The 9 modifiable risk factors responsible for a third of all cancer deaths in the world
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"7725",leadTitle:null,fullTitle:"Innovations In Assisted Reproduction Technology",title:"Innovations In Assisted Reproduction Technology",subtitle:null,reviewType:"peer-reviewed",abstract:"This book deals with all recent advances in clinical and laboratory aspects of assisted reproductive therapy (ART). It elaborates on innovations and developments in the field that have the potential to improve ART outcomes. Chapters cover such topics as newer techniques for evaluating sperm, DNA, and ovarian reserve, including proteomic analysis, sonoendocrinology, preparation and administration of platelet-rich plasma, and in vitro maturation. Authors also address the structure, function, and role of low molecular weight ligands of gonadotropins, as well as the ethical and legal aspects of ART.",isbn:"978-1-83880-549-4",printIsbn:"978-1-83880-548-7",pdfIsbn:"978-1-78985-871-6",doi:"10.5772/intechopen.77538",price:119,priceEur:129,priceUsd:155,slug:"innovations-in-assisted-reproduction-technology",numberOfPages:248,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"24289d13780a3e4215f5a085923990f7",bookSignature:"Nidhi Sharma, Sudakshina Chakrabarti, Yona Barak and Adrian Ellenbogen",publishedDate:"May 6th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/7725.jpg",numberOfDownloads:9688,numberOfWosCitations:3,numberOfCrossrefCitations:2,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:6,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:11,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 2nd 2019",dateEndSecondStepPublish:"September 24th 2019",dateEndThirdStepPublish:"November 23rd 2019",dateEndFourthStepPublish:"February 11th 2020",dateEndFifthStepPublish:"April 11th 2020",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"220214",title:"Prof.",name:"Nidhi",middleName:null,surname:"Sharma",slug:"nidhi-sharma",fullName:"Nidhi Sharma",profilePictureURL:"https://mts.intechopen.com/storage/users/220214/images/system/220214.jpg",biography:"Dr. Nidhi Sharma received a MBBS and MS from Banaras Hindu University,\nVaranasi, India. She is a fellow of the Indian College of Obstetrics and Gynecology, fellow of assisted reproductive techniques, and Professor of Obstetrics and Gynecology at Saveetha University, India. Dr. Sharma has 80 indexed publications and has authored several chapters in textbooks. She received her PhD in Obstetrics and Gynecology from Saveetha University, India, and Diploma in IVF and Reproductive Medicine from UKSH Universitätsklilikum Schleswig-Holstein, Germany. Dr. Sharma has been a member of the teaching faculty of MBBS, MS, and PhD for 15 years. She is course coordinator and academic supervisor of BSc in Reproductive Biology, MSc in Clinical Embryology, Fellowship in Reproductive Medicine, and PhD in Reproductive Medicine at Saveetha University.",institutionString:"Saveetha University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Saveetha University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"224544",title:"Dr.",name:"Sudakshina",middleName:null,surname:"Chakrabarti",slug:"sudakshina-chakrabarti",fullName:"Sudakshina Chakrabarti",profilePictureURL:"https://mts.intechopen.com/storage/users/224544/images/13039_n.jpg",biography:"Dr. Sudakshina Chakrabarti is Associate Professor of Anatomy at Saveetha Medical College and hHospital, Chennai, India. She obtained a MBBS from Kempegowda Institute of Medical Sciences, Bangalore. Dr. Chakrabarti completed a postgraduate degree in Obstetrics and Gynecology from J.J.M Medical College, Davangere, Karnataka, India; an MD in Anatomy from Sri Ramachandra Medical College, Chennai, India; and is currently pursuing a PhD at Saveetha University, Chennai, India.\nShe is an ACLS, BLS, and PALS instructor under the American Heart Association and involved in simulation education. She has recently completed an Advanced Course in Medical Education and is an active member of the Medical Education Unit at Saveetha Medical College and Hospital Chennai with experience in conducting faculty development programs.",institutionString:"Saveetha University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Saveetha University",institutionURL:null,country:{name:"India"}}},coeditorTwo:{id:"209136",title:"Ph.D.",name:"Yona",middleName:null,surname:"Barak",slug:"yona-barak",fullName:"Yona Barak",profilePictureURL:"https://mts.intechopen.com/storage/users/209136/images/9827_n.png",biography:"Dr. Yona Barak obtained a BSc MSc and PhD from Tel Aviv University, Department of Zoology Faculty of Life science . Both theses for these degrees dealt with in vitro maturation of mammalian oocytes. Dr. Barak established IVF laboratories and programs worldwide: one in 1984 at the Tel Aviv Medical Center where she was director of the IVF laboratory for 12 years, and one in 1986 at the Herzliya Medical Center where she served as scientific lab director for about 25 years. She established other programs in the United States, Germany, Czech Republic, Lithuania, Cyprus, Dominican Republic, India, Ukraine, Russia, and Belarus. \nIn 2001, she established, owned, and led the InviMed clinics in Poland. \nThroughout her career, Dr. Barak trained many embryologists worldwide. In 1996, she established and became a lecturer and the clinical director of the MSc program of Gametology and Embryology at Bar Ilan University, Israel. From 1998 to 2003, she was a member of the Faculty Scientific Advisory Board and lecturer of the MSc course for Clinical Embryology at Danube University, Krems Austria, an international program of clinical embryology in cooperation with Bourn Hall, UK and Alpha Scientists in Reproductive Medicine. In 1996, she was elected by the members of Alpha Scientists in Reproductive Medicine as an executive board member. In 1999, she became a vice president of Alpha, and in 2001, she became president and served until 2004\\' and is an honorary member until today. Honorary member of embryologists in Mexico, Argentina, and Italy, and a member of the Israeli National Advisory Committee of Gynecology, Embryology and Neonatology. Dr. Barak is an active scientist who has published research in the field of assisted reproductive technologies. She is a pioneer for Hyaluronate as a replacement for polyvinylpyrrolidone (PVP) in intracytoplasmic sperm injection (ICSI); intracytoplasmic morphologically selected sperm injection (IMSI) (Breakthrough paper; 2002); in vivo maturation (IVM); human oocyte vitrification in closed systems; and more. She is owner and director of Dr. Yona Barak Laboratories for fertility services, and specializes in IMSI.",institutionString:"Dr. Yona Barak Laboratories",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorThree:{id:"216719",title:"Prof.",name:"Adrian",middleName:null,surname:"Ellenbogen",slug:"adrian-ellenbogen",fullName:"Adrian Ellenbogen",profilePictureURL:"https://mts.intechopen.com/storage/users/216719/images/6788_n.jpg",biography:"Adrian Ellenbogen, MD, is Clinical Assistant Professor in Obstetrics and Gynecology at the Rappaport School of Medicine, Technion-Institute of Technology, Haifa, Israel. He conceded fellowship at the IVF Unit, Hammersmith Hospital, London, England. He is also the founder and director (retired) of the IVF unit at Hillel Yaffe Medical Center, Hadera, Israel. In addition, he is Scientific Director for the postgraduate course in Obstetrics Gynecology and Infertility at the Rappaport School of Medicine, as well as Fertility Advisor and head of the Fertility Clinic, Meuheded Female Health Center, Bnai-Brack, Israel. \nDr. Ellenbogen is a member of American Society of Reproductive Medicine, European Society of Human Reproduction, International Society for Mild Approaches in Assisted Reproduction, International Society for In Vitro Fertilization, International Federation of Fertility Society, Israeli Fertility Association, and Israeli Society of Obstetrics and Gynecology. He is an editorial board member and reviewer for the Journal of Reproductive System and Sexual Disorders, and a reviewer for Fertility and Sterility and Harefuah. He has published 52 papers in scientific journals, two book chapters, and has presented 33 plenary lectures in international congresses and organized 12 international scientific meetings. He has presented more than 120 lectures in international and national congresses.\nDr. Ellenbogen pioneered IVF treatment with minimal stimulation and egg donation law in Israel. He has trained physicians in Israel, Dominican Republic, Poland, Macedonia, and Russia in IVF. \nHe received the 2003 Israeli Ministry of Health and Israeli Civil Service Commission Award for Excellency in Labor, the Star Award of the American Society of Reproductive Medicine in in 2012, 2013, 2014, and 2015, and the Award of the Israeli State Physicians Association in 2018 for his contribution to the Israel medical community.",institutionString:"Rappaport School of Medicine",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Hillel Yaffe Medical Center",institutionURL:null,country:{name:"Israel"}}},coeditorFour:null,coeditorFive:null,topics:[{id:"1069",title:"Reproductive Endocrinology and Infertility",slug:"obstetrics-and-gynecology-reproductive-endocrinology-and-infertility"}],chapters:[{id:"70897",title:"The Sperm: Parameters and Evaluation",doi:"10.5772/intechopen.90677",slug:"the-sperm-parameters-and-evaluation",totalDownloads:863,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Sperm abnormalities are a major factor of human infertility. Since 1987, there are several references in different editions of World Health Organization (WHO) manual defining optimal sperm parameters. Over the years, many reproductive specialists have been constantly debating, suggesting and remodeling the frame values in those guidelines. Semen parameters have a leading role both in natural conception and assisted reproduction technologies (ART) outcomes. Deviations expressed in lower sperm count, impaired motility, abnormal morphology, and high percentage of sperm DNA fragmentation are linked to reduced chances to achieve pregnancy. In cases with low sperm count, severe oligoasthenozoospermia (OA) or azoospermia, karyotyping or evaluation with sperm aneuploidy test (SAT) could be an option and genetic counseling will be necessary if there is an obvious deviation or aberration (e.g., translocation, aneuploidy, etc.). Taking care of lifestyle factors as body mass index (BMI), diets, alcohol intake, smoking, using some additional nutrition and vitamin supplements might affect sperm parameters and contribute to the chances of a couple to conceive.",signatures:"Tanya Milachich and Desislava Dyulgerova-Nikolova",downloadPdfUrl:"/chapter/pdf-download/70897",previewPdfUrl:"/chapter/pdf-preview/70897",authors:[{id:"286468",title:"Dr.",name:"Tanya",surname:"Milachich",slug:"tanya-milachich",fullName:"Tanya Milachich"},{id:"286483",title:"Mrs.",name:"Desislava",surname:"Dyulgerova-Nikolova",slug:"desislava-dyulgerova-nikolova",fullName:"Desislava Dyulgerova-Nikolova"}],corrections:null},{id:"70916",title:"Insights of Sperm Pathology and Its Association with Infertility",doi:"10.5772/intechopen.90950",slug:"insights-of-sperm-pathology-and-its-association-with-infertility",totalDownloads:723,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"This section considers the structural characteristics of spermatozoon, its assembly, composition, and mechanism behind regulation of their peculiar function. The spermatozoon is tremendously peculiar cell with an arrangement of structural characteristics which furnish it with remarkable capability of carrying the genome of male to the egg. A variety of genes are only expressed in spermatids and result in the formation of proteins that are very crucial and distinctive to spermatozoa. These proteins package the DNA, form the head of sperm, account the component of matrix and enzymes of acrosome, construct the flagellar structure, and work as ion channels that are associated in modulating the motility of sperm and also become adenylyl cyclase which yields cyclic adenosine monophosphate (cAMP) to induce signaling effect which regulates the function of spermatozoon. These proteins are critical essential to sperm and, sometimes, mutation inhibits their synthesis or disrupts their function which leads to male infertility. Researchers are trying to identify those proteins that are significant for proper function of sperm through gene knockout approach in mice that are probable to be necessary in humans as well. However, various questions still persist regarding the spermatozoon composition, organization, and function and need to be answered.",signatures:"Mohd Sajad and Sonu Chand Thakur",downloadPdfUrl:"/chapter/pdf-download/70916",previewPdfUrl:"/chapter/pdf-preview/70916",authors:[{id:"290919",title:"Mr.",name:"Mohd",surname:"Sajad",slug:"mohd-sajad",fullName:"Mohd Sajad"},{id:"291264",title:"Dr.",name:"Sonu",surname:"Thakur",slug:"sonu-thakur",fullName:"Sonu Thakur"}],corrections:null},{id:"69485",title:"Understanding the Epigenetic Modifications in Sperm Genome",doi:"10.5772/intechopen.88506",slug:"understanding-the-epigenetic-modifications-in-sperm-genome",totalDownloads:709,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Sperm genome condensation is mainly important as the genome expression should be repressed until it is fertilised with oocyte. In most of the mammals, protamines play an important role in genome condensation. In humans, histone variants were present in germ cells when compared with somatic cells. How successful replacement of histones by protamines occurs in most of the mammals is an interesting question. Little information is known about transition proteins that replace histones with protamines. Apart from condensation, which mechanisms prevent expression of X and Y chromosomes in sperm is to be studied. If exposed to genotoxic agents like Metosartan that damage testes should also be considered, in order for assisted reproductive technologies like in vitro fertilisation to succeed.",signatures:"Eswari Beeram",downloadPdfUrl:"/chapter/pdf-download/69485",previewPdfUrl:"/chapter/pdf-preview/69485",authors:[{id:"306939",title:"Dr.",name:"Eswari",surname:"Beeram",slug:"eswari-beeram",fullName:"Eswari Beeram"}],corrections:null},{id:"69869",title:"Ovarian Reserve",doi:"10.5772/intechopen.89772",slug:"ovarian-reserve",totalDownloads:779,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The human ovary is a complex structure that is controlled by endocrine, paracrine, and autocrine mechanisms. The number of eggs retrieved after controlled ovarian stimulation in in vitro fertilization depends on the physiological follicular reserve pool of ovaries. Ovarian reserve is decided genetically and decreases with advancing age and gets affected by ovarian surgery, chemotherapy, radiotherapy, and autoimmune disorders. Environmental influences like chronic smoking, hyperglycemia, and conditions interfering ovarian vascularity also reduce the ovarian reserve. This chapter summarizes the methods to assess the ovarian reserve. This helps in deciding the initiating dose of gonadotropins for controlled ovarian hyper stimulation for optimal follicular response.",signatures:"Nidhi Sharma and Sudakshina Chakrabarti",downloadPdfUrl:"/chapter/pdf-download/69869",previewPdfUrl:"/chapter/pdf-preview/69869",authors:[{id:"220214",title:"Prof.",name:"Nidhi",surname:"Sharma",slug:"nidhi-sharma",fullName:"Nidhi Sharma"},{id:"224544",title:"Dr.",name:"Sudakshina",surname:"Chakrabarti",slug:"sudakshina-chakrabarti",fullName:"Sudakshina Chakrabarti"}],corrections:null},{id:"68708",title:"Paternal Effects on Embryonic, Fetal and Offspring Health: The Role of Epigenetics in the ICSI and ROSI Era",doi:"10.5772/intechopen.88589",slug:"paternal-effects-on-embryonic-fetal-and-offspring-health-the-role-of-epigenetics-in-the-icsi-and-ros",totalDownloads:607,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Paternal effects on the developmental potential of human embryos have been studied since the early 1990s, particularly with respect to newly emerging assisted reproduction technologies. Both genetic and epigenetic paternal effects can influence postfertilization development and cause implantation failure or miscarriage. However, it is only over the last few years that issues related to paternal effects associated with different assisted reproduction techniques on the health status of newborn and adult progeny have been focused. At the same time, new findings point out different, yet unexplored, areas of research into the potentially responsible factors, including the activity of the sperm-derived oocyte-activating factor and the oocyte signaling pathways mediating its action, the methylation status of both imprinted and non-imprinted genes, correct replacement of sperm nuclear protamines with oocyte-derived histones, the histone acetylation status, and the function of sperm-borne small RNAs. It is increasingly important to know how these developmentally important epigenetic regulators can be altered in the context of the current micromanipulation-assisted fertilization techniques, intracytoplasmic sperm injection (ICSI) and round spermatid injection (ROSI). Last but not least, transgenerational transmission of acquired, environmentally conditioned disorders from fathers to offspring is a newly emerging issue which warrants further research.",signatures:"Jan Tesarik",downloadPdfUrl:"/chapter/pdf-download/68708",previewPdfUrl:"/chapter/pdf-preview/68708",authors:[{id:"288616",title:"Dr.",name:"Jan",surname:"Tesarik",slug:"jan-tesarik",fullName:"Jan Tesarik"}],corrections:null},{id:"70737",title:"Implantation: Cross Talk of the Developing Embryo and Endometrium",doi:"10.5772/intechopen.90748",slug:"implantation-cross-talk-of-the-developing-embryo-and-endometrium",totalDownloads:828,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The window of implantation has long posed as a challenge in understanding the exact synchronized cross talk that must take place in order for a developing embryo to be appropriately received by the endometrium. This is due mostly to the fact that it is difficult to study human models of implantation without sacrificing the potential for pregnancy. For many who present with a diagnosis of infertility with an otherwise unexplained etiology, recurrent implantation failure or a displaced window of receptivity may be an underlying, silent cause. As assisted reproductive technology (ART) continues to advance and offer new scientific breakthroughs allowing greater insight and understanding to reproductive failure and infertility, endometrial receptivity testing may offer answers to struggling patients.",signatures:"Lauren Grimm, Amber Cooper, Angie Beltsos and Roohi Jeelani",downloadPdfUrl:"/chapter/pdf-download/70737",previewPdfUrl:"/chapter/pdf-preview/70737",authors:[{id:"312037",title:"M.A.",name:"Lauren",surname:"Grimm",slug:"lauren-grimm",fullName:"Lauren Grimm"},{id:"312038",title:"Dr.",name:"Roohi",surname:"Jeelani",slug:"roohi-jeelani",fullName:"Roohi Jeelani"},{id:"314161",title:"M.D.",name:"Angeline",surname:"Beltsos",slug:"angeline-beltsos",fullName:"Angeline Beltsos"},{id:"314162",title:"Dr.",name:"Amber",surname:"Cooper",slug:"amber-cooper",fullName:"Amber Cooper"}],corrections:null},{id:"68455",title:"The Low-Molecular-Weight Ligands of the Gonadotropin Receptors as the New Generation of the Regulators of the Reproductive Functions and Steroidogenesis",doi:"10.5772/intechopen.88498",slug:"the-low-molecular-weight-ligands-of-the-gonadotropin-receptors-as-the-new-generation-of-the-regulato",totalDownloads:654,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In clinic, the luteinizing (LH) and follicle-stimulating (FSH) hormones and human chorionic gonadotropin (hCG) are used to treat reproductive dysfunctions and in assisted reproductive technology. They are the αβ-heterodimeric complexes and specifically bind to ectodomain of G protein-coupled LH and FSH receptors. This leads to activation of many signaling cascades; some of which are responsible for steroidogenesis, folliculogenesis, and spermatogenesis, while the others, such as β-arrestin pathways, trigger the downregulation of gonadotropin receptors. A low selectivity of the intracellular signaling of gonadotropins and a large number of their isoforms are the main causes of undesirable effects of gonadotropins, limiting their clinical applications. Unlike gonadotropins, the low-molecular-weight (LMW) ligands interact with an allosteric site located in the transmembrane domain of the LH and FSH receptors and selectively activate the certain signaling pathway, preventing a number of side effects of gonadotropins. The LMW ligands are characterized by activity of the full and inverse agonists and neutral antagonists, as well as the positive and negative modulators, and they have the in vivo activity, including when administered orally. This review focuses on the advances in the development of LMW allosteric ligands of the LH and FSH receptors and the prospects for their use in reproductive medicine.",signatures:"Alexander O. Shpakov, Kira V. Derkach, Andrey A. Bakhtyukov and Dmitry V. Dar’in",downloadPdfUrl:"/chapter/pdf-download/68455",previewPdfUrl:"/chapter/pdf-preview/68455",authors:[{id:"75888",title:"Dr.",name:"Alexander",surname:"Shpakov",slug:"alexander-shpakov",fullName:"Alexander Shpakov"},{id:"81685",title:"Dr.",name:"Kira",surname:"Derkach",slug:"kira-derkach",fullName:"Kira Derkach"},{id:"245241",title:"MSc.",name:"Andrey",surname:"Bakhtyukov",slug:"andrey-bakhtyukov",fullName:"Andrey Bakhtyukov"},{id:"303442",title:"Dr.",name:"Dmitry",surname:"Dar’in",slug:"dmitry-dar'in",fullName:"Dmitry Dar’in"}],corrections:null},{id:"69730",title:"Proteomics as a Future Tool for Improving IVF Outcome",doi:"10.5772/intechopen.89880",slug:"proteomics-as-a-future-tool-for-improving-ivf-outcome",totalDownloads:678,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:1,abstract:"New technical and methodical and more efficient approaches beyond preimplantation genetic screening (PGS) are needed to elevate success rates in in vitro fertilization (IVF). One new approach could be the characterization of the embryos’ proteome during the IVF process. This means that specific proteins secreted by the embryo in the surrounding cultivating medium can be analyzed and compared between embryos in order to identify potential markers for a successful embryo transfer and resulting pregnancy. Furthermore, this procedure could result with understanding the processes during the whole time of incubation, from the moment of oocyte fertilization until embryo transfer and subsequently implantation by analyzing the culturing medium used in multiple culture medium exchange during the cultivation period. This procedure of embryo transfer to a new culture medium is essential for the embryo’s development and is performed daily or at least when the embryos reached the stage of embryoblast at day 4. The remaining medium after embryo removal is routinely discarded. However, this medium still can be useful for a detailed analysis of proteins and lipids that were secreted by the embryo during the previous incubation process and could help gaining information on the embryos’ current developmental status.",signatures:"Goran Mitulović and Tanja Panić-Janković",downloadPdfUrl:"/chapter/pdf-download/69730",previewPdfUrl:"/chapter/pdf-preview/69730",authors:[{id:"212804",title:"Dr.",name:"Goran",surname:"Mitulović",slug:"goran-mitulovic",fullName:"Goran Mitulović"},{id:"256238",title:"Dr.",name:"Tanja",surname:"Panić-Janković",slug:"tanja-panic-jankovic",fullName:"Tanja Panić-Janković"}],corrections:null},{id:"70544",title:"Autologous Platelet-Rich Plasma Infusion to Improve Pregnancy Outcome in Suboptimal Endometrium: A Review",doi:"10.5772/intechopen.90651",slug:"autologous-platelet-rich-plasma-infusion-to-improve-pregnancy-outcome-in-suboptimal-endometrium-a-re",totalDownloads:629,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Over the past decade, platelet-rich plasma (PRP) has been used in several fields of medicine to promote cell growth and expedite wound healing for the treatment of arthritis, nerve injury, tendinitis, bone regeneration, cardiac muscle repair, and oral & plastic surgery. Recently, researchers have been applying autologous PRP to bolster the growth of endometrial lining in patients with a history of endometrium-related failed embryo transfers. Evidence reveals that PRP is a rich source of active cytokines and various growth factors, which come from an autologous source that can be easily attained from peripheral blood without risk of disease transmission to the patient. In this review, several studies were analyzed that involved patients 18–42 years of age undergoing hormone replacement therapy (HRT) in preparation for embryo transfer and serial transvaginal ultrasound in conjunction with PRP infusions into the endometrium via an intrauterine insemination (IUI) catheter. Exclusion criteria included patients with endometritis, polyps, or adhesions. Embryo transfers (ET) were performed when the endometrial lining achieved a thickness of >7 mm. The database indicates that PRP infusion therapy is a promising low-cost treatment for HRT patients that significantly increases endometrial thickness and improves pregnancy success in a previous suboptimal ET patient population.",signatures:"Casey Zeffiro, Silvina Bocca, Helena Russell and Mitchel C. Schiewe",downloadPdfUrl:"/chapter/pdf-download/70544",previewPdfUrl:"/chapter/pdf-preview/70544",authors:[{id:"255618",title:"Ph.D.",name:"Mitchel",surname:"Schiewe",slug:"mitchel-schiewe",fullName:"Mitchel Schiewe"},{id:"312738",title:"MSc.",name:"Casey",surname:"Zeffiro",slug:"casey-zeffiro",fullName:"Casey Zeffiro"},{id:"315468",title:"Dr.",name:"Silvina",surname:"Bocca",slug:"silvina-bocca",fullName:"Silvina Bocca"},{id:"315469",title:"MSc.",name:"Helena",surname:"Russell",slug:"helena-russell",fullName:"Helena Russell"}],corrections:null},{id:"69937",title:"Recurrent Pregnancy Loss: Investigations and Interventions",doi:"10.5772/intechopen.89590",slug:"recurrent-pregnancy-loss-investigations-and-interventions",totalDownloads:739,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Recurrent pregnancy loss (RPL) affects 0.8–1.4% of couples, and this prevalence increases with aging. However, etiology is commonly unknown, and most therapies are not supported by strong evidence. There are many examinations that investigate causes of RPL: hormonal status, spermatozoa morphology and DNA fragmentation, immunologic status, uterine assessment, thrombophilia, and others. Recently different types of treatment have emerged, most lacking good evidence. As for example, we may mention the use of anticoagulants, aspirin, corticosteroids, progesterone, and antioxidants and psychological support. It is argued that some procedures such as preimplantation genetic testing for aneuploidy and intracytoplasmic morphologically selected sperm injection would impact on the outcomes and help RPL management. This chapter will discuss the current evidence concerning examinations and treatments that would improve the outcomes in patients with RPL, with recommended practice.",signatures:"Vinicius M. Lopes, Murilo C. Souza-Oliveira, Amanda Evelyn C. Goulart, Eduardo S. Pimentel, Natalia I. Zavattiero Tierno, Tatianna Q. F. Ribeiro, Cristina T. Medina, Valéria L. Mathias Castro, Leilane G. Noleto Lima, Anna Luiza M. Souza and Jean Pierre B. Brasileiro",downloadPdfUrl:"/chapter/pdf-download/69937",previewPdfUrl:"/chapter/pdf-preview/69937",authors:[{id:"307438",title:"Dr.",name:"Vinicius",surname:"Lopes",slug:"vinicius-lopes",fullName:"Vinicius Lopes"},{id:"310745",title:"Mr.",name:"Murilo C.",surname:"Souza-Oliveira",slug:"murilo-c.-souza-oliveira",fullName:"Murilo C. Souza-Oliveira"},{id:"310746",title:"Mr.",name:"Eduardo S.",surname:"Pimentel",slug:"eduardo-s.-pimentel",fullName:"Eduardo S. Pimentel"},{id:"310747",title:"Ms.",name:"Amanda Evelyn C.",surname:"Goulart",slug:"amanda-evelyn-c.-goulart",fullName:"Amanda Evelyn C. Goulart"},{id:"310748",title:"Ms.",name:"Natalia I. Zavattiero",surname:"Tierno",slug:"natalia-i.-zavattiero-tierno",fullName:"Natalia I. Zavattiero Tierno"},{id:"310749",title:"MSc.",name:"Anna Luiza Moraes",surname:"Souza",slug:"anna-luiza-moraes-souza",fullName:"Anna Luiza Moraes Souza"},{id:"310750",title:"Mr.",name:"Jean Pierre B.",surname:"Brasileiro",slug:"jean-pierre-b.-brasileiro",fullName:"Jean Pierre B. Brasileiro"},{id:"310759",title:"Ms.",name:"Valeria L. Mathias",surname:"Castro",slug:"valeria-l.-mathias-castro",fullName:"Valeria L. Mathias Castro"},{id:"310760",title:"Ms.",name:"Tatianna Q. F.",surname:"Ribeiro",slug:"tatianna-q.-f.-ribeiro",fullName:"Tatianna Q. F. Ribeiro"},{id:"310761",title:"MSc.",name:"Cristina T.",surname:"Medina",slug:"cristina-t.-medina",fullName:"Cristina T. Medina"},{id:"310762",title:"Ms.",name:"Leilane G. Noleto",surname:"Lima",slug:"leilane-g.-noleto-lima",fullName:"Leilane G. Noleto Lima"}],corrections:null},{id:"71508",title:"In Vitro Maturation and Fertilization of Oocytes: From Laboratory Bench to Clinical Practice",doi:"10.5772/intechopen.91802",slug:"in-vitro-maturation-and-fertilization-of-oocytes-from-laboratory-bench-to-clinical-practice",totalDownloads:806,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Retrieval of immature oocytes from non-stimulated ovaries, followed by in vitro maturation (IVM), was initially proposed in order to avoid side effects of gonadotropin administration. The goal is to eradicate or significantly decrease the risk of ovarian hyperstimulation syndrome (OHSS) in patients with polycystic ovary syndrome (PCOS) and to reduce drug cost and burden of patients. This technology was also proposed for treatment of normal ovulatory women, fertility preservation, or infrequent conditions as failure of oocyte to mature or repeated development of poor-quality embryos. There is no downregulation, and only a small amount of hormones are injected if at all. In vitro maturation of the oocyte procedure obtained up to 35% clinical pregnancy rate in young women, compared with in vitro fertilization (IVF) in many programs. The obstetric and perinatal outcomes of IVM cycles are comparable with IVF/ICSI cycles; therefore it may gradually substitute IVF in certain cases, as the technique continues to develop and pregnancy rates continue to increase. IVM holds great promises as an alternative to assisted reproductive technologies and may be the procedure of choice not only for infertile patients but also for obtaining oocytes for donation or fertility preservation.",signatures:"Adrian Ellenbogen, Einat Shalom Paz, Medeia Michaeli, Anna Smirnova and Yona Barak",downloadPdfUrl:"/chapter/pdf-download/71508",previewPdfUrl:"/chapter/pdf-preview/71508",authors:[{id:"209136",title:"Ph.D.",name:"Yona",surname:"Barak",slug:"yona-barak",fullName:"Yona Barak"},{id:"216719",title:"Prof.",name:"Adrian",surname:"Ellenbogen",slug:"adrian-ellenbogen",fullName:"Adrian Ellenbogen"}],corrections:null},{id:"70764",title:"Bioethics of Assisted Reproductive Technology",doi:"10.5772/intechopen.90727",slug:"bioethics-of-assisted-reproductive-technology",totalDownloads:989,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"There is no doubt that for a couple who are having difficulties in conceiving, having a child is an objective good. However, it is also indisputable that assisted reproduction techniques raise clear ethical issues. In order to begin this bioethical reflection, it should be clearly established that the early embryo, which can be manipulated or destroyed using these techniques, is a living being of our species. We believe this is unquestionable from a biological point of view, and it therefore deserves our full respect. The bioethical assessment of assisted reproduction techniques includes analysis of the embryo losses caused by their selection and manipulation through preimplantation genetic diagnosis, ‘social freezing’ or the possible lack of rigour in the information provided by the clinics involved, to which must be added the higher morbidity reported in babies born as a result of these procedures.",signatures:"Justo Aznar and Julio Tudela",downloadPdfUrl:"/chapter/pdf-download/70764",previewPdfUrl:"/chapter/pdf-preview/70764",authors:[{id:"312437",title:"Dr.",name:"Justo",surname:"Aznar Lucea",slug:"justo-aznar-lucea",fullName:"Justo Aznar Lucea"},{id:"312692",title:"Dr.",name:"Julio",surname:"Tudela",slug:"julio-tudela",fullName:"Julio Tudela"}],corrections:null},{id:"70483",title:"Human Contraceptives: Current Status, Sperm Antigen Inhibitors and an Insight into PCSK4",doi:"10.5772/intechopen.89721",slug:"human-contraceptives-current-status-sperm-antigen-inhibitors-and-an-insight-into-pcsk4",totalDownloads:684,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Rapid growth of global human population has been implicating to food shortage, social problems and environmental degradation. Contraceptive devices have long been applied as a major method to reduce natality. Current application of this technology relies upon hormonal administration, condom, withdrawal and recently hormonal vaccino-contraceptive. Discoveries of antisperm proteins have been directing current researches toward developments of antisperm antibody (ASA) contraceptions. Actions of ASA are targeting antigens either on the head or on the tail of sperm. Antibodies targeting head antigens aimed at blocking gamete fusion, ZP penetration and/or acrosome reaction. Molecules working on sperm tails are aimed to block sperm motility or energy production. PCSK4 is one sperm antigen firstly expressed on the human sperm acrosome during its initial development on the round spermatid and retains on the acrosome until sperm is matured. It is known to contribute to the post-capacitational hyperactivation of sperm essential for zona penetration. Rat models injected with rabbit-anti human PCSK4 developed incompetent sperm and allowance of these male rats to fertile female rats resulted significant reduction of conception rate. Apart from antibody, synthetic inhibitors of PCSK4 have also been developed. Future developments of ASA contraception are discussed.",signatures:"Dahril Dahril, Widi Nugroho and Aulanni’am Aulanni’am",downloadPdfUrl:"/chapter/pdf-download/70483",previewPdfUrl:"/chapter/pdf-preview/70483",authors:[{id:"287187",title:"Ph.D.",name:"Dahril",surname:"Dahril",slug:"dahril-dahril",fullName:"Dahril Dahril"},{id:"288826",title:"Prof.",name:"Aulanni’am",surname:"Aulanniam",slug:"aulanni'am-aulanniam",fullName:"Aulanni’am Aulanniam"},{id:"294149",title:"Dr.",name:"Widi",surname:"Nugroho",slug:"widi-nugroho",fullName:"Widi Nugroho"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"8471",title:"Prediction of Maternal and Fetal Syndrome of Preeclampsia",subtitle:null,isOpenForSubmission:!1,hash:"327257ae2f4783050d327cd524bf2a3e",slug:"prediction-of-maternal-and-fetal-syndrome-of-preeclampsia",bookSignature:"Nidhi Sharma",coverURL:"https://cdn.intechopen.com/books/images_new/8471.jpg",editedByType:"Edited by",editors:[{id:"220214",title:"Prof.",name:"Nidhi",surname:"Sharma",slug:"nidhi-sharma",fullName:"Nidhi Sharma"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2575",title:"Prolactin",subtitle:null,isOpenForSubmission:!1,hash:"338ea99a4e29b28d7463a976a301711b",slug:"prolactin",bookSignature:"György M. 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\r\n\tThe goal of this book will be to introduce the current change in ambulatory care affected by the new development of medical knowledge, new technology, and social ethics. The COVID-19 pandemic plays an important role in the acceleration of the adoption of telehealth or telemedicine in medical care. Both patients and medical providers adopt it quickly. The new devices make it possible for remote measuring or monitoring vitals or other physical parameters and communication pathways that provide other tools for medical providers to change the pattern of management of different chronic diseases, like hypertension, diabetes, obesity, congestive heart failure, etc. Some techniques can switch some procedures from the hospital to the patient’s home or clinic so, which will not just make such procedures more convenient for patients but also save expense on medical care. The quality of medical care will improve once both medical providers and patients understand such changes, and cooperate proactively. Medical providers can learn how and what tools they can update and apply for caring for patients. Patients can understand and learn how to proactively engage in their health management.
\r\n\r\n\tThe quest to ensure a perfect patient safety record is at the heart of the decades-long quest to improve quality, enhance value, and increase trust in our healthcare delivery systems. Beginning with the landmark report, To Err Is Human, the Institute of Medicine set an ambitious agenda for the medical community to reduce the number of patients harmed by healthcare-related errors and preventable adverse events. As a result, large-scale initiatives were initiated, including electronic medical records, trainee work hours restrictions, and the advent of evidence-based care bundles. To help support the effort, various governmental and non-governmental agencies established funding for patient safety research and actively fostered the development of well-defined Patient Safety Goals via the National Quality Forum. Parallel to targeted efforts aimed at reducing human and systemic errors leading to patient harm, legislative efforts resulted in bills intended to increase public reporting of medical errors and a paradigm shift allowing public support of the concept that most patient injuries are a result of system failures and not provider errors. This book will intend to provide the reader with a comprehensive overview of the current state-of-the-art in patient safety, featuring an easy-to-follow, vignette-based format that focuses on the most important evidence-based developments in this critically important area.
",isbn:"978-1-83768-192-1",printIsbn:"978-1-83768-191-4",pdfIsbn:"978-1-83768-193-8",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"fa37d79f81893fd0a9ab346ae1c3e4a9",bookSignature:"Dr. Xin-Nong Li",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/12102.jpg",keywords:"Pandemic, Telehealth, Communication, High Technology, Chronic Disease, Remote, Monitor, Quality, Diabetes, Hypertension, Digital Device, Cardiovascular Disease",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 26th 2022",dateEndSecondStepPublish:"July 28th 2022",dateEndThirdStepPublish:"September 26th 2022",dateEndFourthStepPublish:"December 15th 2022",dateEndFifthStepPublish:"February 13th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"14 days",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. Li, MD, graduated from Sun Yat-Sen University of Medical Sciences as an Outstanding Student. He later retrained as a resident in the department of internal medicine at the University of Pittsburgh Medical Center. He gained rich professional experience by working at Basel University, Switzerland, the University of Alabama at Birmingham, USA, and Medical School, the University of California at Davis. He is a Fellow of the American College of Physicians and a member of the American Medical Association.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"345917",title:"Dr.",name:"Xin-Nong",middleName:null,surname:"Li",slug:"xin-nong-li",fullName:"Xin-Nong Li",profilePictureURL:"https://mts.intechopen.com/storage/users/345917/images/system/345917.jpg",biography:"Dr. Xin-Nong Li, MD is an internal medicine specialist in Fair Oaks, CA. Dr. Li completed a residency at U Pittsburgh MC Shadyside. He currently practices at Xin-Nong Li, MD, and is affiliated with Mercy San Juan Medical Center. He accepts multiple insurance plans. Dr. Li is board-certified in Internal Medicine.\r\n\r\nEducation:\r\nU Pittsburgh MC Shadyside, Residency Hospital — 1999\r\nU Pittsburgh MC Shadyside, Internship Hospital — 1997\r\nSun Yat Sen University Med Sci, Medical School — 1982",institutionString:"Sutter Health",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Sutter Health",institutionURL:null,country:{name:"United States of America"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"466997",firstName:"Patricia",lastName:"Kerep",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/466997/images/21565_n.jpg",email:"patricia@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully"}},relatedBooks:[{type:"book",id:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. Mauricio Barría",coverURL:"https://cdn.intechopen.com/books/images_new/6550.jpg",editedByType:"Edited by",editors:[{id:"88861",title:"Dr.",name:"R. Mauricio",surname:"Barría",slug:"r.-mauricio-barria",fullName:"R. 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Genetic factors are thought to account for 5-10% of all malignant neoplasms, even though hereditary susceptibility will be variably relevant depending on histotype, anatomic site, and epidemiologic context; additionally, a key role is played by environmental factors. Socioeconomic improvements have resulted in an increase in food availability as well as significant changes in lifestyle habits; with new technologies allowing for automation of manual work, an overall physical activity reduction has been observed leading to unbalances between caloric intake and energy expenditure.
Cancer is no longer a rapidly lethal disease for an increasing number of patients. Knowledge of the main risk factors for cancer development is essential for establishing a comprehensive and integrated treatment plan (tab 1).
1. | \n\t\t\tObesity and overweight | \n\t\t
2. | \n\t\t\tLow fruit and vegetable intake | \n\t\t
3. | \n\t\t\tPhysical inactivity | \n\t\t
4. | \n\t\t\tSmoking | \n\t\t
5. | \n\t\t\tAlcohol consumption | \n\t\t
6. | \n\t\t\tUnprotected sex | \n\t\t
7. | \n\t\t\tUrban air pollution | \n\t\t
8. | \n\t\t\tIndoor air pollution due to household use of solid fuels | \n\t\t
9. | \n\t\t\tSpread of bacterial and viral infections through unsafe health care procedures | \n\t\t
The 9 modifiable risk factors responsible for a third of all cancer deaths in the world
Cancer patients receiving treatment combinations of surgery, radiation therapy and chemotherapy are prone to developing several treatment-related diseases.
Pain, heightened risk of infection, neural deficits, lymphedema, fatigue, nausea and vomiting, loss of flexibility, myopathies, muscle weakness, cachexia, dehydration, emotional distress, shortness of breath are common side-effects capable of negatively affecting patients’ lifestyle and physical activities. Any combination of surgical treatments, chemotherapy, and radiotherapy must be integrated within a global therapeutic plan aimed to reduce the above-mentioned negative effects that may become apparent immediately as well as after several months or years.
Mullan (1985) classified the life of cancer survivors into three stages: 1) Acute Stage, spanning from diagnosis to the first year after primary treatment; 2) Extended Stage, until the 5th year after primary treatment; 3) Permanent Stage, from the 5th year after primary treatment onwards.
The first year after primary treatment should be considered just as the "tip of the iceberg", and it is crucial that any approach to cancer treatment is holistic and comprehensive, based on the assumption that cancer is a chronic illness rather than an acute condition.
The aim of this chapter is not to describe the specifics of early management of patients diagnosed with cancer; however, the authors’ view is that such approach should be as integrative and comprehensive as possible.
It is essential that physicians in the process of planning specific therapeutic interventions (either actions specifically aimed to the primary disease or supportive therapies) extensively profile patients according to their physical status in order to establish an individual patient-tailored strategy.
The integrative management approach relies on a number of basic interventions, including:
Therapeutic changes of lifestyle habits and daily diet;
Specific physical exercises and walking prescriptions;
Physical therapies coupled with psychophysical techniques.
Up to 30-40% of all malignant cancers could be prevented by interventions on diet, physical activities, and daily lifestyle.
Calories intake directly correlates with risk of developing obesity as well as cancer.
Obesity
Approximately 50% of all primary malignant cancers arise in tissues with a primary involvement in obesity physiopatology.
Cancer is responsible of approximately 25% of all deaths in the US.
According to recent predictions, by 2020 the global world population will have reached 7,5 billion, with a cancer incidence and disease-specific mortality of 15 million per year and 12 million per year, respectively.
At present the total US cancer survivors population is made of 5-y cancer survivors for up to 66%, and by 2020 it has been estimated that cancer survivors aged at least 65 years will have been increased by 42% compared to now.
The diet is responsible for approximately 30-35 % of total mortality in the US, with its impact on cancer development depending on histotype and anatomic location; nutrition may play a key role in up to 70% of colorectal cancer-related deaths.
Nowadays, men and women in Occidental countries are progressively increasing in body size, with average body-mass indexes (BMI, i.e. the ratio between weight and squared height) relentlessly soaring beyond the normal range (18.5-24.9); conversely, an increasing number of individuals is falling into the overweight range (25-29.9) as well as the overt obesity range (> 30).
Obesity is easily diagnosed by assessing the increase in horizontal body dimensions compared to height.
One method for measuring such imbalance is the BMI, i.e. the ratio between weight (kilograms) and squared height (centimeters2). BMI ranges identifying malnutrition, normal weight, overweight and different obesity degrees (mild and severe) have been defined.
BMI, however, being frequently used in epidemiological studies to assess the effect of diet as a risk factor, may become a confounding factor; indeed, BMI is less reliable in elderly patients, with height being gradually reduced due to spinal degenerative processes. Likewise, children BMI measurements may be biased by different growth rates in different body areas. Additionally, BMI fail to provide any definite information regarding body composition, i.e. the percentage of lean body mass versus fat mass, bone mineralization status, and total body water, just to name a few examples.
The value of lean body mass is critical because it is the body component consuming higher energy values per weight unit, being therefore critical for any estimations of appropriate caloric intakes.
Any diet based on caloric restriction alone would be ineffective as well as potentially dangerous if no caloric intake assessment were to be calculated according to body composition and estimated energy requirements for performing daily physical activity (including walking, writing, or accomplishing ordinary housework actions).
Obesity plays a critical role in cancer promotion, progression, and therapy resistance; obesity oncogenic actions are thought to be mediated by dysregulation of hormonal networks (i.e., circulating insuline, IGF-1, testosterone, and estrogens levels) as well as through pro-inflammatory effects due to adipose tissues cytokines.
Increased BMI values correlate with circulating inflammatory cytokines levels, that appear to be related to insulin resistance.
A positive correlation between high BMI values (>30) and cancer risk is being observed in different areas worldwide, with significant increases in cancer risk being recorded for every 5 Kg/m2-gain in BMI.
Obesity directly promotes tissue inflammation. Lipids intake should be proportional to that of other nutrients in order to reach an adequate energy balance; in this regard, it should be remembered that 1g of fat provides approximately 9 Kcal of energy, while 1g of carbohydrates or proteins only provides 4.5 Kcal. However, specific lipids significantly differ in their chemical structure and will result in different metabolic responses when given at equal calories levels. Increased amounts of fat per portion, a phenomenon commonly occurring in restaurant and cafèteria, leads to significant inflammatory response spikes, that can be quantified by assessing increases of circulating inflammatory factors; the latter are capable of inducing insulin resistance and free radicals production, resulting in oxidation of cell structures such as nucleic acids, proteins, and membrane lipids. Other lipids possess an anti-inflammatory activity. There is plenty of literature addressing the beneficial administration of omega-3 unsaturated lipids for lessening the inflammatory consequences of several chronic diseases. Omega-3 unsaturated lipids are available either as dedicated over-the-counter preparations or through several common foods, more prominently fish and dried fruit. Omega-3 lipids are unsaturated lipids, i.e. they are in liquid form at room temperature (oils); they can easily undergo oxidation if not protected by intrinsic animals antioxidant systems or by vitamin E addition in commercially available preparations. Their content in fish meat changes according to the species, the fishing site, temperature, type of feeding (algae or other kinds of food for livestock); these features make difficult to calculate the omega-3 unsaturated lipids daily dose. Many public health authorities have been encouraging increases in diet fish intake, but it is important to know diet fish origins because of the risk related to heavy metals; it is therefore necessary to avoid eating exceedingly large amounts fish. Of course, such details are hardly specified, if ever, in epidemiological studies assessing the effects of fish-based diets. Obesity results in a status of enduring subclinical inflammation within fat tissues. In obese individuals both visceral and subcutaneous adipose tissues are infiltrated by macrophages surrounding necrotic adipocytes forming the so-called crown-like structures (CLS). The infiltrating macrophages release inflammatory cytokines whose plasma levels in post-menopausal breast cancer patients were shown to correlate with cancer progression and disease-specific mortality. In both experimental animals and humans the CLS number is directly related to BMI values.
Diets with high concentration in saturated fatty acids (cafeteria food, sausages, dairy products, red meat) are becoming more and more frequent worldwide, leading to a global escalation in overnutrition-related diseases.
Diets rich in saturated fatty acids closely correlate with metabolic syndrome and inflammation, especially inflammation of the white adipose tissue, which is not only a storage organ for lipids but also an endocrine organ.
It has been known since 1885 that hyperglycemia is more frequent among cancer patients than in the healthy population.
Warburg in 1930 highlighted the abnormal glucidic metabolism occurring in cancer cells, i.e. the so-called aerobic glycolysis, defined as the tendency of the cancer tissues to produce lactic acid even in the presence of sufficient oxygen to sustain Krebs cycle and mitochondrial membrane oxidation processes.
Glucose intolerance is an established risk factor for several cancers (including colorectal, breast, prostatic, pancreatic, and gastric cancer). Obesity and glucose intolerance are part of the metabolic syndrome, a condition characterized by increased insulin levels both during fasting and after glucose load. Metabolic syndrome, first described by Reaven in 1988, is defined by the presence of at least three of the following components: intra-abdominal or visceral obesity, glucose intolerance, hypertension, low HDL blood levels, and high triglyceride levels. In 2001, the National Cholesterol Education Program developed an alternative definition, which required the presence of at least 3 of the following 5 factors: increased waist circumference, hypertriglyceridemia, low HDL cholesterol, hypertension, and high levels of fasting glycemic levels. At the roots of metabolic syndrome there are increase in visceral fat, excessive caloric intake, and low physical activity.
The prevalence of metabolic syndrome is steadily increasing all over the world together with the increase in several types of cancer.
In subjects with glucose intolerance (IGT), both the levels of glycemia and fasting insulin are increased. The latter are coupled until glycemia reaches the concentration of 7-8 mM, a level beyond which insulin does not show further increases and may even begin to decline as a result of functional failure of pancreatic β-cells (De Fronzo 1992). This is paralleled by the gradual increase in glycemia, starting with postprandial glycemia.
Many people with newly diagnosed cancer are obese, with further changes in body structure being induced by chemotherapy, surgery, and therapy-related physical inactivity.
Chemotherapy often changes, even a year later, body composition, increasing fat mass and reducing muscle mass, creating a phenotype that could be defined as post-cancer sarcopenic obesity; the latter appears to correlate with a high risk of cancer recurrence.
Modifications in body composition in cancer patients imply that many studies conducted through questionnaires, perhaps using only one scale, were affected by significant biases. The reduction in caloric intake as a strategy to reduce obesity should be assessed on a case by case basis, followed over time, and maintained proportional with nutritional needs of the whole body in order to prevent secondary nutritional deficiencies.
The caloric intake, however, should be calibrated according to the composition of energy sources (carbohydrates, lipids, proteins); the latter, in a typical Mediterranean diet, should be in the ratio of 60%, 25%, 15%, respectively.
The American Cancer Society guidelines suggests that carbohydrates should be in the ratio of 40-65% of the energy pool, the same as for healthy population, lipids in the ratio of 20-35%, of which <10% saturated fats, and proteins should be 10-35%.
Daily protein intake should not be less than 0.8-1 grams per Kg of body weight.
Nutrition does not mean only caloric intake, but also replenishment of the very primary elements that the body uses to live. Nutritionists from different countries define the optimal daily replenishment levels of micronutrients depending on gender, age, and functional status (i.e., pregnancy, sporting activities, etc.). However, patients suffering from cancer will be almost always exhibiting to nutritional deficiencies.
Obesity itself is a malnutrition disease characterized by several deficiencies, including vitamin D deficiency. Many other deficits can be induced by specific therapies (i.e., those impairing renal tubular reabsorption through tubular damage, or intestinal absorption through mucositis, anorexia, and vomiting) and by treatments for related comorbidities (cholesterol-lowering agents, diuretics, anti-hypertensive drugs, etc...) resulting in minerals and antioxidants loss. These events may worsen the peroxidation phenomena of several biological structures, that will have been already compromised by metabolic syndrome and administration of chemotherapy.
Obesity is also associated with insulin resistance, i.e. the insulin inability, despite being available in physiological concentrations, of exerting its metabolic tasks in different body districts.
Insulin resistance assessment is performed in specialized centers, at times requiring expensive and complex methods. Such assessment could be easier by evaluation of blood glucose levels and fasting insulin levels according to the HOMA-IR algorithm, with values above 2.5 being indicative of insulin resistance.
Diet should not cause any further increase in insulin levels, either basal or food-induced.
The daily intake of carbohydrates (i.e., glycemic load) should be proportional with the body composition, the energy percentage (calculated in relation with other energy sources), and the degree of physical activity (including daily activities as well as activities planned by the rehabilitation system to reduce overweight and improve muscular function).
Carbohydrates intake should be progressively reduced throughout the day in light of the circadian increase in insulin resistance, more prominently observed during the last day hours.
Last but not least, it is necessary to avoid foods with high glycemic index (GI). The GI is determined by comparing the post prandial glycemic response of a food with the postprandial glycemic response to the same amount of available carbohydrate from a standard food in the same individual.
Baseline plasma levels of cytokines in obese people return to normal values after weight loss.
The nutritional sources of food themselves are different from those used by our ancestors. The production doesn’t respect the proximity criteria (0 km), seasonality criteria, or crop rotation criteria, resulting in a loss of micro-elements in soil. Fruits and vegetables generally meet more the preservation criteria instead of those of maturation with the result of the unpredictability of their content in terms of micronutrients.
The taste for food has been gradually changing giving priority to a rapid food intake (fast food), high levels of fat, flour and refined sugar. The large use of sweetened drinks contributes to increase the excessive energy introduction.
As for oxygen free radicals (ROS) production, it is related to inflammation during oxidative stress.
In obese patients and in those with cancer the ROS problem has a special role; supplements or diets with high content of vegetables with antioxidant activity have been given. The use of fruits and vegetables showed positive results in reducing the risk for cancer and recurrences.
Data, however, are not univocal. Each vegetable contains many different compounds, their availability is not always in relation with their content (it is a typical example for Beta carotene of carrot), the contents of a type of antioxidant may differ for the production site, stage of maturation to collection, preservation, and preparation methods (tomato sauce contains more available lycopene than raw tomato). The availability of a substance may change in different individuals according to the integrity of the intestinal mucosa (often damaged by chemotherapy) or to the kind of intestinal flora (1-1,5 kg of bacteria). This condition can also modify the food chemical structure, producing harmful or healthy substances for our health as in the case of soy isoflavones transformed into the much more active Equol only in subjects with suitable bacteria. In our blood and urine there’s a large amount of products of bacterial metabolism which may influence our health; it may differ depending on the breed, gender, functional states (pregnancy) and dietary habits: there’s much more complexity in epidemiological studies with the use of the food or nutritional supplements than expected in the research protocol.
The real availability (absorption) of substances in food or in supplements has a good chance to be different from that hypothesized and calculated with questionnaires or bromatological tables.
Diet should not cause any further increase in insulin levels, either basal or food-induced.
The daily intake of carbohydrates (i.e., glycemic load) should be in proportional with the body composition, the energy percentage (calculated in relation with other energy sources), and the degree of physical activity (including daily activities as well as activities planned by the rehabilitation system to reduce overweight and improve muscular function).
Carbohydrates intake should be progressively reduced throughout the day according to the circadian increase in insulin resistance, more prominently observed during the last day hours.
Last but not least, it is necessary to avoid foods with high glycemic index (GI). The GI is determined by comparing the postprandial glycemic response of a food with the postprandial glycemic response to the same amount of available carbohydrate from a standard food in the same individual.
Often using fruit we take more attention to the amount (5 servings a day) and to the concentration in antioxidants rather than the sugar content, which brings us back to the problem of calories and metabolic syndrome (fructose plugged to lead to a lower insulin response, is indeed much more dangerous than glucose for the pathogenesis of metabolic syndrome).
Diet is often unbalanced, not respecting the right proportions between carbohydrates (60%), lipids (25%) and proteins (15%).
The use of processed foods induces a higher salt intake, with effects on blood pressure and 10 on the integrity of structures such as the gastric mucosa with possible susceptibility to cancer.
The use of sweetened drinks and refined flour, without fibers, which are characteristics of white bread and pasta, causes a rapid absorption of carbohydrates and a rapid elevation of blood glucose, followed by a massive insulin response. Insulin is a hormone with multiple activities involved in the regulation of blood glucose, the transport of amino acids, the mobilization of fat from their deposits, the monitoring of urine output and of cell proliferation.
Persistent high levels of insulin indicate a loss of activity of the hormone (insulin resistance) that goes together with obesity, dyslipidemia (low HDL cholesterol, high triglycerides), high blood pressure and, according to data, even the cancer.
Fast food diets, also known with the term “Cafeteria Diet”, are often characterized by an excessive fat content, often saturated, (those who melt at higher temperatures) contained in marbled meat, so defined because at a thin shear it shows impregnation of lipids within the muscle structure, typical of those animals kept under movement restriction.
A high-fatty acids diet an altered ratio between saturated and unsaturated fats, an alteration in the ratio of unsaturated omega-6 (those that have a double bond in position 6 from terminal COOH) and omega-3 (those that have the double bond in position 3, typical of fish, nuts, etc.) causes increase in blood inflammatory markers. In a state of inflammation it leads to resistance to insulin receptors, which is the first step for obesity and metabolic syndrome.
Foods with sugar and refined flour should be reduced or abolished. Bread and pasta should be made with whole grain flours, that give them a distinctive dark color, rice should be strictly integral.
As for pasta it should be investigated whether the product is integral outset or if fibers have been added to starch in a second time. The difference is huge because the slow release of the starch in an originally integral flour can give an IG <40% than the refined flour = 75%. Rice and pasta should never be overcooked.
It is absolutely necessary to avoid using fructose as an alternative to sucrose.
Salt is an important part in the preparation and storage of food. It is blamed for stomach cancer, but may be also critical for its action on blood pressure and, indirectly, on the metabolic and inflammatory situation. Very often it is not calculated in nutritional epidemiological studies in oncology.
During the cooking process an improper use of heat can turn food into a non-profit element, even dangerous for health. The use of high temperatures for long periods can produce carcinogenic substances. The use of cooking helps the extraction of carotenoids from tomatoes and carrots, but degrades the antioxidants in cruciferous vegetables, often investigated for their anticancer properties. The problem regarding the cooking should be extended to the used instruments types (oven, microwave, fry, steam, etc.).
All food should be cooked with adequate methods, tools and cooking times. A typical example may be that of the french fries, for which the interest in compositional characteristics of nutritional caused a controversy about their potential toxicity, related to frying due to the formation of acrylamide.
Caloric restriction is an integral part of religion requirements in several countries (Islamic Ramadan, Orthodox Church abstinence during Christmas, Easter, Assumption, the Jewish tradition of Daniel’s fasting, etc.).
Over the past 30 years there have been more and more studies addressing health benefits related to caloric intake reduction in animal models and in humans.
Data seem to show that maximum benefits may be achieved by applying the highest possible calory reduction without resulting in overt malnutrition, and by prolonging this status as long as possible.
In animal models, caloric reduction of not more than 10-40% of the normal calories intake exerts an anticancer effect which is directly related to its duration.
Caloric restriction induces changes in metabolic and hormonal status in a similar way among animals and humans.
Caloric restriction improves sensitivity to insulin and improves glucose metabolism.
Caloric restriction can reduce oxidative stress.
Caloric restriction can increase life expectancy in animals; however, the restriction of carbohydrates or lipids alone does not seem to influence this result, which instead appears to be related to the reduction in methionine intake by lowering consumption of animal proteins. One year-long caloric restriction alone, even without physical activity, can reduce several markers of inflammation in obese postmenopausal women, including C-reactive protein, serum amyloid, and IL-6.
Accordingly, the excess of caloric intake induces obesity and represents a risk factor for cancer.
From rodents to primates, including humans, caloric restriction has been shown to be one of the most powerful tools in the prevention of carcinogenesis.
However, epidemiological data deriving from forced restrictions during the events of II World War showed conflicting results.
Conversely, Norwegians with a mean caloric intake reduction of about 50%, maintaining a balanced diet, showed a reduction in the incidence of breast cancer compared to controls.
In the Netherlands, a caloric intake reduction (70% in adults, 50% children) was paralleled by an increase in breast cancer but not in other forms of cancer.
The survivors of German and Russian concentration camps showed a sharp increase in all forms of cancer.
This apparent inconsistency of results can be due, in our opinion, to the distinction between caloric restriction and forced malnutrition characterized by the presence of other factors such as emotional stress, infections, etc.
About the component of physical exercise, the American Cancer Society recommends the exercise like part of a continuum of cancer survival care.
The physical exercise is able to reduce the risk to develop the breast cancer and colon on 25% and pulmonary cancer on 30%, uterine cancer and ovary cancer about on 20% and on 9% about the prostate cancer.
After the diagnosis and the treatment there is a reduction from 26 to 40% of recruitment of Brest cancer and of colon cancer with daily physical exercise and also good quality of life.
Also during the prostate cancer the aerobic and endurance physical activity can reduce the fatigue and improve the life\'s quality.
During the hematological cancer especially in non-Hodgkin lymphoma and multiple myeloma, the physical exercise can improve the quality of life with reduction of fatigue and also the aerobic capability in bone marrow transplantation.
The general benefits of physical exercise in cancer treatment are numerous and include: improved cardiac output, increased ventilation, improved flexibility and range of motion; increased muscular strength and endurance; decreased resting heart rate; improved stroke volume, vasodilatation, perfusion; improved metabolic efficiency; improved blood counts; improved psychological attitude to resist to the cancer disease. The cancer-specific benefits are related to cancer treatment toxicity especially to muscular degeneration with 1) fatigue and weakness, 2) neurotoxicity, 3) cardiotoxicity, 4) pulmonary toxicity.
Our therapeutic approach using the physical exercise and walking prescriptions is divided in 3 phases to: 1) recovery of residual capacity; 2) sensory-motor and functional recovery capacity; 3) the quality of life improvement.
The recovery of residual capacity is designed to recovery joint mobility and to increase the uninjured muscle tone after reprogram of flexibility.
In the cancer patient there is usually a marked reduction of the flexibility.
Flexibility is one of the physiological parameters involved in almost all forms of the human movement and is similar to aerobic capacity, strength, and neuromuscular endurance in being a trainable fitness parameter.
Flexibility has been defined as mobility compliance and, alternatively, as the reciprocal counterpart of stiffness. Most of the authors define flexibility either as range of motion at or about a joint. Another definition represents flexibility like the ability of a joint to move throughout its potential range of motion. Those definitions confuse the property of flexibility with the criterion able to measure the range of motion and using hardly synonymous; since potential range of motion is a variable factor among others in deterring flexibility, flexibility cannot be understood simple as relative to it.
We define flexibility like the disposition of body tissues to allow, without injury, excursions at a joint or set of joints. This property is measured by, but not equivalent to, range of motion. Both joint tissues and the surrounding soft tissues contribute to flexibility, although only the latter should be modified in order to enhance flexibility.
To increase this capability is possible to use yoga, slow / static and dynamic stretching techniques, Pilates method; in our experience we prefer anyway Elispheric Imoove method (fig. 5) and exercises deriving from proprioceptive neuromuscular facilitation (PNF). This last technique is designed as a manual, partner-assisted stretching; a partner is needed to provide the fixed resistance against which the lengthened agonist isometrical contracted at or near maximum (to use spindle facilitation).
Some factors that affect flexibility are modifiable, subject to voluntary control to some or large extent, others are not modifiable.
Flexibility decreases with age. In cancer patients, it suggests that regular activities, in order to maintain elasticity, or to do specific stretching programs, are important for aging.
Gender is another factor that influences flexibility. Females are generally more flexible than males especially during the same stretching program; probably women have a larger percentage of elastin in their miofascia.
Flexibility varies during the course of the day. There is greater flexibility of cervical spine during the late afternoon and evening hours and about the lower lumbar spine data show an improvement during daytime later hours.
About the anatomical constraints, the excessive fatty tissue limits range of motion related to the tightness of soft tissue structures. This problem is connected with some conditions of diseases like arthritis, diabetes mellitus, hemophilia and finally the cancer but also is correlated to bad posture in orthostasis or with seated flexed posture.
Other ways to improve flexibility: massage, warm-up and stretching are three basic techniques used to increase flexibility but neither massage or warm-up is as efficient as a proper stretching regimen in increasing flexibility.
The best method to realize stretching involves a series of less than maximal isometric contractions of the agonist muscles in a pre-lengthened state (to set up the stretch), followed by concentric contractions of the antagonist muscle group (to lengthen the agonist) in conjunction with light pressure from a partner when needed and with an instrumentation like sensorized postural bench system (TecnoBody, Italy).Though this mode the objectives are to alleviate muscle tension, to facilitate healing by increasing blood flow, to decrease muscle pain by reducing vasoconstriction. This work is to applied day by day using at the cancer patients home a specific personalized postural bench like Fleximat postural bench (fig. 1 DeltaDue, Italy).
Fleximat
When it is not possible to get a flexibility increase in cancer treatment: there are specific contraindications, due to time and circumstances, where stretching should not be performed to get flexibility improvement. Especially when there are reduced joint receptor and pain sensation, when mobilization of tissue is not possible, for example in post-acute cancer surgical treatment or when stretching or tension in tissue elicits pain.
After the recovery the joint mobility with the flexibility replanning, the improvement of the uninjured muscle tone and strength should be possible using before focused vibratory acoustic stimulation at high intensity with Vissone ( fig. 4 Vissman, Italy ) and after anaerobic work with TRX system. Vibrations are able to induce muscular adaptions to the recovery of muscle tone at the 300 Hz, of frequency and to stimulate the upper motors centers in order to obtain a better performance of controls, responsible for the muscle recruitment. Is noted that so is possible to 1) activate the aerobic metabolism; 2) determine an analgesic effect; 3) increase local circulation and bone density; 4) finally increase the contractile capacity and elasticity of the muscle treated.
To elicit the sensory-motor and functional recovery we need to get acceptable walking.
Human movement usually is defined by the walk and is not limited to bipedal locomotion; however, such locomotion is a fundamental part of daily life and is a prominent focus of public health physical activity guidelines.
The human gait is more complex; going one step forward, although it can start from the hip flexors of the Deep Frontal Line, especially the psoas and iliacus, afterwards, it involves the hip flexion, the knee extension, and the ankle dorsiflexion necessary to step forward, thanks to the myofascia of the Superficial Frontal Line. As the leg travels forward, the entire myofascia prepares to receive the weight of the body and the ground reaction.
Once the heel places on the ground and the step begins, the Superficial Back Line takes over as the back of leg engages into hip extension and plantar flexion. The abductors of Lateral Line, Ischio-Tibial-Tract, and the lateral compartment of the lower leg provide stability that prevents the hip adduction, while the adductor group and the other tissues of the Deep Frontal Line assist the flexion- extension motions and provide stability to the inner arch of the foot and up the inside of the leg. In the upper body, the common contralateral walking pattern involves the Functional Lines bringing the right shoulder forward to counterbalance the left leg when it swings forward and vice versa. Therefore the gist of walking capability is to improve the miofascial flexibility.
The walking objective monitoring evolution, using pedometer and accelerometer technology, offers an opportunity to perform guidelines, including recommendations for cancer patients.
All the studies in literature have used a variety of objective parameters using instruments that have been previously validated. The Yamax pedometer is considered a criterion research quality pedometer (Schneider et al., 2004), the Lifecorder\'s validity is well documented (Crouter et al., 2003; Schneider et al., 2004), and the ActiGraph has been adopted by national surveillance strategies (Troiano et al., 2008) and is probably the most utilized accelerometer in research today.
Therefore is possible to define with the pedometer the sedentary level into < 2,500 steps/ day (basally active) and into < 2,500 to 4,999 steps/day (limited activity); but using an established step-defined physical activity scale is possible to establish a level one for sedentary < 5,000 steps/day ; a level two >5,000 <7,499 steps/day for low active; a level three >7,500 <9,999 steps/day for somewhat active ; a level four >10,000 <12,499 steps/day for active; and a level five ≥ 12,500 steps/day for highly active.
We also noticed that healthy adults can perform between approximately 4,000 and 18,000 steps/day, and, in our opinion, also 7,500-9,9990 steps / day, resulting in between 50/ 85 steps /minute. That would be a reasonable target for the cancer patients in the first Mullan phase.
In order to get a better walking performance in the first phase of Mullan, and also in the second phase, we adopt two integrate procedures: 1) normalization of the foot-ground reaction forces using a personalized viscoelastic insoles to control vertical and shear forces on the foot during the stance phase without the obligatory use of athletic shoes; 2) use of the microgravitary system S.P.A.D (fig. 2) that determine the sensory-motor and functional recovery of the posture during the walking in combination to the development of proprioceptive information from the periphery to the cortical central system.
SPAD
During the first year after the cancer treatment the immune system shows some specific changes in patient with cancer especially in some specific T-cell populations.
There is no scientific evidence that physical therapies, like magnetic fields, are effective in the treatment of cancer itself. Global physics community perfectly knows what the extreme low frequencies and intensity of magnetic fields are. They also know how they provoke the resonance of ions (Ion Cyclotron Resonance), with the exact frequency in order to remove an ion from its orbit of rotation in order to escape.
Only in the last decades the studies in biophysics have shown that with the ion cyclotron resonance is possible to stimulate the passage of ions through the membranes of the cells of the living beings changing their permeability and therefore improving the ion exchange on both sides of the membrane itself. The increase of the bioavailability of the essential ions, makes better the efficiency of the cell itself to achieve its correct metabolism.
The role of electromagnetic fields for control of cancer pain and chemotherapy nausea-induced symptoms remains controversial but this theory is to be correlate to water coherence domains’ theory (G. Preparata, E. Del Giudice, G. Talpo 1999).
The activities and the exchanges of the molecules in the body doesn’t happen by chance, but they follow an “order” dictated by the magnetic field produced by the water, where all the elements fluctuate in phase in the those regions called coherence domains.
Only the molecules which react to the frequency of this magnetic field, interact with each other, starting in ordered way the correct chemical reactions necessary for life of the cell and the organism. An imbalance of this \'order\' jeopardizes the functioning of the cell, with the consequence of the manifestations of the diseases.
The 40% of the water is coherent and it can receive and deliver electromagnetic information, while the remaining 60% is not coherent, equally essential for life; it represents the solvent of the ions and of the fundamental elements to the cellular economy.
Also Montagnier L. in 2009 has recognized the validity of the coherence domains, stating how the water is not an inert substance, but may take special configurations emitting electromagnetic waves that can become an not pharmacological instrument of the therapy and the adjustment, but always deeply medical care.
The cells’ DNA emits extremely low frequency waves, from zero to a few hundred of Hertz. The studies were published on the unbalance of this "range" that disturbs the harmony of the cell, with the onset of the manifestations of diseases. Some chronic diseases such as Alzheimer\'s, Parkinson\'s, multiple sclerosis, rheumatoid arthritis, and the viral diseases such as HIV -AIDS, influenza A and hepatitis C, "inform" the water of our body (biological water) of their presence issuing a special electromagnetic signals that can then be "read and decoded“.
With Ion Cyclotron Resonance we have the possibility to intervene in a not invasive, natural and precise adjustment mechanisms of the body\'s homeostasis, where the only pharmacological support can be not complete.
Therefore you get the possibility:
To rebalance subjective metabolism
To adjust the enzyme functions, the ion channels and the body pH
To strengthen the immune system
To encourage the bioavailability and absorption of nutrients for cell metabolism
To treat neuralgia, headaches and migraines
To stimulate healing in all kinds of wounds, even after surgery.
To balance the water retention
To enhance the effect of drugs and supplements
To detoxify and to allow antioxidant function against free radicals, metabolites, toxins
To stimulate a pain-killer function (acute and chronic)
To get muscle relaxation, from anxiety and stress
To improve the homeostasis recovery under stress (physiological micro trauma and muscle protein catabolism)
To improve the quality of life for cancer patients.
In a preliminary observational study of 43 cancer patient group, they were divided into 3 groups of 14 patients, using also the Ion Cyclotron Resonance with QUEC PHISIS QPS1 (fig. 3) we observed the initial and final values of d-ROMs Test.
The first group only used the QUEC PHISIS QPS1
The second group used the QUEC PHISIS QPS1 and the antioxidants.
The third group only used the antioxidants.
The study shows a significant improvement after 90 minutes before the beginning of the first treatment. The values are improved and consolidated in the time after a month about the end of the cycle of treatments with the values well below average.
Qps 1
Viss
Imoove
The integration between the pharmacology, the biochemistry, the biophysics and the lifestyle with energetic modulation using therapeutic diet through the use of the information and the signals, probably will be able to restore a robust immune response in the tumor-bearing host or to promote by adoptive transfer of activated effector cells or tumor-specific antibodies into the tumor-bearing host.
Bacteria, fungi (yeasts and molds), mycobacteria, prions, protozoa, and viruses are common pathogens infecting humans and animals. They typically exist within the host or in the environment. It has been observed that these microorganisms exhibit a notable difference in the natural survivability in the environment, as well as susceptibility to chemical and physical inactivation. For example, under ambient and dried conditions, human coronaviruses seem to lose their infectivity in a matter of several hours to several days [1], whereas endospores and prions may remain infectious for years to decades or even indefinitely [2, 3].
As more and more data have become available regarding the survivability and susceptibility of pathogens to microbicides, it has been observed that the pathogens seem to demonstrate an order of susceptibility to chemical and physical inactivation. E. H. Spaulding first proposed a classification system for the sterilization and disinfection of medical instruments based on the infection risk in 1939 [4]. On the basis of this classification, the concept of a hierarchy of pathogen susceptibility was proposed, in which microorganisms are placed into several groups and ranked from least susceptible to most susceptible. In this hierarchy concept, bacterial spores were ranked the least susceptible, followed by mycobacteria, non-enveloped viruses, fungi, vegetative bacteria, and enveloped viruses. The susceptibility hierarchy was also believed to be related to the biochemical and biophysical characteristics of a pathogen [5, 6].
This hierarchy concept has been slightly modified and expanded over the years. For example, prions were added and considered less susceptible to inactivation by microbicides than bacterial spores; small non-enveloped viruses were considered less susceptible than large non-enveloped viruses; and the order between mycobacteria and small non-enveloped viruses was sometimes reversed (Figure 1) [7, 8, 9, 10]. Additionally, it has been suggested that the hierarchy concept may be applied either “vertically” (i.e., ranking of susceptibility
Proposed hierarchy of susceptibility of pathogens to microbicides. Note: slightly different versions of the hierarchy concept have been proposed in the literature. Mycobacteria have been placed above small non-enveloped viruses, and molds have been placed above large non-enveloped viruses in certain versions. In some versions, the small and large non-enveloped viruses are combined; and yeasts and molds may be combined.
The hierarchy concept has been quite useful for enabling scientists to better understand the innate difference among various types of pathogens. In the case of newly emerged pathogens, especially, the hierarchy concept has helped stakeholders design and implement a disinfection strategy swiftly with a reasonable level of confidence. The concept also helps the contaminant control for food, pharmaceutical, and biopharmaceutical products, as it is impractical to test every possible contaminating pathogen, and a robust infectivity assay system may be lacking for certain pathogens (e.g., hepatitis E virus).
Despite its usefulness, the hierarchy concept should be interpreted with caution, as it may oversimply the differences and trending of pathogen susceptibilities. Further examination and refinement of the concept may be necessary; and several important questions should be answered. For example, how often do exceptions to the hierarchy occur and what are the underlying reasons? Could a trending be specific to a given type of chemistry? Is the hierarchy the same between susceptibility to both chemical and physical inactivation? Why do pathogens in the same group, or even the same family or genus, sometimes exhibit striking differences in susceptibility? Is there a way to identify and separate reliable/consistent trending versus blurred/variable trending? A deeper look at the efficacy data for various types of microbicidal actives, especially for non-enveloped viruses, may help stakeholders understand the scope, reliability, and limitation of the hierarchy concept so that it can be best utilized.
This chapter reviews the inactivation efficacy data from the literature against non-enveloped viruses for several commonly used types of chemistries, either in formulated or unformulated form, in an effort to generate a separate relative order of susceptibility among these non-enveloped viruses for each type of chemistry and to differentiate consistent versus variable trending. Physical inactivation approaches are not covered in this chapter, although a significant degree of variation also exists for physical treatments. It is not clear that the physical inactivation approaches, in general, are governed by the same hierarchy to susceptibility as is observed for chemical inactivation approaches [12].
Currently, there are a total of 21 families of viruses (including enveloped and non-enveloped) identified for humans [13], which represent only a small part of the entire paradigm of viruses in nature, whose host ranges extend from vertebrates to plants to bacteria. The most common families of non-enveloped viruses for humans and animals include
Family | Example virus | Abbreviation | Genus | Genome | Size (nm) |
---|---|---|---|---|---|
Adenovirus type 2 | AdV-2 | ds DNA | 70–90 | ||
Adenovirus type 5 | AdV-5 | ds DNA | 70–90 | ||
Adenovirus type 8 | AdV-8 | ds DNA | 70–90 | ||
Human astrovirus | HAstV | ss RNA | 28–35 | ||
Feline calicivirus | FCV | ss RNA | 28–40 | ||
Human norovirus | HuNoV | ss RNA | 28–40 | ||
Murine norovirus | MNV | ss RNA | 28–40 | ||
Tulane virus | TuV | ss RNA | 28–40 | ||
Porcine circovirus | PCV | ss DNA | ∼17 | ||
Hepatitis E virus | HEV | ss DNA | 32–34 | ||
Human papillomavirus | HPV | ds DNA | 50–60 | ||
Bovine parvovirus | BPV | ss DNA | 20–28 | ||
Canine parvovirus | CPV | ss DNA | 20–25 | ||
Human parvovirus B19 | B19V | ss DNA | 23–26 | ||
Minute virus of mice | MVM (MMV) | ss DNA | 20–25 | ||
Porcine parvovirus | PPV | ss DNA | 20–25 | ||
Bovine enterovirus | BEV | ss RNA | 30–32 | ||
Coxsackievirus | Cox | ss RNA | 30–32 | ||
Echovirus 11 | Echo11 | ss RNA | 30–32 | ||
Encephalomyocarditis virus | EMCV | ss RNA | 30–32 | ||
Enterovirus 71 | EV-71 | ss RNA | 30–32 | ||
Enterovirus D68 | EV-D68 | ss RNA | 30–32 | ||
Foot and mouth disease virus | FMDV | ss RNA | 30–32 | ||
Hepatitis A virus | HAV | ss RNA | 30–32 | ||
Poliovirus type 1 | PV1 | ss RNA | 30–32 | ||
Rhinovirus | RV | ss RNA | 30–32 | ||
Seneca Valley virus | SVV | ss RNA | 30–32 | ||
Bovine polyomavirus | BPyV | ds DNA | 40–50 | ||
Simian virus 40 | SV40 | ds DNA | 40–50 | ||
Bluetongue virus | BTV | ds RNA | 60–80 | ||
Reovirus type 3 | REO-3 | ds RNA | 60–80 | ||
Rotavirus | Rota | ds RNA | 60–80 |
Common families of human and animal non-enveloped viruses.
Among these, the
It is worth noting that viruses are typically classified taxonomically on the basis of virion properties (size, shape, envelope, physical, and chemical properties, etc.), genome organization, replication mechanism, antigenic properties, and biological properties [13, 14, 15]. The final classification is a combined consideration of these properties. However, the stability and susceptibility to inactivation of a virus may not relate to all of these properties and, as such, may not always align with the taxonomic classification system. For example, the susceptibility of a virus to surfactants may primarily be related to the envelope of the virion and not related to the genome structure or mode of replication.
The susceptibilities of non-enveloped viruses to chemicals have been found to be highly variable and somewhat hard to predict, since they do not always agree with the hierarchy concept. For example, according to the hierarchy concept as modified by Sattar [8], small non-enveloped viruses should be less susceptible than large non-enveloped viruses. Additionally, if there is a fixed hierarchy, all small non-enveloped viruses should either display similar levels of susceptibility or should demonstrate a definitive trend of relative susceptibility, regardless of the type of microbicide. Based on the literature, neither of these predictions appear to hold in every case. The relative order of susceptibility seems chemistry-dependent; and sometimes viruses within the same family or even genus have been found to exhibit unequivocal differences in their susceptibilities (reviewed in [16]). Any trending or hierarchy, therefore, must be reviewed in the context of the type of chemistry, and it should not be assumed that non-enveloped viruses within the same family or genus will always display similar susceptibilities to a given microbicide.
Viral inactivation may be achieved by chemical and/or physical methods. The subset of chemicals commonly used for inactivation of non-enveloped viruses includes alcohols, oxidizers, halogen compounds, quaternary ammonium compounds, phenolics, aldehydes, acids, and alkalines [17, 18, 19]. These differ with respect to efficacy, stability, toxicity, material or surface compatibility, cost, and sensitivity to organic soil load. Soil load is a term used to signify an organic matrix used to challenge the inactivating efficacy of a microbicide. It is intended to mimic secretions or excretions in which the virus would be released from an infected person or animal. Some chemistries (e.g., sodium hypochlorite, phenolics, and aldehydes) are mostly used for environmental or medical device disinfection. Other chemistries (e.g., ethanol) are more commonly used for hand hygiene, while some others (e.g., quaternary ammonium compounds) may be used for both environmental disinfection and skin antisepsis (Table 2).
Class | Chemical | Typical conc. | Usage | Mechanism of viral inactivation | Sensitivity to soil load |
---|---|---|---|---|---|
Alcohols | Ethanol | 50–95% | Disinfection; Antisepsis | Protein denaturation | + |
Isopropanol | 70–90% | Disinfection | Protein denaturation | + | |
Oxidizers | Sodium hypochlorite | 0.01–0.5% | Disinfection | Protein/genome damage | ++ |
Chlorine dioxide | 0.1–1 mg/L | Disinfection; Water treatment | Protein/genome damage | — | |
Hydrogen peroxide | 0.1–10% | Disinfection; Antisepsis | Lipid/protein/genome damage | + | |
Hypochlorous acid | 0.002–0.1% | Disinfection; Water treatment | Protein/genome damage | ++ | |
Peracetic acid | 0.01–1% | Disinfection; Sterilization | Protein denaturation | — | |
Povidone-iodine | 0.02–8% | Disinfection; Antisepsis | Protein/genome damage | ++ | |
Chlorohexidine | 0.02–0.2% | Antisepsis | Protein denaturation | + | |
QAC | BKC, DDAC, etc. | 0.01–0.2% | Disinfection | Lipid/protein damage | + |
Low pH | Acids | ≤ pH 4 | Sanitization; Biomanufacturing | Capsid/protein damage | — |
High pH | NaOH, etc. | ≥ pH 10 | Disinfection; Tissue processing | Capsid/genome damage | — |
Aldehydes | Glutaraldehyde | 0.02–2% | HLD; Sterilization | Crosslinking/protein & genome damage | — |
Formaldehyde | 0.1–5% | Disinfection/Preservation | Alkylating/protein & genome damage | — | |
OPA | 0.02–2% | HLD; Sterilization | Crosslinking/protein damage | — | |
Phenolics | Phenylphenol, etc. | 0.05–5% | Disinfection | Protein damage | — |
Common types of chemistries used for non-enveloped viral inactivation.
Abbreviations used: BKC, benzalkonium chloride; Conc, concentration; DDAC, didecyldimethylammonium chloride; HLD, high-level disinfection; NaOH, sodium hydroxide; OPA, ortho-phthaldehyde; QAC, quaternary ammonium compounds.
The virucidal efficacy of a product is not only determined by the type and concentration of the chemical, but is also heavily influenced by the formulation, pH, exposure (contact or dwell) time, organic soil load, temperature, and surface characteristics (as applicable), etc. [10, 20, 21, 22]. Given the differences between various testing methods, as well as the intrinsic variability of viral infectivity (titration) assays, a general conclusion on the efficacy of a particular type of active ingredient will be enhanced if the efficacy is derived from multiple sets of data and under various application conditions (such as the concentration of the microbicidal active(s), contact time, formulation matrix (as applicable), and organic soil load, etc.) Additionally, in order best to explore the relative ranking of susceptibility between viruses, or the lack thereof, efficacy data from side-by-side studies wherein the same test methodologies and conditions were used would be preferable. Care should be taken when comparing data from different studies, especially if the formulations, test methods, and test conditions were different.
Alcohols, primarily ethanol and isopropanol, are widely used for hand hygiene and environmental disinfection, and their efficacies against bacteria and viruses have been extensively studied [23, 24, 25]. Ethanol at a concentration of 70–90% and isopropanol at 70% have been broadly shown to be effective against enveloped viruses; however, their efficacies against non-enveloped viruses are much more variable.
The trending of the degree of susceptibility of non-enveloped viruses to ethanol and isopropanol is generally clearer and more consistent than it is for many other types of chemistries, thanks to the large amount of data in the literature. The relative ranking of susceptibility of non-enveloped viruses seems to differ between ethanol and isopropanol; and the ranking does not appear to align well with the classical virological taxonomy.
For ethanol, parvoviruses and the polyomavirus simian virus 40 have low susceptibility, while rotavirus (a reovirus) is susceptible (Table 3). Viruses in the
Virusa | Method | Soil/Matrixb | Log10 Reduction after | References | |||
---|---|---|---|---|---|---|---|
30 s | 1 min | 5 min | 10 min | ||||
PPV | Stainless steel | Erythrocytes + BSA | 0.3 | 0.6 | [26] | ||
MVM | Stainless steel | Erythrocytes + BSA | 0.3 | 0.7 | [26] | ||
HEV71 | Suspension test | Medium | < 1 | [27] | |||
HAV | Suspension test | Medium | 0.4 | [28] | |||
HAV | Suspension test | 20% fecal | 0.4 | [28] | |||
HuNoV | Suspension test | 20% stool | <0.5 | [29] | |||
TuV | Suspension test | Medium | <0.5 | [30] | |||
PV1 | Suspension test | 20% fecal | 0.3 | [28] | |||
PV1 | Suspension test | Medium | 0.4 | [31] | |||
PV1 | Glass | Medium | 2.3 | 1.0 | 5.0 | [31] | |
PV1 | Stainless steel | Erythrocytes + BSA | 2.1 | 1.8 | [26] | ||
PV1 | Suspension test | Medium | 4 | [28] | |||
FCV | Suspension test | Medium | 1.7 | 2.2 | [30] | ||
AdV-8 | Suspension test | Medium | 1.9 | [33] | |||
AdV-5 | Stainless steel | Erythrocytes + BSA | 2.4 | >4.1 | [26] | ||
AdV-5 | Stainless steel | Medium | ∼5 | [34] | |||
MNV | Suspension test | Medium | 5 | [30] | |||
Rotavirus | Suspension test | Medium | > 3.1 | [28] | |||
CPV | Stainless steel | Medium | 0.1 | [36] | |||
SV40 | Suspension test | Medium | <1 | [37] | |||
PV1 | Glass | Medium | 2.9 | 2.9 | 5.4 | [31] | |
TuV | Suspension test | Medium | <0.5 | [30] | |||
FCV | Suspension test | Medium | <0.5 | [30] | |||
HEV71 | Suspension test | Medium | <1 | [27] | |||
PV1 | Suspension test | medium | <1 | [37] | |||
PV1 | Glass | Medium | 1.2 | 1.3 | 1.0 | [31] | |
AdV-5 | Stainless steel | Medium | ∼1 | [34] | |||
AdV-8 | Suspension test | Medium | 2.0 | [33] | |||
MNV | Suspension test | Medium | 1.8 | 3.1 | [30] | ||
SV40 | Suspension test | Medium | >4 | [37] | |||
Rotavirus | Suspension test | Medium | > 4 | [42] |
Efficacy of alcohols against non-enveloped viruses.
See Table 1 for abbreviations used for viruses.
BSA, bovine serum albumin; medium, culture medium; RT, room temperature.
Entries in purple font indicate results from undiluted or diluted formulations with the indicated microbicidal active ingredients.
Interestingly, the above order of susceptibility does not appear to hold the same for isopropanol (Table 3). For example, the polyomavirus simian virus 40 is much more susceptible to isopropanol than many other non-enveloped viruses; and poliovirus appears to display a lower susceptibility, similar to that of hepatitis A virus and human enterovirus 71. Murine norovirus is still more susceptible than feline calicivirus to isopropanol, but not as susceptible as simian virus 40 or rotavirus. The apparent difference between adenovirus 5 and adenovirus 8 that has been observed for ethanol has not been observed for isopropanol.
An oxidizer or oxidizing agent is a chemical that has the ability to oxidize other molecules, i.e., to accept their electrons. Common oxidizing agents used for disinfection, sterilization, or antisepsis include hydrogen peroxide, peracetic acid, ozone, and halogen-containing compounds such as sodium hypochlorite (bleach), hypochlorous acid, povidone-iodine, chlorohexidine, and chlorine dioxide, etc. These compounds can react with and alter the proteins and nucleic acids of non-enveloped viruses and render them noninfectious. Oxidizers comprise a large group of chemicals, and the relative order of susceptibility of non-enveloped viruses to oxidizers seems to vary by specific type of active ingredient (Table 4).
Virusa | Method | Soil/Matrixb | Log10 Reduction after | References | |||
---|---|---|---|---|---|---|---|
≤ 1 min | 2 min | 5 min | 10 min | ||||
FCV | Suspension test | Medium | 3 | [29] | |||
FCV | Suspension test | 20% stool | 0.5 | [29] | |||
MNV | Suspension test | Medium | 3 | [29] | |||
MNV | Suspension test | 20% stool | 0.0 | [29] | |||
CPV | Stainless steel | 90% plasma | < 1 | [43] | |||
CPV | Stainless steel | 5% serum | 5 | [43] | |||
HAV | Stainless steel | 5% serum | 5 | [43] | |||
HAV | Stainless steel | 90% plasma | <1 | 5 | [43] | ||
HAV | Suspension test | PBS/20% fecal | 4 | [28] | |||
PV1 | Suspension test | PBS/20% fecal | 4 | [28] | |||
PPV | Stainless steel | Erythrocytes + BSA | 0.6 | 1.0 | [26] | ||
MVM | Stainless steel | Erythrocytes + BSA | 3.0 | 4.4 | [26] | ||
PV1 | Stainless steel | Erythrocytes + BSA | 2.8 | 4.5 | [26] | ||
AdV-5 | Stainless steel | Erythrocytes + BSA | 4 | [26] | |||
PV1 | Glass | Medium | 0.4 | 0.9 | [16] | ||
RV14 | Glass | Medium | >4.9 | [16] | |||
PPV | Stainless steel | Erythrocytes + BSA | 0.5 | [26] | |||
MVM | Stainless steel | Erythrocytes + BSA | 1.5 | [26] | |||
PV1 | Stainless steel | Erythrocytes + BSA | 3.9 | [26] | |||
AdV-5 | Stainless steel | Erythrocytes + BSA | 2.3 | [26] | |||
MNV | Suspension test | Medium | ∼3 | [52] | |||
HAV | Suspension test | Medium | ∼3 | [53] | |||
PV | Suspension test | Medium | >3 | [53] | |||
CPV | Stainless steel | BSA | 1.6 | [34] | |||
MVM | Stainless steel | BSA | 2.3-2.9 | [34] | |||
PPV | Stainless steel | BSA | 3.8-5.5 | [34] | |||
AdV-5 | Stainless steel | BSA | 4.9-5.8 | [34] |
Efficacy of oxidizers against non-enveloped viruses.
See Table 1 for abbreviations used for viruses.
BSA, bovine serum albumin; PBS, phosphate buffered saline; medium, culture medium; RT, room temperature.
Viral-inoculated lettuce was washed with PAA solution for a defined period of time.
Entries in purple font indicate results from undiluted original or diluted formulations with microbicidal active ingredients.
Parvoviruses are generally among the least susceptible viruses to various types of oxidizers, including sodium hypochlorite, hydrogen peroxide, and peracetic acid. However, for sodium hypochlorite, minute virus of mice appears to be more susceptible than porcine parvovirus and canine parvovirus. All picornaviruses appear to exhibit a similar degree of susceptibility to sodium hypochlorite; but within the family of
The trending for hydrogen peroxide seems more complex than that for sodium hypochlorite. For example, there seems a higher level of variability within the
For peracetic acid, hepatitis A virus also seems less susceptible than poliovirus. Both feline calicivirus and murine norovirus are susceptible to peracetic acid and so is adenovirus.
Quaternary ammonium compounds (QAC) are widely used as active ingredients for disinfectants. Among the advantages of QAC are good stability, dual function of disinfection and cleaning, surface activity, low toxicity, and lack of odor, etc. The potential limitation in the microbicidal efficacy and possible effect in promoting antimicrobial resistance of QAC have also been discussed in the literature [54, 55].
Quaternary ammonium compounds are generally efficacious on most vegetative bacteria and enveloped viruses. Their efficacies against non-enveloped viruses, however, are generally much weaker. Nevertheless, several non-enveloped viruses, such as rotavirus, rhinovirus, and coxsackievirus A11, have been shown to be susceptible to QAC. The susceptibility levels among the
Virusa | Method | Soil/matrixb | Log10 reduction after | References | |||
---|---|---|---|---|---|---|---|
30 s | 1 min | 10 min | 60 min | ||||
PPV | Stainless steel | Erythrocytes + BSA | 0.4 | [26] | |||
MVM | Stainless steel | Erythrocytes + BSA | 0.5 | [26] | |||
PV1 | Stainless steel | Erythrocytes + BSA | 0.5 | [26] | |||
AdV-5 | Stainless steel | Erythrocytes + BSA | 1.8 | [26] | |||
AdV-8 | Suspension test | Medium | 1.0-1.8 | [57] | |||
AdV-5 | Suspension test | Medium | 3.7-5.3 | [57] | |||
TuV | Suspension test | Medium | <0.5 | [30] | |||
PV1 | Suspension test | BSA/yeast extract | 0.0 | [58] | |||
AdV-25 | Suspension test | BSA/yeast extract | 0.3 | [58] | |||
Cox A11 | Suspension test | BSA/yeast extract | >5.1 | [58] | |||
FCV | Suspension test | Medium | <0.5 | [29] | |||
MNV | Suspension test | Medium | <0.5 | [29] | |||
Rhinovirus | Glass | Medium | >3.0 | >3.3 | [16] |
Efficacy of QAC against non-enveloped viruses.
See Table 1 for abbreviations used for viruses.
BSA, bovine serum albumin; medium, culture medium; QAC, quaternary ammonium compound.
Entries in purple font indicate results from original or diluted formulations with microbicidal active ingredients.
Acids and alkalines, either used alone or in combination with other active ingredients in formulated products, can be an effective means for viral inactivation. Acids may be used for disinfection, sanitization, textile or face mask pretreatment, or viral clearance during biopharmaceutical manufacturing. Alkalines may also be used for disinfection, sanitization, and viral clearance during biopharmaceutical manufacturing and can be effective against even the least susceptible of pathogens, the prions [58].
It has been widely reported that a low-pH treatment (typically at pH 4 and below) can effectively inactivate most enveloped viruses, although some enveloped viruses, such as bovine viral diarrhea virus, still exhibit a relatively low susceptibility to this treatment pH [22]. The range of susceptibilities of non-enveloped viruses to low pH seems quite scattered and often goes against the “conventional wisdom” that non-enveloped viruses are not susceptible to acidic pH (Table 6). For instance, in the family of
Virusa | Method | Soil/Matrixb | Log10 Reduction after | References | |||
---|---|---|---|---|---|---|---|
20 min | 30 min | 45 min | 1–2 hr | ||||
REO-3 | Suspension test | Medium | 1–3 | [59] | |||
PCV | Suspension test | Medium | >3 | [60] | |||
MVM | Suspension test | Medium | <1 | [61] | |||
MNV | Suspension test | Medium | <0.5 | [30] | |||
TuV | Suspension test | Medium | <0.5 | [30] | |||
PARV4 | Suspension test | Medium | 2–3 | [61] | |||
B19V | Suspension test | Medium | > 4 | [61] | |||
FCV | Suspension test | Medium | 6.3 | [30] | |||
FCV | Suspension test | Medium | >5 | [62] | |||
PV | Suspension test | Medium | <1 | [63] | |||
PV | Suspension test | Medium | <1 | [64] | |||
HAV | Suspension test | Medium | <1 | [64] | |||
MNV | Suspension test | Medium | <0.5 | [30] | |||
TuV | Suspension test | Medium | <0.5 | [30] | |||
Cox A9 | Suspension test | Medium | <1 | [65] | |||
FCV | Suspension test | Medium | ∼3 | [30] | |||
FCV | Suspension test | Medium | ∼4.7 | [62] | |||
RV | Suspension test | Medium | >3 | [65] | |||
FMDV | Suspension test | Medium | >3 | [65] | |||
MVM | Suspension test | Medium | <1 | [66] | |||
EV71 | Suspension test | Medium | <1 | [67] | |||
EV-D68 | Suspension test | Medium | ∼4–5 | <5 | [67] | ||
B19V | Suspension test | Medium | [66] |
Efficacy of low pH against non-enveloped viruses.
The
Feline calicivirus and murine norovirus in the family
Viruses, both enveloped and non-enveloped, are generally susceptible to high pH. At an environment of pH 12 or above, most if not all non-enveloped viruses would be inactivated, with extent depending both on temperature and contact time. Reovirus, simian virus 40, hepatitis A virus, canine parvovirus, poliovirus, murine norovirus, and Tulane virus seem to be less susceptible than minute virus of mice, feline calicivirus, adenovirus, rotavirus, and foot-and-mouth disease virus. It may be worth noting that the order of susceptibility to high pH seems to be in discord with the hierarchy concept by the greatest degree: in this case, an enveloped virus, bovine viral diarrhea virus, seems to be less susceptible than most, if not all, non-enveloped viruses [22]; parvoviruses are not necessarily less susceptible than many other non-enveloped viruses; and the size of the viral particle does not seem to matter much with regard to the degree of susceptibility (Table 7).
Virusa | Method | Soil/Matrixb | Log10 Reduction after | References | |||
---|---|---|---|---|---|---|---|
≤ 1 min | 10 min | 30 min | 1 hr | ||||
MNV | Suspension test | Medium | ∼2 | [30] | |||
TuV | Suspension test | Medium | ∼2.2 | [30] | |||
FCV | Suspension test | Medium | >5.5 | [30] | |||
REO-3 | Suspension test | Medium | 3 | [68] | |||
Cox B | Suspension test | Medium | 5 | [69] | |||
Echo 11 | Suspension test | Medium | 6 | [68] | |||
BVDV | Suspension test | Medium | 2.5 | [70] | |||
HAV | Suspension test | Medium | 2.7 | [59] | |||
SV40 | Suspension test | Medium | 3.9 | [70] | |||
HAV | Stainless steel | 5% serum | 3.0 | [43] | |||
HAV | Stainless steel | 90% plasma | 3.6 | [43] | |||
CPV | Stainless steel | 5% serum | 3.5 | [43] | |||
CPV | Stainless steel | 90% plasma | 5.2 | [43] | |||
MVM | Suspension test | Medium | >4.7 | [71] | |||
MVM | Suspension test | Medium | >4 | [66] | |||
CPV | Suspension test | Medium | 5.6 | [70] | |||
PV | Suspension test | Medium | 5.9 | [70] | |||
AdV-2 | Suspension test | Medium | >6.9 | [70] | |||
AdV-5 | Suspension test | Medium | >6 | [72] | |||
HAV | suspension test | Medium | 2.4 | [59] | |||
PV | suspension test | Medium | 4.1 | [63] | |||
Avian Reo | Suspension test | Medium | 4 | [73] | |||
PV | Suspension test | Medium | 5.1 | [73] | |||
Bovine Rota | Suspension test | Medium | >6 | [73] |
Efficacy of high pH against non-enveloped viruses.
Entries in purple font indicate results from undiluted or diluted formulations with microbicidal active ingredients.
Aldehydes, such as glutaraldehyde, formaldehyde, and
Virusa | Method | Soil/Matrixb | Log10 Reduction after | References | |||
---|---|---|---|---|---|---|---|
5 min | 10 min | 30 min | 60 min | ||||
HAV | Suspension test | Medium | 3.0 | [75] | |||
PPV | Stainless steel | BSA | 1.7–2.8 | [34] | |||
MVM | Stainless steel | BSA | 2.5–3.3 | [34] | |||
PV1 | Suspension test | Medium | >3 | [76] | |||
AdV-5 | Stainless steel | BSA | 4.9–6.3 | [34] | |||
PPV | Stainless steel | Erythrocytes + BSA | 3.6 | [26] | |||
MVM | Stainless steel | Erythrocytes + BSA | >4.4 | [26] | |||
AdV-5 | Suspension test | Medium | >5.0 | [77] | |||
Ortho-phthaldehyde, 0.55% | |||||||
PPV | Stainless steel | Erythrocytes + BSA | 3.6 | [26] | |||
MVM | Stainless steel | Erythrocytes + BSA | >4. | [26] |
Efficacy of aldehydes against non-enveloped viruses.
See Table 1 for abbreviations used for viruses.
BSA, bovine serum albumin; medium, culture medium; RT, room temperature.
Entries in purple font indicate results from original or diluted formulations with microbicidal active ingredients.
In the simplified hierarchy of susceptibility of pathogens to microbicides concept, small non-enveloped viruses are considered less susceptible than large non-enveloped viruses, and both groups of non-enveloped viruses are believed to be less susceptible than enveloped viruses. The hierarchy concept also assumes that the ranking applies to all types of microbicidal actives. Additionally, the hierarchy concept can generally lead to common notions that viruses that share similar virological properties (e.g., same family or genus of virus) may be expected to display similar degrees of susceptibility and that the smaller a virus is, the less susceptible it will be to microbicides in general.
These generalizations are correct, to a degree. For example, most enveloped viruses are indeed more susceptible than non-enveloped viruses to chemical inactivation. It should be noted though that exceptions to the hierarchy concept do exist, e.g., especially in the case of viral susceptibility to acids and alkalines [22], and exceptions are not uncommon for certain other chemistries. The hierarchy concept was never applied specifically to physical inactivation approaches, nor should it be. The evidence for heat inactivation, UV inactivation, and gamma irradiation indicates differing rankings of susceptibility to these modalities. Envelope status and particle size do not, in each case, relate to susceptibility for inactivation by these physical approaches [22, 78, 79, 80].
The validity of the hierarchy concept
The accuracy and usefulness of a hierarchy concept can be improved if the model is broken into separate chemistries for non-enveloped viruses, since many viruses do exhibit a reliable and consistent trend of susceptibility for a specific type of chemical. Table 9 and Figure 2 provide a summary of the relative order of susceptibility for selected non-enveloped viruses under specific types of chemistry.
Chemical | Lower susceptibility | Medium susceptibility | Higher susceptibility |
---|---|---|---|
Ethanol | Animal parvovirus | Poliovirus | Murine norovirus |
Simian virus 40 | Foot and mouth disease virus | Rhinovirus | |
Hepatitis A virus | Human norovirus | Adenovirus 5 | |
Enterovirus 71 | Feline calicivirus | Rotavirus | |
Adenovirus 2, 8 | |||
Isopropanol | Animal parvovirus | Adenovirus 5, 8 | Simian virus 40 |
Hepatitis A virus | Murine norovirus | Rotavirus | |
Enterovirus 71 | |||
Poliovirus | |||
Feline calicivirus | |||
NaOCl | Porcine parvovirus | Minute virus of mice | Feline calicivirus |
Hepatitis A virus | Hepatitis A virus | Adenovirus | |
Poliovirus | Rotavirus | ||
Enterovirus 71 | |||
Murine norovirus | |||
H2O2 | Animal parvovirus | Poliovirus | Rhinovirus |
Hepatitis A virus | Murine norovirus | Feline calicivirus | |
Adenovirus | Rotavirus | ||
PAA | Animal parvovirus | Poliovirus | Feline calicivirus |
Hepatitis A virus | Murine norovirus | ||
Adenovirus | |||
QAC | Animal parvovirus | Feline calicivirus | Rotavirus |
Poliovirus | Murine norovirus | Rhinovirus | |
Adenovirus 8, 25 | Adenovirus 5 | Coxsackievirus A11 | |
Low pH | Minute virus of mice | Human parvovirus 4 | Feline calicivirus |
Hepatitis A virus | Rhinovirus | ||
Poliovirus | Foot and mouth disease virus | ||
Enterovirus 71 | Enterovirus EV-D68 | ||
Coxsackievirus A9 | Human parvovirus B19 | ||
Murine norovirus | |||
Rotavirus | |||
Reovirus | |||
High pH | Bovine viral diarrhea virus | Reovirus | Murine minute virus |
Simian virus 40 | Feline calicivirus | ||
Hepatitis A virus | Adenovirus | ||
Canine parvovirus | Rotavirus | ||
Poliovirus | Foot and mouth disease virus | ||
Murine norovirus | |||
Tulane virus | |||
Aldehydes | Porcine parvovirus | Minute virus of mice | Poliovirus |
Hepatitis A virus | |||
Feline calicivirus | |||
Adenovirus | |||
Reovirus | |||
Rotavirus |
Relative order of susceptibility of non-enveloped viruses to chemical inactivation.
Abbreviations used: H2O2, hydrogen peroxide; NaOCl, sodium hypochlorite; PAA, peracetic acid; QAC, quaternary ammonium compound.
Relative order of susceptibility of non-enveloped viruses per microbicidal chemistry. Note: various types of adenoviruses exhibit different degrees of susceptibility to ethanol and quaternary ammonium compounds.
The Spaulding concept of the hierarchy of susceptibility of pathogens to microbicidal inactivation, along with its modifications, has been widely influential. Multiple industries as well as regulatory agencies have adopted or referenced this concept to various degrees [9, 10, 81, 82]. The concept does provide a good tool for understanding the innate differences and trending of susceptibility among various types of pathogens. For the most part, the hierarchy is insightful and valuable. It is particularly helpful when a pathogen is newly emerged, and limited or no knowledge is yet available regarding its level of susceptibility to microbicides [83, 84]. In fact, the United States Environmental Protection Agency (U.S. EPA) and Centers for Disease Control and Prevention (U.S. CDC) use the hierarchy concept as the basis of the Emerging Viral Pathogen Guidance for Antimicrobial Pesticides and public hygiene [10, 82, 85, 86] specifically to deal with just such a possibility.
It should be cautioned, however, that the hierarchy concept is largely oversimplified and by no means perfect [87]. For viruses, although enveloped viruses are usually more susceptible than non-enveloped viruses, certain enveloped viruses such as bovine viral diarrhea virus can be less susceptible than some non-enveloped viruses (e.g., feline calicivirus) under certain chemistries (e.g., low pH and high pH).
The accuracy and applicability of the hierarchy concept are more complex and limited among non-enveloped viruses. The trending is highly dependent on the type of chemistry; and the size of the virion is not always a primary determinant of viral susceptibility among non-enveloped viruses. If a clearer and more consistent trending can be identified among non-enveloped viruses, albeit only specific to a given type of chemistry, the knowledge should be useful.
To generalize an order of susceptibility, for a specific chemistry, data from side-by-side studies wherein viruses are evaluated concurrently by the same test method and under the same conditions should, ideally, be used. When results from different studies are used, caution should be taken to exclude conditional or case-specific differences that result from the test methodology and/or condition. For instance, a surface (carrier) test may give different log10 reduction results than a suspension test of the same microbicide or formulation under certain situations [88]. For example, the data of Kindermann et al. [47] and Tyler et al. [31] indicate that sodium hypochlorite causes a higher log10 reduction value (LRV) when tested in a suspension test than in a surface test. On the other hand, glutaraldehyde has been found to cause similar log reduction in either methodology, while hydrogen peroxide causes higher LRV in the surface test, which is thought to be likely related to the consumption of hydrogen peroxide by the protein in the virus-suspending solution [31].
The organic soil load in which the challenge virus is suspended prior to inoculation can also impact the viral inactivation outcome, especially for oxidizers, alcohols, and QAC. It would be inaccurate or even misleading if a result from a light organic load (e.g., 5% animal serum or phosphate-buffered saline) were to be directly compared with a test that used a heavier organic load (e.g., 90% blood or 20% fecal suspension). Tung
Other testing conditions may also affect the reduction results. For instance, a higher contact temperature may work in the favor of the virucide under investigation, which may result in a higher log reduction. Nemoto et al. [56] reported that a 0.125% glutaraldehyde solution completely inactivated rotavirus after 10 min under ambient temperature, but not when evaluated on ice. The pH and other components in the product formulation could also affect the viral reduction outcome, presumably by activating the chemical and/or by a synergistic or additive effect between the pH and the active chemical [22, 39, 89]. The efficacy of formulated versus non-formulated microbicides may differ even within the same type and concentration of active(s). For example, formulated QAC and ethanol products have been reported to exhibit strong activities against certain non-enveloped viruses albeit the efficacy may be weaker for non-formulated solutions [45, 54, 90, 91]. Therefore, the formulation of the microbicidal active must be considered. The viral stock (i.e., inoculum) preparation method and the challenge viral titer may also affect the reported viral reduction efficacy. For example, purified virus may be more susceptible than crude virus preparations [49]; viral clumps can make the virus less susceptible [92]; and a higher viral challenge titer could make the chemical harder to achieve an expected log10 reduction. Sometimes, viruses propagated in different host cell types may behave differently. It would therefore be ideal if all studies could use a standardized viral preparation and infectivity assay protocol. This is, of course, practically challenging. Last, but not least, the method for preparing the microbicide and the verification of the active concentration might also differ from lab to lab, thus potentially influencing the efficacy results obtained.
Despite these practically hard-to-avoid differences in test methodology and conditions, some generalizations on the pattern of susceptibility among non-enveloped viruses can still be made with confidence. For instance, it is quite apparent that the
The family
Different types of adenoviruses seem to exhibit varying degrees of susceptibility to ethanol and QAC. For example, adenovirus type 5 appears to be notably more susceptible to ethanol than are adenovirus types 2 and 8. In general, however, adenoviruses are more susceptible than many other non-enveloped viruses. Considering that adenovirus type 5 is listed as one of the allowable challenge viruses for a generic or “broad-spectrum” virucidal efficacy claim (i.e., a product that is effective for adenovirus type 5 may be considered effective against all viruses) [97, 98], this practice may not represent a challenge and lead to an insufficient safety margin, which is not supported by the published data.
Parvoviruses are among the smallest of non-enveloped viruses. The animal parvoviruses (e.g., minute virus of mice, porcine parvovirus, bovine parvovirus, canine parvovirus, etc.) are considered to exhibit very low susceptibility to chemical inactivation [99] and are commonly used as a worst-case model for viral inactivation studies. This literature review generally supports this notion, although it should be noted that the animal parvoviruses do not appear to represent a worst-case challenge for high-pH inactivation, and porcine parvovirus seems less susceptible than minute virus of mice at times. Additionally, human parvovirus B19 seems especially susceptible to acid treatment [100].
It has been observed that the particle size of a virus is not an exclusive or even a primary determinant of susceptibility to microbicides for non-enveloped viruses, albeit this characteristic may play a role. There are numerous reports demonstrating that larger non-enveloped viruses, such as adenoviruses and reoviruses, are less susceptible than some of the smaller non-enveloped viruses for certain chemistries. Interestingly though, rotavirus, a large non-enveloped virus, indeed seems to be the most susceptible among non-enveloped viruses, except to low pH.
The mechanisms underlying the large variation in susceptibility among non-enveloped viruses and the chemistry dependency are not always clear, but they could presumably be related to the physicochemical properties of the virus as well as the mechanisms of action of the chemical inactivants. For alcohols, for instance, it has been proposed that the hydrophobicity or hydrophilicity of the viral particles is an important determinant of susceptibility [101]. Poliovirus, which is hydrophilic, is more susceptible to ethanol than it is to isopropyl alcohol. This is attributed to the fact that ethanol is more hydrophilic than isopropanol. In comparison, the hydrophobic simian virus 40 is susceptible to isopropanol but not to ethanol [101]. Enterovirus 71 (EV71) and enterovirus EV-D68 (EV-D68) are both enteroviruses in the family
A review of the relative order of susceptibility for non-enveloped viruses under each chemistry reveals that the order for some chemicals (e.g. aldehydes) seems to fit the traditional hierarchy concept well (e.g., parvoviruses are less susceptible than larger viruses); but the order for some other chemistries (e.g., low pH) does not seem to agree with the concept as well.
The variability in viral susceptibility to physical treatments is not covered in this chapter; however, a marked degree of variation also exists for physical treatments, both within non-enveloped viruses and between enveloped and non-enveloped viruses [12, 16, 21, 49]. A comparison of the order of susceptibility of viruses to chemical versus physical treatments and an exploration of the underlying mechanisms would be interesting and revealing.
This chapter reviewed the literature on chemical inactivation of non-enveloped viruses, with an emphasis on the relative difference and trending of susceptibility among some relevant (from a public health perspective) non-enveloped viruses under each type of chemistry. The traditional concept of a hierarchy of susceptibility to microbicides provides a useful tool in understanding and predicting the susceptibility of a pathogen; however, the concept tends to be oversimplified. The order of susceptibility among non-enveloped viruses depends on the type of chemistry, and there is no universal order that holds true for all types of chemistries. Picornaviruses and caliciviruses exhibit a particularly high degree of intrafamily variation, and the order may even be reversed between viruses, depending on the chemistry. Additionally, larger non-enveloped viruses are not always more susceptible than some of the smaller non-enveloped viruses. It may be inappropriate to consider adenovirus type 5 as a worst-case non-enveloped virus; and even the animal parvoviruses, universally considered among the least susceptible to chemical inactivation, do not actually represent the least susceptible virus type for certain chemistries.
The author thanks Drs. Raymond Nims and M. Khalid Ijaz for the critical review of the manuscript and discussion.
The author declares no conflict of interest.
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The interactions of myeloma cells with various stromal cells and extracellular matrix components are the main regulator of the biological processes that underlie the progression of the disease and of the classic symptomatology correlated. The bone marrow of myeloma patients has recognized autocrine and paracrine loops that regulate multiple signaling pathways and the malignant phenotype of plasma cells. One of the pivotal biological processes which are responsible for myeloma progression is the formation of new vessels from existing ones, known as angiogenesis. It represents a constant hallmark of disease progression and a characteristic feature of the active phase of the disease. Near angiogenesis, other two ancestral processes were active in the bone marrow: vasculogenesis and vasculogenic mimicry. These processes are mediated by the angiogenic cytokines, interleukins, and inflammatory cytokines directly secreted by plasma cells and stromal cells. Neovascularization is also mediated by direct interaction between plasma cells and the various components of bone marrow microenvironment. The observation of the increased bone marrow angiogenesis in multiple myeloma and its correlation with disease activity and overall survival led to consider angiogenesis as a new target in the treatment of multiple myeloma.",book:{id:"6710",slug:"update-on-multiple-myeloma",title:"Update on Multiple Myeloma",fullTitle:"Update on Multiple Myeloma"},signatures:"Roberto Ria, Antonio Solimando, Assunta Melaccio, Azzurra\nSportelli and Angelo Vacca",authors:null},{id:"31163",doi:"10.5772/35840",title:"Intravascular Leukocyte Chemotaxis: The Rules of Attraction",slug:"intravascular-leukocyte-chemotaxis-the-rules-of-attraction",totalDownloads:2339,totalCrossrefCites:1,totalDimensionsCites:4,abstract:null,book:{id:"1830",slug:"hematology-science-and-practice",title:"Hematology",fullTitle:"Hematology - Science and Practice"},signatures:"Sara Massena and Mia Phillipson",authors:[{id:"106058",title:"Dr.",name:"Mia",middleName:null,surname:"Phillipson",slug:"mia-phillipson",fullName:"Mia Phillipson"},{id:"106366",title:"Dr.",name:"Sara",middleName:null,surname:"Massena",slug:"sara-massena",fullName:"Sara Massena"}]},{id:"37047",doi:"10.5772/32080",title:"Microparticles: Role in Haemostasis and Venous Thromboembolism",slug:"microparticles-role-in-haemostasis-and-venous-thromboembolism",totalDownloads:2451,totalCrossrefCites:0,totalDimensionsCites:4,abstract:null,book:{id:"832",slug:"pathophysiology-and-clinical-aspects-of-venous-thromboembolism-in-neonates-renal-disease-and-cancer-patients",title:"Pathophysiology and Clinical Aspects of Venous Thromboembolism in Neonates, Renal Disease and Cancer Patients",fullTitle:"Pathophysiology and Clinical Aspects of Venous Thromboembolism in Neonates, Renal Disease and Cancer Patients"},signatures:"Anoop K. Enjeti and Michael Seldon",authors:[{id:"90071",title:"Dr.",name:"Anoop",middleName:null,surname:"Enjeti",slug:"anoop-enjeti",fullName:"Anoop Enjeti"},{id:"151786",title:"Dr.",name:"Michael",middleName:null,surname:"Seldon",slug:"michael-seldon",fullName:"Michael Seldon"}]}],mostDownloadedChaptersLast30Days:[{id:"64871",title:"Diagnosis and Classification of Myelodysplastic Syndrome",slug:"diagnosis-and-classification-of-myelodysplastic-syndrome",totalDownloads:3255,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disorder characterized by morphological dysplastic changes in one or more of the major hematopoietic cell lines. MDS can present with varying degrees of single or multiple cytopenias including neutropenia, anemia and thrombocytopenia. Presentation of MDS can range from asymptomatic to life threatening. MDS diagnosis and classification present important challenges, particularly in the distinction from benign conditions. French-American-British (FAB) classification proposed a classification based on easily obtainable laboratory information and was recommended in early and as modified by guidelines of new classification of World Health Organization (WHO). The strategy of diagnostic laboratory in MDS depends on morphological changes and is based on existence of dysplastic changes in the peripheral blood and bone marrow including peripheral blood smear, bone marrow aspirate smear and bone marrow trephine biopsy. The correct morphological interpretation and the use of cytogenetics, immunophenotyping, immunohistochemistry and molecular analysis will give valuable information on diagnosis and prognosis.",book:{id:"7138",slug:"recent-developments-in-myelodysplastic-syndromes",title:"Recent Developments in Myelodysplastic Syndromes",fullTitle:"Recent Developments in Myelodysplastic Syndromes"},signatures:"Gamal Abdul Hamid, Abdul Wahab Al-Nehmi and Safa Shukry",authors:[{id:"36487",title:"Prof.",name:"Gamal",middleName:null,surname:"Abdul Hamid",slug:"gamal-abdul-hamid",fullName:"Gamal Abdul Hamid"},{id:"273724",title:"Dr.",name:"Safa",middleName:null,surname:"Shukry",slug:"safa-shukry",fullName:"Safa Shukry"},{id:"277511",title:"Dr.",name:"Abdulwahab",middleName:null,surname:"Al-Nehmi",slug:"abdulwahab-al-nehmi",fullName:"Abdulwahab Al-Nehmi"}]},{id:"60442",title:"Invasive and Noninvasive Approaches in Prenatal Diagnosis of Thalassemias",slug:"invasive-and-noninvasive-approaches-in-prenatal-diagnosis-of-thalassemias",totalDownloads:1778,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Thalassemia is a significant health problem worldwide. There are two main classifications, α- and β-thalassemias, which are usually caused by the defective synthesis of the α-globin, and which are commonly caused by different mutations of the β-globin chain. Different hemoglobin mutations have been identified to date. Thalassemias can result in profound anemia from early life and, if not treated with regular blood transfusions, can lead to death in the first year. Prenatal diagnosis of thalassemia is the essential part of preventive medicine and is currently dependent on the use of invasive diagnostic tests within the first 2 months of pregnancy. These diagnostic techniques carry a small but significant risk of fetal loss up to 1%. Molecular diagnostic methods have been developed for genotyping thalassemias based on PCR techniques and high-throughput technologies. Noninvasive tests using cell-free DNA (cfDNA) from a maternal blood sample is also an alternative method, thus eliminating the risk of miscarriage. This chapter summarizes the current invasive approaches and the noninvasive methods using cell-free fetal DNA as new molecular diagnostic methods for genotypic diagnosis of thalassemia in clinical practice. Prevention strategies that encompass carrier screening, genetic counseling, and prenatal diagnosis are discussed.",book:{id:"6210",slug:"thalassemia-and-other-hemolytic-anemias",title:"Thalassemia and Other Hemolytic Anemias",fullTitle:"Thalassemia and Other Hemolytic Anemias"},signatures:"Abdullah Tuli and Ebru Dündar Yenilmez",authors:[{id:"183998",title:"Ph.D.",name:"Ebru",middleName:null,surname:"Dündar Yenilmez",slug:"ebru-dundar-yenilmez",fullName:"Ebru Dündar Yenilmez"},{id:"215677",title:"Prof.",name:"Abdullah",middleName:null,surname:"Tuli",slug:"abdullah-tuli",fullName:"Abdullah Tuli"}]},{id:"62044",title:"Sickle Cell Disease: A Genetic Disorder of Beta-Globin",slug:"sickle-cell-disease-a-genetic-disorder-of-beta-globin",totalDownloads:1816,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Sickle cell disease (SCD) is a structural and monogenetic genetic disorder due to a mutation that occurs in the globin β-chain, resulting in the formation of hemoglobin S (Hb S), a protein composed of two normal, and two β-type mutant chains. Estimates indicate that the prevalence among live births is 4.4% in the world. The difficulty in circulating the sickle cell, its interaction with endothelial cells, leukocytes, platelets, endothelial dysfunction, and the abnormal expression of adhesion molecules permeate the beginning of the blood vessel occlusion process as well as pathophysiological aspects of SCD. Among the secondary complications are the stroke, pulmonary hypertension, leg ulcer, renal disorders, and all complications associated with vascular dysfunction. Clinical and biochemical markers of disease severity can be used to predict risk, prevent complications, and increase the expectation and quality of life of the SCD population. The entire scenario generated by Hb S has implications for the health and social inclusion of patients, so the treatment of the person with SCD needs an approach focused on the prevention of these complications in an individualized way.",book:{id:"6210",slug:"thalassemia-and-other-hemolytic-anemias",title:"Thalassemia and Other Hemolytic Anemias",fullTitle:"Thalassemia and Other Hemolytic Anemias"},signatures:"Karen Cordovil",authors:[{id:"228575",title:"M.D.",name:"Karen",middleName:null,surname:"Cordovil",slug:"karen-cordovil",fullName:"Karen Cordovil"}]},{id:"66394",title:"Diffuse Large B-Cell Lymphoma",slug:"diffuse-large-b-cell-lymphoma",totalDownloads:2482,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Diffuse large B-cell lymphoma (DLBCL) is a heterogenous class of aggressive lymphoma and is considered as the most common subtype of non-Hodgkin lymphomas (NHL). Several genetic anomalies such as point mutations, numerical alterations, and, more rarely, translocations and gene amplifications play a role in the pathogenesis of this class of B-cell lymphoma and have been related to specific histological and immunophenotypic subtypes. On the other hand, the treatment protocol in DLBCL did not witness significant changes during the last two decades. The widespread adoption of rituximab as an important adjuvant to standard chemotherapy protocol in CD20+ cases was a notable exception, which provided significant improvement in disease-free survival and overall survival, with limited toxicity. However, no less than 20% of patients diagnosed with DLBCL exhibit relapse after the initial response to R-CHOP regimen, while more than 15% of the patients exhibit primary refractory disease. This is the reason why a review of all the morphological, clinical, and therapeutic particularities of DLBCL is required.",book:{id:"8316",slug:"normal-and-malignant-b-cell",title:"Normal and Malignant B-Cell",fullTitle:"Normal and Malignant B-Cell"},signatures:"Patrascu Ana Maria, Ionela Rotaru, Valeriu Surlin and Stefan Patrascu",authors:[{id:"158096",title:"Associate Prof.",name:"Valeriu",middleName:null,surname:"Surlin",slug:"valeriu-surlin",fullName:"Valeriu Surlin"},{id:"194539",title:"Dr.",name:"Stefan",middleName:null,surname:"Patrascu",slug:"stefan-patrascu",fullName:"Stefan Patrascu"},{id:"290810",title:"Dr.",name:"Ana Maria",middleName:null,surname:"Patrascu",slug:"ana-maria-patrascu",fullName:"Ana Maria Patrascu"},{id:"292959",title:"Dr.",name:"Ionela",middleName:null,surname:"Rotaru",slug:"ionela-rotaru",fullName:"Ionela Rotaru"}]},{id:"61929",title:"Idiosyncratic Drug-Induced Severe Neutropenia and Agranulocytosis: State of the Art",slug:"idiosyncratic-drug-induced-severe-neutropenia-and-agranulocytosis-state-of-the-art",totalDownloads:1621,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"In this chapter, we report and discuss the diagnosis and management of idiosyncratic drug-induced, or drug-associated, severe neutropenia, and agranulocytosis (neutrophil count of <0.5 × 109/L). In this setting, neutropenia remains a potentially serious adverse event due to the frequency of severe sepsis, with severe deep tissue infections (e.g., pneumonia), life-threatening infections, septicemia, and septic shock in two-thirds of all hospitalized patients. Recently, several poor prognostic factors, impacting the hematological recovery, the duration of hospitalization, and the outcome have been identified that may be helpful when identifying “frailty” patients. These factors include: old age, poor performance status, septicemia or shock, comorbidities such as renal failure, and a neutrophil count below 0.1 × 109/L. recovery. In this situation, modern management, with broad-spectrum antibiotics in case of any sepsis sign and hematopoietic growth factors (HGF) (particularly G-CSF), is likely to improve the prognosis, with a current mortality rate around 5%.",book:{id:"6439",slug:"hematology-latest-research-and-clinical-advances",title:"Hematology",fullTitle:"Hematology - Latest Research and Clinical Advances"},signatures:"Emmanuel Andrès and Rachel Mourot-Cottet",authors:[{id:"143493",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Andrès",slug:"emmanuel-andres",fullName:"Emmanuel Andrès"}]}],onlineFirstChaptersFilter:{topicId:"1026",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:122,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. These advances have helped foster better support for animal health, more humane animal production, and a better understanding of the physiology of endangered species to improve the assisted reproductive technologies or the pathogenesis of certain diseases, where animals can be used as models for human diseases (like cancer, degenerative diseases or fertility), and even as a guarantee of public health. Bridging Human, Animal, and Environmental health, the holistic and integrative “One Health” concept intimately associates the developments within those fields, projecting its advancements into practice. This book series aims to tackle various animal-related medicine and sciences fields, providing thematic volumes consisting of high-quality significant research directed to researchers and postgraduates. It aims to give us a glimpse into the new accomplishments in the Veterinary Medicine and Science field. By addressing hot topics in veterinary sciences, we aim to gather authoritative texts within each issue of this series, providing in-depth overviews and analysis for graduates, academics, and practitioners and foreseeing a deeper understanding of the subject. Forthcoming texts, written and edited by experienced researchers from both industry and academia, will also discuss scientific challenges faced today in Veterinary Medicine and Science. In brief, we hope that books in this series will provide accessible references for those interested or working in this field and encourage learning in a range of different topics.",coverUrl:"https://cdn.intechopen.com/series/covers/13.jpg",latestPublicationDate:"August 7th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:11,editor:{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"19",title:"Animal Science",coverUrl:"https://cdn.intechopen.com/series_topics/covers/19.jpg",isOpenForSubmission:!0,editor:{id:"259298",title:"Dr.",name:"Edward",middleName:null,surname:"Narayan",slug:"edward-narayan",fullName:"Edward Narayan",profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",biography:"Dr. Edward Narayan graduated with Ph.D. degree in Biology from the University of the South Pacific and pioneered non-invasive reproductive and stress endocrinology tools for amphibians - the novel development and validation of non-invasive enzyme immunoassays for the evaluation of reproductive hormonal cycle and stress hormone responses to environmental stressors. \nDr. Narayan leads the Stress Lab (Comparative Physiology and Endocrinology) at the University of Queensland. A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null},{id:"20",title:"Animal Nutrition",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",isOpenForSubmission:!0,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"28",title:"Animal Reproductive Biology and Technology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/28.jpg",isOpenForSubmission:!0,editor:{id:"177225",title:"Prof.",name:"Rosa Maria Lino Neto",middleName:null,surname:"Pereira",slug:"rosa-maria-lino-neto-pereira",fullName:"Rosa Maria Lino Neto Pereira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9wkQAC/Profile_Picture_1624519982291",biography:"Rosa Maria Lino Neto Pereira (DVM, MsC, PhD and) is currently a researcher at the Genetic Resources and Biotechnology Unit of the National Institute of Agrarian and Veterinarian Research (INIAV, Portugal). She is the head of the Reproduction and Embryology Laboratories and was lecturer of Reproduction and Reproductive Biotechnologies at Veterinary Medicine Faculty. She has over 25 years of experience working in reproductive biology and biotechnology areas with a special emphasis on embryo and gamete cryopreservation, for research and animal genetic resources conservation, leading research projects with several peer-reviewed papers. Rosa Pereira is member of the ERFP-FAO Ex situ Working Group and of the Management Commission of the Portuguese Animal Germplasm Bank.",institutionString:"The National Institute for Agricultural and Veterinary Research. Portugal",institution:null},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:20,paginationItems:[{id:"82991",title:"Diseases of the Canine Prostate Gland",doi:"10.5772/intechopen.105835",signatures:"Sabine Schäfer-Somi",slug:"diseases-of-the-canine-prostate-gland",totalDownloads:0,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"82956",title:"Potential Substitutes of Antibiotics for Swine and Poultry Production",doi:"10.5772/intechopen.106081",signatures:"Ho Trung Thong, Le Nu Anh Thu and Ho Viet Duc",slug:"potential-substitutes-of-antibiotics-for-swine-and-poultry-production",totalDownloads:1,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Antibiotics and Probiotics in Animal Food - Impact and Regulation",coverURL:"https://cdn.intechopen.com/books/images_new/11578.jpg",subseries:{id:"20",title:"Animal Nutrition"}}},{id:"82905",title:"A Review of Application Strategies and Efficacy of Probiotics in Pet Food",doi:"10.5772/intechopen.105829",signatures:"Heather Acuff and Charles G. Aldrich",slug:"a-review-of-application-strategies-and-efficacy-of-probiotics-in-pet-food",totalDownloads:15,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Antibiotics and Probiotics in Animal Food - Impact and Regulation",coverURL:"https://cdn.intechopen.com/books/images_new/11578.jpg",subseries:{id:"20",title:"Animal Nutrition"}}},{id:"82773",title:"Canine Transmissible Venereal Tumor: An Infectious Neoplasia in Dogs",doi:"10.5772/intechopen.106150",signatures:"Chanokchon Setthawongsin, Somporn Techangamsuwan and Anudep Rungsipipat",slug:"canine-transmissible-venereal-tumor-an-infectious-neoplasia-in-dogs",totalDownloads:14,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg",subseries:{id:"19",title:"Animal Science"}}}]},overviewPagePublishedBooks:{paginationCount:11,paginationItems:[{type:"book",id:"7233",title:"New Insights into Theriogenology",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7233.jpg",slug:"new-insights-into-theriogenology",publishedDate:"December 5th 2018",editedByType:"Edited by",bookSignature:"Rita Payan-Carreira",hash:"74f4147e3fb214dd050e5edd3aaf53bc",volumeInSeries:1,fullTitle:"New Insights into Theriogenology",editors:[{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. 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She is also Invisalign certified. She’s working as a Senior Lecturer in the Department of Orthodontics, SRM Dental College since November 2019. She is actively involved in teaching orthodontics to the undergraduates and the postgraduates. Her clinical research topics include new orthodontic brackets, fixed appliances and TADs. She’s published 4 articles in well renowned indexed journals and has a published patency of her own. Her private practice is currently limited to orthodontics and works as a consultant in various clinics.",institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"323731",title:"Prof.",name:"Deepak M.",middleName:"Macchindra",surname:"Vikhe",slug:"deepak-m.-vikhe",fullName:"Deepak M. Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\r\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\r\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Orthodontist, Assoc Prof in the Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. Her knowledge of English is at an advanced level.",institutionString:null,institution:null},{id:"332914",title:"Dr.",name:"Muhammad Saad",middleName:null,surname:"Shaikh",slug:"muhammad-saad-shaikh",fullName:"Muhammad Saad Shaikh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jinnah Sindh Medical University",country:{name:"Pakistan"}}},{id:"315775",title:"Dr.",name:"Feng",middleName:null,surname:"Luo",slug:"feng-luo",fullName:"Feng Luo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sichuan University",country:{name:"China"}}},{id:"344229",title:"Dr.",name:"Sankeshan",middleName:null,surname:"Padayachee",slug:"sankeshan-padayachee",fullName:"Sankeshan Padayachee",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"315727",title:"Ms.",name:"Kelebogile A.",middleName:null,surname:"Mothupi",slug:"kelebogile-a.-mothupi",fullName:"Kelebogile A. Mothupi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"423519",title:"Dr.",name:"Sizakele",middleName:null,surname:"Ngwenya",slug:"sizakele-ngwenya",fullName:"Sizakele Ngwenya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"337613",title:"Mrs.",name:"Tshakane",middleName:null,surname:"R.M.D. Ralephenya",slug:"tshakane-r.m.d.-ralephenya",fullName:"Tshakane R.M.D. Ralephenya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419270",title:"Dr.",name:"Ann",middleName:null,surname:"Chianchitlert",slug:"ann-chianchitlert",fullName:"Ann Chianchitlert",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419271",title:"Dr.",name:"Diane",middleName:null,surname:"Selvido",slug:"diane-selvido",fullName:"Diane Selvido",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419272",title:"Dr.",name:"Irin",middleName:null,surname:"Sirisoontorn",slug:"irin-sirisoontorn",fullName:"Irin Sirisoontorn",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}}]}},subseries:{item:{id:"23",type:"subseries",title:"Computational Neuroscience",keywords:"Single-Neuron Modeling, Sensory Processing, Motor Control, Memory and Synaptic Pasticity, Attention, Identification, Categorization, Discrimination, Learning, Development, Axonal Patterning and Guidance, Neural Architecture, Behaviours and Dynamics of Networks, Cognition and the Neuroscientific Basis of Consciousness",scope:"Computational neuroscience focuses on biologically realistic abstractions and models validated and solved through computational simulations to understand principles for the development, structure, physiology, and ability of the nervous system. This topic is dedicated to biologically plausible descriptions and computational models - at various abstraction levels - of neurons and neural systems. This includes, but is not limited to: single-neuron modeling, sensory processing, motor control, memory, and synaptic plasticity, attention, identification, categorization, discrimination, learning, development, axonal patterning, guidance, neural architecture, behaviors, and dynamics of networks, cognition and the neuroscientific basis of consciousness. 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