body and is obtained entirely from dietary sources. In addition to its various biological effects in the body, it is also essential for bone metabolism [83]. More than 99% of the total body calcium is found in the bone tissue as a calcium-phosphate mineral complex, while the remaining <1% is distributed between the intracellular and extracellular compartments [83]. While 40% of calcium outside bone tissue is bound to protein, 9% forms ionic complexes, and the remaining 51% is found as free ions [84, 85]. Ionized calcium balances the calcium pool in the intracellular-extracellular area and plays an important role in bone metabolism. This balance is provided by the cooperation of various hormones (PTH, vitamin D) and the organs they affect (kidney, bone and intestinal system) [83, 84, 85]. Where there is vitamin D deficiency (nutritional or genetic) or VDR-inactivating mutations, serum levels of calcium and phosphate, which play an important role in bone development and growth, are reduced and thus rickets/osteomalacia emerge. Rickets is a disease characterized by excessive osteoid tissue accumulation and defective mineralization of the epiphyseal plate, which occurs as a result of insufficient mineralization in the epiphyseal plates of growing bones [1, 2]. Osteomalacia is a disease characterized by a deterioration in the mineralization of the newly formed osteoid and a decrease in bone turnover.
There is a continuous remodeling cycle consisting bone tissue resorption and mineralization. When calcium, phosphorus, and vitamin D are sufficient, this cycle continues in a balanced manner. In the case of negative calcium balance caused by insufficient calcium intake with diet or increased renal calcium loss, vitamin D increases bone resorption in osteoblasts through VDR signaling, resulting in calcium passage from bone to blood, which leads to impaired bone mineralization. Vitamin D increases the expression of RANKL (receptor activator of NF-κB ligand), which is an osteoclastogenic factor from osteoblasts [86, 89]. RANKL stimulates osteoclastogenesis and increases osteoclast formation by binding to its related receptor, RANK [87]. In conclusion, in the case of negative calcium balance, vitamin D tries to keep the serum calcium level in a certain balance by increasing resorption and decreasing mineralization [1].
In the case of a positive calcium balance, the osteoblastogenic activity of vitamin D is prominent. In this situation where anti-resorbtive effect is in the predominant, bone mineral density increases. The occurrence of this effect has been associated with a decrease in the RANKL/OPG (osteoproteogerin) ratio and an increase in LRP-5 (LDL receptor related protein 5) expression [1]. LRP-5 is controlled by the VDR and is a necessary co-receptor for the anabolic effect of osteoblasts [88]. In addition, vitamin D plays a role in the proliferation of chondrocytes in the growth plate through genomic action.
Pro-vitamin-D3, pre-vitamin D3 and then vitamin D3 (cholecalciferol) conversion in the skin is under the control of UV radiation. Serum vitamin D concentration reaches its highest level 24–48 hours after exposure to UV radiation and then shows a gradual decrease. The half-life of serum vitamin D is 36–72 hours. Vitamin D, which is a fat-soluble vitamin, is stored in adipose tissue for later use. The ability of vitamin D to be stored in adipose tissue extends its total half-life in the body up to approximately 2 months.
There is little information on how this enzyme is regulated because of the few studies performed. What is known is that serum vitamin D level is inversely related to the rate of 25-hydroxylation in the liver, and the synthesis of 25OHD3 from vitamin D (cholecalciferol) is regulated by the 25-hydroxylase enzyme
Serum active vitamin D levels in healthy adults vary within extremely narrow ranges, so that even in cases of vitamin D intoxication, serum levels may remain normal. 1-alpha hydroxylation activity in the kidney is controlled by PTH, calcium and phosphorus. Hypocalcemia, increased PTH, and hypophosphatemia will stimulate increases in active vitamin D production through renal 1-alpha hydroxylase enzyme activation, while hypercalcemia, FGF-23 secreted from osteoblasts, and active vitamin D itself have an inhibitory effect on active vitamin D synthesis through the renal 1-alpha hydroxylase enzyme. Active vitamin D increases FGF23 synthesis from osteoblasts. FGF23 suppresses the 1-alpha hydroxylase enzyme and increases the activity of 24 hydroxylase enzymes. In addition, hypercalcemia suppressing PTH and hyperphosphatemia by increasing FGF23 levels results in 1-alpha hydroxylase enzyme activity inhbition [1, 2, 3]. It is also suggested that calcium and phosphate have a direct regulatory effect on 1-alpha hydroxylase enzyme [89].
Calcitonin is known to reduce serum calcium levels through osteoclast inhibition. In addition, this hormone has been shown to increase the expression of CYP27B1, the gene encoding the 1-alpha hydroxylase enzyme, in normocalcemic pregnant women due to the increase in calcium need. In this way, active vitamin D synthesis and consequently intestinal calcium absorption is increased [1, 90]. Apart from calcitonin, it has been suggested that prolactin also increases CYP27B1 expression, especially during lactation, and thus contributes to the increased calcium demand of the body [1, 91].
CYP3A4 enzyme in the liver and intestinal system has also been shown to be effective in the inactivation of 25OHD3 and reduction of active vitamin D [92]. Long-term use of drugs such as phenytoin, rifampicin, and carbamazepine may lead to up-regulation of the CYP3A4 enzyme and thus to a decrease in serum 25OHD3 and active vitamin D levels.
When serum calcium, phosphate and PTH levels are within normal levels, 25OHD3 and 1–25 (OH) 2 D3 are metabolized into biologically inactive forms by activation of 24-alpha hydroxylase enzyme in the kidneys (24–25 dihydroxy vitamin D3 and 1,24, 25 trihydroxy vitamin D3). This enzyme preferably binds to 1–25 (OH) 2 D3, thus limiting the effect of active vitamin D in tissues through inactivation [2]. The low level of 24-hydroxylase enzyme activity leads to high levels of 1–25 (OH) 2D3 and thus hypercalcemia. In addition, it has been suggested that a decrease in this enzyme activity may lead to impairment in intra-membranous bone mineralization [1, 2]. On the other hand, when 1–25 (OH) 2 D3 synthesis decreases, 1-alpha hydroxylase enzyme activity increases and 24-hydroxylase enzyme activity decreases. It is also known that FGF23 increases the activity of 24 hydroxylase enzymes [1, 2].
Numerous studies have shown active vitamin D synthesis by 1-alpha hydroxylase enzyme is not only a renal feature [2, 93]. The gene encoding the 1-alpha hydroxylase enzyme and the vitamin D receptor gene can be expressed in many cells or tissues such as skin, placenta, prostate, parathyroid, bone tissue, colon, lung, breast tissue, monocytes and macrophages, as well as renal cells. It has been reported that active vitamin D synthesized in the aforementioned tissues functions mostly as an intracrine or paracrine factor in the tissues where they are located, and does not contribute to the active vitamin D levels in the circulation, except for some special cases [1, 2]. Since PTH and FGF-23 receptors are not found in these tissues, they are not directly involved in controlling active vitamin D synthesis. However, it is propable that PTH increases the effect of vitamin D through posttranscriptional modification [31]. Unlike in other tissues, in activated macrophages, there is also no negative feedback of active vitamin D on 1-alpha hydroxylase enzyme [91]. Moreover, although the 24-hydroxylase enzyme is expressed in these cells, its function is not fully understood. Cytokines such as IL-1, TNF-α, IFN-γ induce the synthesis of active vitamin D in keratinocytes. Unlike macrophages, keratinocytes have a fully functional 24-hydroxylase enzyme activity and is induced by active vitamin D. In this way, active vitamin D limits its own synthesis in the epidermis through alternative catabolism [1, 2, 93].
Measurement of serum levels of vitamin D, which plays an important role in calcium and phosphorus metabolism and bone mineralization, is routinely performed worldwide. For this, it is preferred to measure the 25OHD level, which has a longer half-life (24–36 hours), can be taken exogenously, and can be synthesized endogenously. The half-life of the 1–25 (OH) 2D3 form is short (4–6 hours), and its serum levels are 1000 times lower than 25OHD. For these reasons, the active form is not preferred for routine measurement. In this section, the measurement methods of 25OHD vitamin are discussed.
To date, many methods have been developed for measuring serum vitamin D levels. These methods are basically divided into two groups. One methodology is the use of competitive binding and immunoassays: radioimmunoassay (RIA), enzyme immunoassay (EIA/ELISA), chemiluminescent immunoassay (CLIA), electrochemiluminescence assay (ECLIA), and competitive protein binding assay. The other methodology involves chemical methods. Chemical methods are based on the non-immunological direct detection methods typically after preparative chromatographic separation. Chemical methods include high performance liquid chromatography (HPLC) and LC/MS (liquid chromatography-mass spectrometer).
The first method used in the measurement of vitamin D is the competitive binding method in which VDBP binds. This method was first reported in 1971 and identifies 25OHD2 and 25OHD3 forms equally [94]. Limitations of this method include the incubation period of 10 days and its inability to separate some polar vitamin D metabolites [24,25(OH)2D, 25,26 (OH)2D ve 25,26 (OH)2D-26,23--lactone] [94]. In the late 1970s, the HPLC method was developed that can exclude the effect of polar vitamin D metabolites causing interference to the chromatographic method [95]. The advantages of this method, which uses a UV absorption technique, include the absence of lipid and polar vitamin D metabolite interference, the ability to measure 25OHD2 and 25OHD3 separated at high resolution, and a high specificity and reliability. Its disadvantages include the use of excess sample amounts, equipment cost, a need for preparative chromatography, and interference by other UV-absorbing compounds, and that the method is somewhat complex and not easily practical. It would not be considered a routine diagnostic test, as it is used in only about 2% of laboratories in the world) [94, 95]. With the later development of the RIA method, the value of quantifying vitamin levels improved. The advantages of this method type are that sample amount can be small and not pre-analytical preparative purification process is required. The assay is economical and easily applicable, and results reliable. As to the disadvantages, chemical and radioactive (with the RIA) waste are issues, and there is cross-reactivity with polar vitamin D metabolites as in the earlier competitive binding type assays. The RIA also is 100% specific for 25OHD3 and 75% specific for 25OHD2, so the final calculation requires an adjustment [94, 96]. Nonetheless automated immunoassay methods are widely used in our country and all over the world (approximately 76% of laboratories in the world) [97]. Requiring less sample volume, not requiring sample preparation, easy equipment supply, easy application, fast results, no cross-reactivity with C3-epimer forms, and low user error are among the reasons why this method is used more widely in the world [97, 98]. Despite its widespread use, this method has some significant disadvantages. In this method, 25OHD2 and 25OHD3 cannot be distinguished and both are measured as total of 25OHD. This may lead to misinterpretation in countries that use ergocalciferol in treatment (eg America) [97]. In addition, automated immunoassay results can be affected by pregnancy, whether sampled from intensive care patients, the presence of chronic disease and liver diseases, all of which affect the amount of VDBP synthesized from the liver [99, 100]. In addition, it has been reported that there is a high probability of interferences involving automated immunoassay measurement methods [97, 101].
Due to the low reliability of immunoassay measurements, this method has begun to be replaced by LC–MS/MS, which is considered to be the “gold standard” method. This method is used in approximately 18% of laboratories around the world, and it is estimated that its prevalence will increase due to its more accurate and precise results [97]. This method provides distinguishing quantitative measurements of both 25OHD2 and 25OHD3 forms in both serum and plasma [102]. Hence, 25OHD2 can be easily monitored in countries where ergocalciferol is widely used. In addition, with this method, C-3 epimer forms of vitamin D, which are present in high levels in serum in the first year, can be separated from other forms, and these metabolites are prevented from causing vitamin D measurement interference [97, 102].
In recent years, instead of measuring the level of vitamin D bound to VDBP, there is a strong belief in the need to measure free vitamin D levels as that is the form that accounts for the principal bioactivity. Routine methods measure the level of 25OHD vitamin bound to VDBP and provide information about the total body pool. In parallel with this, if the total body pool is sufficient, free vitamin D level is estimated to be sufficient. However, the situation is somewhat complex in obese patients, where a negative correlation between the amount of adipose tissue and serum vitamin D levels has been reported. In these cases, it has been reported that serum 25OHD level is lower than those with normal body weight, since large adipose tissue creates a larger pool for vitamin D sequestration [101, 102, 103, 104, 105]. In other words, serum 25OHD level in obese patients may not provide information about the body pool of vitamin D. It is thought that it would be more valuable to measure vitamin D levels that are not bound to binding protein in these cases. However, there is a serious standardization problem in the measurement of free 25OHD [103]. Also, Bikle et al. [106] proposed a method by which free 25OHD vitamin can be calculated. However, studies have shown that the results obtained with this method are not reliable [107]. Finally, direct measurement or indirect calculations of free forms of vitamin D are not yet suitable for routine use.
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Ciurean, Dagmar Schröter and Thomas Glade",authors:[{id:"163703",title:"Prof.",name:"Thomas",middleName:null,surname:"Glade",slug:"thomas-glade",fullName:"Thomas Glade"},{id:"164141",title:"Ph.D. Student",name:"Roxana",middleName:"Liliana",surname:"Ciurean",slug:"roxana-ciurean",fullName:"Roxana Ciurean"},{id:"164142",title:"Dr.",name:"Dagmar",middleName:null,surname:"Schroeter",slug:"dagmar-schroeter",fullName:"Dagmar Schroeter"}]},{id:"58010",doi:"10.5772/intechopen.72304",title:"Fourth Industrial Revolution: Current Practices, Challenges, and Opportunities",slug:"fourth-industrial-revolution-current-practices-challenges-and-opportunities",totalDownloads:6436,totalCrossrefCites:43,totalDimensionsCites:68,abstract:"The globalization and the competitiveness are forcing companies to rethink and to innovate their production processes following the so-called Industry 4.0 paradigm. It represents the integration of tools already used in the past (big data, cloud, robot, 3D printing, simulation, etc.) that are now connected into a global network by transmitting digital data. The implementation of this new paradigm represents a huge change for companies, which are faced with big investments. In order to benefit from the opportunities offered by the smart revolution, companies must have the prerequisites needed to withstand changes generated by “smart” system. In addition, new workers who face the world of work 4.0 must have new skills in automation, digitization, and information technology, without forgetting soft skills. This chapter aims to present the main good practices, challenges, and opportunities related to Industry 4.0 paradigm.",book:{id:"6291",slug:"digital-transformation-in-smart-manufacturing",title:"Digital Transformation in Smart Manufacturing",fullTitle:"Digital Transformation in Smart Manufacturing"},signatures:"Antonella Petrillo, Fabio De Felice, Raffaele Cioffi and Federico\nZomparelli",authors:[{id:"161682",title:"Prof.",name:"Fabio",middleName:null,surname:"De Felice",slug:"fabio-de-felice",fullName:"Fabio De Felice"},{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo"},{id:"205141",title:"Dr.",name:"Federico",middleName:null,surname:"Zomparelli",slug:"federico-zomparelli",fullName:"Federico Zomparelli"},{id:"208748",title:"Dr.",name:"Raffaele",middleName:null,surname:"Cioffi",slug:"raffaele-cioffi",fullName:"Raffaele Cioffi"}]},{id:"35715",doi:"10.5772/38693",title:"The Role and Importance of Cultural Tourism in Modern Tourism Industry",slug:"the-role-and-importance-of-cultural-tourism-in-modern-tourism-industry",totalDownloads:41082,totalCrossrefCites:30,totalDimensionsCites:61,abstract:null,book:{id:"2298",slug:"strategies-for-tourism-industry-micro-and-macro-perspectives",title:"Strategies for Tourism Industry",fullTitle:"Strategies for Tourism Industry - Micro and Macro Perspectives"},signatures:"Janos Csapo",authors:[{id:"118766",title:"Dr.",name:"János",middleName:null,surname:"Csapó",slug:"janos-csapo",fullName:"János Csapó"}]},{id:"38973",doi:"10.5772/51460",title:"Risk Management in Construction Projects",slug:"risk-management-in-construction-projects",totalDownloads:102555,totalCrossrefCites:36,totalDimensionsCites:59,abstract:null,book:{id:"2175",slug:"risk-management-current-issues-and-challenges",title:"Risk Management",fullTitle:"Risk Management - Current Issues and Challenges"},signatures:"Nerija Banaitiene and Audrius Banaitis",authors:[{id:"139414",title:"Dr.",name:"Nerija",middleName:null,surname:"Banaitiene",slug:"nerija-banaitiene",fullName:"Nerija Banaitiene"},{id:"149658",title:"Dr.",name:"Audrius",middleName:null,surname:"Banaitis",slug:"audrius-banaitis",fullName:"Audrius Banaitis"}]},{id:"40977",doi:"10.5772/53885",title:"The Emergence of Scientific Reasoning",slug:"the-emergence-of-scientific-reasoning",totalDownloads:4546,totalCrossrefCites:8,totalDimensionsCites:59,abstract:null,book:{id:"654",slug:"current-topics-in-children-s-learning-and-cognition",title:"Current Topics in Children's Learning and Cognition",fullTitle:"Current Topics in Children's Learning and Cognition"},signatures:"Bradley J. Morris, Steve Croker, Amy M. Masnick and Corinne Zimmerman",authors:[{id:"154336",title:"Prof.",name:"Bradley",middleName:null,surname:"Morris",slug:"bradley-morris",fullName:"Bradley Morris"},{id:"154337",title:"Prof.",name:"Steve",middleName:null,surname:"Croker",slug:"steve-croker",fullName:"Steve Croker"},{id:"154338",title:"Prof.",name:"Amy",middleName:null,surname:"Masnick",slug:"amy-masnick",fullName:"Amy Masnick"},{id:"154339",title:"Prof.",name:"Corinne",middleName:null,surname:"Zimmerman",slug:"corinne-zimmerman",fullName:"Corinne Zimmerman"}]}],mostDownloadedChaptersLast30Days:[{id:"58890",title:"Philosophy and Paradigm of Scientific Research",slug:"philosophy-and-paradigm-of-scientific-research",totalDownloads:14074,totalCrossrefCites:9,totalDimensionsCites:17,abstract:"Before carrying out the empirical analysis of the role of management culture in corporate social responsibility, identification of the philosophical approach and the paradigm on which the research carried out is based is necessary. Therefore, this chapter deals with the philosophical systems and paradigms of scientific research, the epistemology, evaluating understanding and application of various theories and practices used in the scientific research. The key components of the scientific research paradigm are highlighted. Theories on the basis of which this research was focused on identification of the level of development of the management culture in order to implement corporate social responsibility are identified, and the stages of its implementation are described.",book:{id:"5791",slug:"management-culture-and-corporate-social-responsibility",title:"Management Culture and Corporate Social Responsibility",fullTitle:"Management Culture and Corporate Social Responsibility"},signatures:"Pranas Žukauskas, Jolita Vveinhardt and Regina Andriukaitienė",authors:[{id:"179629",title:"Prof.",name:"Jolita",middleName:null,surname:"Vveinhardt",slug:"jolita-vveinhardt",fullName:"Jolita Vveinhardt"}]},{id:"74550",title:"School Conflicts: Causes and Management Strategies in Classroom Relationships",slug:"school-conflicts-causes-and-management-strategies-in-classroom-relationships",totalDownloads:2328,totalCrossrefCites:1,totalDimensionsCites:10,abstract:"Conflicts cannot cease to exist, as they are intrinsic to human beings, forming an integral part of their moral and emotional growth. Likewise, they exist in all schools. The school is inserted in a space where the conflict manifests itself daily and assumes relevance, being the result of the multiple interpersonal relationships that occur in the school context. Thus, conflict is part of school life, which implies that teachers must have the skills to manage conflict constructively. Recognizing the diversity of school conflicts, this chapter aimed to present its causes, highlighting the main ones in the classroom, in the teacher-student relationship. It is important to conflict face and resolve it with skills to manage it properly and constructively, establishing cooperative relationships, and producing integrative solutions. Harmony and appreciation should coexist in a classroom environment and conflict should not interfere, negatively, in the teaching and learning process. This bibliography review underscore the need for during the teachers’ initial training the conflict management skills development.",book:{id:"7827",slug:"interpersonal-relationships",title:"Interpersonal Relationships",fullTitle:"Interpersonal Relationships"},signatures:"Sabina Valente, Abílio Afonso Lourenço and Zsolt Németh",authors:[{id:"324514",title:"Ph.D.",name:"Sabina",middleName:"N.",surname:"Valente",slug:"sabina-valente",fullName:"Sabina Valente"},{id:"326375",title:"Prof.",name:"Abílio Afonso",middleName:"Afonso",surname:"Lourenço",slug:"abilio-afonso-lourenco",fullName:"Abílio Afonso Lourenço"},{id:"329177",title:"Dr.",name:"Zsolt",middleName:null,surname:"Németh",slug:"zsolt-nemeth",fullName:"Zsolt Németh"}]},{id:"58969",title:"Corruption, Causes and Consequences",slug:"corruption-causes-and-consequences",totalDownloads:27687,totalCrossrefCites:13,totalDimensionsCites:15,abstract:"Corruption is a constant in the society and occurs in all civilizations; however, it has only been in the past 20 years that this phenomenon has begun being seriously explored. It has many different shapes as well as many various effects, both on the economy and the society at large. Among the most common causes of corruption are the political and economic environment, professional ethics and morality and, of course, habits, customs, tradition and demography. Its effects on the economy (and also on the wider society) are well researched, yet still not completely. Corruption thus inhibits economic growth and affects business operations, employment and investments. It also reduces tax revenue and the effectiveness of various financial assistance programs. The wider society is influenced by a high degree of corruption in terms of lowering of trust in the law and the rule of law, education and consequently the quality of life (access to infrastructure, health care). There also does not exist an unambiguous answer as to how to deal with corruption. Something that works in one country or in one region will not necessarily be successful in another. This chapter tries to answer at least a few questions about corruption and the causes for it, its consequences and how to deal with it successfully.",book:{id:"6487",slug:"trade-and-global-market",title:"Trade and Global Market",fullTitle:"Trade and Global Market"},signatures:"Štefan Šumah",authors:[{id:"228073",title:"Mr.",name:"Stefan",middleName:null,surname:"Sumah",slug:"stefan-sumah",fullName:"Stefan Sumah"}]},{id:"55499",title:"Human Resources Management in Nonprofit Organizations: A Case Study of Istanbul Foundation for Culture and Arts",slug:"human-resources-management-in-nonprofit-organizations-a-case-study-of-istanbul-foundation-for-cultur",totalDownloads:2399,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The aim of this study is to investigate the efficiency and importance of human resources management in nonprofit organizations. The understanding was included to the literature as personnel management at the beginning of the twentieth century and it turned into an approach as human resources management in the 1980s. It could be observed that many organizations, which deem the human as the most critical stakeholder, adopt a traditional way of personnel management in operating human resources. The employees play a key role in the success of an organization. For this reason, subjects such as recruitment, training, development, career management, performance appraisal, occupational health, and safety are the fundamental functions of human resources management. The study examines to what extent these roles are evaluated through a case study. The subject matter of the study is the most powerful culture and art foundation in Turkey. Compared to many other nonprofit organizations, the foundation actively performs a variety of services within a year worldwide. The fact that the total number of employees might rise up to 800, including the field personnel, indicates the need of a good functioning human resources management. The human resources practices of the foundation are examined and evaluated within that scope.",book:{id:"5826",slug:"issues-of-human-resource-management",title:"Issues of Human Resource Management",fullTitle:"Issues of Human Resource Management"},signatures:"Beste Gökçe Parsehyan",authors:[{id:"189113",title:"Dr.",name:"Beste",middleName:null,surname:"Gokce Parsehyan",slug:"beste-gokce-parsehyan",fullName:"Beste Gokce Parsehyan"}]},{id:"59152",title:"Marketing Strategies for the Social Good",slug:"marketing-strategies-for-the-social-good",totalDownloads:1669,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Social network sites (SNS) have proven to be a good environment to promote and sell goods and services, but marketing is more than creating commercial strategies. Social marketing strategies can also be used to promote behavioral change and help individuals transform their lives, achieve well-being, and adopt prosocial behaviors. In this chapter, we seek to analyze with a netnographic study, how SNS are being employed by nonprofits and nongovernment organizations (NGOs) to enable citizens and consumers to participate in different programs and activities that promote social transformation and well-being. A particular interest is to identify how organizations are using behavioral economic tactics to nudge individuals and motivate them to engage in prosocial actions. By providing an understanding on how SNS can provide an adequate environment for the design of social marketing strategies, we believe our work has practical implications both for academicians and marketers who want to contribute in the transformation of consumer behavior and the achievement of well-being and social change.",book:{id:"6583",slug:"marketing",title:"Marketing",fullTitle:"Marketing"},signatures:"Alicia De La Pena",authors:[{id:"196878",title:"Dr.",name:"Alicia",middleName:null,surname:"De La Pena",slug:"alicia-de-la-pena",fullName:"Alicia De La Pena"}]}],onlineFirstChaptersFilter:{topicId:"4",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"83027",title:"Coping Strategies and Meta-Worry in Adolescents’ Adjustment during COVID-19 Pandemic",slug:"coping-strategies-and-meta-worry-in-adolescents-adjustment-during-covid-19-pandemic",totalDownloads:0,totalDimensionsCites:0,doi:"10.5772/intechopen.106258",abstract:"With the beginning of the COVID-19 pandemic, several limitations and stressful changes have been introduced in adolescent’s daily life. Particularly, Italian teenagers were the first among western populations to experience fears of infection, home confinement, and social restrictions due to a long lockdown period (10 weeks). This study explores the role of coping strategies (task-oriented, emotion-oriented, and avoidance coping) and meta-beliefs about worry as vulnerability factors associated with adolescents’ anxiety. A community sample of adolescents (N = 284, aged 16–18 y.o.) answered questionnaires assessing anxiety symptoms (RCMAS-2), meta-cognitive beliefs and processes about worry (MCQ-C), and coping strategies (CISS). Results show that 37% of participants report clinically elevated anxiety. Emotion-centered coping predicted higher anxiety, whereas task-centered coping resulted associated with decreased anxiety. Cognitive monitoring about their own worry contributes, but to a lesser extent, to higher levels of anxiety. The implications for the intervention are discussed, especially the need to enhance the coping skills of adolescents and mitigate the stress of the COVID-19 pandemic, which could last for a long time.",book:{id:"10671",title:"Adolescences",coverURL:"https://cdn.intechopen.com/books/images_new/10671.jpg"},signatures:"Loredana Benedetto, Ilenia Schipilliti and Massimo Ingrassia"},{id:"83023",title:"Gestational Tryptophan Fluctuation Underlying Ontogenetic Origin of Neuropsychiatric Disorders",slug:"gestational-tryptophan-fluctuation-underlying-ontogenetic-origin-of-neuropsychiatric-disorders",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.106421",abstract:"Neuropsychiatry underlies personality development and social functioning. Borderline personality disorder exhibits high trait aggression and is associated with tryptophan hydroxylase polymorphisms. The acute tryptophan depletion reduces plasma and cerebrospinal fluid tryptophan availability and brain serotonin concentrations, leading to alterations in personality and trait-related behaviors. Tryptophan is essential for fatal neurodevelopment and immunomodulation in pregnancy. Gestational tryptophan fluctuation induced by maternal metabolic disorders or drug administrations may account for the maternal-fetal transmission determining neurogenesis and microbial development, consequentially shaping the long-standing patterns of thinking and behavior. However, it is not possible to assess the gestational tryptophan exposure effects on fetal brain and gastrointestinal system in humans for ethical reasons. The maternal–fetal microbe transmission in rodents during gestation, vaginal delivery, and breastfeeding is inevitable. Chicken embryo may be an alternative and evidence from the chicken embryo model reveals that gestational tryptophan fluctuation, i.e., exposed to excessive tryptophan or its metabolite, serotonin, attenuates aggressiveness and affects peer sociometric status. This chapter discusses the gestational tryptophan fluctuation as a risk factor of personality disorders in offspring and the prevention of personality disorders by dietary tryptophan control and medication therapy management during pregnancy.",book:{id:"11782",title:"Personality Traits - The Role in Psychopathology",coverURL:"https://cdn.intechopen.com/books/images_new/11782.jpg"},signatures:"Xiaohong Huang, Xiaohua Li and Heng-Wei Cheng"},{id:"83014",title:"Culture: A Pillar of Organizational Sustainability",slug:"culture-a-pillar-of-organizational-sustainability",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.106523",abstract:"Sustainability is a concern that permeates all levels of society and is premised on meeting the needs of the present without compromising the ability of future generations to meet theirs. More recently, policies and research have emerged that guide organizations to align their activities with the broader sustainable development agendas, including cultural issues, not just economic, social, and environmental ones. Culture is the material and immaterial attribute of society. It incorporates social organizations, literature, religion, myths, beliefs, behaviors and entrepreneurial practices of the productive segment, use of technology, and expressive art forms on which future generations depend. Thus, cultural sustainability is a fundamental issue and is configured as the fourth pillar of sustainability, equal to social, economic, and environmental issues, which has to do with the ability to sustain or continue with cultural beliefs and practices, preserve cultural heritage as its entity, and try to answer whether any culture will exist in the future. The importance of cultural sustainability lies in its power to influence people. Their beliefs are in the decisions made by society. Thus, there can be no sustainable development without including culture.",book:{id:"11429",title:"Sustainability, Ecology, and Religions of the World",coverURL:"https://cdn.intechopen.com/books/images_new/11429.jpg"},signatures:"Clea Beatriz Macagnan and Rosane Maria Seibert"},{id:"82982",title:"The Well-Being in the Children and Adolescents with ADHD: Possible Influencing Factors and How to Improve It",slug:"the-well-being-in-the-children-and-adolescents-with-adhd-possible-influencing-factors-and-how-to-imp",totalDownloads:0,totalDimensionsCites:0,doi:"10.5772/intechopen.106596",abstract:"In recent years, academics have increasingly emphasized the importance of research into the well-being of children and adolescents. This is because well-being plays an important role in the development of children and adolescents. The literature reports that high levels of well-being facilitate positive functioning in children and adolescents. They contribute to the overall development of the individual and are a key factor in helping children and adolescents to integrate into society. ADHD, the most prevalent neurodevelopmental disorder, affects more than 5% of children and adolescents, and the distress caused by its symptom can seriously undermine the well-being of children and adolescents. Therefore, this chapter discusses this noticeable issue focusing on the following key parts: An understanding of the well-being in children and adolescents, the factors that affect the well-being of children and adolescents with ADHD, and how to improve the well-being of children and adolescents with ADHD.",book:{id:"11444",title:"Happiness - Biopsychosocial and Anthropological Perspectives",coverURL:"https://cdn.intechopen.com/books/images_new/11444.jpg"},signatures:"Jenson Yin and Jie Luo"},{id:"82949",title:"Corruption and Deterioration of Democracy: The Brazilian Lesson",slug:"corruption-and-deterioration-of-democracy-the-brazilian-lesson",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.106194",abstract:"Although it has emerged, nationally and internationally, as one of the largest investigations against political corruption, Operation Car Wash—at its peak of popular prestige—cleared the path for the political rise of Jair Bolsonaro to the Presidency of the Republic of Brazil. And by doing so, to a certain extent, it paved the way for a set of arbitrary practices that today threaten and weaken the main Brazilian democratic institutions. Brazilian democracy today pays a high price for the Judiciary’s lethargic and condescending response to the unorthodox and illegal practices of Federal Judge Sérgio Moro during the golden years of Operation Car Wash (2014–2018). The lesson that the Brazilian episode brings to the international legal community is that the constant disrespect for the rules of due criminal procedure in large cases of corruption erodes the institutional bases that support the proper confrontation of this type of crime. The pertinent fight against corruption in a democracy can only take place in strict obedience to the law.",book:{id:"11772",title:"Corruption - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11772.jpg"},signatures:"Fabio Roberto D’Avila and Theodoro Balducci de Oliveira"},{id:"82867",title:"Indigenous Cultural Expressions and Methodological Frameworks: Some Thoughts",slug:"indigenous-cultural-expressions-and-methodological-frameworks-some-thoughts",totalDownloads:5,totalDimensionsCites:0,doi:"10.5772/intechopen.106236",abstract:"Within the contemporary global world, there appears to be an inevitable lag between the changing factual reality and the concepts and categories scholars use to analyze it, i.e., “indigenous peoples,” “traditional oral expressions,” “ethnicity,” “cultural identity,” and “cultural heritage.” But are these discrepancies insurmountable? This article delves into such mismatches, examining the relentless search for heuristic instruments to deal with the diverse indigenous artistic expressions in their socio-historical and political contexts. It presents some thoughts about the methodological frameworks used to ponder indigenous cultural expressions. The main argument is based on ethnographic research among Zoque and Mayan peoples in the states of Oaxaca and Chiapas in Southern Mexico, while establishing a dialog with ethnographies by other authors on different indigenous regions.",book:{id:"11434",title:"Indigenous Populations - Perspectives From Scholars and Practitioners in Contemporary Times",coverURL:"https://cdn.intechopen.com/books/images_new/11434.jpg"},signatures:"Marina Alonso-Bolaños"}],onlineFirstChaptersTotal:279},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:122,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"243698",title:"Dr.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. 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