Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
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This achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
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We are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
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Thank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
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\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"10356",leadTitle:null,fullTitle:"Natural Medicinal Plants",title:"Natural Medicinal Plants",subtitle:null,reviewType:"peer-reviewed",abstract:"This book, Natural Medicinal Plants is a comprehensive overview of drugs derived from medicinal plants and their use in treating human illnesses such as cancer. Chapters include scientific evidence on flora rich in active ingredients.",isbn:"978-1-83969-276-5",printIsbn:"978-1-83969-275-8",pdfIsbn:"978-1-83969-277-2",doi:"10.5772/intechopen.91542",price:139,priceEur:155,priceUsd:179,slug:"natural-medicinal-plants",numberOfPages:302,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"943e56ccaaf19ff696d25aa638ae37d6",bookSignature:"Hany A. El-Shemy",publishedDate:"May 11th 2022",coverURL:"https://cdn.intechopen.com/books/images_new/10356.jpg",numberOfDownloads:4298,numberOfWosCitations:0,numberOfCrossrefCitations:6,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:13,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:19,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 6th 2020",dateEndSecondStepPublish:"December 4th 2020",dateEndThirdStepPublish:"February 2nd 2021",dateEndFourthStepPublish:"April 23rd 2021",dateEndFifthStepPublish:"June 22nd 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"54719",title:"Prof.",name:"Hany",middleName:null,surname:"El-Shemy",slug:"hany-el-shemy",fullName:"Hany El-Shemy",profilePictureURL:"https://mts.intechopen.com/storage/users/54719/images/system/54719.jpg",biography:"Prof. Hany A. El-Shemy received a Ph.D. in Biochemistry from the University of Cairo, Egypt, and a Ph.D. in Genetic Engineering from the University of Hiroshima, Japan. He holds two patents and has written thirteen international books. He has also published more than 100 SCI journal papers and 55 conference presentations. Dr. El-Shemy was a technique committee member as well as chair of many international conferences. He has also served as editor for journals including PLOS ONE, BMC Genomics, and Current Issues in Molecular Biology. He has received several awards, including state prizes from the Academy of Science, Egypt (2004, 2012, and 2018), the Young Arab Researcher prize from the Shuman Foundation, Jordan (2005), and Cairo University Prizes (2007, 2010, and 2014). He served as an expert for the African Regional Center of Technology, Dakar, Senegal, as well as a visiting professor at Pan African University, African Union. He served as vice president of the Academy of Science and Technology, Egypt, from 2013 to 2014. Since 2014 he has been the dean of the Faculty of Agriculture, Cairo University. In 2018, he was elected a fellow of the African Academy of Science.",institutionString:"Cairo University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"13",institution:{name:"Cairo University",institutionURL:null,country:{name:"Egypt"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"991",title:"Herbalism",slug:"herbalism"}],chapters:[{id:"78514",title:"Natural Products Altering GABAergic Transmission",doi:"10.5772/intechopen.99500",slug:"natural-products-altering-gabaergic-transmission",totalDownloads:156,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Gamma-amino butyric acid (GABA) is a major inhibitory neurotransmitter found in several regions of the brain and known to have various significant physiological roles as a potent bioactive compound. Malfunction of GABAergic neuronal signaling prompts to cause severe psychiatric symptoms in numerous mental disorders. Several drugs are available in clinical practice for neuropsychiatric disorders targeting through GABAergic pathway, with notable adverse effects. Interestingly, in recent years, researchers are focusing on natural compounds altering GABAergic neurotransmission for various psychiatric disorders due to its wide range of therapeutic efficacy and safety. The enormous variety of natural compounds, namely alkaloids, flavonoids, terpenoids, polyacetylenic alcohols, alkanes and fatty acids were reported to alter the GABAergic transmission through its receptors and or by influencing the transmission, synthesis and metabolism of GABA. Natural compounds are able to cross the blood brain barrier and influence the GABA functions in order to treat anxiety, mania, schizophrenia and cognitive disorders. Therefore, this current chapter describes on natural products which have the potential to alter the GABAergic neurotransmission and its therapeutical benefits in treating several neuropsychiatry disorders using various pharmacological methods.",signatures:"Sayani Banerjee, Chennu Manisha, Deepthi Murugan and Antony Justin",downloadPdfUrl:"/chapter/pdf-download/78514",previewPdfUrl:"/chapter/pdf-preview/78514",authors:[{id:"344701",title:"Dr.",name:"Antony",surname:"Justin",slug:"antony-justin",fullName:"Antony Justin"},{id:"427929",title:"Dr.",name:"Sayani",surname:"Banerjee",slug:"sayani-banerjee",fullName:"Sayani Banerjee"},{id:"427930",title:"Dr.",name:"Chennu",surname:"Manisha",slug:"chennu-manisha",fullName:"Chennu Manisha"},{id:"427931",title:"Dr.",name:"Deepthi",surname:"Murugan",slug:"deepthi-murugan",fullName:"Deepthi Murugan"}],corrections:null},{id:"76353",title:"The Ghanaian Flora as a Potential Source of Anthelmintic and Anti-Schistosomal Agents",doi:"10.5772/intechopen.97417",slug:"the-ghanaian-flora-as-a-potential-source-of-anthelmintic-and-anti-schistosomal-agents",totalDownloads:218,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Parasitic infections including schistosomiasis and soil transmitted helminthiasis are the most commonly encountered Neglected Tropical Diseases (NTDs) in the world. These diseases remain a major public health concern affecting millions of people especially those living in poor regions where access to effective conventional health care is a challenge. Interventions to control these infections in endemic areas have not been successful due to the high cost of drugs, limited availability as well as inequity of access to preventive chemotherapies. Another problem is the development resistance to the limited number of recommended medications due to their intensive use in both human and live-stock. There is an increasing awareness of the potential of natural products as chemotherapeutic agents to combat parasitic infections. Natural products may offer an unlimited source of chemically diverse drug molecules which may be safe, efficient, less toxic, less expensive and readily available for use especially in low-income countries. The Ghanaian flora provides such a ready source for new therapeutic interventions for the local population. Several researches have provided evidence of the anti-parasitic activity of Ghanaian medicinal plants. This chapter provides a review with special focus on medicinal plants collected from Ghana with anthelmintic and anti-schistosomal activity. Evidence of pharmacological activities of crude extracts, fractions and bioactive phytoconstituents as well as possible mechanisms of action where investigated are discussed.",signatures:"Evelyn Asante-Kwatia, Abraham Yeboah Mensah, Lord Gyimah and Arnold Donkor Forkuo",downloadPdfUrl:"/chapter/pdf-download/76353",previewPdfUrl:"/chapter/pdf-preview/76353",authors:[{id:"217045",title:"Dr.",name:"Arnold Forkuo",surname:"Donkor",slug:"arnold-forkuo-donkor",fullName:"Arnold Forkuo Donkor"},{id:"303360",title:"Dr.",name:"Evelyn",surname:"Asante-Kwatia",slug:"evelyn-asante-kwatia",fullName:"Evelyn Asante-Kwatia"},{id:"309974",title:"Prof.",name:"Abraham Yeboah",surname:"Mensah",slug:"abraham-yeboah-mensah",fullName:"Abraham Yeboah Mensah"},{id:"347910",title:"Mr.",name:"Lord",surname:"Gyimah",slug:"lord-gyimah",fullName:"Lord Gyimah"}],corrections:[{id:"76505",title:"Corrigendum: The Ghanaian Flora as a Potential Source of Anthelmintic and Anti-Schistosomal Agents",doi:null,slug:"corrigendum-the-ghanaian-flora-as-a-potential-source-of-anthelmintic-and-anti-schistosomal-agents",totalDownloads:null,totalCrossrefCites:null,correctionPdfUrl:null}]},{id:"75561",title:"Traditional African Medicine",doi:"10.5772/intechopen.96576",slug:"traditional-african-medicine",totalDownloads:322,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"African traditional medicine is defined as one of the holistic health care system comprised of three levels of specializations namely divination, spiritualism, and herbalism. The traditional healer provides healing services based on culture, religious background, knowledge, attitudes, and beliefs that are prevalent in his community. Hence the current chapter focuses on the different types of african healing system, traditional healers, traditional practices and modern herbalism and also describes the phytochemical and pharmacological evidences of the traditional african herbs like Acanthus montanus (Acanthaceae), Amaranthus spinosus (Amaranthaceae), Bridelia ferruginea (Euphorbiaceae) etc.",signatures:"Motamarri V.N.L. Chaitanya, Hailemikael Gebremariam Baye, Heyam Saad Ali and Firehiwot Belayneh Usamo",downloadPdfUrl:"/chapter/pdf-download/75561",previewPdfUrl:"/chapter/pdf-preview/75561",authors:[{id:"339686",title:"Dr.",name:"Motamarri V.N.L.",surname:"Chaitanya",slug:"motamarri-v.n.l.-chaitanya",fullName:"Motamarri V.N.L. Chaitanya"},{id:"340066",title:"MSc.",name:"Firehiwot",surname:"Belayneh",slug:"firehiwot-belayneh",fullName:"Firehiwot Belayneh"},{id:"340068",title:"Prof.",name:"Heyam",surname:"Saad Ali",slug:"heyam-saad-ali",fullName:"Heyam Saad Ali"},{id:"348052",title:"BSc.",name:"Hailemikael",surname:"Gebremariam Baye",slug:"hailemikael-gebremariam-baye",fullName:"Hailemikael Gebremariam Baye"}],corrections:null},{id:"76298",title:"Ethnomedicine Study on Medicinal Plants Used by Communities in West Sumatera, Indonesia",doi:"10.5772/intechopen.96810",slug:"ethnomedicine-study-on-medicinal-plants-used-by-communities-in-west-sumatera-indonesia",totalDownloads:143,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Currently, the development of conventional medicine is getting more advanced, it cannot be denied that medicinal plants still occupy their main role as medicine for various human diseases, especially in developing countries. This is rooted in the knowledge of the local community about plants that can be used as medicine for various diseases. Ethnomedicine is a field of study that raises local knowledge of the community to maintain their health. From numerous studies on the field, 33 species of plants have been found which are believed by the natives to West Sumatra as medicine. Ethnomedicinal data were analyzed using Index of Cultural Significance (ICS) value. The results of the analysis showed that the species of plants that is voted most important for the community were soursop (Annona muricata) and red betel (Piper sp.). In general, the part of plant that is most often used as medicine is the leaf, and the way to consume it is by boiling it so that you can get the herbs from the plant extract.",signatures:"Skunda Diliarosta, Monica Prima Sari, Rehani Ramadhani and Annisa Efendi",downloadPdfUrl:"/chapter/pdf-download/76298",previewPdfUrl:"/chapter/pdf-preview/76298",authors:[{id:"342268",title:"Dr.",name:"Skunda",surname:"Diliarosta",slug:"skunda-diliarosta",fullName:"Skunda Diliarosta"},{id:"346504",title:"Ms.",name:"Rehani",surname:"Ramadhani",slug:"rehani-ramadhani",fullName:"Rehani Ramadhani"},{id:"346505",title:"Ms.",name:"Annisa",surname:"Efendi",slug:"annisa-efendi",fullName:"Annisa Efendi"},{id:"346920",title:"Mrs.",name:"Monica",surname:"Prima Sari",slug:"monica-prima-sari",fullName:"Monica Prima Sari"}],corrections:null},{id:"75771",title:"Advanced Pharmacological Uses of Marine Algae as an Anti-Diabetic Therapy",doi:"10.5772/intechopen.96807",slug:"advanced-pharmacological-uses-of-marine-algae-as-an-anti-diabetic-therapy",totalDownloads:231,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Marine seaweeds are a promising source of bioactive secondary metabolites that can be utilized in drug development and nutraceuticals. Diabetes mellitus is a leading non-communicable disease, and it is the third leading cause of death worldwide. Among the types of diabetes, type 2 became the major health problem as it is associated with severe health complications. Since available oral hypoglycemic drugs cause several adverse effects, it is worth searching for a natural cure with fewer or no side effects that may benefit patients with type 2 diabetes. Among the marine seaweeds, brown and red seaweeds are extensively studied for the anti-diabetic activity compared to the green seaweeds. Bioactive compounds present in marine seaweeds possess anti-diabetic potential through diverse mechanisms, mainly by reducing postprandial hyperglycemia and associated complication. Most of the studies emphasized that the marine seaweeds control the hyperglycemic condition by inhibiting carbohydrate hydrolyzing α-amylase,α glucosidase enzymes, and the inhibitory effect of dipeptide peptidase-4 that are involved in the degradation of incretins. Similarly, bioactive compounds in marine seaweeds can reduce diabetes complications by inhibiting angiotensin-converting enzymes, aldose reductase, protein tyrosine phosphatase 1B enzyme. This chapter focuses on the anti-diabetic potential of marine brown, green, and red seaweeds through different mechanisms.",signatures:"Thilina Gunathilaka, Lakshika Rangee Keertihirathna and Dinithi Peiris",downloadPdfUrl:"/chapter/pdf-download/75771",previewPdfUrl:"/chapter/pdf-preview/75771",authors:[{id:"219479",title:"Prof.",name:"Dinithi",surname:"Peiris",slug:"dinithi-peiris",fullName:"Dinithi Peiris"},{id:"343219",title:"Mrs.",name:"Thilina",surname:"Gunathilaka",slug:"thilina-gunathilaka",fullName:"Thilina Gunathilaka"},{id:"356401",title:"Dr.",name:"Lakshika Rangee",surname:"Keerthirathna",slug:"lakshika-rangee-keerthirathna",fullName:"Lakshika Rangee Keerthirathna"}],corrections:null},{id:"75758",title:"Safety Review of Herbs and Supplements in Heart Disease, Diabetes, and COVID-19",doi:"10.5772/intechopen.96811",slug:"safety-review-of-herbs-and-supplements-in-heart-disease-diabetes-and-covid-19",totalDownloads:229,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Usage of supplements has increased dramatically this last decade. From herbs to vitamins and mineral, consumers are interested in improving health, self-treatment and preventing diseases. Often using information from the internet to self-prescribe, many consumers believe that natural products are safe, while many others avoid using these products because of the lack of an approval process by health officials in many countries. Herbs and other supplements including proteins, vitamins and minerals provide significant benefits to health. The lack of guidance from health professionals however can be problematic. When combined with drugs and disease, herbs can interact and cause side effects. Some of the steps to evaluate the safe use of supplements is to know their mechanism of action, clinical effect, and consumers’ medical history. For example, an herb that induces liver enzymes will reduce the effect of a drug that is metabolized by these same enzymes. This can be life threating if the patient depends on this drug for normal function. Based on drug-herb interaction experience and literature review, this book chapter provides insights into safe use of echinacea, licorice, turmeric, and black seed in patients with heart disease, diabetes, and COVID-19.",signatures:"Paula Vieira-Brock",downloadPdfUrl:"/chapter/pdf-download/75758",previewPdfUrl:"/chapter/pdf-preview/75758",authors:[{id:"343363",title:"Ph.D.",name:"Paula",surname:"Vieira-Brock",slug:"paula-vieira-brock",fullName:"Paula Vieira-Brock"}],corrections:null},{id:"76486",title:"Pharmacological Investigation of Genus Pistacia",doi:"10.5772/intechopen.97322",slug:"pharmacological-investigation-of-genus-em-pistacia-em-",totalDownloads:199,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Several plants in the genus Pistacia are used in the treatment of various pathogenic and non-pathogenic disorders. Especially important are the major species belonging to this genus such as Pistacia lentiscus, Pistacia atlantica, Pistacia vera, Pistacia terebinthus, and Pistacia khinjuk, among others; these have been reported for their potential benefits both in medical and commercial purposes. In addition, members of this genus exhibit numerous ethnomedicinal uses, such as analgesic, anti-inflammatory, anticancer, antimicrobial, antihypertension, antihyperlipidemic, antiviral, and antiasthma. In light of these potential uses, the present chapter aimed to collect and summarize the literature about all of this medicinal information. Accordingly, this chapter focuses on the pharmacological uses and benefits of the genus Pistacia, especially those related to health issues.",signatures:"Abdur Rauf, Yahya S. Al-Awthan, Naveed Muhammad, Muhammad Mukarram Shah, Saikat Mitra, Talha Bin Emran, Omar Bahattab and Mohammad S. Mubarak",downloadPdfUrl:"/chapter/pdf-download/76486",previewPdfUrl:"/chapter/pdf-preview/76486",authors:[{id:"192295",title:"Dr.",name:"Abdur",surname:"Rauf",slug:"abdur-rauf",fullName:"Abdur Rauf"},{id:"207131",title:"Prof.",name:"Mohammad S.",surname:"Mubarak",slug:"mohammad-s.-mubarak",fullName:"Mohammad S. Mubarak"},{id:"348414",title:"Dr.",name:"Yahya",surname:"Al-Awthan",slug:"yahya-al-awthan",fullName:"Yahya Al-Awthan"},{id:"348415",title:"Dr.",name:"Naveed",surname:"Muhammad",slug:"naveed-muhammad",fullName:"Naveed Muhammad"},{id:"348417",title:"Prof.",name:"Muhammad",surname:"Mukarram Shah",slug:"muhammad-mukarram-shah",fullName:"Muhammad Mukarram Shah"},{id:"348418",title:"Dr.",name:"Saikat",surname:"Mitra",slug:"saikat-mitra",fullName:"Saikat Mitra"},{id:"348419",title:"Dr.",name:"Talha",surname:"Bin Emran",slug:"talha-bin-emran",fullName:"Talha Bin Emran"},{id:"348420",title:"Dr.",name:"Omar",surname:"Bahattab",slug:"omar-bahattab",fullName:"Omar Bahattab"}],corrections:null},{id:"77125",title:"Medicinal Plants and Traditional Practices of Baiga Tribe in Amarkantak Region of Eastern Madhya Pradesh",doi:"10.5772/intechopen.97697",slug:"medicinal-plants-and-traditional-practices-of-baiga-tribe-in-amarkantak-region-of-eastern-madhya-pra",totalDownloads:221,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The present ethnobotanical study was carried out in Amarkantak region eastern part of Madhya Pradesh during January 2018 to January 2019 to document the medicinal plants used by the Baiga tribes. Traditional medicinal plants used by the Baiga tribes of 37 plant species belonging to 35 genera and 28 families used to menstrual disorder, piles, sore throat, respiratory disorder, haematuria, miscarriage, jaundice, fever, insanity, leucorrhoea, bleeding during pregnancy, spermatorrhea, infertility in women, motiabind, scorpion bite, wounds of animals, stomach disorder, intestinal worms, diabetes, leukoderma, rheumatism, scabies, wart and easy delivery etc. and other various unreported medicinal plants are reported here.",signatures:"Ramesh Kumar Ahirwar",downloadPdfUrl:"/chapter/pdf-download/77125",previewPdfUrl:"/chapter/pdf-preview/77125",authors:[{id:"340104",title:"Dr.",name:"Ramesh",surname:"Kumar Ahirwar",slug:"ramesh-kumar-ahirwar",fullName:"Ramesh Kumar Ahirwar"}],corrections:null},{id:"77433",title:"Extraction of Bioactive Compounds from Medicinal Plants and Herbs",doi:"10.5772/intechopen.98602",slug:"extraction-of-bioactive-compounds-from-medicinal-plants-and-herbs",totalDownloads:1280,totalCrossrefCites:2,totalDimensionsCites:5,hasAltmetrics:1,abstract:"Human beings have relied on herbs and medicinal plants as sources of food and remedy from time immemorial. Bioactive compounds from plants are currently the subject of much research interest, but their extraction as part of phytochemical and/or biological investigations present specific challenges. Herbalists or scientists have developed many protocols of extraction of bioactive ingredients to ensure the effectiveness and the efficacy of crude drugs that were used to get relief from sickness. With the advent of new leads from plants such as morphine, quinine, taxol, artemisinin, and alkaloids from Voacanga species, a lot of attention is paid to the mode of extraction of active phytochemicals to limit the cost linked to the synthesis and isolation. Thus, the extraction of active compounds from plants needs appropriate extraction methods and techniques that provide bioactive ingredients-rich extracts and fractions. The extraction procedures, therefore, play a critical role in the yield, the nature of phytochemical content, etc. This chapter aims to present, describe, and compare extraction procedures of bioactive compounds from herbs and medicinal plants.",signatures:"Fongang Fotsing Yannick Stéphane, Bankeu Kezetas Jean Jules, Gaber El-Saber Batiha, Iftikhar Ali and Lenta Ndjakou Bruno",downloadPdfUrl:"/chapter/pdf-download/77433",previewPdfUrl:"/chapter/pdf-preview/77433",authors:[{id:"224515",title:"Dr.",name:"Fongang Fotsing",surname:"Yannick Stéphane",slug:"fongang-fotsing-yannick-stephane",fullName:"Fongang Fotsing Yannick Stéphane"},{id:"227816",title:"Dr.",name:"Bankeu Kezetas",surname:"Jean Jules",slug:"bankeu-kezetas-jean-jules",fullName:"Bankeu Kezetas Jean Jules"},{id:"227817",title:"Prof.",name:"Lenta Ndjakou",surname:"Bruno",slug:"lenta-ndjakou-bruno",fullName:"Lenta Ndjakou Bruno"},{id:"349790",title:"Prof.",name:"Gaber",surname:"El-Saber Batiha",slug:"gaber-el-saber-batiha",fullName:"Gaber El-Saber Batiha"},{id:"357350",title:"Dr.",name:"Iftikhar",surname:"Ali",slug:"iftikhar-ali",fullName:"Iftikhar Ali"}],corrections:null},{id:"77108",title:"Controversy, Adulteration and Substitution: Burning Problems in Ayurveda Practices",doi:"10.5772/intechopen.98220",slug:"controversy-adulteration-and-substitution-burning-problems-in-ayurveda-practices",totalDownloads:229,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Ayurveda is an Indian traditional system of medicine. In present era, world is looking towards herbal medicine because of acceptability and safety. Medicinal plants constitute an effective source of Ayurvedic and other traditional system of medicines as well as modern medicine. In India, about 80% of the rural population depends on herbal medicines in primary health care level. A large percentage of plants used in herbal industries are subject of controversy. Non-availability of plants, poor understanding and parallel evolved knowledge systems are some of the reasons attributed to it. The existing practices of polynomial nomenclature system of Sanskrit, different perceptions in various communities, vernacular equivalents, all are cumulative factors for controversy, adulteration and substitution. “ Sandigdha Dravaya “ is a term used for that type of medicinal plants which are mentioned in Ayurvedic classics but their exact botanical source is not known. Adulterants and substitutes are the common practices in herbal raw material trade. Adulteration is a debasement of an article. The motives for intentional adulteration are normally commercial that which involves deterioration, admixture, sophistication, inferiority, spoilage and other unknown reasons. Substitution is a replacement of equivalent drugs in place of original drugs. The principles to select substitute drugs are based on similar Rasa, Guna, Virya, Vipaka and mainly the Karma. At present the adulteration and Substitution of the herbal drugs is the burning problem in herbal industry and in Ayurvedic practices. So it is necessary to develop reliable methodologies for correct identification, standardization and quality assurance of Ayurvedic drugs.",signatures:"Puneshwar Keshari",downloadPdfUrl:"/chapter/pdf-download/77108",previewPdfUrl:"/chapter/pdf-preview/77108",authors:[{id:"339545",title:"Dr.",name:"Puneshwar",surname:"Keshari",slug:"puneshwar-keshari",fullName:"Puneshwar Keshari"}],corrections:null},{id:"76024",title:"Phytochemical Profile and Antiobesity Potential of Momordica charantia Linn.",doi:"10.5772/intechopen.96808",slug:"phytochemical-profile-and-antiobesity-potential-of-em-momordica-charantia-em-linn-",totalDownloads:175,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Momordica charantia L. is growing in many tropical and subtropical regions; the fruits of bitter melon are also gradually becoming popular for treating diabetes and associated diseases. Over 248 compounds belonging to the lipids, phenolics and terpenoids class are reported by diverse studies. However, M. charantia L. appears to be an inimitable species that synthesizes a diverse range of natural products in the fruits, leaves, stems and roots. The cucurbitane types of triterpenes exist in the various tissues of the plant in their aglycone as well as glycosylated forms. The bitter melon seems to exert their lipid lowering and antiobesity effects via several mechanisms like PPARs, LXRs, SREBPs, and Sirts mediated fat metabolism in various tissues, prevent adipocyte hypertrophy and visceral fat accumulation. M. charantia L. has been comprehensively studied worldwide for its therapeutic properties to treat a number of diseases like diabetes, dyslipidaemia, obesity, and certain cancers. This chapter apparently displays an encompassing literature review on vast potential of bitter melon as antiobesity agent and assembles data on complex phytochemistry.",signatures:"Pushpa Anantrao Karale, Shashikant Dhawale and Mahesh Karale",downloadPdfUrl:"/chapter/pdf-download/76024",previewPdfUrl:"/chapter/pdf-preview/76024",authors:[{id:"340628",title:"Ph.D. Student",name:"Pushpa",surname:"Anantrao Karale",slug:"pushpa-anantrao-karale",fullName:"Pushpa Anantrao Karale"},{id:"346847",title:"Dr.",name:"Shashikant",surname:"Dhawale",slug:"shashikant-dhawale",fullName:"Shashikant Dhawale"},{id:"346907",title:"Dr.",name:"Mahesh",surname:"Karale",slug:"mahesh-karale",fullName:"Mahesh Karale"}],corrections:null},{id:"79065",title:"Medicinal Plants and Its Pharmacological Values",doi:"10.5772/intechopen.99848",slug:"medicinal-plants-and-its-pharmacological-values",totalDownloads:178,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Plants have been used as a source of medicine for the treatment of different diseases from thousands of years ago. There is numerous evidences are available for use of plants as a medicine in the treatment of diseases in Indian, Egyptian, Chinese, Greek and Roman system of medicine. Pharmacognosy is the study of medicines derived from natural sources, mainly from plants which may further lead to development of new drug. The exploration, extraction and screening of biological diversity such as herbs, spices, microbes and other natural resources is the worldwide activity in recent years. Phytochemicals are the naturally available bioactive compounds which are derived from different plant parts and are primarily responsible for biological activities. The most important chemical compounds which are present in the plants are alkaloids, phenols, saponins, carbohydrates, terpenoids, steroids, flavonoids and tannins etc.",signatures:"Smita G. Bhat",downloadPdfUrl:"/chapter/pdf-download/79065",previewPdfUrl:"/chapter/pdf-preview/79065",authors:[{id:"343927",title:"Ph.D. Student",name:"Smita G.",surname:"Bhat",slug:"smita-g.-bhat",fullName:"Smita G. Bhat"}],corrections:null},{id:"78916",title:"Traditional Usage of Plants of Costus Species in Assam, India",doi:"10.5772/intechopen.100532",slug:"traditional-usage-of-plants-of-costus-species-in-assam-india",totalDownloads:133,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Customary use of plants in the treatment of ailments in Assam, India is a typical situation. Ethno medicinal study was led in a few topographically unique zones of the state and utilization of plants from Costus species were reported. The extent of study chose for the investigation range across seven organizational regions spread across Assam, India. The regions include Dibrugarh, Golaghat, Tinsukia, Dhemaji, Karbi Anglong, Goalpara and Kokrajhar. Different plants were reported and plants fitting with the said species were chosen for determining the relevance concerning its use in customary medication. The survey divulged that plants associated to three species of the genus Costus namely Costus speciosus, Costus pictus and Costus scaber were espied to be primarily ubiquitous in traditional medicine in the discrete contemplated regions. The species were predominantly utilized as prime ingrediants in hepatoprotactive and anti-diabetic formulations. Costus speciosus was perceived to be chiefly used in the treatment of hepatic disorders and ailments. Costus pictus was observed to be used customarily in the upper Assam region bordering Nagaland for treating diabetes and Costus scaber was being used in the area bordering Arunachal Pradesh for tending people with jaundice, snake bite etc. The research climaxed with the profiling of the costus species as annotated from the ethnomedicinal survey.",signatures:"Biman Bhuyan, Dipak Chetia and Prakash Rajak",downloadPdfUrl:"/chapter/pdf-download/78916",previewPdfUrl:"/chapter/pdf-preview/78916",authors:[{id:"272268",title:"Prof.",name:"Biman",surname:"Bhuyan",slug:"biman-bhuyan",fullName:"Biman Bhuyan"},{id:"420787",title:"Mr.",name:"Prakash",surname:"Rajak",slug:"prakash-rajak",fullName:"Prakash Rajak"},{id:"420788",title:"Prof.",name:"Dipak",surname:"Chetia",slug:"dipak-chetia",fullName:"Dipak Chetia"}],corrections:null},{id:"76563",title:"Benefaction of Medicinal Plant Uraria picta",doi:"10.5772/intechopen.97731",slug:"benefaction-of-medicinal-plant-em-uraria-picta-em-",totalDownloads:22,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Medicinal plants are very significant as they not only maintain the health and vitality but most importantly also cure the various ailments in humans and animals without causing any toxic side effects. These are readily available and cost effective therapeutic agents. Uraria picta was first proposed by Desvaux, (1813), is highly medicinal and critically endangered plant species found throughout India and other parts of the world like Africa, Australia, Philippines, Malaysia, Japan, Nigeria etc. This herb is full of antiseptic, anti-inflammatory, antimicrobial, anti-emetic, aphrodisiac, analgesic, cardiovascular and expectorant properties. Due to its high therapeutic use and growing need, the plant is becoming rare and endangered, therefore it is necessary to create awareness of this plant to support its propagation in large numbers. This herb also shows properties of anti-cancer and anti-cholinergic properties hence can manage depressions, anxiety, sleeping problems. Analgesic property helps in reducing body pain.",signatures:"Harsha Kashyap",downloadPdfUrl:"/chapter/pdf-download/76563",previewPdfUrl:"/chapter/pdf-preview/76563",authors:[{id:"341318",title:"Dr.",name:"Harsha",surname:"Kashyap",slug:"harsha-kashyap",fullName:"Harsha Kashyap"}],corrections:null},{id:"75500",title:"Spices-Reservoir of Health Benefits",doi:"10.5772/intechopen.96471",slug:"spices-reservoir-of-health-benefits",totalDownloads:222,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Spices contribute to the quality, nutritive value, and flavor of food. Since ancient times, they hold a great medicinal value. Their antimicrobial, antiviral, antibacterial, anti-inflammatory, and other numerous properties have made them a potent source of therapeutic agents. Phytochemical analysis revealed presence of active constituents such as eugenol, curcumin, carotenoids in clove, turmeric, saffron respectively that explains the efficacious nature of these spices. Owing to their easy availability and consumption, it is advised to make spices daily part of our diet though in balanced amount as sometimes excess usage bear few consequences. Evaluating multiple benefits offered by these as immunity boosters especially in times of pandemic and incorporating them in our routine diet would improve disease management strategies. This chapter discusses the reservoir of activities exhibited by few spices along with the components responsible for these activities. Here, we also discussed their negative effects if at all.",signatures:"Cheryl Sachdeva and Naveen Kumar Kaushik",downloadPdfUrl:"/chapter/pdf-download/75500",previewPdfUrl:"/chapter/pdf-preview/75500",authors:[{id:"341343",title:"Assistant Prof.",name:"Naveen Kumar",surname:"Kaushik",slug:"naveen-kumar-kaushik",fullName:"Naveen Kumar Kaushik"},{id:"341345",title:"Ms.",name:"Cheryl",surname:"Sachdeva",slug:"cheryl-sachdeva",fullName:"Cheryl Sachdeva"}],corrections:null},{id:"75373",title:"Historical Evidence and Documentation of Remedial Flora of Azad Jammu and Kashmir (AJK)",doi:"10.5772/intechopen.96472",slug:"historical-evidence-and-documentation-of-remedial-flora-of-azad-jammu-and-kashmir-ajk-",totalDownloads:343,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Determining the pharmacognostic specifications of medicinal plants used in several drugs is very necessary and actually crucial. Ethnobotany has significant role in understanding the active relations between the biological diversity and cultural systems. Azad Jammu and Kashmir (AJK) is gifted with variety of medicinal plants. The theme of this chapter is to present information about wild medicinal plants in different areas of Azad Jammu and Kashmir. Common woody species are Diospyros lotus, Taxus wallichiana, Viburnum cylindricum, and perennial herbs comprise Geranium nepalense, Oxalis acetosella and Androsace umbellata. Betula utilis, Berberis lycium, Cedrus deodara, Abies pindrow, Pinus wallichiana, Juglans regia and Salix species with large number of herbal diversity at elevations are common. Most of people use wild plants as traditional food and medicine. This ethnic flora not only plays important role in human health care but it is also an important source for present and future drug development. There is need for correct documentation, conservation of plants samples in herbarium of research institutes, and growing plants in gardens.",signatures:"Fozia Abasi, Muhammad Shoaib Amjad and Huma Qureshi",downloadPdfUrl:"/chapter/pdf-download/75373",previewPdfUrl:"/chapter/pdf-preview/75373",authors:[{id:"343051",title:"Dr.",name:"Muhammad Shoaib",surname:"Amjad",slug:"muhammad-shoaib-amjad",fullName:"Muhammad Shoaib Amjad"},{id:"343054",title:"Ms.",name:"Fozia",surname:"Abasi",slug:"fozia-abasi",fullName:"Fozia Abasi"},{id:"343057",title:"Dr.",name:"Huma",surname:"Qureshi",slug:"huma-qureshi",fullName:"Huma Qureshi"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"497",title:"Soybean and Nutrition",subtitle:null,isOpenForSubmission:!1,hash:"11aa0c9ed0f6ea8da765be93b50954bb",slug:"soybean-and-nutrition",bookSignature:"Hany El-Shemy",coverURL:"https://cdn.intechopen.com/books/images_new/497.jpg",editedByType:"Edited by",editors:[{id:"54719",title:"Prof.",name:"Hany",surname:"El-Shemy",slug:"hany-el-shemy",fullName:"Hany El-Shemy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"496",title:"Soybean and Health",subtitle:null,isOpenForSubmission:!1,hash:"66d40dbc031b2825ba95f7ac2bfae1b6",slug:"soybean-and-health",bookSignature:"Hany El-Shemy",coverURL:"https://cdn.intechopen.com/books/images_new/496.jpg",editedByType:"Edited by",editors:[{id:"54719",title:"Prof.",name:"Hany",surname:"El-Shemy",slug:"hany-el-shemy",fullName:"Hany El-Shemy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3244",title:"Soybean",subtitle:"Bio-Active Compounds",isOpenForSubmission:!1,hash:"b21aa6107fce439bd06d53fbe0bc3c9e",slug:"soybean-bio-active-compounds",bookSignature:"Hany A. 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Lobato, Beatriz Martineli Lima, Barbara Rodrigues Quadros, Allan Klynger da Silva Lobato, Izabelle Pereira Andrade and Letícia de Abreu Faria",dateSubmitted:"October 21st 2019",dateReviewed:"November 28th 2019",datePrePublished:"March 25th 2020",datePublished:"April 8th 2020",book:{id:"8004",title:"Nitrogen Fixation",subtitle:null,fullTitle:"Nitrogen Fixation",slug:"nitrogen-fixation",publishedDate:"April 8th 2020",bookSignature:"Everlon Cid Rigobelo and Ademar Pereira Serra",coverURL:"https://cdn.intechopen.com/books/images_new/8004.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"39553",title:"Prof.",name:"Everlon",middleName:"Cid",surname:"Rigobelo",slug:"everlon-rigobelo",fullName:"Everlon Rigobelo"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"158046",title:"Dr.",name:"Elaine Maria Silva Guedes",middleName:"Guedes",surname:"Lobato",fullName:"Elaine Maria Silva Guedes Lobato",slug:"elaine-maria-silva-guedes-lobato",email:"elaine.guedes@ufra.edu.br",position:null,institution:null},{id:"313880",title:"Dr.",name:"Barbara",middleName:null,surname:"Rodrigues Quadros",fullName:"Barbara Rodrigues Quadros",slug:"barbara-rodrigues-quadros",email:"barbara.quadros@ufra.edu.br",position:null,institution:null},{id:"313881",title:"Dr.",name:"Izabelle",middleName:null,surname:"Pereira Andrade",fullName:"Izabelle Pereira Andrade",slug:"izabelle-pereira-andrade",email:"izabelle.andrade@ufra.edu.br",position:null,institution:null},{id:"314476",title:"Dr.",name:"Allan Klynger Da Silva",middleName:null,surname:"Lobato",fullName:"Allan Klynger Da Silva Lobato",slug:"allan-klynger-da-silva-lobato",email:"allan.lobato@ufra.edu.br",position:null,institution:{name:"Universidade Federal Rural da Amazônia",institutionURL:null,country:{name:"Brazil"}}},{id:"314477",title:"Dr.",name:"Leticia Abreu",middleName:null,surname:"Faria",fullName:"Leticia Abreu Faria",slug:"leticia-abreu-faria",email:"leticia.faria@ufra.edu.br",position:null,institution:{name:"Universidade Federal Rural da Amazônia",institutionURL:null,country:{name:"Brazil"}}},{id:"314484",title:"Mr.",name:"Elizeu Monteiro Pereira",middleName:null,surname:"Junior",fullName:"Elizeu Monteiro Pereira Junior",slug:"elizeu-monteiro-pereira-junior",email:"ta.elizeujr@gmail.com",position:null,institution:{name:"Universidade Federal Rural da Amazônia",institutionURL:null,country:{name:"Brazil"}}},{id:"314489",title:"Ms.",name:"Beatriz Martinelli",middleName:null,surname:"Lima",fullName:"Beatriz Martinelli Lima",slug:"beatriz-martinelli-lima",email:"biamartinelli13@gmail.com",position:null,institution:{name:"Universidade Federal Rural da Amazônia",institutionURL:null,country:{name:"Brazil"}}}]}},chapter:{id:"71453",slug:"advancement-of-nitrogen-fertilization-on-tropical-environmental",signatures:"Elizeu Monteiro Pereira Junior, Elaine Maria Silva Guedes Lobato, Beatriz Martineli Lima, Barbara Rodrigues Quadros, Allan Klynger da Silva Lobato, Izabelle Pereira Andrade and Letícia de Abreu Faria",dateSubmitted:"October 21st 2019",dateReviewed:"November 28th 2019",datePrePublished:"March 25th 2020",datePublished:"April 8th 2020",book:{id:"8004",title:"Nitrogen Fixation",subtitle:null,fullTitle:"Nitrogen Fixation",slug:"nitrogen-fixation",publishedDate:"April 8th 2020",bookSignature:"Everlon Cid Rigobelo and Ademar Pereira Serra",coverURL:"https://cdn.intechopen.com/books/images_new/8004.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"39553",title:"Prof.",name:"Everlon",middleName:"Cid",surname:"Rigobelo",slug:"everlon-rigobelo",fullName:"Everlon Rigobelo"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"158046",title:"Dr.",name:"Elaine Maria Silva Guedes",middleName:"Guedes",surname:"Lobato",fullName:"Elaine Maria Silva Guedes Lobato",slug:"elaine-maria-silva-guedes-lobato",email:"elaine.guedes@ufra.edu.br",position:null,institution:null},{id:"313880",title:"Dr.",name:"Barbara",middleName:null,surname:"Rodrigues Quadros",fullName:"Barbara Rodrigues Quadros",slug:"barbara-rodrigues-quadros",email:"barbara.quadros@ufra.edu.br",position:null,institution:null},{id:"313881",title:"Dr.",name:"Izabelle",middleName:null,surname:"Pereira Andrade",fullName:"Izabelle Pereira Andrade",slug:"izabelle-pereira-andrade",email:"izabelle.andrade@ufra.edu.br",position:null,institution:null},{id:"314476",title:"Dr.",name:"Allan Klynger Da Silva",middleName:null,surname:"Lobato",fullName:"Allan Klynger Da Silva Lobato",slug:"allan-klynger-da-silva-lobato",email:"allan.lobato@ufra.edu.br",position:null,institution:{name:"Universidade Federal Rural da Amazônia",institutionURL:null,country:{name:"Brazil"}}},{id:"314477",title:"Dr.",name:"Leticia Abreu",middleName:null,surname:"Faria",fullName:"Leticia Abreu Faria",slug:"leticia-abreu-faria",email:"leticia.faria@ufra.edu.br",position:null,institution:{name:"Universidade Federal Rural da Amazônia",institutionURL:null,country:{name:"Brazil"}}},{id:"314484",title:"Mr.",name:"Elizeu Monteiro Pereira",middleName:null,surname:"Junior",fullName:"Elizeu Monteiro Pereira Junior",slug:"elizeu-monteiro-pereira-junior",email:"ta.elizeujr@gmail.com",position:null,institution:{name:"Universidade Federal Rural da Amazônia",institutionURL:null,country:{name:"Brazil"}}},{id:"314489",title:"Ms.",name:"Beatriz Martinelli",middleName:null,surname:"Lima",fullName:"Beatriz Martinelli Lima",slug:"beatriz-martinelli-lima",email:"biamartinelli13@gmail.com",position:null,institution:{name:"Universidade Federal Rural da Amazônia",institutionURL:null,country:{name:"Brazil"}}}]},book:{id:"8004",title:"Nitrogen Fixation",subtitle:null,fullTitle:"Nitrogen Fixation",slug:"nitrogen-fixation",publishedDate:"April 8th 2020",bookSignature:"Everlon Cid Rigobelo and Ademar 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\r\n\tTrauma surgery is the specialization in surgery that focuses on the treatment and care of injuries, often life-threatening, that are caused by impact forces. The causes of impact forces are many, but some of the more common ones include traffic accidents, falls, sports and crush injuries, as well as gunshot or stab wounds. The trauma surgeon is responsible for initially resuscitating and stabilizing and later evaluating and managing the patient. Trauma surgery includes general emergency surgery, vascular emergency surgery, and thoracic emergency surgery but also urologic, cardiac, pediatric, musculoskeletal, gynecological, transplant emergency surgery, and all surgical specialties. Largely performed by surgeons specializing in emergency medicine, this surgery can be conducted for many reasons but occurs most often in urgent or critical cases in response to trauma, cardiac events, poison episodes, brain injuries, and pediatric medicine. Emergency surgical patients often have complex and challenging problems, which may include major traumatic injury, sepsis, shock, and serious abdominal conditions. For patients who have serious acute surgical or traumatic conditions, inefficiencies in the system of retrieval, triage, diagnostic investigation, access to the operating theatre, and appropriate post-operative care may lead to an increased risk of morbidity and mortality.
",isbn:"978-1-83768-439-7",printIsbn:"978-1-83768-438-0",pdfIsbn:"978-1-83768-440-3",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"05102f198619f7cc1312eb39a352026c",bookSignature:"Associate Prof. Selim Sözen",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/12354.jpg",keywords:"Major Abdominal Trauma, Solid Organ Trauma, Bones Fracture, Pelvic Fracture, Spine Trauma, Sports Trauma, Lung Trauma, Facial Trauma, Orbital Trauma, Neck Trauma, Fractures, Brain Trauma",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 17th 2022",dateEndSecondStepPublish:"July 15th 2022",dateEndThirdStepPublish:"September 13th 2022",dateEndFourthStepPublish:"December 2nd 2022",dateEndFifthStepPublish:"January 31st 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"15 days",secondStepPassed:!1,areRegistrationsClosed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"Dr. Selim Sözen is an expert in general surgery who received his medical degree from Ondokuz Mayıs University, Turkey. From 1999 to 2004, he was an assistant doctor at Ankara Atatürk Education and Research Hospital. He joined the Department of General Surgery, Medicine Faculty, Namık Kemal University, He is a member of the Turkish Surgical Association and a review board member for several journals. He has published 109 articles in scientific journals and presented 64 poster papers at scientific congresses.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"90616",title:"Associate Prof.",name:"Selim",middleName:null,surname:"Sözen",slug:"selim-sozen",fullName:"Selim Sözen",profilePictureURL:"https://mts.intechopen.com/storage/users/90616/images/system/90616.png",biography:"Dr. Selim Sözen is an expert in general surgery who received his medical degree from Ondokuz Mayıs University, Turkey, in 1998. From 1999 to 2004, he was an assistant doctor at Ankara Atatürk Education and Research Hospital, Turkey. From 2004 to 2013, he worked as a specialist at different government hospitals in Turkey. He joined the Department of General Surgery, Medicine Faculty, Namık Kemal University, Turkey, as an associate professor in 2013. He completed liver transplantation surgery at İnönü University, Turkey, in 2014–2015. Since 2016, Dr. Sözen has run his own surgery clinic in İstanbul, Turkey. He is a member of the Turkish Surgical Association and a review board member for several journals. He has published 109 articles in scientific journals and presented 64 poster papers at scientific congresses. 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1. Introduction
Clostridium difficile is a gram-positive, spore forming anaerobic bacillus that can survive on environmental surfaces for years in the spore (dormant) stage. First cultured in 1935 by Hall and O’Toole, C. difficile was a relatively unknown organism until 1978 [1]. It was initially thought to be a mostly harmless colonizer of the human intestinal tract. In 1893, a young woman died after gastric surgery from a “diphtheric colitis” as described by John Finney and Sir William Osler [2]. In 1978, Dr. John G. Bartlett determined that C. difficile was associated with the ailment that had killed the young woman 85 years prior and was now termed pseudomembranous colitis (PMC) [3].
C. difficile is currently the most common cause of antibiotic-associated pseudomembranous colitis in the healthcare setting and caused 20–30% of those with uncomplicated antibiotic-associated diarrhea [4]. According to the Centers for Disease Control, the number of cases of C. difficile infections (CDIs) in patients discharged from acute-care facilities doubled from 149,000 to 300,000 between 2001 and 2005 and based on recent trends has reached nearly 500,000 cases per year [5, 6]. There are occasionally other causes of antibiotic associated colitis due to organisms such as Staphylococcus aureus, Klebsiella oxytoca, enterotoxin-producing strains of Clostridium perferingens, or Salmonella [7]. Treatment duration for most microbial infections is usually around 14 days but prolonged exposure to broad-spectrum antibiotics has been associated with increased rates of both initial C. difficile infection and recurrence of C. difficile infection [8, 9].
The damage caused by C. difficile is due to the ability of the microbe to attach to the mucosa of the colon and release of exotoxins into the mucosa. The toxins may cause diarrhea, dilation of the colon (toxic megacolon), (Figure 1) sepsis, and death. Transmission is person to person via the fecal-oral route with ingestion of spores that germinate into vegetative bacteria within the small intestine. C. difficile produces two toxins—toxins A and B. These are large proteins (308 and 270 kDa, respectively) that cause severe inflammation and necrosis of the mucosal tissue by inactivating Rho, Rac, and Cdc42 targets within the epithelial cells through irreversible glycosylation [10, 11]. Toxin B is thought to be a gene duplication event of toxin A but is 10 times more cytotoxic than toxin A [12, 13].
Figure 1.
Toxic megacolon related to Clostridium difficile infection. Credit: University of Pittsburgh Department of Pathology.
The bacteria are normally found in up to 25% of hospitalized adults and up to 70% of the hospitalized pediatric population [14]. It does not cause disease until the normal flora is disrupted and C. difficile is allowed to proliferate. C. difficile infection has a very high economic cost associated with it in the United States and Europe due to high reinfection rates of approximately 30% and risk of relapse of 60% producing over 900,000 cases and an estimated $1.1–$3.2 billion per annum burden [15, 16].
Antibiotic therapy that disrupts the normal flora are usually to blame but proton pump inhibitors and other gastric acid suppression medications are increasingly associated with increases in C. difficile overgrowth [17]. Although the cephalosporin class, clindamycin, and the fluoroquinolones are all thought to place a patient at a higher risk of infection, all antibiotics, including oral vancomycin and metronidazole, can induce pseudomembranous colitis due to their ability to eliminate most normal intestinal flora in combination with the increased resistance patterns of more virulent strains of C. difficile [3, 14, 18, 19] The NAP1 strain is particularly important as it is associated with fluoroquinolone use and has risen in incidence in Canada, Europe, and the United States with increased virulence, toxin production, mortality, treatment failures, and relapse [20, 21].
The incidence and virulence of this pathogen has been steadily increasing over the last several decades contributing to higher morbidity and mortality. The increasingly older patient population with its higher acuity of medical issues and immunosenescence, the increased use of proton pump inhibitors, and the continued use of antibiotics has all allowed C. difficile to leave a greater impact in healthcare settings. In this chapter, we will explore the risk factors, diagnosis, treatment, and prevention of C. difficile infections in the intensive care unit (ICU).
2. A historical perspective on Clostridium difficile
Pseudomembranous colitis became a common complication of antibiotic use in the 1950s at the beginning of the antibiotic era and was found often in postoperative patients with an incidence of 14–27% [22, 23]. S. aureus was the suspected pathogen and standard treatment became oral vancomycin [24].
Tedesco et al. described “clindamycin colitis” in 1974 utilizing culture and endoscopy to diagnose pseudomembranous colitis associated with antibiotic use after 21% of patients given clindamycin developed diarrhea and 10% developed pseudomembranous colitis [25]. Incidentally, S. aureus did not grow from stool cultures from any of the patients. This study, more than prior publications, crystallized the connection between antibiotic use and development of pseudomembranous colitis. Green, while studying penicillin-induced death in guinea pigs in 1974 described stool cytopathic changes that he attributed to the activity of a latent virus. In retrospect, this appears to be the first identification of the effects of C. difficile cytotoxin [26]. Between 1977 and 1979, using hamster models, multiple teams of researchers identified C. difficile as the causative agent of pseudomembranous colitis, including detecting toxin B produced by C. difficile [27–30]. “Clindamycin colitis” became known as “antibiotic-induced colitis” and most of the studies done in the 1980s demonstrated that cephalosporins were the most frequently implicated agents followed secondly by broad‑spectrum penicillins, including amoxicillin [30–33].
Although there are many causes of pseudomembranous colitis, the majority of cases since the late 1970s have been caused by C. difficile infection. Pseudomembranous colitis is limited to the proximal colon in 20–30% of cases and may therefore be missed by sigmoidoscopy, providing more credence to performing a complete colonoscopy to identify anatomic lesions [25, 34]. With the current availability of C. difficile toxin assays, colonoscopy is rarely necessary. The first test used to diagnose C. difficile involved neutralization of the cytotoxin by C. sordellii antitoxin. This remains the most sensitive and specific diagnostic test, but is expensive and requires 24–48 hours for results [35] that has led to the development of latex particle agglutination [36–38], dot immunoblot [39], PCR [40, 41], stool culture on selective media [42, 43], and enzyme immunoassay (EIA) [44, 45]. Because of differences between the hamster model and humans, it was originally believed that toxin A was important in human disease and many early EIA tests only detected toxin A, leading to false negative tests [46, 47].
3. Clinical signs and symptoms
Watery diarrhea with a distinct odor is usually the hallmark of C. difficile infection. Mild disease consists of crampy, watery diarrhea without systemic symptoms. This cohort constitutes 70% of patients with C. difficile infection as only about 30% of patients with C. difficile infection are febrile and 50% have a leukocytosis [48]. In severe disease, fecal leukocytes are generally high and diagnosis can be confirmed with endoscopy demonstrating pseudomembranous colitis. Other signs and symptoms of severe disease include abdominal pain, leukocytosis, and fever or other systemic symptoms. Leukocytosis is directly correlated with the severity of the disease. The elevation in white blood cell count can be as marginal as 15,000 cells/mL or as high as 50,000 cells/mL. Complications may include paralytic ileus, toxic megacolon, or other life threatening conditions. Postoperative patients and other patients with altered gastrointestinal motility may have pseudomembranous colitis without diarrhea secondary to ileus. Computed tomography is useful with characteristics of colitis readily seen on imaging that may include colonic wall thickening and associated ascites or toxic megacolon [21, 49].
Patients in the ICU tend to demonstrate the same spectrum of disease signs and symptoms as other infected persons. However, due to their illnesses, comorbidities weakened immune system and reduced ability to heal; the progression of the disease may advance more rapidly. Therefore, continual assessment of diarrhea and other symptoms of C. difficile infection is necessary as the severity may progress and further impact the already impaired and critical status of the patient in the ICU.
4. Risk factors for Clostridium difficile infection
Risk factors for C. difficile infection fall under three categories. First category includes disruptions of the endogenous intestinal flora, perturbations of the mucosa, or immunomodulation by exogenous factors that can occur as a result of medications, procedures, or radiation therapy. Most hospitalized patients with C. difficile infection have been exposed to antibiotics within the past 30 days. More recently, it has been noted that medications that suppress gastric acid, including proton-pump inhibitors and H2-receptor blockers, increase risk of C. difficile infection, though study results are not uniform and the mechanism is not known [50–54]. For patients with primary or recurrent C. difficile infection, consideration should be given to discontinuation of gastric acid suppressants unless the patient’s risk for GI bleeding outweighs the risk of C. difficile infection treatment failure. Chemotherapy, medications for autoimmune conditions, transplant medications, and radiation of the bowel increase the risk of C. difficile infection by disrupting the normal intestinal mucosal barrier and inhibiting the body’s immunodefenses. Nasogastric tubes and enemas, presumably because of alteration of the normal flora and/or pH, increase patients’ risk of C. difficile infection [55].
The second category of risk factors relates to how patients contract C. difficile infection. The most common method is by coming in contact with C. difficile spores from the hands of health care workers. Risk of contracting C. difficile infection is directly related to length of stay (LOS). Patients with longer LOS have multifactorial risk factors that include more severe illnesses that have a higher likelihood that they will require antibiotics and more prolonged exposure and interactions with health care workers [56, 57]. A patient’s risk of contracting C. difficile infection is also related to C. difficile infection pressure that relates to the number of patients with C. difficile infection in a given care area [58]. Certain C. difficile strains, including the epidemic BI/NAP1/027 strain, have been isolated from prepared foods, pets, and from livestock [59–61].
The third category of risk factors relates to innate host susceptibility. Age >65 years is related to both an increased risk of primary C. difficile infection as well as an increased risk of more severe C. difficile infection. It is not known whether this is related to immune senescence, more frequent antibiotic usage, or increased comorbidities. The four comorbidities that place patients at greatest risk are sepsis, pneumonia, urinary tract infections, and skin infections—all of which generally require antibiotics for treatment. Patients hospitalized with higher numbers of conditions are more likely to contract C. difficile infection than patients with fewer conditions [48]. More recently, it has been noted that peripartum women and infants also appear to be at increased risk for C. difficile infection, including severe C. difficile infection related to the epidemic BI/NAP1/027 strain [62, 63]. Patients with inflammatory bowel disease (IBD) are more susceptible to C. difficile infection for reasons that are likely multifactorial, including antibiotic exposure, altered gut mucosal integrity, and immunosuppressive therapy. Patients with C. difficile infection superimposed on a flare of IBD are at risk for a particularly fulminant course. Because of altered gut physiology, patients with IBD may not develop pseudomembranes and may have a complicated diagnosis. Additionally, administration of glucocorticoids to treat the IBD exacerbation may predispose to C. difficile infection progression [64, 65]. Studies have shown that patients with HIV/AIDS or chronic kidney disease requiring hemodialysis are also at increased risk of C. difficile infection, possibly due to increased health care worker exposure or less robust immune response [66, 67].
5. Diagnosis
In the modern era, multiple tools have been developed to identify and detect C. difficile to include cultures, polymerase chain reaction (PCR), and enzyme immunoassays (EIA). Culturing C. difficile is difficult due to the strict anaerobic nature of the organism and the oxygen sensitivity that can kill the living organism. Utilizing an anaerobic chamber with a composition of 5% CO2, 10% H2, and 85% N2, along with an air lock, has allowed the culturing, preservation, and storage of the living organism and spores [35, 43]. Once the organism has been cultured, PCR or EIA techniques can be utilized to detect toxin within the culture. These same techniques can be used independently of a culture to detect toxin within the stool sample. PCR has been successfully used since 1985 to amplify the 8.1 kilo base-pairs of the toxin A gene. Using 35 cycles of alternating 95–55°C temperatures and a Southern blot to isolate the 252 base-pair DNA fragment, PCR has become easy and commonplace for identification of the toxins [40, 41]. EIA has similarly been used since the early 80s for detection of both toxin A and B. The early tests were able to detect levels of toxin to 0.1 ng using a double sandwich microtiter plate with specificities of 98.6% and 100% for toxin A and toxin B, respectively [42–45]. More recently, glutamate dehydrogenase-immunoassay has been used as an initial screening tool with a chemiluminescent toxin-immunoassay for confirmation of both toxins A and B. The combined two-step process has a sensitivity and specificity of 100% [68]. The premise of the EIA tests is that antibodies to the toxins are attached to a plate. When the toxins pass over the antibodies, they become bound. A second preparation of antibodies with a marker attached to them is then added and a device to detect the markers allows for quantitative evaluation of the toxins present.
In addition to laboratory tests, computed tomography is useful to evaluate for toxic megacolon and colitis. When there is high clinical suspicion yet laboratory diagnostic tests have yielded negative results, the definitive test is colonoscopy. The appearance of pseudomembranes in the clinical setting of C. difficile infection is confirmatory for the diagnosis (Figure 2). Table 1 displays the various current diagnostic modalities.
Figure 2.
Clostridium difficile associated pseudomembranous colitis. Credit: North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.
Test
Detection
Time
Usefulness
Culture
Clostridium difficile
34 days
Nonspecific and not useful for detection of toxins
Culture-toxins
Toxigenic Clostridium difficile
3–4 days
Must have initial growth from culture prior to testing for toxins
Cytotoxin
Toxin B
2–3 days
Costly and time-consuming. Results not immediately available
EIA toxin A & B
Toxin A & B
2–3 hours
Very quick but not sensitive. Need 3 specimens for increased sensitivity
EIA GDH
Clostridium difficile
2–3 hours
Screening test. Detects presence of bacteria but not specific
Toxin B gene
Toxigenic Clostridium difficile
2–3 hours
Very sensitive for detection of toxigenic strains of Clostridium difficile using PCR
Colonoscopy
Pseudomembranes
<1 hour
Very specific and sensitive for the detection of pseudomembranes
CT scan
Colitis
<1 hour
Very sensitive for colitis but not specific for Clostridium difficile infections
Table 1.
Diagnostic modalities for the identification of Clostridium difficile in the ICU.
Intensivists should be familiar with the tests offered in their institution and be able to interpret the laboratory results in the context of clinical presentation. When clinical suspicion for C. difficile infection is high, the intensivist should initiate empiric therapy for C. difficile infection regardless of the diagnostic test results [48].
6. Treatment
Once diagnosed, the first line of treatment is to discontinue implicated antibiotics, gastric acid suppression medications, and antiperistaltic medications, including narcotics and antimotility agents. Reduced peristalsis may prolong toxin exposure to the colonic mucosa [7]. Unfortunately, a large proportion of patients who develop C. difficile infection have documented infections that require treatment with antibiotics, and in the ICU setting, this proportion may reach 60% [69]. When it is not possible to stop antibiotic therapy, it is best to tailor coverage to more narrow spectrum agents once cultures and sensitivities are available. It is recommended to transition as soon as possible to β-lactams, macrolides, aminoglycosides, antistaphylococcal drugs, tetracyclines, and other agents that have a lower likelihood of causingC. difficile infection [70].
Oral vancomycin is the only agent currently approved for treatment of C. difficile infection, although metronidazole in both oral and intravenous forms has been shown to be effective in treating C. difficile infection. Intravenous vancomycin has not been shown to be effective. Metronidazole has become the preferred agent for initial treatment of C. difficile infection because of lower cost [71, 72] and because of concerns over the possibility of increased development of vancomycin-resistant enterococcus [73, 74]. Metronidazole should be considered first-line therapy for mild to moderate C. difficile infection; however, it does have disadvantages compared to oral vancomycin. In a study involving 207 patients with C. difficile infection, 22% of patients remained symptomatic after 10 day therapy with metronidazole and 27% developed a relapse [75]. In a separate randomized trial involving 150 patients, the cure rate for metronidazole was only 76% compared with a 97% cure rate after treatment with vancomycin for the treatment of severe C. difficile infection [49]. Based on these studies and other data, oral vancomycin should be considered superior in the treatment of severe infections when GI motility is intact (Table 2) [49]. The pharmacology of oral vancomycin lends itself to being more effective as it is not absorbed by the GI tract and reaches the colon in high concentrations. The usual dosing regimen of 125 mg achieves levels of vancomycin 500–1000 times the minimal inhibitory concentration (MIC) of 90% of C. difficile in stool [48].
Severity
Preference
Medications
Mild CDI
1st line Alternate (PO) Alternate (IV)
Metronidazole: 500 mg PO every 8 hours Vancomycin: 125 mg PO every 6 hours or Fidaxomicin: 200 mg PO every 12 hours Metronidazole: 500 mg IV every 8 hours
Severe CDI
1st line Alternate (IV)
Vancomycin: 125 mg PO every 6 hours Metronidazole: 500 mg IV every 8 hours
Life-threatening CDI
1st line
Vancomycin: 500 mg every 6 hours via NGT or by enema plus Metronidazole: 500 mg IV every 8 hours
Relapsed CDI
1st line
Treatment based on severity as above
Table 2.
Treatment modalities for Clostridium difficile infections.
If the patient has ileus or severe pseudomembranous colitis and medication cannot be given orally, the use of rectal instillation of vancomycin solutions is supported by case reports [70, 76, 77]. The addition of intravenous metronidazole to either oral or intracolonic vancomycin in severely ill patients with ileus has been described, although this approach has not been adequately studied [78, 79].
Fidaxomicin is the first member in a new class of narrow spectrum macrocyclic antibiotics that are enterally administered and minimally absorbed in the GI tract. Having excellent in vitro and in vivo activity against C. difficile, including NAP1/BI/027 strains, and, while exhibiting limited activity in vitro and in vivo against components of the normal gut flora, fidaxomicin is an excellent candidate for replacing other agents in the treatment of C. difficile infections [80]. In a prospective, multicenter, double-blind, randomized, parallel-group trial involving 596 patients, of which 287 received fidaxomicin and 309 received vancomycin, 88.2% of patients in the fidaxomicin group and 85.8% of those in the vancomycin group met the criteria for clinical cure. In addition, treatment with fidaxomicin was associated with a significantly lower rate of recurrence than was treatment with vancomycin (15.4 vs. 25.3%). More studies are warranted but results are promising [49, 81, 82].
Regardless of the type of medication, early treatment has been supported as the most effective pharmacologic treatment. A study by Zahar et al. conducted in three French ICUs has demonstrated that early treatment of ICU-acquired C. difficile infection results in mortality rates consistent with a control population of other ICU patients that have developed diarrhea that is not C. difficile infection associated. Treatment was initiated within 24 hours of onset and consisted of either metronidazole or oral vancomycin. The study involved 5,260 patients with an incidence of ICU-acquired diarrhea of 9.7%. All those with diarrhea were tested for C. difficile infection and 13.5% of those tested had confirmed toxin A or B by EIA and further confirmation by culture. None of the positive cultures produced any of the hypervirulent NAP1/027 strains seen in North American outbreaks. Overall mortality of ICU-acquired C. difficile infection was not independently associated with higher mortality rates compared to other patients with diarrhea in the ICU when matched for severity of illness, comorbidities, or complications occurring in the ICU. However, both the overall hospital stay and ICU stay was prolonged in the ICU-acquired C. difficile infection patients when compared to ICU patients as a whole (median 4 vs. 20 days) and ICU patients with diarrhea not associated with C. difficile infection (median 17 vs. 20 days). Despite these prolonged median stays, analysis did not demonstrate a statistically significant difference in length of stay with an estimated increase in overall ICU stay of 6.3 days ± 4.3, p = 0.14 compared to other ICU patients with diarrhea [83].
Microbial therapy with fecal transplantation can be accomplished with instillation of liquid preparations of stool from healthy donors. This method has proven successful for treating recurrent C. difficile infection in 70–100% of cases [84]. Probiotics may prevent attachment of C. difficile to epithelial cells and can reduce the incidence of C. difficile infection. Saccharomyces boulardii in particular has proven to be effective [49] whereas the use of Lactobacillus with conventional antibiotic therapy has shown mixed results including some studies showing no benefit in the treatment of C. difficile infection in several randomized controlled trials [85–88].
Use of anion exchange resins, such as cholestyramine and colestipol, with the hope of binding C. difficile cytotoxins in the treatment of C. difficile infection, has not only been shown to be effective [89, 90], but also carries the theoretical risk of binding intraluminal vancomycin, thus resulting in subtherapeutic vancomycin levels [91]. Intravenous immunoglobulins have been suggested for treatment of C. difficile infection but due to an insufficient evidence base and conflicting data, its use cannot be generally recommended until further studies have been conducted [92, 93]. Subtotal colectomy should be considered if there is no response to medical therapy within 3–4 days or if the patient remains seriously ill to avoid complications such as colonic perforation and sepsis [7].
7. Treatment failure and relapse
Patient characteristics that predispose to metronidazole failure include low serum albumin, continued exposure to the inciting antibiotic, and residence in the ICU [94, 95]. Particularly worrisome and concerning is the finding that relapsing or recurrent infections occur in up to 30% of patients treated for C. difficile infection whether the initial treatment was metronidazole or vancomycin [96]. This could be due to reinfection with the same endogenous strain or from a different strain acquired exogenously. Patients that had an initial infection followed by reinfection have a 50–65% chance of further repeated episodes. A metaanalysis by Garey et al. found that reexposure to antimicrobials, gastric acid suppression, and older age are all associated with an increased risk of recurrent C. difficile infection [97]. Patients that have three or more episodes of C. difficile infection, considered to be multiple C. difficile infection recurrence, are best treated with a tapered regimen of oral vancomycin. The initial dose of vancomycin administered is at the usual 125 mg by mouth four times a day for 10–14 days but then one dose per day is removed one week at a time until the patient is taking one dose every 2–3 days. The rationale for this regimen is that as the doses are spaced out, the colonic flora has time to regenerate [48].
8. Generating optimal colonic flora for risk reduction
There is an urgent need for alternative means of preventing and treating C. difficile infection in high-risk individuals. Metagenomics have improved our understanding of the “colonization resistance barrier” and how this could be optimized. The “colonization resistance barrier” in the normal healthy colon consists of high microbial diversity, substrate/area competition, immune response modulation and short-chain fatty acid (SCFA) production [16, 98]. These factors are often missing in the elderly. Decreased pH, oxidation-reduction potentials, and higher concentrations of short-chain fatty acids have been suggested to inhibit C. difficile growth and toxin production throughout in vitro and in vivo studies. There is, therefore, evidence in support of a colonization resistance barrier against C. difficile infection [16, 98].
For instance, in vitro, Bifidobacterium longum and Bifidobacterium breve have been show to significantly reduce the growth of the toxigenic strain C. difficile LMG21717 [99]. In a randomized, placebo-controlled, double-blind trial at a long-term elderly care facility, the effectiveness of a Lactobacillus casei strain Shirota (LcS) infused beverage was demonstrated by altering Clostridium infection rates among the residents. Daily consumption of the beverage resulted in a significantly lower incidence of fever and improved bowel movements. When compared to a resident control group drinking a placebo beverage, stool studies from the experimental LcS group showed significantly higher number of both Bifidobacterium and Lactobacillus (p < 0.01), significantly lower number of destructive bacteria such as C. difficile (p < 0.05), and a higher fecal acetic acid concentration. This study was also conducted among the facility’s staff and a significant difference in the intestinal microbiota, fecal acetic acid, and pH was also observed between the LcS and placebo groups [100].
There is some evidence to support that plant based diets may reduce the number of pathobionts such as C. difficile and increase the number of protective species such as Lactobacillus [100–103]. Altered flora with resulting altered bile metabolism within the gut by flora favored by plant-based diets have implications in colonocyte protection [102]. Intestinal microbiota are able to produce short chain fatty acids (SCFA), such as acetate, propionate, and butyrate, through metabolism of dietary fiber. These SCFA have been shown to be colonocyte protective. A strong positive correlation has been found between Faecalibacterium prausnitzii and butyrate production in the gastrointestinal tract, suggesting that this species may be associated with higher fiber intake and reduced risk, not only for C. difficile infection, but also for other common comorbidities in the elderly including cardiovascular disease, colon cancer, diabetes, and obesity [104]. A move toward a diet that decreases risk for contracting C. difficile infection should be encouraged, not only in the elderly, but also generally, because of the broad implications.
9. Prevention of hospital spread
Disinfectant products based on quaternary ammonium compounds, commonly used to clean patient rooms, are not sporicidal. Therefore, using sporicidal hypochlorite-based disinfectants on surfaces is recommended. However, use of antisporicidal agents outside an outbreak is not associated with lower rates of C. difficile infection [105, 106].
Hand hygiene is the most important preventive measure to reduce transmission of C. difficile spores. Soap and water has been demonstrated to be superior to alcohol based hand rubs and other forms of hand sanitation with regard to transmission by healthcare workers [21, 107]. Hospital hygiene hand protocols should be followed assiduously at all times. Other precautions that should be utilized include isolation of the patient, barrier precautions, and use of chlorine based chemical wipes [107]. These precautions should not be lifted based on stool studies as there are no diagnostic methods to determine response to treatment. Rather, the decision should be made on clinical signs and symptoms with resolution of diarrhea, fevers, and leukocytosis. A strong antibiotic stewardship program is essential to limit the use of antibiotics that may cause C. difficile infection and is generally a good principle to follow. It has been demonstrated that up to 25% of antibiotic administration is not indicated, even in the ICU [108].
10. Clostridium difficile infection in the intensive care unit
Diarrhea is a common problem in the ICU affecting up to 40% of patients admitted. Severely burned patients may have an incidence of greater than 90% [109, 110]. Enteral tube feeding is the most common cause of diarrhea in the ICU; other causes include hypoalbuminemia, intestinal ischemia, and medications. C. difficile infection is the most common infectious cause of diarrhea in the ICU [111, 112]. The severity of C. difficile infection is increasing which is possibly related to the emergence of more virulent strains such as the BI/NAP1/027 strain, prompting more admissions to the ICU for management of C. difficile infection related complications [113].
In a systematic review and metaanalysis of 22 published studies from 1983 to 2015 that included 80,835 ICU patients, the effects of C. difficile infection on morbidity and mortality were investigated. Karanika et al. found that prevalence of C. difficile infection among ICU patients was 2% but 5-fold greater in those patients with diarrhea (11%). Those patients that were diagnosed with C. difficile infection had a 25% incidence of the severe form of the disease and diagnosed with pseudomembranous colitis. ICU mortality was not significantly different between the group with C. difficile infection and the nonC. difficile infection group based on seven studies that enrolled a combined 12,165 patients. However, the overall hospital mortality between those same groups was significantly increased in the C. difficile infection group with 32% mortality compared to 24% (p = 0.03). Similarly, length of ICU and hospital stay among C. difficile infection patients was longer when compared to nonC. difficile infection patients. Based on five studies with over 10,000 patients, C. difficile infection patients had an average ICU stay of 24 days and overall hospital stay of 50 days compared to 19 days and 30 days, respectively, for the nonC. difficile infection group (p = 0.001) [114].
Even though only 3% of patients with C. difficile infection require subtotal colectomy for fulminant C. difficile colitis, 20% of ICU patients with severe C. difficile infection will still require partial colectomy or diversion [115, 116]. Colectomy in this setting is associated with a 50% mortality [90]. Mortality rates are lower when surgical intervention is undertaken within 48 hours of lack of response to medical therapy [117]. During NAP1/027 outbreaks, patients with age >65 years, leukocytosis and elevated lactate appear to benefit the most from early colectomy [118].
In a series of 29 patients with severe or severe/complicated C. difficile infection refractory to oral vancomycin ± rectal vancomycin and intravenous metronidazole therapy who underwent fecal microbiota transplantation (FMT) plus continued vancomycin, overall treatment response was 93% (27/29), including 100% (10/10) for severe C. difficile infection and 89% (17/19) for severe/complicated C. difficile infection. A single FMT was performed in 62%, two FMTs were performed in 31%, and three FMTs in 7% of patients. Continued use of non C. difficile infection antibiotics predicted repeat FMT. Thirty-day all-cause mortality after FMT was 7%. Of the two patients who died within 30 days, one underwent colectomy and succumbed to sepsis; the other died from septic shock related to C. difficile infection [84]. Further research into the use of FMT combined with continued vancomycin is needed.
11. Modern outbreaks
In 2003, a major outbreak of C. difficile occurred in Quebec, Canada and was identified as ribotype 027, strain BI/NAP1. This strain has been identified in >50% of all isolates from hospitals in Europe and North America [4, 10, 20]. Prior to the 2003 outbreak, this strain only accounted for 14 of over 6000 (<0.02%) typed strains collected from U.S. cases during the period of 1984 to 1993. Following the 2003 outbreak in Canada, 96 of 187 (51%) strains tested positive for 027 in eight U.S. outbreaks [119].
The BI/NAP1/027 strain belongs to a hypervirulent group of strains along with types 001, 017, and 078. In particular, the binary toxin produced by 027 was not seen previously. It is thought to be synergistic with the production of toxin A and B. Strain BI/NAP1/027 was found to be highly resistant to fluoroquinolone classes of antibiotics and was also found to produce 16-fold higher concentrations of toxin A and 23-fold higher concentrations of toxin B than less virulent toxinotype 0 strains. The binary toxin has been associated with more severe diarrhea when combined with toxin A and B. When produced alone, binary toxin does not appear to produce disease [3, 10] but does appear to be a marker of both C. difficile infection severity and recurrence [120]. The emergence is generally believed to be related to fluoroquinolone exposure though not to the particular type of fluoroquinolone [121, 122].
12. Conclusions
C. difficile is a very diverse group of toxin producing organisms. Newer technologies have allowed the identification of numerous toxinotypes and ribotypes with varying virulence factors and toxin production. Multiple lineages contain hypervirulent strains. The large degree of horizontal gene transfer through transposons, bacteriophages, and homologous recombination has dispersed genetic material and pathogenic properties among different strains.
The increased prevalence of ribotypes 027, 017, and 078 may be solely due to population expansion over the last decade or due to a nosocomial enrichment of the proper environment and conditions for the expansion and transference of these virulent strains. The sudden rise may also be related to the delay in purifying selection pressures seen in the more recently diverging lineages. However, a more likely explanation for increasing incidence is the right combination of elderly patients in a contaminated environment with antibiotic and acid suppression medications. Given the high incidence of colonized guts in the hospitalized pediatric population (70%), the hospitalized adult population (25%), the animal kingdom (40%), and the natural environment (50%), reducing exposure is near impossible [14].
The high virulence, along with a highly mobile genome capable of antibiotic resistance, has prompted further research in the development of vaccinations. Sanofi-Aventis is currently undergoing trials with a vaccine containing formalin-inactivated toxins A and B. To date, 100 healthy subjects have been exposed to the vaccine without any serious side effects [123].
The hardiness of C. difficile spores and the ease with which this bacterium alters its genome has allowed it to flourish and survive among a variety of hosts and reservoirs. More virulent strains are a real possibility given the mobility of code sequencing regions within the genome. As the population continues to age and makes an increasingly stronger presence throughout the healthcare system, especially in the ICU, C. difficile will continue to plague patients and healthcare providers until further measures are discovered to control transmission. The increased burden will stress the current resources and facilities financially, geographically, and the pool of available care takers. To date, the best treatment modalities include eliminating the implicated antibiotics, early initiation of oral vancomycin and metronidazole, and strict infection-control engineering to prevent the initial infection.
\n',keywords:"Clostridium difficile, intensive care unit, pseudomembranous colitis, toxic megacolon, NAP1",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/55694.pdf",chapterXML:"https://mts.intechopen.com/source/xml/55694.xml",downloadPdfUrl:"/chapter/pdf-download/55694",previewPdfUrl:"/chapter/pdf-preview/55694",totalDownloads:1492,totalViews:397,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,impactScore:0,impactScorePercentile:20,impactScoreQuartile:1,hasAltmetrics:0,dateSubmitted:"December 14th 2016",dateReviewed:"April 13th 2017",datePrePublished:null,datePublished:"September 27th 2017",dateFinished:"May 29th 2017",readingETA:"0",abstract:"Clostridium difficile has become an increasingly common infectious agent in the healthcare setting. It is generally associated with antibiotic use and causes diarrhea as well as other complications such as pseudomembranous colitis (PMC) and toxic megacolon. This organism poses a serious threat to patients in the intensive care unit (ICU) as it increases hospital length of stay, morbidity, and mortality. Recurrence rates are typically higher in the ICU population as those patients usually have immunocompromised systems, more exposure to antibiotics and proton pump inhibitors, loss of normal nutritional balance, and alterations in their colonic flora. Emergence of more virulent and pathogenic strains has made combating the infection even more difficult. Newer therapies, chemotherapeutic agents, and vaccinations are on the horizon. However, the most effective treatments to date are ceasing the inciting agent, reduction in the use of proton pump inhibitors, and prevention of the disease. In this chapter, we will explore the risk factors, diagnosis, treatment, and prevention of C. difficile infections (CDI) in the ICU.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/55694",risUrl:"/chapter/ris/55694",book:{id:"5831",slug:"clostridium-difficile-a-comprehensive-overview"},signatures:"William C. Sherman, Chris Lewis, Jong O. Lee and David N. Herndon",authors:[{id:"203959",title:"Dr.",name:"William",middleName:null,surname:"Sherman",fullName:"William Sherman",slug:"william-sherman",email:"climbmt@yahoo.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"The University of Texas Medical Branch at Galveston",institutionURL:null,country:{name:"United States of America"}}},{id:"203979",title:"Dr.",name:"Christopher",middleName:null,surname:"Lewis",fullName:"Christopher Lewis",slug:"christopher-lewis",email:"chrlewis@utmb.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"The University of Texas Medical Branch at Galveston",institutionURL:null,country:{name:"United States of America"}}},{id:"203980",title:"Dr.",name:"Jong",middleName:null,surname:"Lee",fullName:"Jong Lee",slug:"jong-lee",email:"jolee@utmb.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"The University of Texas Medical Branch at Galveston",institutionURL:null,country:{name:"United States of America"}}},{id:"203981",title:"Dr.",name:"David",middleName:null,surname:"Herndon",fullName:"David Herndon",slug:"david-herndon",email:"dherndon@utmb.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"The University of Texas Medical Branch at Galveston",institutionURL:null,country:{name:"United States of America"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. A historical perspective on Clostridium difficile",level:"1"},{id:"sec_3",title:"3. Clinical signs and symptoms",level:"1"},{id:"sec_4",title:"4. Risk factors for Clostridium difficile infection",level:"1"},{id:"sec_5",title:"5. Diagnosis",level:"1"},{id:"sec_6",title:"6. Treatment",level:"1"},{id:"sec_7",title:"7. Treatment failure and relapse",level:"1"},{id:"sec_8",title:"8. Generating optimal colonic flora for risk reduction",level:"1"},{id:"sec_9",title:"9. Prevention of hospital spread",level:"1"},{id:"sec_10",title:"10. Clostridium difficile infection in the intensive care unit",level:"1"},{id:"sec_11",title:"11. Modern outbreaks",level:"1"},{id:"sec_12",title:"12. Conclusions",level:"1"}],chapterReferences:[{id:"B1",body:'Hall IC, O\'Toole E. Intestinal flora in newborn infants with a description of a new pathogenic anaerobe, Bacillus difficilis. 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Faecal microbiota transplantation plus selected use of vancomycin for severe-complicated Clostridium difficile infection: Description of a protocol with high success rate. Alimentary Pharmacology & Therapeutics. 2015;42(4):470-476'},{id:"B85",body:'Lawrence SJ, Korzenik JR, Mundy LM. Probiotics for recurrent Clostridium difficile disease. Journal of Medical Microbiology. 2005;54:905-906'},{id:"B86",body:'McFarland LV, Surawicz CM, Greenberg RN, et al. A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. The Journal of the American Medical Association. 1994;271:1913-1918'},{id:"B87",body:'Surawicz CM, McFarland LV, Greenberg RN, et al. The search for a better treatment for recurrent Clostridium difficile disease: Use of high-dose vancomycin combined with Saccharomyces boulardii. Clinical Infectious Diseases. 2000;31:1012-1017'},{id:"B88",body:'Wullt M, Hagslatt ML, Odenholt I. Lactobacillus plantarum 299v for the treatment of recurrent Clostridium difficile-associated diarrhoea: a doubleblind, placebo-controlled trial. Scandinavian The Journal of Infectious Diseases. 2003;35:365-367'},{id:"B89",body:'Ariano RE, Zhanel GG, Harding GK. The role of anion-exchange resins in the treatment of antibiotic-associated pseudomembranous colitis. Canadian Medical Association journal. 1990;142:1049-1051'},{id:"B90",body:'Mogg GA, Burdon DW, Keighley M. Oral metronidazole in Clostridium difficile colitis. British Medical Journal. 1979;2:335'},{id:"B91",body:'Taylor NS, Bartlett JG. Binding of Clostridium difficile cytotoxin and vancomycin by anion-exchange resins. The Journal of Infectious Diseases. 1980;141:92-97'},{id:"B92",body:'Salcedo J, Keates S, Pothoulakis C, et al. Intravenous immunoglobulin therapy for severe Clostridium difficile colitis. Gut. 1997;41:366-370'},{id:"B93",body:'Juang P, Skledar SJ, Zgheib NK, et al. Clinical outcomes of intravenous immune globulin in severe Clostridium difficile associated diarrhea. American Journal of Infection Control. 2007;35:131-137'},{id:"B94",body:'Fernandez A, Anand G, Friedenberg F. Factors associated with failure of metronidazole in Clostridium Difficile-associated disease. Journal of Clinical Gastroenterology. 2004;38:414-418'},{id:"B95",body:'Nair S, Yadav D, Corpuz M, et al. Clostridium difficile colitis: Factors influencing treatment failure and relapse: A prospective evaluation. The American Journal of Gastroenterology. 1998;93:1873-1876'},{id:"B96",body:'Bouza E, Muñoz P, Alonso R. Clinical manifestations, treatment and control of infections caused by Clostridium difficile. Clinical Microbiology and Infection. 2005;11(4 Suppl):57-64'},{id:"B97",body:'Garey KW, Sethi S, Yadav Y, DuPont HL. Meta-analysis to assess risk factors for recurrent Clostridium difficile infection. The Journal of Hospital Infection. 2008;70(4):298-304'},{id:"B98",body:'Latorre M, Krishnareddy S, Freedberg DE. Microbiome as mediator: Do systemic infections start in the gut? World Journal of Gastroenterology. 2015;21(37):10487-10492'},{id:"B99",body:'Valdés-Varela L, Hernández-Barranco AM, Ruas-Madiedo P, Gueimonde M. Effect of Bifidobacterium upon Clostridium difficile growth and Toxicity when Co-cultured in different prebiotic substrates. Frontiers in Microbiology. 2016;7:738'},{id:"B100",body:'Nagata S, Asahara T, Wang C, Suyama Y, Chonan O, Takano K, Daibou M, Takahashi T, Nomoto K, Yamashiro Y. The effectiveness of Lactobacillus beverages in controlling infections among the residents of an aged care facility: A randomized Placebo-Controlled Double-Blind Trial. Annals of Nutrition & Metabolism. 2016;68(1):51-59'},{id:"B101",body:'Chung KT, Kuo CT, Chang FJ. Detection of lactobacilli and their interaction with clostridia in human gastrointestinal tracts and in vitro. 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Lancet. 1998;351(9103):633-636'},{id:"B106",body:'Mayfield JL, Leet T, Miller J, Mundy LM. Environmental control to reduce transmission of Clostridium difficile. Clinical Infectious Diseases. 2000;31(4):995-1000'},{id:"B107",body:'Cooper CC, Jump RL, Chopra T. Prevention of infection due to Clostridium difficile. Infectious Disease Clinics of North America. 2016;30(4):999-1012'},{id:"B108",body:'Lawrence KL, Kollef MH. Antimicrobial stewardship in the intensive care unit: Advances and obstacles. American Journal of Respiratory and Critical Care Medicine. 2009;179(6):434-438'},{id:"B109",body:'Kelly TW, Patrick MR, Hillman KM. Study of diarrhea in critically ill patients. Critical Care Medicine. 1983;11:7-9'},{id:"B110",body:'Thakkar K, Kien CL, Rosenblatt JI, Herndon D. Diarrhea in severely burned children. JPEN Journal of Parenteral and Enteral Nutrition. 2005;29:8-11'},{id:"B111",body:'Liolios A, Oropello JM, Benjamin E. Gastrointestinal complications in the intensive care unit. Clinics in Chest Medicine. 1999;20:329-345'},{id:"B112",body:'Wiesen P, Van Gossum A, Preiser JC. Diarrhoea in the critically ill. Current Opinion in Critical Care. 2006;12:149-154'},{id:"B113",body:'Labbe AC, Poirier L, Maccannell D, et al. Clostridium difficile infections in a Canadian tertiary care hospital before and during a regional epidemic associated with the BI/NAP1/027 strain. Antimicrobial Agents and Chemotherapy. 2008;52:3180-3187'},{id:"B114",body:'Karanika S, Paudel S, Zervou FN, Grigoras C, Zacharioudakis IM, Mylonakis E. Prevalence and clinical outcomes of Clostridium difficile infection in the intensive care unit: A systematic review and Meta-Analysis. Open Forum Infectious Diseases. 2015;3(1):ofv186'},{id:"B115",body:'Rubin MS, Bodenstein LE, Kent KC. Severe Clostridium difficile colitis. Diseases of the Colon and Rectum. 1995;38:350-354'},{id:"B116",body:'Grundfest-Broniatowski S, Quader M, Alexander F, et al. Clostridium difficile colitis in the critically ill. Diseases of the Colon and Rectum. 1996;39:619-623'},{id:"B117",body:'Ali SO, Welch JP, Dring RJ. Early surgical intervention for fulminant pseudomembranous colitis. The American Surgeon. 2008;74:20-26'},{id:"B118",body:'Byrn JC, Maun DC, Gingold DS, et al. Predictors of mortality after colectomy for fulminant Clostridium difficile colitis. Archives of Surgery. 2008;143:150-154'},{id:"B119",body:'Sebaihia M, Wren BW, Mullany P, Fairweather NF, Minton N, et al. The multi-drug resistant human pathogen Clostridium difficile has a highly mobile, mosaic genome. Nature Genetics. 2006;38:779-786'},{id:"B120",body:'Pichenot M, et al. Fidaxomicin for treatment of Clostridium difficile infection in clinical practice: A prospective cohort study in a French University Hospital. Infection. 2017 (Forthcoming).'},{id:"B121",body:'McFarland LV, Clarridge JE, Beneda HW, Raugi GJ. Fluoroquinolone use and risk factors for Clostridium Difficile-associated disease within a Veterans Administration health care system. Clinical Infectious Diseases. 2007;45(9):1141-1151'},{id:"B122",body:'Biller P, Shank B, Lind L, et al. Moxifloxacin therapy as a risk factor for Clostridium difficile-associated disease during an outbreak: attempts to control a new epidemic strain. Infection Control and Hospital Epidemiology. 2007;28(2):198-201'},{id:"B123",body:'Study of a Candidate Clostridium Difficile Toxoid Vaccine (Cdiffense) in Subjects at Risk for C. Difficile Infection [Internet]. 2016. Available from: https://clinicaltrials.gov/ct2/show/NCT01887912 [Accessed: March 2, 2017]'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"William C. Sherman",address:null,affiliation:'
Department of Surgery, University of Texas Medical Branch – Galveston, Galveston, Texas, United States of America
Department of Surgery, University of Texas Medical Branch – Galveston, Galveston, Texas, United States of America
'},{corresp:null,contributorFullName:"Jong O. Lee",address:null,affiliation:'
Department of Surgery, University of Texas Medical Branch – Galveston, Galveston, Texas, United States of America
'},{corresp:"yes",contributorFullName:"David N. Herndon",address:"dherndon@utmb.edu",affiliation:'
Department of Surgery, University of Texas Medical Branch – Galveston, Galveston, Texas, United States of America
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Barrera-Rivas, Norma A. Valle-Hurtado, Graciela M.\nGonzález-Lugo, Víctor M. Baizabal-Aguirre, Alejandro Bravo-Patiño,\nMarcos Cajero-Juárez and Juan J. Valdez-Alarcón",authors:[{id:"191123",title:"Dr.",name:"Juan José",middleName:null,surname:"Valdez-Alarcón",fullName:"Juan José Valdez-Alarcón",slug:"juan-jose-valdez-alarcon"},{id:"195005",title:"Mrs.",name:"Claudia Ibeth",middleName:null,surname:"Barrera-Rivas",fullName:"Claudia Ibeth Barrera-Rivas",slug:"claudia-ibeth-barrera-rivas"},{id:"195006",title:"MSc.",name:"Norma Anahí",middleName:null,surname:"Valle-Hurtado",fullName:"Norma Anahí Valle-Hurtado",slug:"norma-anahi-valle-hurtado"},{id:"195007",title:"MSc.",name:"Graciela M.",middleName:null,surname:"González-Lugo",fullName:"Graciela M. 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1. Introduction
A current drawback of additive manufacturing (AM) parts is that the material properties of the parts produced are much lower than that of parts manufactured using traditional manufacturing such as milling, injection molding, and traditional composite manufacturing methods [1, 2, 3]. If the material properties of the parts produced using AM could be increased to be similar with that of traditional manufacturing methods, a new era of design could be opened up. This would be accomplished by the ability to use AM to make parts that could not be produced using any other methods due to their complex geometry. With the advent of computer-aided design (CAD) software, the design process was changed, but limitations of what can be made in the virtual world versus what can be manufactured in the real world still exist. With the incorporation of AM into the final production processes, the complexity of the geometries that could be manufactured increases. This increase in complexity of part geometry can allow for a decrease in the over complexity of the part, subassembly, or whole assembly, along with helping to relieve supply chain issues. For instance, by combing multiple parts into one, the need for several fasteners can be eliminated. This decreases the number of parts needed, number of components to analyze, and possible points of failure.
An appealing advantage of vat photopolymerization over material extrusion processes, such as fusion deposition modeling (FDM), is the ability to manufacture parts that have isotropic material properties [4]. For parts produced using FDM, the part has the properties of the material in the plane of printing, but perpendicular to that it becomes dependent on the mechanical adhesion of the polymer layers to each other for the part’s mechanical properties [4]. For parts manufactured using vat photopolymerization, it is possible to produce parts that have near isotropic mechanical properties [4]. Although the part is produced in a layer-by-layer process, as like in FDM, the thermoset polymer is not completely cured within each layer before the part is raised and the next layer is printed. This allows for unreacted polymer functional groups in a previous layer to react with the polymer curing in the current layer being printed. Because of the ability of vat photopolymerization to produce parts with near isotropic properties, the orientation of the part while printing does not depend on what direction force will be applied to the finished part, but what orientation of the part will optimize the printing process.
One of the limiting factors of vat photopolymerization is the material properties of the resins used to create parts. The parts produced using these resins are often weak and brittle, limiting their use for many end-use structural applications [5]. One method of improving the properties of a material is the incorporation of a reinforcement material in the creation of a composite. Short-fiber composites have traditionally been produced via injection and compression molding. By using short fibers as a reinforcement, the same manufacturing method used for polymers can be used to form the composites, but with increased material properties [6].
Short-fiber composites usually find their applications in situations where isotropic material properties are desired, typically manufactured via injection or compression molding, but the manufacturing processes can influence the fiber orientation due to the flow of the material during manufacturing final material properties [7]. While the flow-induced alignment can be taken advantage of to some extent, it can be limited due to the requirements of the mold design and can be an undesired effect when isotropic properties are desired [8].
With short fibers already in widespread use as a reinforcement material for traditional manufacturing methods, such as injection and compression molding, they have found their way into use for additive manufacturing methods as well [1, 3, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19]. For FDM there are numerous types of reinforcements ranging from nanoparticle to continuous fiber, of both natural and synthetic materials, which are currently being researched and available for sale on a commercial level [1, 3, 16]. Whereas FDM-based methods have a number of publications in the area of short-fiber composite characterization, the area of vat photopolymerization manufactured composites is lacking in published studies and available data using carbon fiber as a reinforcement.
There have been various nanosized reinforcements studied as a method of increasing the material properties of vat photopolymerization manufactured parts such as: cellulose nanocrystals (CNC), multi-wall carbon nanotubes (MWCNTs), and silver nanoparticles (AgNPs) [12, 13, 14, 18]. Feng et al. [14] used lignin-coated cellulose nanocrystals (L-CNC) at 0, 0.1, 0.5, and 1 weight percent with an acrylic matrix. The research was carried out using Form+1 (Formlabs, Somerville, MA), which is a bottom-up desktop vat photopolymerization printer. At a loading of 0.5 wt.% L-CNC, there was an increase in the tensile strength and Young’s modulus by 3% and 5%, respectively [14]. This was achieved only after a thermal post-cure being carried out on the specimens with the non-post-cured specimens showing unimproved or reduced properties depending on the loading of L-CNC [14]. The decrease in material properties that was seen at higher weight percent was attributed to poor dispersion of the L-CNC and poor adhesion between the L-CNC and matrix [14].
Sandoval et al. [12] investigated a composite made from MWCNTs at 0.025 and 0.1 weight percent with an epoxy-based matrix using the commercial resin, DSM Somos® WaterShed™ 11,120. A top-down printer, the 3D Systems SLA-250/50 machine (3D Systems, Rock Hill, SC) was modified from a 47 liter vat to a 500 ml vat with the sweeping mechanism removed, and a peristaltic pump was used to recirculate the resin mixture [12]. The research looked at the increasing tensile strength and fracture strength of the resin. For 0.025 wt.% of MWCNTs, an increase in tensile strength of 5.7% with an increase in fracture strength of 26% was reported. While at 0.10 wt.%, an increase of 7.5% and 33% in tensile and fracture strength, respectively, was reported, but it was pointed out that at the higher loading of 0.1% MWCNTs, there were issues with agglomeration of the MWCNTs [12]. The elongation at break decreased 28% for the MWCNTs reinforced resin, and the fracture mode was reported as a brittle-type verse as more of a ductile failure mode that was seen in the pure resin [12].
Short glass fibers have been studied more as reinforcement materials for vat photopolymerization in part due to the decrease in opacity when compared with that of carbon fiber [3]. In one study, Cheah, C. et al. [19] looked at using short glass fibers 1.6 mm in length at various fiber volume fractions of 0, 5, 10, 15, and 20% and a urethane acrylic matrix, DeSolite SCR310. The experiment was carried out for comparing molded and 3D printed samples. Although the paper does not state what machine was used to print the samples, it can be inferred that a top-down style was used [19]. Cheah et al. saw improvements for all fiber volumes, with increased mechanical properties achieved by increasing fiber amount, and part shrinkage can be reduced. For a fiber volume of 20%, they were able to achieve an increase in tensile strength of 24% and an 80% increase in the Young’s modulus [19]. The top-down vat photopolymerization machine that was employed resulted in the manufacture of composites that were close to unidirectional in fiber orientation due to the scraping step in between layers [19]. While the creation of unidirectional composites is desirable in some applications, the leveling step would prevent the printing of an isotropic part and therefore could limit potential applications and restrict the printing process based on how the part must be printed.
Along with short glass fibers, there have also be studies that have looked into the use of continuous glass fiber as a reinforcement in vat photopolymerization. Karalekas et al. [2] placed a single layer of nonwoven glass fiber mats, of various thicknesses, within specimens produced using vat photopolymerization. This was done by pausing the printer at a predetermined build height, placing the mat of the specimen, and resuming the print [2]. Karalekas et al. were able to show an increase in the Young’s modulus, but a decrease in tensile strength for thinner mats. For the thicker mats, the Young’s modulus was shown to decrease; this was contributed to the inability for the photopolymer to fully cure with in the thicker mats [2]. While this study was able to show that continuous glass fibers could be placed into the part for reinforcement, the fact that it was added by hand during the build process is inefficient, especially if multiple layers of fiber are to be used in the manufacturing of a part, and would be difficult for the manufacturing of complex parts.
Some research has been carried out using continuous carbon fiber by Gupta et al. [17] where to overcome the issues of fully curing the part, a dual curing system was used. The dual curing system employed a photo initiator for initially curing the fiber and matrix in the desired geometry and a thermal initiator to cure the remaining resin. While Gupta et al. were able to show that the system was fully cured, they did not report any information on the material properties of the composite produced and appeared to have limited success in incorporating the initiator into the liquid resin [17]. The ability for the thermal initiator to cure the areas that the UV light cannot, due to the opacity of the carbon fiber, could be a promising method of incorporating carbon fiber into vat photopolymerization produced, shown in Figure 1.
Figure 1.
Dual curing system.
There are a host of complications from suspending fiber to achieving optimal cure with opaque fibers hindering the UV light. Some success has been achieved by introducing glass fibers into vat printers, while struggling to keep a homogeneous resin mixture as the fibers settle to the bottom of the print bed [20].
SLA composite parts have been approached with different tactics in the past. Some success has been achieved in the smaller particle reinforcement with chemical and rheological approaches. For filler-sized particles, approaches such as suspension with shear thinning polymers have been attempted to produce SLA ceramics [21, 22]. Another tactic used is surface modification of the filler to reduce conglomerations and improve the stability of the dispersion [23]. Other research has shown that certain fibers can be aligned and suspended via shear flow or electric field induction [24, 25, 26, 27]. However, using a more common and larger fiber does not allow all these techniques to be applied and requires a different approach.
Fiber suspension is a critical and complicated issue when looking at the disparaging density ranges of fibers to resin combinations. If a homogeneous resin bath cannot be maintained throughout the print, the resulting parts will either have no reinforcement or possibly too much reinforcement to successfully print. An adaptation to a Moai 130 SLA vat printer was designed in this study to provide a homogeneous reinforced resin bath for printing using standard printing parameters. The adaptation ensures the glass fiber is suspended in the build plate region of the vat for the entirety of any print allowing a homogeneous composite component to be manufactured.
2. Equipment and processing
2.1 Opaque reinforcement
A Moai Laser vat photopolymerization printer manufactured by Peopoly, and purchased from MatterHackers, (Lake Forest, CA) as a DIY kit, was assembled and calibrated. The Moai is a bottom-up printer that uses a 405 nm 70-micron spot size laser and is based on an open-sourced design. The photopolymer resin used in this research was Moai Standard Clear resin, by Peopoly purchased from MatterHackers (Foothill Ranch, CA). It is an acrylic-based photopolymer designed to work with the Moai printer being used in this research.
The primary carbon fiber used was Toray T-700. The fiber was purchased from Composite Envisions (Wausau, WI) as a chopped 3 mm fiber and comes sized for epoxies. The fiber was then milled in a Retsch Rotor Beater Mill SR 300 (Retsch GmbH, Haan, Germany) using a 120 μm screen. The milled fiber was then sieved using a stack of screens, with a stacking sequence of 2 mm, 250 μm, 106 μm, and 76 μm. The fibers were collected in between the 106 μm and 76 μm screens. A sample of fibers were observed using an Axovert 40Mat (Carl Zeiss AG, Oberkochen, Germany), with images obtained by a ProgRes C10plus camera (Jenoptik AG, Jena, Germany), to determine the average length along with the length distribution. The processed fibers were then placed in an oven at 80°C and dried for a minimum of 8 hours before use. The distribution of the length of 300 fibers of the milled Toray fibers had an average length 74.1 ± 40.2 μm, and the distribution of the measured lengths is shown in Figure 2.
Figure 2.
Milled Toray T-700 fiber length distribution.
A variety of thermal initiators were investigated in order to identify the optimum thermal initiator to be used in a dual cure system. The thermal initiators were evaluated based off of the thermal initiators solubility with the resin system, the stability of the resin system at room temperature, and the temperatures needed for post-curing of the samples. The thermal initiators investigated were Dilauroyl Peroxide (Luperox LP), Cumene Hydroperoxide, Dicumyl Peroxide, Tert-Butyl Peroxybenzoate (Luperox P), Benzoyl Peroxide (Luperox A98) and were purchased and used as received from Sigma-Aldrich® (St. Louis, MO).
To prepare the resin system, the resin and fiber were first mixed with a high-speed mixer and then sonicated for 5 minutes. After sonication the thermal initiator was added and mixed again with a high-speed mixer. The resin system was then degassed in a vacuum chamber and then immediately used to manufacture samples.
For all samples that are manufactured using the 3D printer for this research, the longitudinal axis of the parts was varied in the x-axis of the printer to examine the effects of part orientation relative to the build surface. For all samples prepared, the finished parts were washed in ethanol after being removed from the build platform. This allows for the removal of any uncured resin, and in the case of the fiber-reinforced samples any loose fibers from the surface. The supports that were generated during the printing process are left in place at this time to support the sample while it was being post-cured.
The neat (non-fiber-reinforced) samples were post-cured in an in-house built cure oven, consisting of three 25 Watt LED UV (405 nm) light banks, a heating element, and a rotating platform. The temperature and the time for the post-cure can be adjusted by the use of proportional-integral-derivative (PID) controller. For the neat samples, a temperature of 80°C was used while being exposed to the UV light for 1 hour. All fiber-reinforced samples were post-cured using a VWR Forced Convection Oven (VWR International, Radnor, PA), with the temperate and times determined from the DSC results. After post-curing the supports were removed from the sample, and the area where the supports were attached was sanded with increasingly finer grits of sand paper, ranging from 60 to 600, with care taken to preserve the sample geometry, which varies depending on the desired testing. This was done to diminish the effects of surface defects (due to support material) on the tested samples.
Composite and neat specimens were printed using a Moai 130 inverted SLA printer with the acrylic vat. Printing was performed using factory settings of the Moai 130, with one exemption. The peel step time was extended to allow more time for the higher viscosity resin mixture to flow in the printed area between layers. A standard Peopoly UV acrylic-based SLA resin was utilized as the resin of choice for both the neat specimens and composite specimens.
2.2 High-density reinforcement
A higher-density short-fiber reinforcement, E-glass fiber procured from Fiber Glast Development Corporation (Brookville, OH), was also studied. Fiber glass was selected for its high degree of transparency to UV light to not reduce the effectiveness of the UV cure. Reinforcing the resin while still allowing for good initial cure from the printer and achieving optimal polymerization through post curing was a goal. The particular glass fibers were 0.8 mm fibers denoting that the fibers have a possible length up to 0.8 mm and smaller, resulting in a mean length of 230 μm.
When manufacturing the neat specimens, no unique changes to the printing process occurred. The resin was simply poured into the vat and printing commenced per standard operating procedure for the Moai 130. The composite resin consisted of 85% resin and 15% fiber glass by volume. The composite resin batches were high-speed mixed and degassed prior to introducing the resin to the printer. The viscosity of the neat resin was found to be 517 Pa*s and the composite mixture was 950 Pa*s using a Brookfield DV-II+ Pro Viscometer. This study focused on 15% fiber volume fraction, as higher fiber loading further increased the viscosity, causing premature recirculating pump failures.
With the composite resin system mixed and degassed, the resin was introduced to a modified vat. The resin tank in the Moai 130 SLA printer was adapted to allow for a flow field in the print region. Inlet ports were fixed to the front of the vat, and outlet ports were fixed to the back of the vat. A diagram and picture setup can be seen in Figure 3. This setup allows for a constant flow and circulation of resin mixture with a changeover rate faster than the settling of the fibers in the resin.
Figure 3.
Diagrams of pumping setup.
Pumping the abrasive resin mixture was accomplished using a 12-volt peristaltic pump. The peristaltic pump utilized 6.4 mm inner diameter tube, which was also the same as the vat connections and made for a seamless transition to recirculate the resin mixture. At max output the motor could achieve 400 ml/min with a hose inner diameter (ID) of 6.4 mm.
After the printing process was complete, the prints where washed with ethanol to remove any UV resin buildup. The print supports were kept in place until after being post cured. To ensure a full cure, all prints were placed in a UV oven for 60 min and 60°C. The oven consisted of a three 25 W LED UV lights and a heating element. The specimens were placed on a rotating platform in the oven. The rotation of the bed allowed for an even distribution of UV Light.
3. Testing and results
3.1 Opaque reinforcement characterization
3.1.1 Testing
The selected thermal initiators were evaluated experimentally via differential scanning calorimetry (DSC) in accordance with ASTM E2160 [28]. The testing was carried out from 25–180°C at a ramp rate of 10°C/min, using a Q20 DSC (TA Instruments, New Castle, DE). For each sample, two runs were carried out. The first was of an uncured sample, and the second was a sample that had been UV cured by placing the DSC pan in the UV cure oven 25.4 mm away from the light source for 1 minute at room temperature. This was done to determine the thermal initiators’ onset temperature and to experimentally determine if any reactions are occurring after UV curing. The samples were tested at a fiber volume (Vf) of 5% and a thermal initiator content of 1 wt.% of thermal initiator. The neat Moai resin was also included to determine if there is any activation of the photo initiator at elevated temperatures. Graphs produced from the DSC data were made using TA Universal Analysis (TA Instruments, New Castle, DE).
Tensile testing was carried out using an Instron 5567 load frame (Instron, Norwood, MA), a 25.4 mm extensometer, and a 2 kN load cell. The load frame was controlled and data collected using Bluehill software (Instron, Norwood, MA). While there are no ASTMs directly concerning 3D printed materials, all tensile testing will be carried out referencing ASTM D638 [29] and ASTM 3039 [30]. The specimen geometry was of the type IV according to ASTM D638 [21]. The type IV specimen was chosen due to the limiting size of the build plate (130 × 130 mm) of the Moai printer being used to conduct this research. All samples were tested at a constant cross-head rate of 1 mm/min, so failure of the specimen occurred within 1–10 minutes of testing, per ASTM D3039 [30]. The flexural testing was carried out using an Instron 5567 load frame (Instron, Norwood, MA) with a 2 kN load cell. The load frame was controlled and data collected using Bluehill software (Instron, Norwood, MA). The flexural testing, referencing ASTM D790 [23], was carried out as a three-point bending utilizing center loading, with specimens having a span-to-thickness ratio of 16:1 and a cross-head rate of 1 mm/min. For each sample, five specimens were tested. The maximum tensile strength and Young’s modulus were found as specified in ASTM D638 Section 11.2 and 11.4 respectively, and the maximum flexural strength and flexural modulus were found as specified in ASTM D790 Section 12.2 and 12.5, respectively [29, 31].
Scanning electron microscopy (SEM) was utilized to examine the fracture surface of tested samples. This will allow for examination of the fracture surface in determining failure types and to evaluate the dispersion and the orientation of the fibers within the sample [32]. Samples were attached to cylindrical aluminum mounts with colloidal silver paste (SPI Supplies, West Chester, Pennsylvania, USA). The specimens were sputter coated (Cressington 108auto, Ted Pella, Redding, California, USA) with a conductive layer of gold. Images were obtained with a JEOL JSM-6490LV scanning electron microscope (JEOL USA, Inc., Peabody MA, USA); energy-dispersive X-ray information was collected at an accelerating voltage of 15 kV using a Thermo Scientific UltraDry Premium silicon drift detector with NORVAR light element window and Noran System Six imaging system (ThermoFisher Scientific, Madison WI, USA).
3.1.2 Results
In order to fully cure all of the resin within the sample, the use of a dual cure system that uses both a photo initiator and a thermal initiator was investigated. The results of the DSC testing are shown in Figure 4 (non-UV-cured samples) and Figure 5 (UV-cured samples) are summarized in Table 1.
Thermal initiator onset temperature from DSC curves.
Based off of the results from the thermal initiator testing, Luperox P was chosen as the thermal initiator to be evaluated for the dual cure resin system and was determined to be effective at a 0.5 wt.%. The 10 hour half-life is the temperature at which half the content of the peroxide is lost after 10 hours. Making all of these peroxides a stable option for the processing will still have peroxide available during the thermal post curing process.
The fiber volume consistency results are summarized in Table 2. The top section of the samples has a higher fiber volume than what the resin mixture was designed to have (5% Vf). This is due to the lowering of the bed plate into the vat trapping more fibers in between the sample and bottom of the vat then desired. The reason believed for the samples to have lower and similar fiber volume gradients despite the different print times is that the area around the sample being printed becomes depleted of fibers as the sample is printed. This slowly lowers the fiber volume of the sample as it is going through the printing process.
Layer height (μm)
Print time (hours)
Top (% Vf)
Middle (% Vf)
Bottom (% Vf)
100
3.0
5.23 ± 0.02
4.84 ± 0.10
3.57 ± 0.27
50
5.25
5.45 ± 0.15
4.50 ± 0.13
3.88 ± 0.01
Table 2.
Summarized fiber volume consistency results for flexural samples.
Because the flexural specimens have a larger cross-sectional area throughout the entire specimen, the fiber gradient appears more pronounced. Similar burn off testing was carried out with the tensile specimens with the exception that only the two ends of the specimen were tested. The average difference in the fiber volume of the top and bottom portions of the tensile specimens changes by on average of 0.8% for the specimens printed in the 90° orientation. This lower difference could be due to the varying specimen geometry, or that due to their large size, less specimens were printed at the same time to keep the print time short. This allowed for more spacing between the specimens and could have prevented the fiber from becoming depleted from around the specimens being printed.
To aid in sample identification, the follow naming scheme will be implemented for the remainder of this paper. It will consist of the main material parameter being looked at along with the layer height and print orientation. The lettering is in Ref. to the material parameter: M is Moai resin as supplied, LP is Moai resin mixed with thermal initiator (Luperox P), and C consists of carbon fiber, thermal initiator (Luperox P), and Moai resin. The number following the lettering is the layer height (100 μm or 50 μm). The number following the hyphen is the angle (0° or 90°) between the longitudinal axis of the sample and the build platform during the manufacturing process. The summarized results of the tensile and flexural testing are shown in Table 3. The samples are identified with a superscript in the first column and identified with the superscripts of other groups in which significant statistical difference between the results was found via an ANOVA analysis and post-hoc Tukey HSD test at a 95% confidence interval. The samples are compared across four different groups: 0° orientation, 90° orientation, 100 μm layer height, and 50 μm layer height.
Sample
Tensile strength (MPa)
Young’s modulus (GPa)
Flexural strength (MPa)
Flexural modulus (GPa)
M100-0
58.9 ± 5.0
2.72 ± 0.06
86.0 ± 9.5
2.52 ± 0.07
M100-90
66.1 ± 0.4
2.87 ± 0.05
96.2 ± 1.7
2.42 ± 0.01
M50-0
43.4 ± 7.7
2.81 ± 0.15
82.2 ± 11.2
2.42 ± 0.05
M50-90
64.6 ± 1.6
2.89 ± 0.12
100.8 ± 3.4
2.62 ± 0.06
LP100-0
36.9 ± 7.9
3.17 ± 0.15
27.9 ± 5.4
2.34 ± 0.15
LP100-90
27.6 ± 22.5
3.17 ± 0.26
14.6 ± 3.0
2.47 ± 0.21
LP50-0
50.3 ± 7.7
3.04 ± 0.11
23.9 ± 3.7
2.55 ± 0.23
LP50-90
68.8 ± 5.9
2.83 ± 0.01
13.2 ± 0.6
2.50 ± 0.20
CF100-0
52.4 ± 3.7
3.29 ± 0.29
84.9 ± 4.3
2.59 ± 0.06
CF100-90
41.4 ± 2.6
3.39 ± 0.52
66.1 ± 0.5
2.31 ± 0.11
CF50-0
50.6 ± 6.6
3.46 ± 0.17
43.4 ± 5.5
2.64 ± 0.12
CF50-90
11.69 ± .28
2.92 ± 0.01
19.4 ± 2.5
2.58 ± 0.16
Table 3.
Summarized tensile and flexural testing results.
When comparing the Young’s modulus of the samples, there was an increase of 21% between the M100-0 and CF100-0 samples and an increase of 27% for the M50-0 and the CF50-0 with an increase in Young’s modulus for the CF50-0 samples when compared with the CF100-0 of 5%. While showing only 4% increase between the LP100-0 and CF100-0 samples and 13% increase for the LP50-0 and CF50-0, evidence of the weak interfacial properties of the short-fiber composite samples can be seen in Figure 6.
Figure 6.
Fracture surface of CF50-0 (A) X200 and (B) X250 magnification.
In Figure 6, the smooth channels left behind from the carbon fiber in A, the clean (lack of bonded matrix material) fibers present in B, and the smooth holes in B are all signs of weak interfacial properties due to poor bonding between the matrix and fiber [6, 34]. This limits the ability for the matrix to transfer stress to the fibers and therefore reduce its overall properties [6]. If the composite had better interfacial properties, there would have been evidence of fiber breakage, which was not present in any of the SEM images taken [6, 34].
When comparing the modulus of the carbon fiber samples printed at different layer heights (100 μm and 50 μm), the increase in modulus of 5% can be attributed to the partial alignment of the fibers in the loading direction. The CF100-90 has a higher modulus than the CF50-90 samples. While this would be expected if the material was going from isotropic material to a special orthotropic material due to fiber alignment, it is not the case for these samples due to cracks being present in the CF50-90 samples [6]. The alignment of the fibers via layer height is demonstrated in Figure 7 with the yellow arrows highlighting the various fiber orientations.
Figure 7.
Fracture surface of (A) CF100-90 and (B) CF50-90 specimens.
When comparing the strength of the Moai resin samples, the samples printed in the 90° print orientation for the Moai resin have a higher strength when compared with the same samples printed in the 0° print orientation. This is due to the effects of the support material being removed and leaving behind notches in the specimen. These notches then act as small stress concentrators resulting in lower strength of the sample [35]. Due to these effects, the Moai resin samples tested at a print orientation of 90° are a better representation of the actual ultimate tensile strength of the neat resin material. The samples tested with just the thermal initiator (Luperox P) added also showed flaws the contributed to a lower tensile strength result. These are from cracks that were present on the surface of the samples, which originated during the thermal curing process. These cracks originated from the volumetric shrinkage that occurs during the post-curing process as the degree of conversion within the system increases [36].
The lower strength of the carbon fiber samples is due in part to the end effects of the fiber reinforcement acting as stress concentrators within the composite [6]. This is caused by the large number of very short fibers (much less than the critical length) in the distribution of the lengths, seen in Figure 2, being present in the sample [6]. The strength of short-fiber composites is also affected by the length of the carbon fiber being used. To get the maximum amount of reinforcement from the carbon fiber, the fiber needs to be over a critical length to maximize the load transfer between the fiber and matrix [6]. The shorter length of the fibers (76 μm) being used is below the critical length needed for the system (433 μm using a shear lag model) [6]. This results in the load not being fully transferred to the fiber and limiting the composites performance [6].
Overall the flexural modulus of the samples was not improved by the addition of the carbon fiber. This could be primarily due to the lower fiber volume (5%) of the samples, causing them to have results similar to that of the neat resin samples. During the flexural testing, the specimens are subjected to the more complex stress state (compressive, tensile, and shear) when compared with the tensile testing [28, 29].
The effect of the fiber volume gradient that was present in the samples would also have a more pronounced effect of the results when compared with the tensile testing. For the tensile specimens, the gage section had similar fiber volume amount within the measured section. Among the flexural specimens, the whole specimen (within the span length) is tested allowing for failure to occur in the regions of lower fiber volume.
For the flexural testing, the samples are subjected to compressive, tensile, and shear stresses that lead to the multiple failure mechanisms affecting the flexural properties of material [29]. The tensile stresses can lead to fiber breakage and debonding, while compressive stresses can lead to fiber shear and/or buckling and kinking [29]. The fibers exhibited characteristics indicating poor interfacial strength between the fiber and matrix. This along with the low fiber content and weak shear properties of carbon fiber would lead to the failure of the flexural testing to coincide more with that of the compressive type failures, which are governed more by the matrix properties [6, 37, 38].
The samples made with just Luperox P added showed the same type of surface cracking after post-curing as was seen in the tensile samples. This led to them having the weakened flexural strength as seen in the tensile samples made of the same constituents. The carbon fiber samples exhibited poorer flexural strength than the neat Moai resin samples due to the effects of the fiber ends acting as stress concentration, weak interfacial properties, low fiber content, and the presence of voids [6].
3.2 High-density reinforcement characterization
3.2.1 Testing
Printed specimens were characterized for density, 3 pt. flexure, notched fracture toughness, and dynamic mechanical analysis (DMA). The testing conducted is to illustrate the performance enhancements and the quality of cure and consistency of the resulting composite parts.
Density calculations were performed to ensure the fibers were evenly dispersed, following ASTM D792-13 Test Method A [39]. An Ohaus Adventurer (Ohaus Corp., Parsippany, NJ) scale was used to weigh four sections from four different specimens. Using a Mettler Toledo (Mettler Toledo, Columbus, OH) density determination kit, the density comparison was conducted between samples printed using the flow process and one specimen without resin flow. Where A is the weight of the sample in air, B is the weight of the sample in water and the density of water and air with subscripts O and L respectively to calculate the density of the samples.
ρ=AA−BρO−ρL+ρLE1
The flexural testing was carried out using an Instron 5567 load frame (Instron, Norwood, MA) with a 2 kN load cell. The load frame was controlled and data collected using Bluehill software (Instron, Norwood, MA). The flexural testing, referencing ASTM D790 [31], was carried out as a three-point bending utilizing center loading, with specimens having a span-to-thickness ratio of 16:1 and a cross-head rate of 1 mm/min. For each sample, five specimens were tested and the maximum flexural strength and flexural modulus were found as specified in ASTM D790 Section 12.2 and 12.5, respectively [29, 31].
Notch fracture testing was carried out using ASTM D5045 [40] standard with an Instron 5567 load frame and a 2kN load cell. Single-edge-notch bending (SENB) specimens were created as rectangular bars 7 mm × 13 mm x 63 mm. These bars were notched post processing using a vertical mill and a final fine crack initiated with a razor blade. Five neat and five reinforced samples were tested and post-test measured using a Keyence VHX-7000 Digital Microscope for the crack length determination.
Glass fiber is highly transparent to UV light, but DMA was performed to ensure that each part was optimally cured. To perform this, ASTM D5418-15 [41] was followed. Three samples of both neat and glass fiber-reinforced specimens were printed. Duel cantilever DMA was chosen because the Tg can easily be evaluated at the peak of the tan(δ) curve. Each sample was printed at 60 mm x 13 mm × 4 mm to fit in the duel cantilever grips. A TA Instruments DISCOVERY DMA850 was used with a temperature range of 30–150°C, a frequency of 1 Hz, an amplitude of 15 μm, and a heating rate of 1°C/min.
3.2.2 Results
As observed in other research attempts, the high-density fiber glass quickly settles to the bottom of the print. This results in components that have the desired reinforcement at the beginning of the print, but little to no reinforcement after the glass settles to the bottom of the VAT and is unable to flow into the print area. The printer does not have a swipe step or means of resin movement, which allows the fibers to settle to the bottom. With the fiber on the bottom, the fiber free resin is allowed to flow back into the print area with very few fibers present. Therefore, the density of the composite will vary from the top of the print to the bottom of the print without a pumping system. When examining the samples, a gradient of fibers/density could easily be seen without a microscope with the specimens printed without flow.
Comparison of glass content and distribution between prints with no pump and pump can be seen in Figure 8. The fiber distribution is consistent from the start to finish for the specimen printed with the pump providing a flowing resin mixture. Figure 8B is the end of the print and Figure 8D is the beginning of the part but after the scaffolds had already been printed. Similarly, Figure 8A is the end of the print and Figure 8C is the start of the part but after the scaffolds. It can be seen that even at the start of the part, there is very little glass in the part and diminishes to nearly no fiberglass by the end of the print. No discernable differences were found when observing parts printed with the circulation pump. Figure 8 images are taken using a Keyence VHX 7000 digital microscope (Keyence Corp of America, Itasca, IL).
Figure 8.
A, end of print with no pump; B, end of print with pump; C, start of print with no pump; D, start of print with pump.
Table 4 shows the density averages of the specimens printed. The theoretical density of the composite specimens at 15% fiber volume fraction, assuming no voids, was 1.42 g/cm3. The three samples that used the pumping system only had a 1.4% deviation from the target density. As predicted, the density of the no flow specimen was much lower as the majority of the volume did not have any fiberglass present. The composite specimens created with the flow field were consistent and very close to the theoretical density.
Process
Density g/cm3
No pumping
1.26
Sample 1
1.39
Sample 2
1.40
Sample 3
1.39
Table 4.
Densities of specimens examined.
For fracture toughness, the Keyence microscope was used to measure the crack length in each specimen. The calibration factor was then calculated for the SENB specimen, and this factor ensured that each specimen was comparable. This calibration factor is denoted as fx and takes the geometry of each specimen into account. In this equation KIC is the fracture toughness, PQ is the max flexure load, B is the thickness at the crack and, W is the width at the crack.
KIC=PQBW12fxE2
An increase in fracture toughness of 32.5% was observed when adding 15% glass fiber to the resin. These results can be observed below in Figure 9. This is a tremendous improvement to one of the historically low properties of a UV curable resin. Also, the standard deviation narrowed in the results when testing reinforced specimens, providing a more consistent performing product.
Figure 9.
Average fracture toughness of neat and glass-reinforced samples.
The increase in fracture toughness by addition of short fibers is not uncommon, and the difference in fracture surface helps discuss the increase. Figure 10A is the nearly perfectly smooth brittle failure of the Neat specimen, and Figure 10B shows the reinforced fracture surface. The reinforced fracture surface exhibits a multitude of fracture surface redirections because of the obstructing fibers, greatly increasing the fracture surface area. Fiber pullout can also be seen on the surface providing increased toughness and ductility.
Figure 10.
Fracture toughness surface: A, neat; B, fiberglass.
The flexural results are a great indicator of a part’s quality and encompass the overall performance of the resulting composite. One of the most obvious improvements is the reproducibility of the results that can be seen in Figure 13. By introducing fiberglass to the system, there was not only a substantial improvement in modulus but overall a more predictable performance was obtained. During testing, crazing could be observed on the tensile side of the flexural specimen during the plastic deformation portion of the test on just the reinforced specimens. Abrupt brittle failure occurred on all the neat specimens with each specimen having multiple fracture surfaces. The change in the average maximum flexural stress, average flexural modulus, and average max strain is shown in the graphs below (Figure 11). The addition of the 15% fiberglass increased the average flexure stress by 18%, increased the average modulus by 38%, and effectively did not change the average strain to failure.
Figure 11.
Comparison of neat and glass fiber-reinforced samples of: Modulus, flexure strength, and flexure strain.
The fracture surfaces can be seen in Figure 12A for the Neat specimen and Figure 12B for the reinforced specimen. The brittle failure on the neat specimens is very clean and consistent. While the fracture surface of the reinforced specimen shows signs of more cumulative damage. In Figure 12B, the tensile side of the flexural specimen on the right where the bright white shades on the surface can be seen and at the neutral axis going to the left the compression side shows a clear resin appearance. On the compression side of the specimen, there was little evidence of permanent deformation. On the tensile side, the specimen has crazing, which is the white portion of the specimens on the right side of the neutral axis. This microscopic evidence supports the results of increasing the modulus significantly and improving the toughness of the printed specimen by retaining the strain to failure of the neat polymer. The fibers are providing continued stress transfer and continuity beyond the polymers ability.
Figure 12.
Flexural specimens: A, neat; B, fiberglass.
Figure 13 is the fracture surface from the Figure 12B on the tensile side of the specimen. The image shows clean fiber pullouts and areas of crazing. The fibers are not at a critical length where stress transfer is expected to be significant enough to fracture the fibers in the tensile. Also, seen in this image is the randomness of fiber orientation in the left to right directions, but rarely in the z-direction of the print, which is top to bottom. This orientation is due to the fiber length being greater than the print layer height, allowing for fiber alignment to be reduced to one plane.
Figure 13.
Flexural fracture surface at 200×.
To understand if the level of cure of the reinforced specimens was equal to the neat specimens, DMA was performed. The Tg was found using the tan(δ) curve. The neat resin was considered to be optimally cured by the recommended manufacture processing and post curing of the resin, with the reinforced specimens receiving the same processing parameters. Examining the curves of the neat samples, the average Tg was found to 107.59°C. Sample 3 had the closest actual Tg to the average and can be seen below in Figure 14.
Figure 14.
Neat sample 3 of DMA testing.
The three composite specimens yielded an average Tg of 109.19°C. Glass sample 1 had the closest Tg to this value, and the graph can be seen below in Figure 15. Adding fiberglass to a neat resin usually results in an improvement in Tg. It was found that by adding the glass fiber to the resin matrix, the Tg increased by 1.6°C. This increase in Tg does confirm that the specimens were comparably cured with and without the fiberglass reinforcement.
Figure 15.
Glass sample 1 of DMA testing.
4. Conclusions
From the DSC results, it was determine that the neat Moai resin did not exhibit any curing due to thermal processing, but with the incorporation of a thermal initiator, the resin would cure both with and without prior UV curing. Luperox P was chosen as the thermal initiator that yielded the best results from the ones evaluated, from both processing and material properties perspective.
From the tensile testing results, the carbon fiber samples showed an increase in Young’s modulus of 21% for a 100 μm layer height, and a 27% for a 50 μm layer height. The change in the modulus due to the lower layer height is due to the fibers being aligned in the loading direction within the sample. This demonstrates that manipulating a part’s properties based off of fiber length and layer height could be possible. This increase was less than what was predicted by theoretical models. The lower modulus was thought to be caused by large distribution of fiber lengths and poor interfacial properties between the carbon fiber and matrix. These defects also lead to the carbon fiber samples having a lower tensile strength than the neat Moai resin samples. With improvements in these areas, the tensile properties of the composite could be further improved.
The flexural strength, flexural modulus, and fracture toughness showed no noticeable gains in material properties from the use of the carbon fiber reinforcement. For the flexural testing, this is thought to be because of the low fiber volume (5%) and high fiber volume inconsistency of the samples. While factors such as interfacial strength, fiber length distribution and volume consistency, and low fiber volume content lowered the effectiveness of the carbon fiber as a reinforcement, the main limiting factor is the fiber length itself. The shorter length of the fibers (76 μm) being used is below the critical length needed for the system (433 μm using a shear lag model) [6]. While it would be possible to incorporate fibers of this length into the resin and print parts, they could not have isotropic properties due to forced alignment of the layer height. The effects of fibers folding over within the layers could also affect the ability for the part to print successfully. This could be by limiting the amount of matrix material available to keep the layers attached to one and another. To avoid this, it would require a layer height at least as larger as the fiber length itself. This is outside of the capabilities of even industrial grade vat photopolymerization printers, that typical print at around 200 μm on the top end of layer height [30]. The incorporation of carbon fiber and the subsequent shadowing of the photo initiator from the UV source would even further limit the depth of cure that could be achieved. So while it might not be feasible to use fiber with a length of 433 μm, increasing the fiber length and tightening the fiber length distribution would aid in increasing the material properties for the samples studied in this research.
Additive manufacturing of high-density reinforcement composites using SLA vat printing can be accomplished using the newly developed adaptation of flow induction. Composites with reinforcements having largely disparaging densities can be homogenously manufactured with standard operational settings. This study proved out that the short glass fibers can be incorporated into a 3D printed part resulting in tremendous improvements in mechanical properties while maintaining print cure and consistency. This patent pending design (US Patent Application 63/073,260) can allow for 3D printing to continue to expand its offerings and capabilities.
Acknowledgments
This work was supported by the Army Research Laboratory Award #W911NF-16-0242.
Conflict of interest
The authors declare no conflict of interest.
\n',keywords:"stereolithography, composites, carbon fiber, fiber glass, and dual cure",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/79627.pdf",chapterXML:"https://mts.intechopen.com/source/xml/79627.xml",downloadPdfUrl:"/chapter/pdf-download/79627",previewPdfUrl:"/chapter/pdf-preview/79627",totalDownloads:105,totalViews:0,totalCrossrefCites:0,dateSubmitted:"September 17th 2021",dateReviewed:"October 29th 2021",datePrePublished:"December 10th 2021",datePublished:null,dateFinished:"December 10th 2021",readingETA:"0",abstract:"Stereolithography (SLA) is a widely utilized rapid additive manufacturing process for prototypes and proof-of-concept models with high resolution. In order to create structurally sound components using SLA, reinforcement needs to be incorporated in the UV-based resins typically used. However, the introduction of reinforcement into vat-based SLA printers has had limited success due to a host of processing challenges including the creation of a homogeneous resin mixture and UV-inhibiting constituents. The effectiveness of using a dual curing system, consisting of a photo and thermal initiator, for the additive manufacturing of carbon fiber short-fiber composites via vat photopolymerization, was investigated. The necessary processing parameters were developed that resulted in successful printing and curing of composites at a 5% fiber volume. Manufacturing with reinforcements that have different densities from the resin creates separation issues, either suspending to the top or settling to the bottom. Following the approaches discussed in this chapter, an even distribution of short fibers was achieved throughout SLA printed samples using a modified commercial printer. Separation was overcome by inducing a continuous flow of reinforced liquid resin in the printer vat during printing. This flow field adaptation allows commercial SLA printers the ability to produce composite parts with different densities of the constituents utilized.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/79627",risUrl:"/chapter/ris/79627",signatures:"Patrick Simpson, Michael Holthaus, Luke Gibbon and Chad Ulven",book:{id:"10974",type:"book",title:"Advanced Additive Manufacturing",subtitle:null,fullTitle:"Advanced Additive Manufacturing",slug:null,publishedDate:null,bookSignature:"Prof. Igor V. Shishkovsky",coverURL:"https://cdn.intechopen.com/books/images_new/10974.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-83962-821-4",printIsbn:"978-1-83962-820-7",pdfIsbn:"978-1-83962-822-1",isAvailableForWebshopOrdering:!0,editors:[{id:"174257",title:"Prof.",name:"Igor V.",middleName:null,surname:"Shishkovsky",slug:"igor-v.-shishkovsky",fullName:"Igor V. Shishkovsky"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Equipment and processing",level:"1"},{id:"sec_2_2",title:"2.1 Opaque reinforcement",level:"2"},{id:"sec_3_2",title:"2.2 High-density reinforcement",level:"2"},{id:"sec_5",title:"3. Testing and results",level:"1"},{id:"sec_5_2",title:"3.1 Opaque reinforcement characterization",level:"2"},{id:"sec_5_3",title:"3.1.1 Testing",level:"3"},{id:"sec_6_3",title:"Table 1.",level:"3"},{id:"sec_8_2",title:"3.2 High-density reinforcement characterization",level:"2"},{id:"sec_8_3",title:"3.2.1 Testing",level:"3"},{id:"sec_9_3",title:"Table 4.",level:"3"},{id:"sec_12",title:"4. 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Electric field induced formation of one-dimensional bismuth ferrite (BiFeO3) nanostructures in electrospinning process. Materials and Design. 2016;94:487-495'},{id:"B25",body:'Liu Y, Chung J-H, Liu W, Ruoff R. Dielectrophoretic assembly of nanowires. The Journal of Physical Chemistry. 2006;B 110:14098-14106'},{id:"B26",body:'Li Y, Wu Y. Coassembly of graphene oxide and nanowires for large-area nanowire alignment. Journal of the American Chemical Society. 2009;131:5851-5857'},{id:"B27",body:'Yunus D, Shi W, Sohrabi S, Liu Y. Shear induced alignment of short nanofibers in 3D printed polymer composites. Nanotechnology. 2016;27:49'},{id:"B28",body:'ASTM. E2160-04 Standard Test Method for Heat of Reaction of Thermally Reactive Materials by Differential Scanning Calorimetry. West Conshohocken, PA: ASTM International; 2018'},{id:"B29",body:'ASTM. D638-14 Standard Test Method for Tensile Properties of Plastics. West Conshohocken, PA: ASTM International; 2014'},{id:"B30",body:'ASTM. D3039/D3039M-17 Standard Test Method for Tensile Properties of Polymer Matrix Composite Materials. West Conshohocken, PA: ASTM International; 2017'},{id:"B31",body:'ASTM. D790-17 Standard Test Methods for Flexural Properties of Unreinforced and Reinforced Plastics and Electrical Insulating Materials. West Conshohocken, PA: ASTM International; 2017'},{id:"B32",body:'Zhang H, Zhang Z, Breidt C. Comparison of short carbon fibre surface treatments on epoxy composites: I. Enhancement of the mechanical properties. Composites Science and Technology. 2004;64(13):2021-2029'},{id:"B33",body:'Dixon KW. Decomposition rates of organic free radical initiators. In: Polymer Handbook. Vol. 4. New York: John Wiley & Sons, Inc.;1999'},{id:"B34",body:'Purslow D. Matrix fractography of fibre-reinforced epoxy composites. Composites. 1986;17(4):289-303'},{id:"B35",body:'Anderson TL. Fracture Mechanics: Fundamentals and Applications. Boca Rarton, FL: CRC Press; 2005'},{id:"B36",body:'Braga RR, Ballester RY, Ferracane JL. Factors involved in the development of polymerization shrinkage stress in resin-composites: A systematic review. Dental Materials. 2005;21(10):962-970'},{id:"B37",body:'Chambers AR, Earl JS, Squires CA, Suhot MA. The effect of voids on the flexural fatigue performance of unidirectional carbon fibre composites developed for wind turbine applications. International Journal of Fatigue. 2006;28(10):1389-1398'},{id:"B38",body:'Parry TV, Wronski AS. Kinking and tensile, compressive and interlaminar shear failure in carbon-fibre-reinforced plastic beams tested in flexure. Journal of Materials Science. 1981;16(2):439-450'},{id:"B39",body:'“Standard Test Methods for Plane-Strain Fracture Toughness and Strain Energy Release Rate of Plastic Materials”, D5045-14. West Conshohocken, PA: ASTM International; 2014'},{id:"B40",body:'“Standard Test Method for Plastics: Dynamic Mechanical Properties: In Flexure (Dual Cantilever Beam)”, D5418-15. West Conshohocken, PA: ASTM International; 2015'},{id:"B41",body:'ASTM D792-13 Standard Test Methods for Density and Specific Gravity (Relative Density) of Plastics by Displacement. West Conshohocken, PA: ASTM International; 2013'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Patrick Simpson",address:null,affiliation:'
North Dakota State University, Fargo, North Dakota, United States of America
North Dakota State University, Fargo, North Dakota, United States of America
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The Open Access model is applied to all of our publications and is designed to eliminate subscriptions and pay-per-view fees. This approach ensures free, immediate access to full text versions of your research.
As a gold Open Access publisher, an Open Access Publishing Fee is payable on acceptance following peer review of the manuscript. In return, we provide high quality publishing services and exclusive benefits for all contributors. IntechOpen is the trusted publishing partner of over 140,000 international scientists and researchers.
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XML Typesetting and pagination - web (PDF, HTML) and print files preparation
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Permanent and unrestricted online access to your work
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Your Author Service Manager will inform you of any items not covered by the OAPF and provide exact information regarding those additional costs before proceeding.
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Open Access Funding
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Proven world leader in Open Access book publishing with over 10 years experience
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The Open Access Publishing Fee (OAPF) is payable only after your book chapter, monograph or journal article is accepted for publication.
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OAPF Publishing Options
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850 GBP Journal Article (Across Portfolio)
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During the launching phase journals do not charge an APC, rather they will be funded by IntechOpen.
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Services included are:
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An online manuscript tracking system to facilitate your work
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Personal contact and support throughout the publishing process from your dedicated Author Service Manager
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English language copyediting and proofreading, including the correction of grammatical, spelling, and other common errors
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XML Typesetting and pagination - web (PDF, HTML) and print files preparation
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Discoverability - electronic citation and linking via DOI
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Permanent and unrestricted online access to your work
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What isn't covered by the Open Access Publishing Fee?
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If your manuscript:
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Your Author Service Manager will inform you of any items not covered by the OAPF and provide exact information regarding those additional costs before proceeding.
\n\n
Open Access Funding
\n\n
To explore funding opportunities and learn more about how you can finance your IntechOpen publication, go to our Open Access Funding page. IntechOpen offers expert assistance to all of its Authors. We can support you in approaching funding bodies and institutions in relation to publishing fees by providing information about compliance with the Open Access policies of your funder or institution. We can also assist with communicating the benefits of Open Access in order to support and strengthen your funding request and provide personal guidance through your application process. You can contact us at funders@intechopen.com for further details or assistance.
\n\n
For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
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Added Value of Publishing with IntechOpen
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Choosing to publish with IntechOpen ensures the following benefits:
\n\n
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Indexing and listing across major repositories, see details ...
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Long-term archiving
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Visibility on the world's strongest OA platform
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Live Performance Metrics to track readership and the impact of your chapter
\n\t
Dissemination and Promotion
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Benefits of Publishing with IntechOpen
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Proven world leader in Open Access book publishing with over 10 years experience
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+5,700 OA books published
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Most competitive prices in the market
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Optimized processes that assure your research is made available to the scientific community without delay
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Personal support during every step of the publication process
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+184,650 citations in Web of Science databases
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Currently strongest OA platform with over 175 million downloads
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Within academia, it has frequently been seen as the bastion of medical teaching, even as a handmaid of surgery. To the general public over recent years, it is represented by the enormously popular public exhibitions of plastinated cadavers and body parts. Increasingly within medical teaching, it has acquired a far more humanistic face, epitomized by ceremonies at the start and end of dissection to connect the dead body with the once living individual and his/her families. Modern anatomy has also developed a strong research ethos. These movements can be traced in the many editions of Gray’s Anatomy, from 1858 to the present day. However, the humanistic side of anatomy reminds us that anatomy is not merely a science, since its ethical dimensions are legion as it has transformed from a dubiously moral and barely legal activity to one that now aims to manifest the highest of ethical standards. Nevertheless, it continues to have challenging dimensions, such as its ongoing dependence upon the use of unclaimed bodies in many societies. These challenges are reminders that anatomy does not remain stationary.",book:{id:"5933",slug:"human-anatomy-reviews-and-medical-advances",title:"Human Anatomy",fullTitle:"Human Anatomy - Reviews and Medical Advances"},signatures:"David Gareth Jones",authors:[{id:"35851",title:"Prof.",name:"Gareth",middleName:null,surname:"Jones",slug:"gareth-jones",fullName:"Gareth Jones"}]},{id:"55203",doi:"10.5772/intechopen.68775",title:"Innovative Technologies for Medical Education",slug:"innovative-technologies-for-medical-education",totalDownloads:2124,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"This chapter aims to assess the current practices of anatomy education technology and provides future directions for medical education. It begins by presenting a historical synopsis of the current paradigms for anatomy learning followed by listing their limitations. Then, it focuses on several innovative educational technologies, which have been introduced over the past years to enhance the learning. These include E-learning, mobile apps, and mixed reality. The chapter concludes by highlighting future directions and addressing the barriers to fully integrating the technologies in the medical curriculum. As new technologies continue to arise, this process-oriented understanding and outcome-based expectations of educational technology should be embraced. With this view, educational technology should be valued in terms of how well the technological process informs and facilitates learning, and the acquisition and maintenance of clinical expertise.",book:{id:"5933",slug:"human-anatomy-reviews-and-medical-advances",title:"Human Anatomy",fullTitle:"Human Anatomy - Reviews and Medical Advances"},signatures:"Pascal Fallavollita",authors:[{id:"85455",title:"Prof.",name:"Pascal",middleName:null,surname:"Fallavollita",slug:"pascal-fallavollita",fullName:"Pascal Fallavollita"}]},{id:"54586",doi:"10.5772/67897",title:"Human Brain Anatomy: Prospective, Microgravity, Hemispheric Brain Specialisation and Death of a Person",slug:"human-brain-anatomy-prospective-microgravity-hemispheric-brain-specialisation-and-death-of-a-person",totalDownloads:1557,totalCrossrefCites:0,totalDimensionsCites:3,abstract:"Central nervous system seems to float inside a craniospinal space despite having miniscule amount of CSF. This buoyancy environment seems to have been existing since embryogenesis. This indicates central nervous system always need microgravity environment to function optimally. Presence of buoyancy also causes major flexure to occur at midbrain level and this deep bending area of the brain, better known as greater limbic system seems to regulate brain functions and site for cortical brainwave origin. These special features have made it as a possible site for seat of human soul and form a crucial part in discussion related to death. Besides exploring deep anatomical areas of the brain, superficial cortical areas were also studied. The brainwaves of thirteen clinical patients were analysed. Topographical, equivalent current dipoles and spectral analysis for somatosensory, motor, auditory, visual and language evoked magnetic fields were performed. Data were further analysed using matrix laboratory method for bilateral hemispheric activity and specialization. The results disclosed silent word and picture naming were bilaterally represented, but stronger responses were in the left frontal lobe and in the right parieto-temporal lobes respectively. The sensorimotor responses also showed bilateral hemispheric responses, but stronger in the contralateral hemisphere to the induced sensation or movements. For auditory-visual brainwave responses, bilateral activities were again observed, but their lateralization was mild and could be in any hemisphere. The conclusions drawn from this study are brainwaves associated with cognitive-language, sensorimotor and auditory-visual functions are represented in both hemispheres; and they are efficiently integrated via commissure systems, resulting in one hemispheric specialization. Therefore, this chapter covers superficial, integrative and deep parts of human brain anatomy with emphasis on brainwaves, brain functions, seat of human soul and death.",book:{id:"5933",slug:"human-anatomy-reviews-and-medical-advances",title:"Human Anatomy",fullTitle:"Human Anatomy - Reviews and Medical Advances"},signatures:"Zamzuri Idris, Faruque Reza and Jafri Malin Abdullah",authors:[{id:"42580",title:"Prof.",name:"Jafri",middleName:"Malin",surname:"Abdullah",slug:"jafri-abdullah",fullName:"Jafri Abdullah"},{id:"73844",title:"Prof.",name:"Zamzuri",middleName:null,surname:"Idris",slug:"zamzuri-idris",fullName:"Zamzuri Idris"},{id:"200214",title:"Dr.",name:"Faruque",middleName:null,surname:"Reza",slug:"faruque-reza",fullName:"Faruque Reza"}]},{id:"66388",doi:"10.5772/intechopen.85177",title:"Orexin System and Avian Muscle Mitochondria",slug:"orexin-system-and-avian-muscle-mitochondria",totalDownloads:864,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"In mammals, orexin A and B (also known as hypocretin 1 and 2) are two orexigenic peptides produced primarily by the lateral hypothalamus that signal through two G-protein-coupled receptors, orexin receptors 1/2, and have been implicated in the regulation of several physiological processes. However, the physiological roles of orexin are not well defined in avian (non-mammalian vertebrate) species. Recently, we made a breakthrough by identifying that orexin and its related receptors 1/2 (ORXR1/2) are expressed in avian muscle tissue and cell line, and appears to be a secretory protein. Functional in vitro studies showed that orexin A and B differentially regulated expression of the orexin system, suggesting that orexins might have autocrine, paracrine, and/or endocrine roles. Administration of recombinant orexin modulated mitochondrial biogenesis, dynamics, function, and bioenergetics. In this chapter, we include a brief overview of the (patho) physiological role of orexin, comparative findings between mammalian and avian orexin, and in-depth analysis of orexin’s action on avian muscle mitochondria.",book:{id:"7870",slug:"muscle-cells-recent-advances-and-future-perspectives",title:"Muscle Cells",fullTitle:"Muscle Cells - Recent Advances and Future Perspectives"},signatures:"Kentu Lassiter and Sami Dridi",authors:[{id:"274577",title:"Ph.D. Student",name:"Kentu",middleName:null,surname:"Lassiter",slug:"kentu-lassiter",fullName:"Kentu Lassiter"},{id:"274579",title:"Dr.",name:"Sami",middleName:null,surname:"Dridi",slug:"sami-dridi",fullName:"Sami Dridi"}]},{id:"66964",doi:"10.5772/intechopen.85903",title:"Vascularisation of Skeletal Muscle",slug:"vascularisation-of-skeletal-muscle",totalDownloads:926,totalCrossrefCites:0,totalDimensionsCites:3,abstract:"Skeletal muscle is mainly involved in physical activity and movement, which requires a large amount of glucose, fatty acids, and oxygen. These materials are supplied by blood vessels and incorporated into the muscle fiber through the cell membrane. In contrast, metabolic waste is discarded outside the cell membrane and removed by blood vessels. The formation of a functional, integrated vascular network is a fundamental process in the growth and maintenance of skeletal muscle. On the other hand, vascularization is one of the main central components in skeletal muscle regeneration. In order for regeneration to occur, blood vessels must invade the transplanted muscle. This is confirmed by the fact that muscle regeneration occurred from the outside of the muscle bundle toward the inner regions. In fact, it is likely that capillary formation is a key process to start muscle regeneration. Thus, vascularization activates muscle regeneration, and a decrease in vascularization could lead to disruption the process of muscle regeneration. Also, a better understanding of vascularization of skeletal muscle necessary for the successful formation of collateral arteries and recovery of injured skeletal muscle may lead to more successful strategies for skeletal muscle regeneration and engineering. So, in this chapter, we want to review vascularization in skeletal muscle.",book:{id:"7870",slug:"muscle-cells-recent-advances-and-future-perspectives",title:"Muscle Cells",fullTitle:"Muscle Cells - Recent Advances and Future Perspectives"},signatures:"Kamal Ranjbar and Bayan Fayazi",authors:[{id:"143655",title:"Ph.D. Student",name:"Kamal",middleName:null,surname:"Ranjbar",slug:"kamal-ranjbar",fullName:"Kamal Ranjbar"},{id:"299168",title:"Dr.",name:"Bayan",middleName:null,surname:"Fayazi",slug:"bayan-fayazi",fullName:"Bayan Fayazi"}]}],mostDownloadedChaptersLast30Days:[{id:"70162",title:"Rehabilitation of Lateral Ankle Sprains in Sports",slug:"rehabilitation-of-lateral-ankle-sprains-in-sports",totalDownloads:1246,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Lateral ankle sprains are one of the most common injuries in athletes. The rate of injury is as high as 70%. The most commonly involved ligament is the anterior talofibular ligament (ATFL), followed by the calcaneofibular (CFL) and posterior talofibular ligament (PTFL). The common mechanism of injury is inversion with excessive ankle supination in forced plantarflexion when the ankle joint is in its most unstable position. There are three grades of ankle sprains: Grade I, mild with an incomplete tear of ATFL; Grade II, moderate with a complete tear of ATFL with or without an incomplete tear of CFL; and Grade III, severe with complete tear of ATFL and CFL. Grades I and II respond well to functional treatment. Functional treatment includes RICE protocol, i.e., rest, ice, compression, and elevation. It also includes range of motion and strengthening exercises, proprioceptive training, and sports-specific exercises. Bracing and taping of the ankle joint help in preventing the sprains and also reduce the recurrence of the injury. Grade III ankle injury may be treated with surgery if the symptoms persist post functional treatment. The guidelines provided for the treatment of ankle sprains are of general validity, but each athlete is different with different needs. Hence, a personalized exercise protocol should be followed to achieve best results.",book:{id:"9413",slug:"essentials-in-hip-and-ankle",title:"Essentials in Hip and Ankle",fullTitle:"Essentials in Hip and Ankle"},signatures:"Rachana Dabadghav",authors:[{id:"305115",title:"M.Sc.",name:"Rachana",middleName:null,surname:"Dabadghav",slug:"rachana-dabadghav",fullName:"Rachana Dabadghav"}]},{id:"55330",title:"Mesencephalon; Midbrain",slug:"mesencephalon-midbrain",totalDownloads:3385,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"The mesencephalon is the most rostral part of the brainstem and sits above the pons and is adjoined rostrally to the thalamus. It comprises two lateral halves, called the cerebral peduncles; which is again divided into an anterior part, the crus cerebri, and a posterior part, tegmentum. The tectum is lay dorsal to an oblique coronal plane which includes the aquaduct, and consist of pretectal area and the corpora quadrigemina. In transvers section, the cerebral peduncles are seen to be composed of dorsal and ventral regions separated by the substantia nigra. Tegmentum mesencephali contains red nucleus, oculomotor nucleus, thochlear nucleus, reticular nuclei, medial lemnisci, lateral lemnisci and medial longitudinal fasciculus. In tectum, the inferior colliculus and superior colliculus have main nucleus, which are continuous with the periaqueductal grey matter. The mesencephalon serves important functions in motor movement, particularly movements of the eye, and in auditory and visual processing. The mesencephalic syndrome cause tremor, spastic paresis or paralysis, opisthotonos, nystagmus and depression or coma. In addition cranial trauma, brain tumors, thiamin deficiency and inflammatory or degenerative disorders of the mesencephalon have also been associated with the midbrain syndrome.",book:{id:"5933",slug:"human-anatomy-reviews-and-medical-advances",title:"Human Anatomy",fullTitle:"Human Anatomy - Reviews and Medical Advances"},signatures:"Ayla Kurkcuoglu",authors:[{id:"200913",title:"Prof.",name:"Ayla",middleName:null,surname:"Kurkcuoglu",slug:"ayla-kurkcuoglu",fullName:"Ayla Kurkcuoglu"}]},{id:"64758",title:"Introductory Chapter: Histological Microtechniques",slug:"introductory-chapter-histological-microtechniques",totalDownloads:2281,totalCrossrefCites:2,totalDimensionsCites:2,abstract:null,book:{id:"7329",slug:"histology",title:"Histology",fullTitle:"Histology"},signatures:"Vonnie D.C. Shields and Thomas Heinbockel",authors:[{id:"70569",title:"Dr.",name:"Thomas",middleName:null,surname:"Heinbockel",slug:"thomas-heinbockel",fullName:"Thomas Heinbockel"}]},{id:"63843",title:"Salivary Glands",slug:"salivary-glands",totalDownloads:3945,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Saliva is a fluid secreted by the salivary glands that keeps the oral cavity moist and also coats the teeth along with mucosa. The salivary gland possesses tubuloacinar units, and these are merocrine. The functional unit of the salivary glands is the terminal secretory piece called acini with a roughly spherical or tubular shape. It also consists of branched ducts for the passage of the saliva and also plays an important role in the production and modification of saliva. Each type of duct is lined by different types of epithelia, on the basis of its location. Myoepithelial cells are contractile cells with respect to intercalated and secretory endpieces. Parotid, submandibular, and sublingual glands are the major salivary glands. The minor salivary glands are labial and buccal gland, glossopalatine gland, and palatine and lingual glands. Saliva plays an important role in mastication, speech, protection, deglutition, digestion, excretion, tissue repair, etc. Secretion stimulated in response to sympathetic stimulation will differ in protein and electrolyte from that due to parasympathetic stimulation. The concentration of saliva depends only on the rate of flow and not on the nature of stimulus. Saliva guides the clinician toward the optimal mode of treatment and guides the patient toward ultimate prognosis.",book:{id:"7329",slug:"histology",title:"Histology",fullTitle:"Histology"},signatures:"Sonia Gupta and Nitin Ahuja",authors:[{id:"245048",title:"Dr.",name:"Sonia",middleName:null,surname:"Gupta",slug:"sonia-gupta",fullName:"Sonia Gupta"},{id:"258367",title:"Dr.",name:"Nitin",middleName:null,surname:"Ahuja",slug:"nitin-ahuja",fullName:"Nitin Ahuja"}]},{id:"55062",title:"Human Anatomy: A Review of the Science, Ethics and Culture of a Discipline in Transition",slug:"human-anatomy-a-review-of-the-science-ethics-and-culture-of-a-discipline-in-transition",totalDownloads:2292,totalCrossrefCites:10,totalDimensionsCites:13,abstract:"Anatomy has undergone radical changes over its history, and even now its appearance varies between audiences. Within academia, it has frequently been seen as the bastion of medical teaching, even as a handmaid of surgery. To the general public over recent years, it is represented by the enormously popular public exhibitions of plastinated cadavers and body parts. Increasingly within medical teaching, it has acquired a far more humanistic face, epitomized by ceremonies at the start and end of dissection to connect the dead body with the once living individual and his/her families. Modern anatomy has also developed a strong research ethos. These movements can be traced in the many editions of Gray’s Anatomy, from 1858 to the present day. However, the humanistic side of anatomy reminds us that anatomy is not merely a science, since its ethical dimensions are legion as it has transformed from a dubiously moral and barely legal activity to one that now aims to manifest the highest of ethical standards. Nevertheless, it continues to have challenging dimensions, such as its ongoing dependence upon the use of unclaimed bodies in many societies. 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\r\n\tEducation and Human Development is an interdisciplinary research area that aims to shed light on topics related to both learning and development. This Series is intended for researchers, practitioners, and students who are interested in understanding more about these fields and their applications.
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