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",isbn:"978-1-80356-678-8",printIsbn:"978-1-80356-677-1",pdfIsbn:"978-1-80356-679-5",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"6dcb071a2e978694b6b1cb9c20afc1a3",bookSignature:"Prof. Hai-Zhi Song",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11494.jpg",keywords:"Electric Field Effect, Nano-Materials, Electric Field Design, Antenna, Microelectronics, Optoelectronics, Electric Field Stimulation, Brain and Nerve, Electric Field Imaging, Atomic Electric Field, Space Science, Climate",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 22nd 2022",dateEndSecondStepPublish:"May 26th 2022",dateEndThirdStepPublish:"July 25th 2022",dateEndFourthStepPublish:"October 13th 2022",dateEndFifthStepPublish:"December 12th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"a month",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"A pioneering researcher in the fields of new materials, optoelectronic devices, and quantum information processing, appointed vice director of the Science and Technology Committee of SWITP, author/co-author of more than 170 research papers, and holder of 40 patents.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"196114",title:"Prof.",name:"Hai-Zhi",middleName:null,surname:"Song",slug:"hai-zhi-song",fullName:"Hai-Zhi Song",profilePictureURL:"https://mts.intechopen.com/storage/users/196114/images/system/196114.jpg",biography:"Curriculum Vitae\n\nName: Hai-Zhi Song \nGender: male\nDate of Birth: Oct. 20, 1968\nPlace of Birth: Shanxi, China\nAffiliation and Address: \nSouthwest Institute of Technical Physics\nNo.7, Section 4, Renminnan Road, Chengdu 610041, China\nAnd\nInstitute of Fundamental and Frontier Sciences,\nUniversity of Electronic Science and Technology of China,\nNo. 4, Section 2, Jianshebei Road, Chengdu 610054, China\n\nWork Phone: +86-28-68180751, +86-28-83208728\nMobile Phone: +86-158-28239155\nFax: +86-28-83201896\nE-mail: hzsong1296@163.com, hzsong@uestc.edu.cn\n \nEducation \nSept, 1990 – July, 1995:Peking University, PhD, Thesis “Visible luminescence of porous silicon and its mechanism”, Researches on hydrogen-influenced Schottky diodes and silicon-based light-emitting materials. \nSept, 1986 – July, 1990:Nanjing University, Bachelor of Science, Thesis “Study of refractory metal silicides”, Research on Ohmic contact of semiconductors.\n\nWork Experience \nJuly, 1995 – Sept. 1997: Nanjing University, Nanjing, China, Postdoctoral Researcher, Research on silicon-based light-emitting materials. \nOct, 1997 – Sept. 1998: Catholic University Leuven, Leuven, Belgium, Visiting free Researcher, Research on amorphous semiconductors. \nOct, 1998 – Sept. 2001: Tsukuba University, Tsukuba, Japan, Assistant Professor, Research on semiconductor quantum dots. \nOct, 2001 – March 2012: Fujitsu Lab. Ltd., Atsugi, Japan, Researcher/Senior Researcher, Researches on Semiconductor Quantum Dots for Quantum Information, Semiconductor Optoelectronic Materials and Devices. \nApril, 2012 – March 2014: University of Tokyo, Tokyo, Japan, Senior Researcher, Researches on Quantum Information Processing Devices. \nApril, 2014 – now: Southwest Institute of Technical Physics, Chengdu, China, Professor, Researches on Semiconductor Optoelectronic Materials and Devices. \nJune, 2015 – now: University of Electronic Science and Technology, Chengdu, China, Professor, Researches on Nanoscaled Semiconductors and Quantum Information Processing Devices.\n \nAchievements\nSystematically studied the property of porous silicon materials and verified their mechanism; found green and ultraviolet luminescence, and clarified the multiple luminescence mechanisms of nanocrystalline-silicon embedded in SiO2, which is valuable to silicon-based optoelectronic integration; realized enhanced hole mobility in amorphous silicon, verified the existence of deep trap states in amorphous selenium, providing ways to improve amorphous optoelectronic materials. \nDiscovered lateral coupling between self-assembled quantum dots (QDs) and their tuning effect to 2D electron gas; illustrated and deeply explained the metal-insulator transition in 2D ordered QD arrays, all of which are worth in optoelectronic application of semiconductor QDs. \nDeveloped Sb-free technique to double the InAs/GaAs QD density and suppress the atomic interdiffusion, helped producing 1.3 um QD lasers, which won Japanese national prizes and had been merchandized; developed 1.06 um quantum-well lasers, which have been used to produce pure-green lasers robust against high temperature. \nFound a way to access buried QDs by scanning tunneling microscope; achieved a way to prepare diluted QDs by post-annealing and clarified its mechanisms; invented a technique to control the size and site of QDs by atomic-force microscopy lithography, and an apparatus to detect single electron spin states by optically-detected magnetic resonance; designed a few types of micropillar cavities applicable to realize 1.55 um highly-efficient, even coherent (strongly coupled) InAs/InP QD single photon sources; produced fiber-integrated photon-entangled sources, all of which are very useful to the applications of QDs in quantum information processing. \nDeveloped focal-plane single-photon avalanche detectors, providing central devices for 3D laser detecting and ranging system; explored antimonide middle- and long-wavelength infrared detectors and the surface plasmon enhancement effect in such detectors; advanced the acetone-sensing function of Eu-doped SnO2 nano-belt; found Nickle Phosphide serving as a good catalyst in hydrogen-producing. Realized a series of optoelectronic quantum devices for quantum information processing, such as fiber-integrated photon-pair-entangler, chiplet heralded single photon emitter, fiber quantum memories, quantum number generator, etc.\n\nHonor and Group Memberships \nSelected Scholar of the Recruitment Program of Global Experts, China\nEditorial member of “Laser Technology”\nEditorial member of “Journal of Electronic Science and Technology”\nEditorial member of “Internal J. Mat. Sci. Appl”\nMember of APS (American Physics Society)\nMember of OSA (Optical Society of America)\nPermanent Member of China Physical Science and Technology\nPermanent Member of the Chinese Optical Society\nTechnical committee member of PIERS, organizing a series of “quantum information processing and devices” sessions\nTechnical committee member of ICICM",institutionString:"Southwest University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Southwest University",institutionURL:null,country:{name:"China"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"20",title:"Physics",slug:"physics"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"453623",firstName:"Silvia",lastName:"Sabo",middleName:null,title:"Mrs.",imageUrl:"https://mts.intechopen.com/storage/users/453623/images/20396_n.jpg",email:"silvia@intechopen.com",biography:null}},relatedBooks:[{type:"book",id:"8356",title:"Metastable, Spintronics Materials and Mechanics of Deformable Bodies",subtitle:"Recent Progress",isOpenForSubmission:!1,hash:"1550f1986ce9bcc0db87d407a8b47078",slug:"solid-state-physics-metastable-spintronics-materials-and-mechanics-of-deformable-bodies-recent-progress",bookSignature:"Subbarayan Sivasankaran, Pramoda Kumar Nayak and Ezgi Günay",coverURL:"https://cdn.intechopen.com/books/images_new/8356.jpg",editedByType:"Edited by",editors:[{id:"190989",title:"Dr.",name:"Subbarayan",surname:"Sivasankaran",slug:"subbarayan-sivasankaran",fullName:"Subbarayan Sivasankaran"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2270",title:"Fourier Transform",subtitle:"Materials Analysis",isOpenForSubmission:!1,hash:"5e094b066da527193e878e160b4772af",slug:"fourier-transform-materials-analysis",bookSignature:"Salih Mohammed Salih",coverURL:"https://cdn.intechopen.com/books/images_new/2270.jpg",editedByType:"Edited by",editors:[{id:"111691",title:"Dr.Ing.",name:"Salih",surname:"Salih",slug:"salih-salih",fullName:"Salih Salih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"18655",title:"Male Circumcision: An Appraisal of Current Instrumentation",doi:"10.5772/18543",slug:"male-circumcision-an-appraisal-of-current-instrumentation",body:'The topic of male circumcision (MC) is of considerable current interest, largely because of widespread publicity generated by research findings attesting to its ability to prevent HIV infection during heterosexual intercourse. In addition, its long-recognized ability to protect against other sexually transmitted infections (STIs) has also been well publicized in recent times, especially now that support has been provided by large randomized controlled trials (RCTs).
While MC can be performed at any age, the ease with which circumcision can be performed in infancy makes this time of life preferable to intervention later in childhood or in adulthood. As well as the issue of safety, convenience, simplicity and consequent cost reductions, circumcision in infancy provides greater net benefits over the lifetime of the individual.
It provides immediate 10-fold protection against urinary tract infections and thus kidney damage in baby boys, and greater protection against penile cancer than circumcision later in life, virtually eliminating the risk of this disease with its high morbidity and mortality (Morris, 2007; Morris, 2010; Tobian et al., 2010; Morris et al., 2011). Another benefit is prevention of phimosis, a common cause of sexual problems in adolescent boys and men, and a major risk factor for penile cancer. It also lowers to risk of inflammatory skin conditions such as balanoposthitis. Circumcised men have superior hygiene (O\'Farrell
If one tallies up all of the conditions listed above, 1 in 3 uncircumcised men will require medical attention from a condition stemming from their uncircumcised state (Morris, 2007). Moreover, such an analysis shows that the benefits exceed the risks by over 100 to 1, and far more if one factors in the severity of the consequences, including mortality and morbidity, that can occur in uncircumcised males and their sexual partners in adulthood.
MC is, without doubt, a multi-benefit procedure. Yet many analyses of its benefits make the mistake of addressing its effect with respect to just one medical condition. For a true assessment of its value it is necessary to carry out a summation of all the benefits, quoting the total inclusive of spin-offs every time.
Because of the current focus on efficient and effective MC in regions of the world where HIV prevalence is high, in the present chapter we will begin by summarizing the HIV findings. In the context of biomedical engineering, we will then examine the devices that have been devised for the surgical procedure itself. The intention of these devices has been to help reduce risk to delicate penile structures during surgery and also to ensure a favourable cosmetic outcome of the circumcision procedure.
In 2007 MC was endorsed by the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (World Health Organisation and UNAIDS, 2007a) as being an important, proven strategy for prevention of heterosexually-transmitted HIV in high prevalence settings. Such advice was the culmination of 20 years of research that led to the findings of three large randomized controlled trials in different parts of sub-Saharan Africa (Auvert et al., 2005; Bailey et al., 2007; Gray et al., 2007). After rigorous examination of the data, the Cochrane committee concluded that “inclusion of male circumcision into current HIV prevention guidelines is warranted” and that “No further trials are required” (Siegfried et al., 2009; Siegfried
Therefore, whilst the long-term goal should be one of circumcising in infancy, the immediate need in settings where life-threatening HIV prevalence is high is to circumcise uninfected heterosexually-active adult and adolescent males.
Critics of this approach cite the "ABC" policy (Abstinance, Behaviour, Condoms) (Coates et al., 2008) as being sufficient. While condoms are 80–90% effective if always used properly (Halperin et al., 2004), including during foreplay, the reality is that for a host of reasons such as passion over-riding common sense, dislike for condoms, reckless behaviour often fuelled by inebriation, and/or not having a condom available, many people either do not use them consistently or at all (Donovan & Ross, 2000; Szabo & Short, 2000; Caballero-Hoyos & Villasenor-Sierra, 2001; Ferrante et al., 2005; Jadack et al., 2006; Kang et al., 2006; Sanchez et al., 2006; Yahya-Malima et al., 2007; Munro et al., 2008; Wawer et al., 2009). This research included RCTs in which men were given counselling and free condoms (Wawer et al., 2009). A review of 10 studies from Africa found that overall there was no association between condom use and reduced HIV infection, with two studies actually showing a positive association between use of a condom and HIV infection (Slaymaker, 2004; Lopman et al., 2008). Part of the reason, however, is that condom use is likely to be higher when one person knows they are HIV-positive and does not want to infect their partner. Circumcision can thus be regarded as providing backup protection. It is much like seatbelts and airbags used in combination to reduce the road toll (Cooper et al., 2010). Buckling up the seatbelt has to be done, whereas the airbag is always there. Imperfect though it is, once circumcised a male enjoys a guaranteed degree of protection for life. The widespread acceptance of MC as an important HIV prevention measure has led to a new “ABC” now being advocated: Antivirals, Barriers and Circumcision. Not instead of the original ABC, but additionally. This clearly recognizes that MC is part of a package of prevention measures.
An as-treated meta-analysis of the initial findings from the three RCTs found that the protective effect was 65% (Weiss et al., 2008). This was identical to the summary risk ratio for the 15 observational studies that adjusted for potential confounders. Follow-up analyses have indicated an increase in the 60% protective effect seen in the Kenyan trial to 65% at 3.5 years (Bailey et al., 2008) and 4.5 years (Bailey et al., 2010) In the Ugandan trial by 5 years the protective effect had increased to 73% (Kong et al., 2011). Such a level of protection is similar to that afforded by influenza vaccines (Fiore et al., 2007; Kelly et al., 2009). Even higher protection (80%) was found in the analysis of data from 18 sub-Saharan African countries (Gebremedhin, 2010).
The high protective effect of MC should not detract from the need to adopt the other ABC measures as well.
MC also reduces HIV infection in women by 20–46% (Baeten et al., 2009; Weiss et al., 2009; Baeten et al., 2010; Hallett
Several different partial remedies can act cumulatively, each contributing not just towards a reduction in infection rates but also towards the ultimate public health goal of herd immunity. It is here, rather than in the realms of individual healthcare, that the true value of MC lies. Not surprisingly, MC is now regarded as a “surgical vaccine” (Morris, 2007; Schoen, 2007b; Ben et al., 2009). It provides a behaviour-independent secure foundation upon which other forms of protection can build.
As a prelude to the discussion of MC technique and the various devices for achieving foreskin removal, it is important to emphasize the biological evidence that has now accumulated that indicates the vulnerability of the inner lining of the foreskin to infection of the man by HIV.
During an erection the foreskin can either retract fully or only partially. Either way, during intercourse the thin, mucosal inner surface of the foreskin is exposed to the partner\'s body fluids (Szabo & Short, 2000). The foreskin then traps the infectious inoculum when the penis becomes flaccid again (Cameron et al., 1989). The mucosal inner lining is only lightly keratinized (Patterson et al., 2002; McCoombe & Short, 2006; Ganor et al., 2010) and is rich in Langerhans cells (Patterson et al., 2002). Dendrites from these project to just under the surface (Mc Coombe & Short, 2006). The higher susceptibility of the inner lining to infection by live, tagged HIV has been demonstrated in cultured tissue (Patterson et al., 2002). Internalization of HIV involves the presence on Langerhans cells of the c-type lectin, Langerin, that can bind HIV and internalize it (Turville et al., 2002). The Langerin is then involved in its transport to regional lymph nodes (Turville et al., 2002). In the inner (but not the outer) foreskin, tumor necrosis factor-α can activate Langerhan’s cells; stimulatory cytokines then cause an influx of CD4+ T-cells into the epithelial layer (Fahrbach et al., 2010). The higher permeability of the inner foreskin is associated with increased interaction of HIV target cells with external factors, such as HIV. HIV can, moreover, infect T-cells independently of Langerhans cells (Boggiano & Littman, 2007). HIV’s success in establishing a systemic infection might nevertheless depend on its early interaction with Langerhans cells (Boggiano & Littman, 2007; Hladik et al., 2007). At low viral levels Langerin is able to clear HIV, shunting it to intracellular granules for degradation, but this mechanism becomes overwhelmed at higher viral loads (de Witte et al., 2007; Schwartz, 2007). By confocal imaging microscopy and mRNA quantification, the demonstration of abundant and superficially present potential HIV target cells (CD3+ and CD4+ T-cells, Langerhans cells, macrophages and submucosal dendritic cells) has provided anatomical support for the protective effect of circumcision (Hirbod et al., 2010). There was no difference between positive and negative HSV-2 serostatus.
In 2010 it was found that HIV infected cells, but not free HIV, form viral synapses with apical foreskin keratinocytes, followed by rapid internalization by Langerhans cells, whose projections (dendrites) weave up between the keritanocytes in the inner foreskin, the infection occurring within 1 hour (Ganor & Bomsel, 2010; Ganor et al., 2010). The Langerhans cells then formed conjugates with T-cells thereby transferring the HIV. The thick keratin layers in the outer foreskin prevent infection (Ganor & Bomsel, 2010).
Ulcerative disease and tearing are more common in uncircumcised men, adding to the risk of HIV entry (Alanis & Lucidi, 2004). A large 2-year RCT found significantly lower penile coital injuries amongst men in the circumcised arm of the trial, adjusted odds ratio being 0.71 for soreness, 0.52 for scratches/abrasions/cuts, and 0.62 for bleeding (Mehta et al., 2010). HSV-2 infection increases HIV risk in men and women by 3-fold (Freeman et al., 2006). Men with a higher foreskin surface area appear more likely to be infected with HIV (Kigozi et al., 2009b). Inflammation of the epithelium of the foreskin is another factor that can increase infection risk and has been noted in 4.2% of men with neither HIV nor HSV-2, 7.8% of men with HSV-2 only, 19% of men with just HIV, and 32% of men with both (Johnson et al., 2009). For stromal inflammation, the figures were 14%, 30%, 33% and 61%. Both epithelial and stromal inflammation were more common in men with accumulations of smegma. Even in the absence of visible lesions the mucosal tissue can show histological signs of inflammation (Hirbod et al., 2010). Wetness under the foreskin is an indicator of poor hygiene and is associated with a 40% increase in risk of HIV infection (O\'Farrell
In high HIV prevalence settings, MC has been shown to be cost-effective for prevention of this virus (Williams et al., 2006; Uthman et al., 2011). In sub-Saharan Africa the cost of MC is always lower than the cost of anti-retroviral treatment; by how much depends on the method of circumcision used. Prevention is of enhanced importance here, because no outright cure currently exists for HIV infection.
As mentioned earlier, even in settings in which HIV prevalence is low – such as the USA – calculations by the Centers for Disease Control and Prevention (CDC) have indicated that circumcision of infants would be cost-saving for HIV prevention (Sansom et al., 2010). The CDC has been giving favourable consideration, based on the wide-ranging benefits, to encouraging infant MC in the USA (Smith et al., 2010). Earlier analyses, based on just some of the benefits, were favourable (Schoen et al., 2006). These did not consider the benefits to women such as reduction in cervical cancer and various STIs besides oncogenic HPV (Morris et al., 2006).
The ongoing penetration of HIV into the heterosexual community and rise in the number and proportion of new diagnoses from heterosexually-acquired infection in previously low HIV prevalence settings has led to calls for MC to be encouraged strongly in infancy (Cooper et al., 2010).
Worldwide 30–32% of males are circumcised (World Health Organization, 2008b). Most are a consequence of Muslim tradition that mandates MC. Religion dictates MC at day 8 for Jewish infants. In much of sub-Saharan Africa and other parts of the world such as indigenous peoples of Australia and the Pacific islands, MC is performed as part of coming of age ceremonies for boys. In the 1800s MC became popular in Britain and countries with an Anglo-Celtic heritage such as the USA and Australia. While a decline took place in the UK starting in the 1930s and in Australia and New Zealand in the 1970s, rates in the USA have remained high amongst Anglo-Celtic whites and Afro-American blacks (Xu et al., 2007). Hospital discharge data that suggest a decline do not take into account earlier discharge from maternity wards shifting the procedure from hospitals (where circumcisions are recorded in official statistics) to doctor\'s offices (where they are not), and the fact that not all hospitals record infant MC after delivery. The campaigning by MC opponents that led to withdrawal of Medicaid funding for MC in 17 states has had an adverse effect on the ability of the poor to access MC services for their children (Leibowitz et al., 2009; Morris et al., 2009). In a 2008 report, hospital discharge data in Maryland found 75.3% of 96,457 male infants were circumcised after birth and survey data from 4,273 mothers showed a rate of 82.3% (Cheng et al., 2008). Rate was higher in white and Afro-American blacks and lower amongst Hispanic and Asian infants. The continued influx of migrants, mostly Hispanic, in whom MC is culturally foreign, has been a major factor in the declining prevalence of MC in the US population as a whole. Subsequent generations are, however, more likely to adopt local US customs by having their baby boys circumcised. In Australia a reversal of the downward trend has become evident, no doubt fuelled by widespread news media publicity of the many benefits, especially in HIV prevention.
Excision of the foreskin can adopt various styles. These can be divided into what is referred to commonly as either a “high\'” or a “low” style (Fig. 1).
There is no published evidence as to whether one style or the other offers greater protection from HIV. The RCTs of MC for HIV prevention used either the forceps-guided method (which is “moderately high and loose”: http://www.circlist.com/instrstechs/forcepsguide.html) (Auvert et al., 2005; Bailey et al., 2007) or the sleeve technique (which is “high” and either “tight” or “loose”: http://www.circlist.com/ instrstechs/doublecirc.html) (Gray et al., 2007). Proponents of the “low” style argue that the antigen receptor cells responsible for admitting HIV to the uncircumcised male are concentrated in the frenulum and inner foreskin, implying that this tissue should be removed completely in order to obtain maximum benefit from the circumcision. Opponents consider that post-circumcision changes in residual mucosal tissue (changes that are loosely termed "keratinization") render its removal unnecessary. The authors\'
Depiction of flaccid penis before and after circumcision showing what gets removed for extremes of style; in each case the tissue to be removed is shown in orange. (A) before and (B) after for the “low and loose” style: Almost all the inner foreskin has been removed along with an equal amount of outer foreskin. No tension has been placed in the shaft skin, with the result that the flaccid penis droops and the sulcus is not held fully open. Thus, despite circumcision, it remains possible for smegma to accumulate. (C) before and (D) after for the “low and tight” style: The maximum possible amount of inner foreskin has been removed along with the whole of the outer foreskin
view is that, unless or until proof positive emerges to the effect that a “high” style confers as great a degree of prophylaxis as a “low” style, the Precautionary Principle should be applied and circumcisions should be done in the “low” style.
Traditional circumcisions done using "tug-&-chop" methods (Fig. 2) already provide us with ample examples of residual inner foreskin. There appears to be scope for a population study here, comparing HIV infection rates amongst groups with “high” and “low” styles of circumcision.
The “tug-and-chop” method of circumcision.
Another somewhat contentious style issue is the matter of tightness. Often, tightness is considered to be nothing more than a cosmetic matter. However, theoretical models of STI transmission tend to suggest that benefit is gained from the sulcus being dry. This implies that circumcisions should be sufficiently tight to hold the sulcus open, such that no moisture will accumulate there.
The third style issue to be resolved relates to removal or retention of the frenulum. As well as having high concentrations of antigen receptor cells targeted by HIV, the highly vascular frenulum is particularly susceptible to tearing or other damage during intercourse, as well as being a frequent site of lesions produced by other STIs (Szabo & Short, 2000). Persistent debate relates to resulting changes in sexual sensitivity; anecdotal evidence from those who have had their frenulum surgically removed suggest that no loss of sensitivity occurs. It is also worthy of note that the frenulum can be lost as a result of tearing; such loss does not appear to give rise to complaint about effects long-term.
In the light of all of the above, there appears to be a good cause not just to circumcise but to circumcise in a particular way. It seems appropriate for the surgery to specifically target certain classes of cells for removal, at the same time achieving a result that holds the sulcus open so that it remains dry and clean, unable to harbour a viral payload either in smegma or in residues of erogenously triggered body fluids.
We will now present information on current approaches to circumcision, mostly stemming from experience in developed nation settings, the USA in particular. We will start with infants and then move on to adults and older boys. We will end with speculation about what is needed for low-resource settings in terms of devising novel devices.
There is no standard circumcision procedure and the issue of standards has been a rallying call for years. At the Western Section American Urological meeting in 2007 Dr Sam Kunin, who practices in Los Angeles, compared and contrasted clamps and discussed what he considered should be the minimal standards for circumcision (Kunin, 2007a).
The postnatal period provides an ideal window of opportunity for circumcision (Schoen, 2007a). The newborn, having recently experienced the considerable trauma of birth, has elevated levels of normal stress-resistance hormones. Neonates heal quickly, are resilient, and use of local anaesthesia means little or no pain. Since the inner and outer foreskin layers readily adhere to each other afterwards, sutures are rarely needed in this age group.
Photo of a baby boy having a circumcision.
There is no evidence of any long-term psychological harm arising from circumcision. The risk of damage to the penis is extremely rare and avoidable by using a competent, experienced doctor. Unfortunately, because it is such a simple, low-risk procedure, it had once been the practice to assign this job to junior medical staff, with occasional devastating results. Anecdotes of such rare events from the past should be viewed in perspective. Parents or patients nevertheless need to have some re-assurance about the competence of the operator. Also the teaching of circumcision to medical students and practitioners needs to be given greater attention because it is performed so commonly and needs to be done well. Models to teach interns and others have, moreover, been produced (Erikson, 1999; Cohen, 2002).
Surgical methods often use a procedure that protects the penis during excision of the foreskin.
Safe implementation of the Jewish tradition of circumcision on the eighth day of life led to the development of what is termed the "Traditional Jewish Shield". At one time made from silver (a material chosen for its natural aseptic qualities), the identical method is now to be found in conjunction with single-use disposable equipment. The objective of the device is to prevent accidental injury to the glans.
The traditional Jewish equipment typifies the "Tug-&-Chop" method. Similar shielding can equally be achieved with forceps or a haemostat, whereupon it becomes known as the forceps-guided technique. Cutting can be done with scissors, a scalpel or an electrocautery device. In all instances the mucosal skin that is stretched between the sulcus and the distal face of the shield remains intact. Given the current state of knowledge, such a style of circumcision must be regarded as sub-optimal.
Wholly freehand circumcisions did occur, but at theoretically greater risk of injury to the glans.
None of the traditional devices automatically result in removal of the frenulum. If that is required, it must be done as a separate procedure.
In the 1930s in the United States, the search for a means of bloodless circumcision of infants began. Yellen set out the principles involved (Yellen, 1935), but it fell to others (Goldstein, 1939; Ross, 1939; Bronstein, 1955; Kariher & Smith, 1955) to produce workable devices to implement the concept. Numerous patent applications for circumcision instruments were filed during this period, especially in the United States as can be seen by referring to the US Patent and Trademark Office database (USPTO), but few of the inventions passed into mass production and routine use. Meantime, in Europe, a similar but apparently unpatented device known as the Winkelmann Clamp was gaining favour (untraced in the European Patent Office database).
Such devices can be divided into two categories: Those that rely on ischaemic necrosis and those that do not. Ischaemic necrosis involves the deliberate killing-off of tissue by strangulation of its blood supply for a period of days, as in the Ross Ring and the Plastibell® (the trade name given to Kariher and Smith\'s device). The other devices first crush the blood vessels, typically for a period of some minutes, and then provide protection for the glans when the foreskin is severed. Conventional wound healing follows. In infants, the crushing action is sufficient to seal the wound such that sutures are not normally needed.
In consequence of the design fundamentals of the Gomco (GOldstein Medical COmpany) clamp (the trade name given to Goldstein\'s device) and the Winkelmann Clamp, these two clamps have the potential to remove almost all inner foreskin. The inner, "bell" component reaches beneath the prepuce in a way that places the cut near to the coronal rim of the glans. In consequence, as regards HIV prophylaxis, the resulting style of a circumcision done with these clamps is preferable to any "Tug-&-Chop" method.
In the USA the most commonly used devices are the Gomco clamp (67%), the Mogen clamp (10%) and the Plastibell (19%) (Stang & Snellman, 1998). Pictures of these appear later and can also be found in references: (Langer & Coplen, 1998; Alanis & Lucidi, 2004). The latter article in particular discusses the procedure, as well as contraindications. A technique that uses the Plastibell as a template for paediatric circumcision has been developed (Peterson et al., 2001). Rather than waiting for the bell to slough off days later, sutures are made at the time and the bell is removed. A similar “adult circumcision template” was later created for use in men, with good results (Decastro et al., 2010).
The various devices serve to protect the penis when excising the prepuce. The type of clamp used affects the time taken for the procedure, being on average 81 seconds for the Mogen clamp and 209 seconds for the Gomco clamp (Kurtis et al., 1999). In a head-to-head trial of length of procedure the Mogen took 12 minutes, compared with 20 minutes for the Plastibell (Taeusch et al., 2002). The latter time is far greater than others generally achieve (see 8.2.4 below). Although simpler to use and more pain-free than the other two (Kurtis et al., 1999; Kaufman et al., 2002; Taeusch et al., 2002), the Mogen clamp removes less foreskin. The Gomco is the oldest and is the most refined instrument (Wan, 2002). Its use is widespread, a study in Togo confirming its superiority to grips-only circumcision (Gnassingbé et al., 2010).
Since some of these more elaborate methods can take up to 30 minutes to perform they therefore expose the baby to a greater period of discomfort. In contrast, a circumcision can be completed in 15–30 seconds by a competent practitioner using methods that are part of traditional cultures.
Interestingly, strict sterile conditions were reported not to be necessary to prevent infection in ritual neonatal circumcision in Israel (Naimer & Trattner, 2000).
Rather than tightly strapping the baby down, swaddling and a pacifier has been suggested (Herschel et al., 1998; Howard et al., 1998; Howard
Dr Tom Wiswell and other experts strongly advocate the neonatal period as being the best time to perform circumcision, pointing out that the child will not need sutures (owing to the thinness of the foreskin (Schoen, 2005)) nor general anaesthesia, or additional hospitalization (Wiswell & Geschke, 1989; Wiswell & Hachey, 1993; Wiswell, 1995; Wiswell, 1997; Wiswell, 2000). Wiswell pointed out (personal email communication in Apr 2009) that “starting in the 1970s there was a movement away from delivery room circumcisions at minutes of life until several hours to several days of life. This was mainly because of the recognition of the transition period to extrauterine life that babies go through. ‘Stresses’ can have an adverse effect on this process, particularly on the heart and lungs. In an otherwise healthy infant, though, there is no need to delay until 2 weeks of age.”
All circumcisions should involve adequate anaesthesia, using either EMLA cream, dorsal penile nerve block, penile ring block, or a combination of these prior to the operation (http://www.circinfo.net/anesthesia.html). Without an anaesthetic the child experiences pain, during the procedure and for a maximum of 12–24 hours afterwards. That the baby could remember for a
Whatever the method, post-operative care, as advised by the doctor, must be undertaken, usually by the parents. Cosmetic results have met with unanimous parental acceptance (Duncan et al., 2004).
Healing is rapid in infancy (Schoen, 2005), complication rate is very low (0.2%–0.6%) (Wiswell & Geschke, 1989; Cilento et al., 1999; Christakis et al., 2000; Ben Chaim et al., 2005), and cost is much lower than when performed later in life (Schoen et al., 2006).
For males with haemophilia, special pre-operative treatment is required (Balkan et al., 2010; Yilmaz et al., 2010). A satisfactory outcome can be achieved with a specialized cost-effective device (Karaman et al., 2004; Sewefy, 2004). Just as for healthy individuals (see below), cyanoacrylate tissue adhesives (Glubran and Glubran 2) have been found to be effective for circumcision of haemophilia patients (Haghpanah et al., 2011).
Circumcision is more traumatic, disruptive and expensive for men and older boys than it is for infants (Schoen, 2007a). For those aged 4 months to 15 years some authorities advocate a general anaesthetic. Others strongly disagree, saying that since a general anaesthetic carries a small risk, a local anaesthetic, often with a mild sedative, is what should be used for all children (Schoen, 2007a).
Unlike infant circumcisions, sutures/stitches or wound staples are usually needed for men and older children, although use of synthetic tissue adhesives such as 2-octyl-cyanoacrylate (Dermabond) (Cheng & Saing, 1997; Subramaniam & Jacobsen, 2004; Ozkan et al., 2005; Elmore et al., 2007; Elemen et al., 2010; Lane et al., 2010; D\'Arcy & Jaffry, 2011) have proven to be effective alternatives. These are safe, easy to use, reduce operating time, lower postoperative pain and give a better cosmetic appearance (Ozkan et al., 2005; Elmore et al., 2007).
Excellent cosmetic results were reported for all of 346 patients aged 14 to 38 months using electro-surgery, which presents a bloodless operative field (Peters & Kass, 1997). Metal of any kind (such as the Gomco clamp that is used commonly in infant MC) has to of course be avoided in this procedure.
Laser surgery is gaining popularity, but requires both specialized equipment and training. The method has its own associated shields (Chekmarev, 1989; Zhenyuan, 1989; Gao & Ni, 1999).
Gentle tissue dissection with simultaneous haemostasis has been achieved using an ultrasound dissection scalpel for circumcision (Fette et al., 2000).
A randomized trial found that a bipolar diathermy scissors circumcision technique led to less blood loss (0.2 versus 2.1 ml), shorter operating time (11 versus 19 min) and lower early and late postoperative morbidity as compared with a standard freehand scalpel procedure (Méndez-Gallart et al., 2009). Bipolar scissors also appear to offer a method of bloodless removal of the frenulum prior to application of any one of a number of circumcision clamps for the remainder of the procedure.
Unless combined with other surgery, circumcision later obviously requires a separate (occasionally overnight) visit to hospital. Healing is slower than in newborns and the rate of complications is greater, but still low: 1–4% (Auvert et al., 2005; Cathcart et al., 2006; Bailey et al., 2007; Gray et al., 2007; Krieger et al., 2007). Most common is postoperative bleeding (0.4–0.8%), infection (0.2–0.4%), wound disruptions (0.3%), problems with appearance (0.6%), damage to the penis (0.3%), insufficient skin removed (0.3%), delayed wound healing (0.1%), delayed healing (0.2%), swelling at the incision site or haematoma (0.1–0.6%) or need to return to the theatre (0.5%). An average of 3.8% adverse events has been seen for the first 1–100 circumcisions a clinician does (Krieger et al., 2007). For the next 100 this decreases to 2.1% and by the time they have done 200–400 it drops to less than 1%. Beyond 400 it is 0.7%. The incidence of penile adhesions after a circumcision decreases with age, but at any age they often resolve spontaneously (Ponsky et al., 2000). Pain sometimes can last for days afterwards and those older than 1 to 2 years may remember.
Cost is also much greater than for neonatal circumcision. Cost can be reduced by having the surgery performed on an outpatient basis.
A local anaesthetic is all that is needed for MC, so reducing anaesthetists’ charges which can be quite high for a general anaesthetic. The WHO has produced a manual for circumcision of men under local anaesthesia (World Health Organisation, 2006). Various methods can be used for local anaesthesia, including dorsal penile nerve block and ring block. Recently, a no-needle jet of 0.1 ml 2% lidocaine solution sprayed at high pressure directly on to the penile skin circumferentially around the proximal third of the penis has proven to be quick and effective, and has obvious appeal (Peng et al., 2010a).
Conventional surgery under general anaesthetic normally uses the sleeve-resection technique, described in a series of diagrams with technical details by Elder (2007). This method takes longer and for this reason many surgeons will insist on using a general anaesthetic. By its nature sleeve resection removes mainly shaft skin, not foreskin, so having potential implications for HIV infection. An alternative is the Dissection Method. These two methods are often confused. Illustrated by Mousa (Mousa, 2007), the Dissection Method separates inner and outer foreskin in a manner similar to a very loose "tug and chop" circumcision, but then proceeds to excise most of the inner and all of the outer foreskin along with some shaft skin. The amount of shaft skin removed depends on the tightness required; inner foreskin is left only as necessary to provide an anchorage for sutures reconnecting the shaft skin to the sulcus.
Interestingly, genital surgery in women often involves a course of topical estrogen in advance in order to increase thickening, cornification and keratinization of the vaginal epithelium (Short, 2006). This helps surgical outcome and has led to the suggestion that similar pre-treatment be carried out prior to circumcision in men.
Pain from conventional surgery can last for up to a week or longer afterwards, during which time absence from work may be required. Some men, however, report no pain, just minor discomfort from the stitches. A large RCT found that at the 3-day post-circumcision follow-up, 48% reported no pain, 52% very mild pain, and none moderate or severe pain (Bailey et al., 2007). By 8 days, 89% had no pain and 11% mild pain. Vasectomy in men circumcised previously as adults (and who can thus attest to the difference) is said to be much more painful.
The following devices were in common use for male circumcision prior to the start of the HIV epidemic. The patent information quoted relates to the country of residence of the inventor(s). In many instances other patents exist, especially in the USA, the European Union and, since its formation in 1967, the records of the World Intellectual Property Organisation (WIPO).
Inventor: Unknown
Primary patent: None(historic)
Patent priority date: Not applicable
Patient age range: Full-term neonate to adult
Category: Tug-&-Chop shield
The traditional Jewish shield.
Procedure: The foreskin is pulled forward and the shield slipped over it. The excess prepuce is then excised by running a scalpel or similar knife across the distal face of the device.
Inventor: Goldstein, A.A.
Primary patent: United States Design Patent USD119180 (no Utility Patent has been traced)
Patent priority date: 16 Mar 1939
Patient age range: Full-term neonate to adult
Category: Bell clamp / scalpel guide
The Gomco Clamp showing components, in a range of sizes, that are assembled during the procedure described in the text.
Procedure: First of all, a dorsal slit is made in the foreskin and the foreskin is separated from the glans. The bell of the Gomco clamp is then placed over the glans, and the foreskin is pulled over the bell. The base of the Gomco clamp is placed over the bell, and the Gomco clamp\'s arm is fitted. After the surgeon confirms correct fitting and placement (and the amount of foreskin to be excised), the nut on the Gomco clamp is tightened, causing the clamping of nerves and blood flow to the foreskin. The Gomco clamp is left in place for about 5 minutes to allow clotting of blood to occur, then the foreskin is dissected off using a scalpel. The Gomco\'s base and bell are then removed, and the penis is bandaged. It is a fairly bloodless circumcision technique. The circumcision is relatively quick compared to the Plastibell. It was the most popular method for circumcisions between 1950 and 1980 and is still common today, especially in the USA. A training video of a neonatal Gomco circumcision using dorsal penile nerve block and a sucrose pacifier, conducted by Dr Richard Green, Stanford University School of Medicine, is available at http://newborns.stanford.edu/Gomco.html
Dr Sam Kunin, an experienced urological surgeon in Los Angeles, has developed a clever, and very effective, method in which local anaesthetic is injected into the distal foreskin (Kunin, 2007b). Doing so separates the inner and outer foreskin therefore allowing the inner layer to be pulled against the bell of the Gomco clamp, and results in a maximum amount of inner layer being removed (http://www.samkuninmd.com). He points out that the inner lining is the area most prone to adhesions, irritations, yeast and bacterial infections, particularly in diabetics.
Gomco clamps exist in sizes from neonatal to adult. Suturing is required post-infancy.
Inventor:Provisionally attributed to the German urological surgeon Karl Winkelmann (1863–1925).
Primary patent:None traced
Patent priority date:None traced
Patient age range:Infant to mid-puberty, according to manufacturer.
Category:Bell clamp / scalpel guide
The Winkelmann Clamp.
Procedure: Nominally the same as the Gomco clamp described above. Despite its ready availability, the Winkelmann Clamp appears not to have been trialled in connection with the search for devices suitable for campaigns of mass circumcision.
Inventors:Kariher, D.H. and Smith, T.W.
Primary patent:US3056407
Patent priority date: 18 May 1955
Patient age range:Full-term neonate to onset of puberty
Category:Ischaemic necrosis device using string ligature
Procedure: The Plastibell is a clear plastic ring with handle and has a deep groove running circumferentially. The adhesions between glans and foreskin are divided with a haemostat (artery forceps) or similar probe. Then the foreskin is cut longitudinally starting at the distal end dorsally to allow it to be retracted so that the glans (the head of penis) is exposed (Elder, 2007). The appropriately sized device is chosen and applied to the exposed glans. The ring is then covered over by the foreskin. A ligature is tied firmly around the foreskin, crushing the skin against the groove in the Plastibell. Then the excess skin protruding beyond the ring is trimmed off, something that is possible using surgical scissors rather than a scalpel. Finally, the handle is broken off. The entire procedure takes 5 to 10 minutes, depending on the experience and skill of the operator. The compression against the underlying plastic shield causes the foreskin tissue to necrotize. The ring falls off in 3 to 7 days leaving a circumferential wound that will heal over the following week. Typically, the glans will appear red or yellow until it has cornified (Gee & Ansell, 1976; Holman et al., 1995).
The Plastibell device is a clear plastic ring with handle and has a deep groove running circumferentially. Upper diagram: How it is used for an infant circumcision (diagram modified from
The Plastibell continues to be available in sizes applicable from newborn to early puberty. The metallic precursor, the Ross Ring (Ross, 1939), also came in adult sizes, but adult Plastibell circumcision appears to be unknown. The metallic ring is long discontinued, rendered obsolete by its disposable plastic equivalent. Cosmetic results have met with unanimous parental acceptance (Duncan et al., 2004).
Dr Terry Russell in Brisbane, Australia, developed in 1993 a simple, pain-free method involving 2 hours EMLA cream with the penis wrapped in cling wrap (done by the parents prior to arrival at the clinic), followed by a modified Plastibell circumcision (Russell & Chaseling, 1996). The technique is described in detail on his website (http://www.circumcision.com.au). Dr Russell has used it in 30,000 circumcisions on boys of all ages from neonate to puberty, including 400 older boys every year. More recently he has obtained excellent results with another topically applied anaesthetic cream, LMX4 (4% lidocaine) that is faster acting, more effective and has fewer side effects (C.T. Russell, personal communication). Because complete local anaesthesia is achieved by EMLA or LMX4 cream, Dr Russell reports that no pain is experienced for 5 hours after the Plastibell is applied, so claims the circumcision is completely pain free at all stages. The only major complication in 30,000 circumcisions was one boy who developed mild methemoglobinaemia (from the EMLA cream) that, after immediate hospital admission, resolved spontaneously overnight, with no medical intervention required.
Prof Roger Short orchestrated the production of a video that teaches the Russell method. Dr Russell featured in this "no scalpel circumcision" video. Also featured was one of Prof Short’s students from Botswana, who took it there for teaching purposes. Another, filmed in Vanuatu of a traditional circumcision using a sharpened bamboo, was produced for use in Papua New Guinea (PNG) where, unlike most Pacific Islands, circumcision is uncommon. These were aimed primarily to reduce HIV/AIDS in Botswana and PNG.
Since the simple plastic Plastibell device is now off patent it can be produced at very low cost, but parallel production cannot use the name Plastibell, which remains to this day a Registered Trade Mark. Nevertheless, the device has the potential to help reduce HIV in poor countries (Short, 2004).
Dr. Sam Kunin points out, however, that "the [Plasti]bell techniques leave too much inner skin. Besides the inherent problems of this method with later adhesions and buried penis, allows for possible migration of the bell down the shaft, with ensuing potential damage to the penile skin" (personal communication). A Nigerian study also noted that incorrect technique can lead to proximal migration of the Plastibell in neonatal boys (Bode et al., 2009). Correct training in this method is thus essential. An Iranian study involving 7,510 term neonates found that Plastibell circumcision incorporating thermal cautery of the frenulum reduces bleeding (0.4% versus 0.05%), but led to greater urinary retention (0.03% versus 0.9%) (Kazem et al., 2010). Modifications to the standard procedure by authors in the UK have improved outcomes, particularly the risk of bleeding (Mahomed et al., 2009).
A study in Pakistan found that for babies under 3 months of age, the time taken for the Plastibell to fall off was 8.7 days (Samad et al., 2010). This increased gradually to 16.8 days for children over 5 years.
Inventor:Bronstein, H.
Primary patent:US2747576
Patent priority date:3 Feb 1955
Patient age range:Full-term neonate to adult
Category:Tug-&-Chop shield with inbuilt crushing action
The Mogen Clamp.
Procedure: Firstly, adhesions between glans and foreskin are divided and a haemostat is placed along the dorsal midline with its tip about 3 mm short of the corona before being locked into place. The Mogen clamp is opened fully. A key step in Mogen circumcision is the safe placement of the clamp. To push the glans out of the way, the surgeon\'s thumb and index finger pinch the foreskin below the dorsal haemostat. The Mogen clamp is then slid across the foreskin from dorsal to ventral following along the same angle as the corona. The hollow side of the clamp faces the glans. Before locking the clamp shut, the glans is manipulated to be sure it is free of the clamp\'s jaw. If it is, the clamp is locked. Once locked the foreskin is excised flush with the flat surface of the clamp with a 10 inch blade scalpel. The clamp is left on for a few moments to ensure haemostasis. It is then unlocked and removed. The glans is liberated by thumb-traction at the 3 and 4 o\'clock positions that pull the crush line apart.
This device can be and has been used across the whole age range. However, recent safety issues involving the glans being drawn into the clamp are reported to have brought about the bankruptcy of the original manufacturer (Tagami, 2010).
With the possible exception of the Plastibell, the traditional devices appear not to be well suited to field use by personnel not fully trained as medical professionals. This has led to the development of a number of new designs. Before moving on to consider each in detail, we first address the issue of the design objectives.
Over 30% of the world’s male population enters adulthood already circumcised, their foreskins having been removed in infancy, childhood or around puberty, either as a prophylactic measure for prevention of disease, for hygiene reasons, family tradition, cultural reasons, religious requirements, or treatment of foreskin-related medical conditions (World Health Organisation, 2007b). That still leaves hundreds of millions of uncircumcised males who are (or later in life will become) sexually active, but lack the baseline protection provided by MC against a wide range of STIs and other adverse medical conditions.
Valiant MC scale-up efforts are in progress in sub-Saharan Africa. It is, however, unrealistic to expect existing surgical resources to be diverted to the task of circumcising these millions of men worldwide. Such expertise is already fully committed elsewhere. What is required is an ad hoc contingent of circumcisers, a cohort of people with sufficient training to carry out circumcisions safely, effectively, with a good cosmetic outcome and minimum disturbance to lifestyle. Given the vast numbers involved, recruitment from outside the pre-existing medical profession is inevitable. Such a need has, moreover, been recognized by those "on the ground" in sub-Saharan Africa (Sahasrabuddhe & Vermund, 2007; Sharlip, 2008; Wamai et al., 2008; World Health Organization, 2008).
Herein lies the justification for introducing newer methods of circumcision reliant on advances in biomedical engineering. What is needed is a device and method that de-skills the surgical process to the point where it can be safely and effectively undertaken by people whose prior educational achievement would not otherwise have admitted them to the medical profession. Then, and only then, can a campaign of mass circumcision take place without major poaching of skilled personnel from other healthcare programmes.
Prudent planning nevertheless envisages a fully qualified person to be nearby, acting as supervisor and capable of completing by conventional surgery any circumcision that goes wrong when attempted by ordinary members of the task force using de-skilled methodology. Dispensing totally with such supervision and backup would, in the authors\' opinions, be too risky.
No matter what method is used, adequate training in technique is crucial. To this end a low-cost penile model has been developed as a teaching aid for use in low-resource settings (Kigozi et al., 2011).
As with previous global public health campaigns such as the one that successfully achieved the eradication of smallpox, it is imperative to bring MC services to the people rather than expect the people to visit distant facilities. Take the example of the peasant farmer. He cannot leave his livestock and his family unattended for days on end whilst he travels, probably on foot, to a clinic many miles away. Hence our second requirement for the ideal new MC device: It must be suitable for use in conditions of limited asepsis. A clean consulting room in a village health clinic would be a luxury, as would a mobile facility built into a shipping container and driven around by truck. Think more in terms of a clean cloth draped over a table in a bamboo or mud hut, with village elders in attendance waving their ceremonial fly whisks and the circumciser arriving on foot with all necessary equipment in a small rucksack. No roads, no electricity, no running water. The 2nd author, Chris Eley, saw exactly this at a religiously-motivated circumcision in Seram, Indonesia, in 1987 (Operation Raleigh expedition 11E, led by the late Major Wandy Swales TD). On that occasion the surgery was done freehand by a well-qualified and highly proficient Egyptian doctor, using injected local anaesthesia, forceps, surgical scissors and sutures.
One obvious consequence of such remoteness is that facilities for re-sterilizing equipment are non-existent. Therefore the ideal device should be single-use. That applies not only to the clamp itself, but also to all ancillary equipment such as any tool needed to close it, plus syringes, forceps and so on. Think here of a whole single-use kit packaged as one, not just a clamping device on its own.
Against this outline of medical objectives, social and logistical background, we can begin to construct a checklist of the design parameters to be met by candidate devices.
Already mentioned:
Suitable for use by persons without recognised medical qualifications, with limited supervision.
Suitable for field use; no requirement for an aseptic environment.
Single use / disposable.
To this list must be added:
Cost: Rather obviously this needs to be minimized, but the raw cost of the device is only a small part of the total financial commitment. Staffing, provisioning and transport in remote areas can dwarf the cost of the circumcision device that the team intends to fit. The design of the device nevertheless remains crucial. For example, does it need a trained attendant to remove it? If so, staffing costs may straight away have escalated in comparison with a rival device not routinely requiring such follow-up.
Simplicity: The ideal device should be easy to comprehend. Not only does that simplify training, it also simplifies the obtaining of each prospective patient\'s informed consent. Simplicity also reduces the possibility of user error. This implies minimizing the number of components, avoiding all possibility of mis-assembly (such as getting something the wrong way round) and misuse (such as making a scalpel cut on the wrong side of a clamping ring). Enter what we politely refer to here as "The Law of the Inevitable Cussidness of Inanimate Objects", better known as Sod\'s (or Murphy’s) Law (http://en.wikipedia.org/wiki/Murphy\'s_law). If something possibly can go wrong, it will. Botched circumcisions cause immense psychological distress. The duty of care owed is of the highest order. One good measure of simplicity is the number of components in a device, the lower that number the better.
Size range: Where the intent is to produce a single design for the whole male population, the smallest device should fit a full-term neonate and the largest should fit the most well-endowed male. But what about those in-between? There is a balance to be struck here between, on the one hand, having a device that is precisely sized so that it is correct for each patient and, on the other hand, needing to carry a vast stock of different sizes. A certain latitude in sizing is needed, such that an acceptable circumcision results even if the device is a few millimetres off the ideal. This is not merely a matter of stockholding; critical sizing invites increased error due to the use of mis-selected devices and it also increases waste arising when an incorrect size is selected and removed from its sterile packaging but discarded before use.
Sterility: Delivery to remote locations requires robust packaging, but that is only half the story. Not all sterilization processes can be applied to all materials. There are known pitfalls with many plastics. Cobalt-60 exposure (gamma irradiation) is a very effective way of sterilizing, but is totally unsuited to a number of plastics; many discolour and become brittle when irradiated. Full consideration of this materials science issue is beyond the scope of the present chapter; just note and beware! The present alternative is the environmentally questionable Ethylene Oxide method. In time, it may become possible to use ultra-high voltage electrostatic fields on an industrial scale, but that is still in the future (Wang et al., 1992; Meijer, 2008).
Suitable materials: Devices that are intended to remain in contact with body tissue for an extended period must be hypoallergenic. Factors such as contact time and plasticizer residues must be scrutinized. The device supply chain should be secure against pirate copies and adulteration of the original specification.
Disposability: Waste disposal must be managed, not just in respect of the usual medical sharps, but also in respect of sloughed-off clamps and associated necrotic tissue. In some societies the payment of a bounty for the return of the spent device might be appropriate as a way of bringing about proper disposal.
No fraudulent re-use: Single-use devices should be exactly that. A key question might be "Does the device self-destruct at the end of the procedure?".
Avoidance of wound dehiscence: “Clip-&-Wear” clamps with an exceptionally narrow clamping ring can bring about wound dehiscence, especially when the circumcision style is tight such that the shaft skin is significantly stretched. What was intended merely to grip takes on the potential to cut, doing so proximally to the intended scar line and thus forcing remedial action that results in a tighter circumcision than originally envisaged. This problem appears to be age-related and gives rise to some criticism of the widespread use of ischaemic necrosis techniques in adults (Vernon Quaintance, The Gilgal Society, personal communication). There may be good cause for separating out older sexually-active adults and providing them with conventional surgery. Local factors appear to intrude here, especially nutritional status, a well-known determinant of wound healing capacity.
Even and adequate clamping pressure: Devices using the process of ischaemic necrosis need to apply their strangulation pressure evenly right around the intended scar line. Unless effective counter-measures are taken, pressure discontinuities can arise, especially at hinge positions and/or latch positions. This gives rise to the possibility of continued marginal blood flow at these points. In terms of infection, such marginal leaking is exceptionally dangerous. A good design for an ischaemic necrosis clamp is one that has no discontinuity in the clamping ring and which, throughout the wear period, maintains an absolutely even pressure sufficient to bring about total cessation of blood flow across the whole of the intended scar line.
Resistance to premature removal by a meddlesome patient: Premature removal of an ischaemic necrosis clamp can precipitate a clinical emergency. Therefore it is vital that the latching mechanism of the clamp should be secure against tampering. The risk of such tampering is greatest when dealing with post-infancy paediatric patients.
Minimum requirement for pre-treatment: In the world of veterinary medicine, immunization against tetanus is recommended when ischaemic necrosis is used for procedures such as tail docking of lambs by means of the Elastrator device (Thedford, 1983). We commend the idea of similar pre-treatment before any ischaemic necrosis procedure is used for MC.
Cultural acceptability: A whole raft of issues can arise here, any one of which might scupper a proposal to use a particular design of clamp in a particular area. For example, is a device invented in Israel assured of acceptance in Islamic Republics that do not even acknowledge the existence of the Jewish state? Will circumcision ever be accepted by Hindus, many of whom value their foreskins as evidence of not being Muslim? During the partition of India in 1947, strangers suspected of being of the opposite faith were disrobed and put to death on no more evidence than their circumcision status (Kamra, 2002). Rather less dramatically, there is the question of whether a clip-&-wear clamp protrudes beyond the end of the penis during the wear period. Not a problem in societies where loose, flowing robes are normal attire, but an entirely different matter when the male is habitually dressed in tight jeans.
The authors are aware of eight products designed to fulfil the demand for a field-use device, all being either in full production or in the final stages of development and testing. These are now considered individually, in alphabetical order of trade name. Only the original patents or patent applications in the inventor\'s country of residence are listed; increments may exist in the same country as well as there being patents elsewhere.
It should be noted that some clamps have been the subject of ongoing development after their initial market launch. Care is needed when reading reports of field trial results. Early criticisms may have been rendered obsolete by subsequent design changes.
Inventor:Tomlinson, D.R.
Primary patent:US2005/022404
Patent priority date:25 Jun 2004
Patient age range:Full-term neonate only
Website:http://www.accucirc.com
Category:Automated cutter
The AccuCirc device.
Procedure: The AccuCirc uses two innovative components, a Foreskin Probe/Shielding Ring that ensures the glans is protected with the foreskin properly aligned and a Single-Action Clamp that ensures adequate haemostasis and the precise delivery of the protected, circular blade. These work together to protect the infant from injury. This device simplifies the circumcision procedure and eliminates the need for a dorsal slit, as well as removing potential for mismatching of parts. It comes in a self-contained kit. This is completely disposable and no part is retained on the infant.
Inventor:Canoğlu, V.A.
Primary patent: TR2003/00403
Patent priority date:28 Mar 2003
Patient age range: Full-term neonate to adult (experimental in adult sizes)
Website:http://www.alisklamp.com
Category:Ischaemic necrosis device
Ali’s clamp.
Procedure: The Ali\'s Klamp (a.k.a. “Alisklamp” and “Ali’s clamp”; Telif Haklari ABAGROUP Ltd) is a single-use ischaemic necrosis device; the foreskin is crushed between two plastic surfaces. The recommended procedure includes severing of the excess tissue. During that process, the tube protects the glans from accidental injury. Note that the final scar line forms at the position of the clamping ring, not at the position of the scalpel cut. In theory the user could dispense with the scalpel cut, leaving the whole foreskin to necrotise. The procedure is illustrated in a two-part video available on the manufacturer\'s website.
The Ali\'s Klamp differs from the SmartKlamp (below) only in one significant respect: The clamping ring is angled to match the typical slant of the coronal rim of the glans. In theory this achieves better capture of inner foreskin ventrally. The Ali\'s clamp apparently shares with the SmartKlamp one notable design weakness. An unwilling or meddlesome patient could, in theory, open the clamp by placing a flat object such as a table knife between the tube and the locking arms and then twisting. Additionally, such action would render the device liable to unscrupulous re-use several times over, until such time as the nominally single-use latching mechanism wore out.
A review of 7,500 boys who underwent circumcision with this device under local anaesthesia concluded that cosmetic appearance was better than conventional circumcision of 5,700 boys (Senel et al., 2010). Duration was 4.5 ± 1.5 minutes versus 23 ± 4 minutes, respectively. Complications were seen in 2% of Ali’s clamp versus 10.4% for conventional circumcision, the most common for the Ali’s clamp being buried penis (1.04%), followed by infection (0.6%), bleeding (0.4%). A mass circumcision of 2,013 male infants, children, adolescents and adults (mean age 7.8 ± 2.5 years) over a 7-day period, noted a duration of 3.6 ± 1.2 minutes and complication rate of 2.93% in those < 2 years of age, mostly from buried penis (0.98%) and excessive foreskin (0.98%) (Senel et al., 2011). In older children, adolescents and adults complication rate was 2.39%, 2.51% and 2.40%, respectively. Overall, excessive foreskin (0.7%) was ther most common complication, followed by bleeding (0.60%), infection (0.55%), wound dehiscence (0.25%), buried penis (0.25%), and urine retention (0.10%). There was no effect on erectile function and libido, and a 96% satisfaction rate was recorded.
Originally available only for children, adult sizes reportedly now exist for use on a trial basis. Correspondence received mid-February 2011 from Dr. Ali Canoğlu claims a successful field trial in Africa. At the time of writing official independent reports have not yet been published.
Inventor:Salleh, I.
Primary patent: MY2008/000195
Patent priority date:16 Jan 2008
Patient age range:Full-term neonate to puberty
Website:http://www.ismailclamp.com/
Category:Ischaemic necrosis device
The Ismail Klamp.
Procedure: The Ismail Klamp is another single-use ischaemic necrosis device, functioning in the same way as the Ali\'s Klamp, SmartKlamp and Tara KLamp. The distinguishing feature of Dr. Ismail Salleh\'s device is that the clamping ring can be loosened as well as tightened during the process of application. This the manufacturer describes as "Reversible Clamping". Such a feature is undoubtedly an advantage if a tight style of circumcision is required; it gives greater scope for clamp adjustment. Against that advantage must be offset two risks: A meddlesome patient might loosen the clamp during the healing period and the clamp might be re-used unscrupulously.
Inventors:Fuerst, O., Kilemnick, I. and Shohat, S.
Primary patent: (Application:) IL2010/000568
Patent priority date:16 Jul 2009
Patient age range:Adult only at present
Website:http://www.prepex.com/
Category:Ischaemic necrosis device
The PrePex device. (Photo supplied by Circ MedTech ©2011)
Developed in 2009/10 by Dr. Oren and Tzameret Fuerst, Ido Kilemnick & Shaul Shohat (Fuerst et al., 2010) and marketed by a company called Circ MedTech Limited (incorporated in the British Virgin Islands), this device is designed for use in non-sterile environments by minimally trained healthcare professionals.
Possibly unique for modern clamps, publicized abstracts of safety and efficacy trials held in Rwanda found it to be suitable for use without anaesthesia. Four hundred milligrams of oral Brufen is routinely offered 30 minutes after placement of the clamp, but no other drug use is involved. Whilst the surplus foreskin can be severed, in these trials the foreskin was left to necrotize intact thus facilitating a quick and bloodless procedure that can be handled by minimally trained healthcare professionals in non-sterile settings. The company affirms that there have been no complications to the urine stream as a result of the necrotized foreskin being left in situ.
In common with other ischaemic necrosis clamps, the PrePex device requires no sutures.
Procedure: After sizing and marking of the circumcision line based on the circumcision style desired (high/low), the Elastic Ring, loaded on to the Delivery Ring, is placed at “deploy-ready” position on the penis base (proximal). The foreskin tip is stretched open to allow insertion of the Inner Ring, directly under the coronal sulcus. The Elastic Ring is then deployed within the Inner Ring groove, initiating the ischaemic process and the Delivery Ring is removed. The patient resumes his activities with only the Elastic Ring visible. After 7 days, the device is removed by flicking the Elastic Ring out of the groove and extracting the inner ring with fingers or a standard medical spatula.
Regulatory issues (as declared by the manufacturer): "The device has a CE mark and is manufactured using USP Class VI biocompatible elastomeric materials compliant to ISO_13485 Medical Devices (Quality Management systems) and FDA, 21_CFR177.2600."
Declared contra-indication: The device is contraindicated for patients with phimosis if the chosen procedure leaves the foreskin intact.
Once evidence of the style of circumcision achieved by this device is made public, this latecomer to the design contest is expected to show significant advantages over its competitors – especially if the claim of suitability for routine use without anaesthesia is validated in more extensive trials.
Inventor:Shang, J.
Primary patent: CN2003/000903
Patent priority date:20 Oct 2003
Patient age range:Full-term neonate to adult
Website:http://www.snnda.com/enindex.asp
Category:Ischaemic necrosis device
The Shang Ring device.
Procedure: The "Shenghuan Disposable Minimally Invasive Circumcision Anastomosis Device", developed in China by Jianzhong Shang, involves minimal tissue manipulation and is said to give a simpler, quicker and safer circumcision than conventional techniques (Masson et al., 2010). It consists of two concentric plastic rings that sandwich the foreskin of the penis, allowing circumcision without stitches or notable bleeding. As well as substantially reduced operating times, MC using this device is associated with a low complication rate, and the technique can easily be taught to both physicians and non-physicians. The Shang Ring is produced by Wuhu Snnda Medical Treatment Appliance Technology Co. Ltd, Wuhu City, China.
When tested on 1,200 patients aged 5 to 95 years operating time was 2.5 minutes for patients with excessive foreskin and 3.5 minutes for those with phimosis (Peng et al., 2008). After application it is worn for a week, with no incidents of device dislocation or damage to the frenulum. Peng et al. describe the use of oral diethylstilbestrol (at a dosage of 2 mg/night) as a way to prevent nocturnal erections during the wear period. We do not find favour with this, due to the known environmental persistence of DES and the long-term effects of this synthetic oestrogen (Newbold et al., 2006). In this study by Peng et al. the incision healed in 96.3%, leaving minimal inner foreskin, with no scarring and good cosmetic results. Antibiotics were not used, and only 0.67% got an infection. After removal, of the device 0.58% had some minimal bleeding around the incision and 2.4% had wound dehiscence of the incision caused by nocturnal erection, but this could be prevented by continuation of diethylstilbestrol for 3 days. It was treated by simply closing the incised rim with a butterfly adhesive plaster, followed by topical disinfectant; no stitches were required. Patients reported less pain than occurs for conventional methods.
Use of the Shang Ring has become a method of choice in the People\'s Republic of China. Evaluation of a standardized surgical protocol for its use, involving 328 men, showed an operating time of 4.7 ± 1.3 minutes, pain scores of 0.2 ± 0.6 during the surgery, 1.6 ± 1.0 24 hours postoperatively, 1.7 ± 1.1 twenty four hours prior to ring removal, and 2.7 ± 1.4 during ring removal (Cheng et al., 2009). In this study, complications included infection in 0.6%, bleeding in 0.6% and wound dehiscence in 0.6%; none of the latter required suturing. Penile oedema occurred in 4.9%. The time for complete wound healing was 20.3 ± 6.7 days. Satisfaction was 99.7%.
A study in 824 boys with phimosis or redundant foreskin found duration was 2.6 ± 1.2 minutes (Yan et al., 2010). Wounds healed and rings were removed at 13.4 ± 5.8 days revealing a well-smoothed incision and good cosmetic results. Complications were low and included infection in 0.6%, oedema in 3.2%, delayed removal of the ring in 1.5%, and redundant and asymmetric mucosa attributable to performance in 0.9%.
Another study in China, of 402 patients, found duration (4.7 ± 1.3) minutes, blood loss (2.6 ± 1.8 ml), and postoperative satisfaction (99.5%) for Shang Ring circumcision were significantly better than conventional circumcision, and International Index of Erectile Dysfunction (IIEF-5; not “IIRF-5” as stated in the paper) was no different (Li et al., 2010). In 351 males aged 4 to 58 (mean 31) circumcised for phimosis or redundant foreskin using the Shang Ring, infection was seen in 1.4%, mild oedema in 2.6%, moderate oedema in 1.4%, and wound dishescence in 1.7%, with no postoperative bleeding being observed (Peng et al., 2010b).
A proof of concept study in Kenya for the roll-out of MC for HIV prevention found a time of 4.8 ± 2.0 minutes for the procedure and 3.9 ± 2.6 minutes for device removal, with 6 mild adverse events in the 40 men who underwent Shang Ring circumcision (Barone et al., 2011). These included 3 penile skin injuries, 2 cases of oedema and one infection, all of which resolved with conservative management. Partial ring detachment occurred in 3 between days 2 to 7, none of which required treatment or ring removal. Erections with the ring were well tolerated. By day 2, eighty percent of the men had returned to work, and at 42 days all said they were very satisfied with their circumcision and would recommend it to others.
Aside from the matter of diethylstilbestrol use, without which there appears to be a danger of an erection displacing the device, possible further criticisms relate to the discontinuity of the clamping ring at both the hinge and clasp. It should also be noted that it gives no protection whatsoever to the glans during the severing of the prepuce.
The same inventor has also obtained a patent in respect of another, more recent but very different design. The relevant patent is CN2009/000406. It is unclear whether the later design is intended to supersede the original, or compete with it.
Inventor:Ten Have, H.F.
Primary patent: MY0100375
Patent priority date:30 Jan 2001
Patient age range:Full-term neonate to mid-puberty
Website:http://smartcircumcision.com/index.html
Category:Ischaemic necrosis device
The SmartKlamp.
Procedure: The SmartKlamp is an ischaemic necrosis device functioning in broadly the same way as the Ali\'s Klamp, Ismail Klamp and Tara KLamp.
Since its invention by Henri Ferdinand Ten Have, the commercial history of the SmartKlamp has to some extent interfered with its development and availability. Originally produced only in child sizes by the Dutch company Circumvent BV (Hengelo, The Netherlands), supply ceased when Circumvent BV went into liquidation, having apparently over-spent on research and development of the adult model. It should perhaps be noted that Circumvent\'s experimental adult device had an angled clamping ring similar in principle to that now found in the Ali\'s Klamp.
The apparently identical product in child sizes has now appeared in Malaysia, marketed by a supplier called Smartcircumcision. Aldemir and co-workers described the device thus: "This fits on the penis much as the others do. After 4 days the connection between its inner tube and casing is cut and removed. The inner tube is then left to fall off spontaneously in time. Median operative time is 8 minutes, compared with 18 minutes for conventional dissection, and cosmetic result, judged blinded by a urologist, was better. Parents\' satisfaction scores were the same" (Aldemir et al., 2008).
The SmartKlamp differs from the Ali\'s Klamp only in one significant respect: The clamping ring is not angled to match the typical slant of the coronal rim of the glans. In theory this achieves less satisfactory capture of inner foreskin ventrally, but the original manufacturer claimed it is possible to adjust the foreskin to compensate. The SmartKlamp apparently shares with the Ali\'s Klamp one notable design weakness. An unwilling or meddlesome patient could, in theory, open the clamp by placing a flat object such as a table knife between the tube and the locking arms and then twisting. Additionally, such action would render the device liable to unscrupulous reuse several times over, until such time as the nominally single-use latching mechanism wore out.
A training video is available for purchase from the current supplier\'s website.
Inventor: Surat, T.b.
Primary patent:(Application:) MY2006/000281
Patent priority date:23 Jan 2006
Patient age range:Full-term neonate to adult
Website:http://www.sunathrone.com/
Category:Ischaemic necrosis device
The Sunathrone device.
Procedure: The Sunathrone clamp differs markedly from the other ischaemic necrosis devices considered here, in that the crushing action is achieved by means of a wrap-around "cuff" rather than concentric rings. Nominally this introduces a problem of pressure discontinuity at the hinge and latch, but Dr. Tasron bin Surat\'s design overcomes that by means of springy cuff extensions that bridge these gaps.
In order to achieve sufficient pressure between the cuff and the tube, a special tool called a "Sunalever" is required to close the Sunathrone clamp. This is a large item, sized according to the device being applied to the patient. It can be seen in use on the web page http://www.circlist.com/instrstechs/sunathrone.html. In the absence of on-site sterilization facilities, one Sunalever would have to be packaged with each clamp. This has implications in terms of cost, package size and waste disposal.
Two points in favour of this design are that the latching mechanism is highly tamper-resistant and, once the bayonet joint of the tube (ringed in yellow in the image above) is unplugged, nothing protrudes beyond the tip of the glans. The manufacturers claim suitability for use in cases of buried penis, the relatively large diameter of the cuff preventing the glans from withdrawing into the abdomen and forming adhesions during the healing period.
Inventor: Singh, G.S.T.
Primary patent: US5649933
Patent priority date:20 Apr 1992
Patient age range:Full-term neonate to adult
Website:Tara Medic does not have its own website. See instead:
http://www.circlist.com/instrstechs/taraklamp.html
Category:Ischaemic necrosis device
The Tara KLamp.
Procedure: The Tara KLamp is the original single-use “clip-&-wear” ischaemic necrosis device to have gone into commercial production. Procedure for use is substantially the same as for the Ali\'s Klamp, Ismail Klamp and SmartKlamp. Since its invention nearly 20 years ago by Gurchran Singh Tara Singh, the Tara KLamp has undergone a number of design changes the most notable of which relates to its size, which has reduced considerably, thus making the current version more convenient to wear than the original.
The latching mechanism of the Tara KLamp is especially secure, making this design suitable for use on unwilling, meddlesome or autistic boys.
Considerable criticism of the Tara KLamp has arisen in consequence of a paper published by Lagarde and associates (Lagarde et al., 2009). The authors of the present chapter are in possession of documentary evidence apparently proving that Lagarde\'s team did not attend Tara Medic\'s training course relating to use of the Tara KLamp. Furthermore, these documents also appear to show that Lagarde\'s team departed from the procedure set down in the package insert. If true, we suggest the resulting criticism of the Tara KLamp to be unfair and possibly unwarranted. Unpublished studies by the Health Department of KwaZulu-Natal apparently failed to replicate the problems and the Tara KLamp has now been accepted as the “preferred device” for use in Kwa-Zulu Natal.
We suggest that, at the very least, Lagarde\'s findings should be set aside pending further investigation. Safety and efficacy trials of the Tara KLamp should be repeated by a different team. Such a trial might usefully address one further issue: Whether or not the Tara KLamp can be successfully used without the foreskin being severed, instead leaving it to necrotise in situ as is done with the PrePex device.
Early in 2011 the World Health Organisation formed a Technical Advisory Group (TAG) with a remit to look at evidence and make recommendations to WHO regarding choice of circumcision clamp, but to date the TAG has not published any recommendations (Personal correspondence between co-author C. Eley and the co-Chairman on 21 Feb 2011). It is to be hoped that, when they do, it will be a shortlist for local consideration rather than a recommendation favouring one particular device globally. It is the considered opinion of the present authors that it would be inappropriate for there to be a single winner in this contest. The best clamp in any given situation is likely to be a function of local factors.
MC can be performed at any age, but infancy is the ideal time for reasons of safety, procedural simplicity, convenience, minimal risk and cost (Wiswell & Geschke, 1989; Wiswell & Hachey, 1993; Wiswell, 1995; Wiswell, 1997; Wiswell, 2000). The benefits in respect of UTIs and penile cancer are, moreover, maximized if circumcision takes place in infancy. Circumcising prior to onset of sexual activity rather than later also means a completely healed penis, so that risk of infection, such as by HIV, during the healing period is reduced.
Thus the present campaigns to circumcise adults should be seen as a mere catching-up exercise, making good past omissions to circumcise pre-puberty. The ultimate aim should be to make infant MC a global norm, the health rewards being too great to overlook (Morris, 2007; World Health Organisation, 2007a,b; Tobian et al., 2009; Cooper et al., 2010).
MC has no long-term adverse consequences (Morris, 2007; Smith et al., 2010; Tobian et al., 2010). Good quality research studies that include thermal imaging show similar sensation during arousal for the circumcised and uncircumcised penis (Payne et al., 2007). The lack of any diminution in sexual function, satisfaction or sensation is now backed up by evidence from large RCTs (Bailey et al., 2007; Krieger et al., 2008). In fact 64% of the men in one of the trials reported an increase in their penile sensitivity and 54% reported greater ease in reaching orgasm (Krieger et al., 2008). This did not mean an increase in premature ejaculation. The fact that circumcision does not impair, and for many may enhance, a man’s sensation and sexual pleasure, should reassure men considering whether to get circumcised (Sharlip, 2008). MC is preferred by most women for reasons of hygiene, sexual activity, reduced STI risk, and greater enjoyment of intercourse (Williamson & Williamson, 1988; Badger, 1989a,b; Moses et al., 1998; Nnko et al., 2001; Kigozi et al., 2009a).
Biomedical engineering clearly has its place in delivering MC, despite the existence of methods and traditions that are many thousands of years old. Recent progress in instrumentation design has resulted in devices that have begun to address the need for circumcisions that are quick, safe and convenient, and that can be used in “field” settings. Such advances in biomedical engineering are essential in ensuring a safe and practical way of dealing with the numbers of males of all ages in the modern world who need to be circumcised.
As the population grows older, the prevalence of aortic valve disease, particularly aortic stenosis, is swelling, making it currently, the most prevalent form of valvular heart disease [1, 2, 3]. Surgery and percutaneous interventions of the aortic valve are frequently needed in patients with severe symptomatic aortic valve disease, the timing for these procedures’ conditional on a comprehensive evaluation of the dysfunctional aortic valve and the resultant repercussions on the rest of the heart, particularly the left ventricle (LV). Parameters used to predict favorable/unfavorable results from aortic valve surgery or intervention include LV ejection fraction (EF), presence and severity of left ventricular hypertrophy (LVH), LV end-systolic volume (LVESV), degree of leaflet calcification, and trans-aortic valve gradients. Because of the LV deformation indices potential to detect subclinical LV dysfunction, they are being used with increasing frequency in the management of patients with aortic valve disease [4] and advancing the timing for aortic valve surgery or intervention, before the LV is irreversibly damaged.
Our objective with this chapter is to describe the use of strain imaging, particularly global longitudinal strain in the assessment of cardiac function in patients with aortic valve disease. We review the current clinical applications of strain analysis in patients with aortic valve disease, highlighting strengths and weaknesses and emphasizing normal and abnormal findings in aortic stenosis (AS) aortic regurgitation (AR) and mixed aortic valve disease (ASAR); we summarize unresolved issues, potential future research priorities, and recommended indications for incorporating this technique into the clinical practice of patients with aortic valve disease.
Strain is defined as the fractional change in length of a myocardial segment relative to its baseline length, it is expressed as a percentage. Strain rate is the temporal derivative of strain, providing information on the speed at which the deformation occurs. Echocardiography, because of its dynamic nature, is ideally suited for the evaluation of cardiac mechanics through the application of deformation indices [5, 6]. Two echocardiographic techniques have dominated the clinical and research arena of deformation echocardiography: (1) tissue Doppler imaging, and (2) speckle tracking imaging. Both techniques lend to the derivation of multiple parameters of myocardial function. Tissue Doppler Imaging (TDI) was the first method used to measure myocardial deformation by echocardiography. The method is well validated and has been shown to provide valuable data in a wide range of conditions. Tissue Doppler is currently used mainly for evaluation of diastolic LV function, its use in aortic valve disease will not be discussed in this chapter. Speckle tracking, mainly through the use of global longitudinal strain (GLS), is increasingly used to identify subclinical myocardial dysfunction in patients with valvular heart disease and to identify optimal timing for surgery or intervention and prognosticate outcomes after surgery/intervention, and is the main focus of this review.
Aortic stenosis inflicts progressive pressure overload on the LV with compensatory concentric hypertrophy (Figure 1). Initially, the increased wall thickness and conservation of normal LV chamber dimensions offsets the increased LV pressure, maintaining a normal ejection fraction. If the aortic stenosis is not corrected it will inexorably lead to reduced myocardial perfusion, and eventual fibrosis with consequent drop in ejection fraction. It is well recognized that LV GLS is superior to LVEF in detecting perturbations in myocardial function. Compared with normal controls, severe aortic stenosis patients have impaired strain in all three layers of the LV myocardium. LV strain analysis in aortic stenosis has been evaluated in different settings as noted in the following sections.
Severe aortic stenosis: global longitudinal strain (GLS) in a patient with severe aortic stenosis with an aortic valve area (AVA) of 1.1 cm2 maximal velocity (AV V2) of 3.9 m/s and a mean gradient of 48 mm Hg. Left ventricular end-diastolic and end-systolic volumes (EDV, ESV) are normal as well as the LV ejection fraction (EF). The GLS is normal at −20% indicating absence of any LV dysfunction.
Measuring LV ejection fraction is crucial in the management of patients with asymptomatic severe aortic stenosis (AS). According to the current American Heart Association/American College of Cardiology and European Society of Cardiology guidelines there is a Class I indication (Level of Evidence: B) to perform aortic valve intervention in asymptomatic patients with severe AS when the LVEF becomes <50% [7, 8]. Predictors of poor outcome in aortic stenosis include advanced age, significant leaflet calcification, rapid disease progression and decreased left ventricular (LV) ejection fraction (EF). Patients can develop impaired LVEF due to afterload mismatch or from true depression of myocardial contractility due to myocardial fibrosis. Myocardial fibrosis occurs early in the natural history of aortic stenosis, affecting diastolic and systolic function and offering a substrate for ventricular arrhythmias, playing a role in the progression to heart failure and sudden cardiac death. These observations indicate that current echocardiographic assessment of LV function by measuring only the LVEF is insufficient and that new parameters detecting subtle myocardial impairment are needed to improve risk stratification and predict outcomes in patients with AS.
Several studies have defined the added value of global longitudinal strain over LVEF to characterize and prognosticate the clinical evolution of patients with aortic stenosis:
There is growing evidence suggesting the prognostic role of global longitudinal strain (GLS), in asymptomatic patients with AS. The American Society of Echocardiography (ASE) on cardiac chamber quantification acknowledged the incremental value of LV GLS over traditional LVEF measurements, and recommended its clinical use in patients [9].
Conventional measures of LVEF can be preserved until end-stage disease due to the compensatory development of concentric hypertrophy, and thus lacks accuracy in identifying subtle changes in myocardial contractility [2].
Subclinical myocardial dysfunction with impaired LV GLS is frequently seen in patients with severe AS with preserved LVEF and no symptoms. Left ventricular global longitudinal strain deteriorates over time and impaired LV GLS at baseline is associated with an increased risk for progression to the symptomatic stage and the need for aortic valve surgery or intervention [10].
A relationship between aortic stenosis severity and alterations in LV deformation indices has been demonstrated in the following studies:
Strain and strain rate parameters relate to LV function and aortic stenosis severity. Further, they appear to be superior to tissue velocity and conventional echocardiography in detecting subtle changes in myocardial function after AVR before LV mass and LV function show improvement [11].
Despite unchanged LVEF, GLS gradually decreased as severity of AS increases. GLS measured by 2D-speckle tracking imaging might be useful to assess subtle changes in LV function in AS patients [12].
LV strain analysis has been demonstrated to provide prognostic information in patients with aortic stenosis:
A recent met analysis, including 1067 asymptomatic patients, with AS and preserved LVEF, showed that LVGLS is strongly associated with mortality, with >2.5-fold increase in risk of death in patients with impaired LVGLS (−14.7% or less) [13].
GLS detects subclinical dysfunction and has incremental prognostic value over traditional risk markers including hemodynamic severity, symptom class, and LVEF in patients with AS. Incorporation of GLS into risk models can improve the identification of the optimal timing for AV replacement [14].
Kusunose et al. [15] demonstrated on 395 patients that Longitudinal strain (LS) is independently associated with death in patients with AS and preserved LVEF, in addition they made the point that the flow/gradient pattern should also be considered as an important parameter. In the management of AS patients the use apical 4 chamber LS should be considered a new parameter of evaluation of LV function and prognosis [16].
LV GLS is independently associated with all-cause mortality in AS patients. It can further risk stratify severe AS patients and may influence the optimal timing of aortic valve replacement [2].
GLS is an independent predictor of all-cause mortality in severe AS, irrespective of their type of treatment. GLS <9.7% indicates a significantly higher 1- and 5-year mortality in non-AVR patients. Therefore, GLS should be regularly assessed for enhanced risk stratification and clinical decision-making [17].
In normal LVEF patients with significant aortic stenosis, brain natriuretic peptide (BNP) and LV-GLS provide incremental prognostic information over established predictors, suggesting that both play a synergistic role in defining outcomes [18].
A drop in LVGLS in bicuspid aortic valve (BAV) with preserved LVEF is not infrequent and was independently associated with increased risk of events (mainly aortic valve replacement events), as found by Kong et al. [19] in 513 patients (68% men; mean age 44 ± 18 years) with BAV and preserved LVEF (>50%).
Subclinical coronary artery disease is common in moderate and severe aortic stenosis, and should be suspected when regional longitudinal dysfunction is predominant in the apical and mid ventricular segments [20].
Sublayer strain analysis may add additional information in the characterization of LV function in patients with aortic stenosis. The following studies address this issue:
In severe AS, longitudinal strain impairment affects all three myocardial layers but is more noticeable in the endocardial layer. This becomes more manifest in the advanced phases of the disease when symptoms appear [21].
Bilayer strain ratio (subendocardial and subepicardial) can reliably differentiate patients with varying degrees of AS severity and is a sensitive marker of LV function. These findings suggest that the evaluation of subendocardial and subepicardial radial strain might be a novel method for assessing LV mechanics in patients with AS [22].
Medically treated patients with AS have worsening of GLS despite preserved LVEF, first appearing in the subendocardial layer. Global circumferential strain (GCS) becomes progressively impaired in moderate and severe AS. Improvement in LV strain after AVR is seen earlier with GLS than with GCS [23].
There is differential impairment in LV systolic strain in all three cardiac axes in patients with AS. Left ventricular longitudinal strain impairment is proportional to AS severity. Subendocardial longitudinal strain correlates better with AS severity than subepicardial longitudinal strain while correlations between circumferential and radial strain and AS severity are weak [24].
Compared with normal controls, severe aortic stenosis patients have impaired strain in all three layers of the LV myocardium [25].
Several studies have characterized the LV deformation indices in patients with low gradient aortic stenosis:
GLS is depressed in patients with paradoxic low flow (PLF) AS. This implies that subclinical myocardial dysfunction may be more prominent in PLF AS compared with normal-flow AS and suggests the possible diagnostic and prognostic value of two-dimensional global strain in identifying PLF AS [26].
In patients with low flow-low gradient aortic stenosis, 2-dimensional strain parameters are strong predictors of outcome. Peak longitudinal strain rate may add incremental prognostic value beyond what is obtained from N-terminal pro-B-type natriuretic peptide and peak stress left ventricular ejection fraction [27].
Sato et al. [28] demonstrated in 204 patients that longitudinal LV function is severely impaired in patients with paradoxical low-flow, low-gradient (LFLPG) AS and they have a poor prognosis. GLS could stratify the high-risk group for future adverse outcomes.
Patients with paradoxical low-flow severe aortic stenosis (PLF-AS) reportedly have higher left ventricular hydraulic load and more systolic strain dysfunction than patients with normal-flow aortic stenosis. Holmes et al. [29] investigated the relationship of systolic loading and strain to PLF-AS in 120 patients. Patients with PLF-AS were found to have more valvular load, lower energy loss coefficient, more arterial load and increased systemic vascular resistance and more total hydraulic load. They concluded that Increased hydraulic load, from more severe valvular stenosis and increased vascular resistance, and longitudinal strain impairment are associated with PLF-AS and their interplay is likely fundamental to its pathophysiology.
Dahou et al. [30] examined the impact of left ventricular (LV) global longitudinal strain (GLS) measured at rest and at dobutamine stress echocardiography on the outcome of 202 patients with low LV ejection fraction and low-gradient aortic stenosis. GLS was found to be independently associated with mortality in patients with low LV ejection fraction, low-gradient aortic stenosis. Stress GLS measured during dobutamine stress echocardiography provided incremental prognostic value beyond GLS measured at rest in these patients. Hence, these authors concluded that measurement of GLS at rest and during dobutamine stress echocardiography may be helpful to enhance risk stratification in low LV ejection fraction, low-gradient aortic stenosis.
In patients with LF-LG AS and low LVEF, reduced right ventricular longitudinal strain (RVLS) was found by Dahou et al. [31] to be independently associated with increased risk of mortality. Furthermore, stress RVLS provided incremental prognostic value beyond that obtained from rest RVLS. Thus, RVLS measurement at rest and with dobutamine stress may be helpful to enhance risk stratification in this high-risk population.
The added effect of hypertension in deformation indices abnormalities has been defined in the following studies:
Hypertension has significant negative effect on LV mechanics in patients with aortic stenosis. Blood pressure is associated with deterioration of LV global longitudinal and circumferential strains in aortic stenosis patients independently of clinical and demographic characteristics [32].
In AS, both the AS severity and concomitant hypertension attenuate radial tissue Doppler imaging strain in the inferior LV wall. The subendocardial radial strain is mainly influenced by AS severity, while midmyocardial radial strain is attenuated by both hypertension and AS severity [33].
The contributions of LV strain analysis in the surgical or interventional management of patients with aortic stenosis has been extensively documented. The following statements summarize the conclusions of several studies addressing the use of strain imaging as it relates to valve replacement or intervention in patients with aortic stenosis.
LV longitudinal systolic strain is depressed despite preserved LV ejection fraction and fractional shortening in AS. A significant association exists among natriuretic peptides, myocardial longitudinal contractility, and the degree of symptoms. Reverse LV remodeling after aortic valve replacement with regression of myocardial hypertrophy results in improvement of LV longitudinal myocardial strain and decrease of Nt-pro-BNP plasma levels. LV strain analysis has the potential to identify patients with asymptomatic AS who might benefit from earlier surgical intervention to preserve overall LV function [34].
In patients with symptomatic severe aortic stenosis undergoing aortic valve replacement, reduced GLS (Particularly in the setting of normal LVEF) provides important prognostic information beyond standard risk factors [35].
Shortly after balloon valvuloplasty for severe congenital AS, there is an improvement in systolic myocardial deformation. However, two-dimensional speckle-tracking echocardiographic parameters do not return to normal at 3-year follow-up. These abnormalities in systolic deformation cannot be fully attributed to residual stenosis or aortic regurgitation [36].
Marcus et al. [36] showed in 37 children that shortly after balloon valvuloplasty for severe congenital AS, there is an improvement in systolic myocardial deformation. However, two-dimensional speckle tracking echocardiography parameters do not return to normal at 3-year follow-up. These abnormalities in systolic deformation cannot be fully attributed to residual stenosis or aortic regurgitation.
Kafa et al. [37] evaluated 208 patients that underwent AVR for severe AS, measuring GLS pre and 12–24 months post AVR and found that in patients with severe aortic stenosis, approximately 20% of patients who survived more than 1 year after aortic valve replacement had an abnormal LV-GLS value on postoperative echocardiography, despite a preserved postoperative LVEF and demonstrable left ventricular mass regression. This finding was independently associated with adverse events, concluding that appropriately timed aortic valve replacement relieves left ventricular wall stress and prevents a decline in LVEF.
In asymptomatic/minimally symptomatic patients with severe bioprosthetic AS undergoing redo aortic valve replacement (AVR), baseline LV-GLS provides incremental prognostic value over established predictors and could potentially aid in surgical timing and risk stratification [38].
AVR reverses LA abnormalities and regains normal atrial function, a behavior which is directly related to the severity of preoperative LV outflow tract obstruction. Early identification of LA size enlargement and functional disturbances might contribute to better patient’s recruitment for AVR [39].
Speckle echocardiography analysis of left atrial (LA) myocardial deformation is considered a promising tool for the evaluation of LA subclinical dysfunction in patients undergoing AVR, giving a potentially better risk stratification for the occurrence of postoperative atrial fibrillation [40].
Gelsomino et al. [41] explored the influence of global longitudinal strain measured with two-dimensional speckle-tracking echocardiography on left ventricular mass regression (LVMR) in 83 patients with pure aortic stenosis (AS) and normal left ventricular function undergoing aortic valve replacement (AVR) and found that global longitudinal strain accurately predicts LV mass regression in patients with pure AS undergoing AVR.
In summary LV GLS can detect subclinical myocardial dysfunction in patients with severe aortic stenosis, and progressively worsens with increasing aortic stenosis severity. Impaired LV GLS is independently associated with increased mortality in high-gradient aortic stenosis, in low-flow, low-gradient severe aortic stenosis with preserved LVEF, and in low-flow, low-gradient severe aortic stenosis with reduced LVEF. Strain analysis of specific myocardial sublayers may add value to the evaluation of strain in aortic stenosis. Coronary artery disease and hypertension produce additional variables in strain analysis that need to be considered. Finally, there is increasing support for the use of strain imaging to determine the need and timing for aortic valve surgery or intervention in patients with aortic stenosis.
In contrast to aortic stenosis, aortic regurgitation (AR) generates LV volume overload with progressive LV dilatation, initially with preservation of LVEF and wall thickness (eccentric LV hypertrophy), but eventually with the development of LV systolic dysfunction expressed by a drop in LVEF (Figure 2). Several studies have described the value of strain imaging in the management of patients with aortic regurgitation. The results and conclusion statement of these studies are summarized in the following paragraphs:
In patient with AR, LV strain analysis can detect early subclinical myocardial dysfunction before the development of impaired LVEF. Using tissue Doppler imaging, Marciniak et al. [42] demonstrated that patients with severe AR had significant impairment of LV longitudinal strain, in contrast to patients with moderate AR where there was no difference with controls.
Smedsrud et al. [43] evaluated 47 AR patients and 31 controls with Longitudinal peak systolic strain rate and found they were significantly decreased in the patient’s population (P < 0.001). Global longitudinal peak systolic strain rate was also significantly decreased in aortic stenosis and regurgitation compared to the control group (−1 ± 0.5, −0.9 ± 0.3, and −1.6 ± 0.3, P = 0.001). As far as the comparison between patients with aortic stenosis and aortic regurgitation, neither global strain rate nor strain rate for each wall was found to be different. They concluded that there was reduced global longitudinal strain in patients with chronic AR with preserved LV ejection fractions. Global longitudinal strain might therefore disclose incipient myocardial dysfunction with a consequent potential for improved timing of aortic valve surgery.
Di Salvo et al. [44] evaluated 26 young patients (3-16 years) with asymptomatic AR and found LV average longitudinal strain to be significantly reduced in patients with progressive AR compared to those with stable AR (−17.8 ± 3.9% vs. −22.7 ± 2.7%, p = 0.001). On multivariate analysis, the only significant risk factor for progressive AR was average LV longitudinal strain (p = 0.04, cut-off value > −19.5%, sensitivity 77.8%, specificity 94.1%, area under the curve 0.889). These authors concluded that two-dimensional strain imaging can discriminate young asymptomatic patients with progressive AR. This could allow young patients with AR to have a better definition of surgical timing before the occurrence of irreversible myocardial damage.
Kaneko et al. [45] evaluated 36 chronic AR patients undergoing surgical correction and found, with the use of speckle-tracking strain imaging, that LV subendocardial dysfunction was present in patients with chronic severe AR and preserved EF, this improved after surgical correction.
Park et al. [46] evaluated 60 patients with chronic AR with LV global strain rate on apical four chamber image (GS-4CH). During 64 months follow-up duration, 16 patients (26.7%) were deceased and 38 patients (63.3%) underwent aortic valve replacement (AVR). Deceased group had lower longitudinal strain (−12.05 ± 3.72% vs. -15.66 ± 4.35%, p = 0.005). On multivariate analysis by cox proportional hazard model adjusting for age, sex, body surface area, history of atrial fibrillation, blood urea nitrogen, LV dilatation, LV ejection fraction and AVR, decreased GS-4CH proved to be an independent predictor of mortality in patients with chronic AR (hazard ratio 1.313, 95% confidence interval 1.010–1.706, p = 0.042). They concluded that GS-4CH may be a useful predictor of mortality in patient with chronic AR.
Alashi et al. [47] evaluated 1063 patients with asymptomatic severe chronic AR and preserved LVEF to examine the prognostic utility of left ventricular (LV) global longitudinal strain (GLS). A significantly higher proportion (log-rank p = 0.01) of patients with LV-GLS worse than median (−19.5%) died versus those with an LV-GLS better than median [86 of 513 (17%) vs. 60 of 550 (11%)]. The risk of death at 5 years significantly increased with an LV-GLS of worse than −19%. They concluded that in asymptomatic patients with ≥III+ chronic AR and preserved LVEF, worsening LV-GLS was associated with longer term mortality, providing incremental prognostic value and improved reclassification.
Alashi et al. [48] evaluated 865 patients with ≥3+ chronic AR and preserved LVEF undergoing AV surgery, a baseline LV-GLS value worse than −19% was associated with reduced survival. In a subgroup of patients who returned for 3- and 12-month postoperative follow-up examinations, persistently impaired LV-GLS was associated with increased mortality.
Severe aortic regurgitation: this patient had severe aortic regurgitation with normal LV end-diastolic and end-systolic volumes (EDV, ESV) and preserved systolic function as estimated by a normal LV ejection fraction (EF) of 68%; however, there is already evidence of insipient LV dysfunction as demonstrated by a mild drop in global longitudinal strain at −14%.
In summary, in patients with severe AR LV strain analysis detects early subclinical myocardial. Dysfunction before there is a drop in LVEF. This provides the potential for improving AVR/intervention timing. In addition GLS may be a useful predictor of mortality in AR patients by providing incremental prognostic value and improved reclassification. Finally, persistently impaired LVGLS in AR is associated with increased mortality.
Very little information has been published on the use of strain imaging in the management of patients with mixed aortic valve disease (Figure 3). The next paragraph summarizes the findings and conclusions in one study:
Longitudinal LV function is reduced in both pressure and volume overload, and both of this overload patterns are equally harmful to the ventricle. Gorgulu et al. [49] evaluated a total of 27 subjects with mixed aortic valve disease (53 ± 15 years). Fifteen healthy subjects (mean age 50 ± 6 years) were enrolled as the control group. Longitudinal peak systolic strain rate values of each segment derived from analysis of a total of 804 segments were significantly decreased in this patient population (P < 0.001). Global longitudinal peak systolic strain rate was also significantly decreased in aortic stenosis and regurgitation compared to the control group (−1 ± 0.5, −0.9 ± 0.3, and −1.6 ± 0.3, P = 0.001). As far as the comparison between patients with aortic stenosis and aortic regurgitation, neither global strain rate nor strain rate for each myocardial segment was found to be different.
Severe aortic stenosis and regurgitation: this example illustrates the presence of severe LV dysfunction as demonstrated by a marked drop of GLS to −6% despite a borderline drop of LV ejection fraction to 50%. The combination of severe aortic stenosis and regurgitation likely produces significant volume and pressure overload of the LV with significant LV dysfunction that is unmasked by strain analysis.
Although strain analysis is been used with increasing frequency for the evaluation of cardiac function, there are still issues with reproducibility of deformation analysis data, particularly when different echocardiography machines or analysis software is used. Until this issue is resolved the current recommendation is to use the same machine and software when obtaining comparative studies.
The fidelity of the strain data sets is dependent on the quality of the echocardiographic data, unfortunately endocardial contrast enhancing agents cannot be used during strain analysis, therefore strain analysis sometimes has to be obtained with substandard images. The current recommendation is not to report strain values if the echocardiographic images are of poor quality. Hopefully work-around solutions will be found to permit strain analysis with endocardial enhancement agents use.
The current literature supports actionable interventions according to fairly well-defined values of decreased LV ejection fraction, this is not as developed on the characterization of LV dysfunction according to levels of decreased strain values.
Although the literature on strain is fairly robust in aortic stenosis, it is only moderately developed in aortic regurgitation and almost not existent in mixed aortic valve disease.
Despite some of the shortcomings of strain analysis in aortic valve disease we have reviewed, we feel the added value this technique provides, justifies its use in the day to day imaging management of patients with diseases of the aortic valve. Our practice and recommendation is to characterize and sequentially follow global longitudinal strain in patients with moderate and severe aortic stenosis and/or moderate and severe aortic regurgitation. In asymptomatic patients with severe AS or AR and normal EF, the presence of an abnormal GLS should alert the clinician for the need of closer follow up or possibly aortic valve replacement/intervention.
The following studies highlight areas of study with high potential for development in the area of strain analysis in patients with aortic valve disease.
Broch et al. [50] studied, 31 patients with moderate to severe AR, 15 elite endurance athletes, and 17 healthy control subjects using three-dimensional speckle-tracking echocardiography. Global circumferential strain (GCS), global longitudinal strain (GLS), end-systolic circumferential wall stress (ESSc), end-systolic meridional wall stress (ESSm), and the wall stress ratio (ESSc/ESSm) were measured. LV end-diastolic volumes were similar in athletes and patients with AR and significantly larger than in healthy control subjects. Values of GLS in control subjects, athletes, and patients with AR were −18.8 ± 1.9%, −17.3 ± 2.0%, and −16.4± 2.0%, respectively (control subjects vs. athletes and patients, P < .05), whereas values of GCS were −16.9 ± 2.0%, −15.5 ± 1.9%, and −17.9 ± 2.6%, respectively (athletes vs. control subjects and patients, P < .01). The authors concluded that in compensated AR, relatively high GCS compensates for reduced GLS in a manner consistent with the preserved ejection fractions observed in these patients.
Uncovering post-exercise myocardial dysfunction in patients with asymptomatic AS with preserved left ventricular function can aid in risk assessment of these patients [51].
Left ventricular myocardial strain gradient using a novel multi-layer transthoracic echocardiography technique positively correlates with severity of aortic stenosis [23].
Early diastolic strain rate in relation to systolic and diastolic function and prognosis in aortic stenosis [52].
Preoperative left atrial strain predicts postoperative atrial fibrillation in patients undergoing aortic valve replacement for aortic stenosis [40].
Deformation imaging, particularly in the form of global longitudinal strain, has evolved as a powerful tool in the evaluation of ventricular function in patients with aortic valve disease. GLS is particularly suited to detect subclinical LV dysfunction, before a drop in LV ejection fraction, providing the opportunity to intervene earlier to prevent serious and permanent LV dysfunction. The role of GLS in the management of aortic stenosis is quite robust, illuminating nuances of LV dysfunction in aortic valve disease such as impact in severity of AS, prognosis, timing for surgery and interventions, low gradient aortic stenosis and presence of associated coronary artery disease, among others. Similar added value has been demonstrated in the application of GLS in the detection of subclinical LV dysfunction in patients with aortic regurgitation. Very little information exists in the use of GLS in patients with mixed aortic valve disease providing an opportunity for future research in this important group of patients with aortic valve disease.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. 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From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. 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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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Generally, the phytochemical constituents of plants fall into two categories based on their role in basic metabolic processes, namely primary and secondary metabolites. Primary plant metabolites are involved in basic life functions; therefore, they are more or less similar in all living cells. On the other hand, secondary plant metabolites are products of subsidiary pathways as the shikimic acid pathway. In the course of studying, the medicinal effect of herbals is oriented towards the secondary plant metabolites. Secondary plant metabolites played an important role in alleviating several aliments in the traditional medicine and folk uses. In modern medicine, they provided lead compounds for the production of medications for treating various diseases from migraine up to cancer. Secondary plant metabolites are classified according to their chemical structures into various classes. In this chapter, we will be presenting various classes of secondary plant metabolites, their distribution in different plant families and their important medicinal uses.",book:{id:"6302",slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Rehab A. Hussein and Amira A. El-Anssary",authors:[{id:"212117",title:"Dr.",name:"Rehab",middleName:null,surname:"Hussein",slug:"rehab-hussein",fullName:"Rehab Hussein"},{id:"221140",title:"Dr.",name:"Amira",middleName:null,surname:"El-Anssary",slug:"amira-el-anssary",fullName:"Amira El-Anssary"}]},{id:"64851",doi:"10.5772/intechopen.80348",title:"Herbal Medicines in African Traditional Medicine",slug:"herbal-medicines-in-african-traditional-medicine",totalDownloads:14206,totalCrossrefCites:30,totalDimensionsCites:52,abstract:"African traditional medicine is a form of holistic health care system organized into three levels of specialty, namely divination, spiritualism, and herbalism. The traditional healer provides health care services based on culture, religious background, knowledge, attitudes, and beliefs that are prevalent in his community. Illness is regarded as having both natural and supernatural causes and thus must be treated by both physical and spiritual means, using divination, incantations, animal sacrifice, exorcism, and herbs. Herbal medicine is the cornerstone of traditional medicine but may include minerals and animal parts. The adjustment is ok, but may be replaced with –‘ Herbal medicine was once termed primitive by western medicine but through scientific investigations there is a better understanding of its therapeutic activities such that many pharmaceuticals have been modeled on phytochemicals derived from it. Major obstacles to the use of African medicinal plants are their poor quality control and safety. Traditional medical practices are still shrouded with much secrecy, with few reports or documentations of adverse reactions. However, the future of African traditional medicine is bright if viewed in the context of service provision, increase of health care coverage, economic potential, and poverty reduction. Formal recognition and integration of traditional medicine into conventional medicine will hold much promise for the future.",book:{id:"6302",slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Ezekwesili-Ofili Josephine Ozioma and Okaka Antoinette Nwamaka\nChinwe",authors:[{id:"191264",title:"Prof.",name:"Josephine",middleName:"Ozioma",surname:"Ezekwesili-Ofili",slug:"josephine-ezekwesili-ofili",fullName:"Josephine Ezekwesili-Ofili"},{id:"211585",title:"Prof.",name:"Antoinette",middleName:null,surname:"Okaka",slug:"antoinette-okaka",fullName:"Antoinette Okaka"}]},{id:"54028",doi:"10.5772/67291",title:"Chemical Composition and Biological Activities of Mentha Species",slug:"chemical-composition-and-biological-activities-of-mentha-species",totalDownloads:7474,totalCrossrefCites:13,totalDimensionsCites:46,abstract:"The genus Mentha L. (Lamiaceae) is distributed all over the world and can be found in many environments. Mentha species, one of the world’s oldest and most popular herbs, are widely used in cooking, in cosmetics, and as alternative or complementary therapy, mainly for the treatment of gastrointestinal disorders like flatulence, indigestion, nausea, vomiting, anorexia, and ulcerative colitis. Furthermore, it is well documented that the essential oil and extracts of Mentha species possess antimicrobial, fungicidal, antiviral, insecticidal, and antioxidant properties. The economic importance of mints is also evident; mint oil and its constituents and derivatives are used as flavoring agents throughout the world in food, pharmaceutical, herbal, perfumery, and flavoring industry. To provide a scientific basis for their traditional uses, several studies have been conducted to determine the chemical composition of mints and assess their biological activities. This chapter describes the therapeutic effects and uses of Mentha species and their constituents, particularly essential oils and phenolic compounds; some additional biological activities will also be considered.",book:{id:"5612",slug:"aromatic-and-medicinal-plants-back-to-nature",title:"Aromatic and Medicinal Plants",fullTitle:"Aromatic and Medicinal Plants - Back to Nature"},signatures:"Fatiha Brahmi, Madani Khodir, Chibane Mohamed and Duez Pierre",authors:[{id:"193281",title:"Dr.",name:"Fatiha",middleName:null,surname:"Brahmi",slug:"fatiha-brahmi",fullName:"Fatiha Brahmi"},{id:"199693",title:"Prof.",name:"Khodir",middleName:null,surname:"Madani",slug:"khodir-madani",fullName:"Khodir Madani"},{id:"199694",title:"Prof.",name:"Pierre",middleName:null,surname:"Duez",slug:"pierre-duez",fullName:"Pierre Duez"},{id:"203738",title:"Prof.",name:"Mohamed",middleName:null,surname:"Chibane",slug:"mohamed-chibane",fullName:"Mohamed Chibane"}]},{id:"58270",doi:"10.5772/intechopen.72437",title:"Toxicity and Safety Implications of Herbal Medicines Used in Africa",slug:"toxicity-and-safety-implications-of-herbal-medicines-used-in-africa",totalDownloads:3376,totalCrossrefCites:16,totalDimensionsCites:39,abstract:"The use of herbal medicines has seen a great upsurge globally. In developing countries, many patronize them largely due to cultural acceptability, availability and cost. In developed countries, they are used because they are natural and therefore assumed to be safer than allopathic medicines. In recent times, however, there has been a growing concern about their safety. This has created a situation of ambivalence in discussions regarding their use. Some medicinal plants are intrinsically toxic by virtue of their constituents and can cause adverse reactions if inappropriately used. Other factors such as herb-drug interactions, lack of adherence to good manufacturing practice (GMP), poor regulatory measures and adulteration may also lead to adverse events in their use. Many in vivo tests on aqueous extracts largely support the safety of herbal medicines, whereas most in vitro tests on isolated single cells mostly with extracts other than aqueous ones show contrary results and thus continue the debate on herbal medicine safety. It is expected that toxicity studies concerning herbal medicine should reflect their traditional use to allow for rational discussions regarding their safety for their beneficial use. While various attempts continue to establish the safety of various herbal medicines in man, their cautious and responsible use is required.",book:{id:"6302",slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Merlin L.K. Mensah, Gustav Komlaga, Arnold D. Forkuo, Caleb\nFirempong, Alexander K. Anning and Rita A. Dickson",authors:[{id:"190435",title:"Dr.",name:"Caleb",middleName:null,surname:"Firempong",slug:"caleb-firempong",fullName:"Caleb Firempong"},{id:"212111",title:"Dr.",name:"Gustav",middleName:null,surname:"Komlaga",slug:"gustav-komlaga",fullName:"Gustav Komlaga"},{id:"217045",title:"Dr.",name:"Arnold Forkuo",middleName:null,surname:"Donkor",slug:"arnold-forkuo-donkor",fullName:"Arnold Forkuo Donkor"},{id:"217049",title:"Prof.",name:"Merlin Lincoln Kwao",middleName:null,surname:"Mensah",slug:"merlin-lincoln-kwao-mensah",fullName:"Merlin Lincoln Kwao Mensah"},{id:"217488",title:"Dr.",name:"Alexander K.",middleName:null,surname:"Anning",slug:"alexander-k.-anning",fullName:"Alexander K. Anning"},{id:"223959",title:"Prof.",name:"Akosua Rita",middleName:null,surname:"Dickson",slug:"akosua-rita-dickson",fullName:"Akosua Rita Dickson"}]},{id:"26489",doi:"10.5772/28224",title:"Alternative and Traditional Medicines Systems in Pakistan: History, Regulation, Trends, Usefulness, Challenges, Prospects and Limitations",slug:"alternative-and-traditional-medicines-systems-in-pakistan-history-regulation-trends-usefulness-chall",totalDownloads:9199,totalCrossrefCites:9,totalDimensionsCites:21,abstract:null,book:{id:"542",slug:"a-compendium-of-essays-on-alternative-therapy",title:"A Compendium of Essays on Alternative Therapy",fullTitle:"A Compendium of Essays on Alternative Therapy"},signatures:"Shahzad Hussain, Farnaz Malik, Nadeem Khalid, Muhammad Abdul Qayyum and Humayun Riaz",authors:[{id:"73162",title:"Dr.",name:"Shahzad",middleName:null,surname:"Hussain",slug:"shahzad-hussain",fullName:"Shahzad Hussain"},{id:"82266",title:"Dr.",name:"Farnaz",middleName:null,surname:"Malik",slug:"farnaz-malik",fullName:"Farnaz Malik"},{id:"124185",title:"Dr.",name:"Humayun",middleName:null,surname:"Riaz",slug:"humayun-riaz",fullName:"Humayun Riaz"},{id:"124186",title:"Mr.",name:"Muhammad Abdul",middleName:null,surname:"Qayyum",slug:"muhammad-abdul-qayyum",fullName:"Muhammad Abdul Qayyum"},{id:"125340",title:"Mr.",name:"Nadeem",middleName:null,surname:"Khalid",slug:"nadeem-khalid",fullName:"Nadeem Khalid"}]}],mostDownloadedChaptersLast30Days:[{id:"64851",title:"Herbal Medicines in African Traditional Medicine",slug:"herbal-medicines-in-african-traditional-medicine",totalDownloads:14207,totalCrossrefCites:30,totalDimensionsCites:52,abstract:"African traditional medicine is a form of holistic health care system organized into three levels of specialty, namely divination, spiritualism, and herbalism. The traditional healer provides health care services based on culture, religious background, knowledge, attitudes, and beliefs that are prevalent in his community. Illness is regarded as having both natural and supernatural causes and thus must be treated by both physical and spiritual means, using divination, incantations, animal sacrifice, exorcism, and herbs. Herbal medicine is the cornerstone of traditional medicine but may include minerals and animal parts. The adjustment is ok, but may be replaced with –‘ Herbal medicine was once termed primitive by western medicine but through scientific investigations there is a better understanding of its therapeutic activities such that many pharmaceuticals have been modeled on phytochemicals derived from it. Major obstacles to the use of African medicinal plants are their poor quality control and safety. Traditional medical practices are still shrouded with much secrecy, with few reports or documentations of adverse reactions. However, the future of African traditional medicine is bright if viewed in the context of service provision, increase of health care coverage, economic potential, and poverty reduction. Formal recognition and integration of traditional medicine into conventional medicine will hold much promise for the future.",book:{id:"6302",slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Ezekwesili-Ofili Josephine Ozioma and Okaka Antoinette Nwamaka\nChinwe",authors:[{id:"191264",title:"Prof.",name:"Josephine",middleName:"Ozioma",surname:"Ezekwesili-Ofili",slug:"josephine-ezekwesili-ofili",fullName:"Josephine Ezekwesili-Ofili"},{id:"211585",title:"Prof.",name:"Antoinette",middleName:null,surname:"Okaka",slug:"antoinette-okaka",fullName:"Antoinette Okaka"}]},{id:"61866",title:"Plants Secondary Metabolites: The Key Drivers of the Pharmacological Actions of Medicinal Plants",slug:"plants-secondary-metabolites-the-key-drivers-of-the-pharmacological-actions-of-medicinal-plants",totalDownloads:8875,totalCrossrefCites:56,totalDimensionsCites:140,abstract:"The vast and versatile pharmacological effects of medicinal plants are basically dependent on their phytochemical constituents. Generally, the phytochemical constituents of plants fall into two categories based on their role in basic metabolic processes, namely primary and secondary metabolites. Primary plant metabolites are involved in basic life functions; therefore, they are more or less similar in all living cells. On the other hand, secondary plant metabolites are products of subsidiary pathways as the shikimic acid pathway. In the course of studying, the medicinal effect of herbals is oriented towards the secondary plant metabolites. Secondary plant metabolites played an important role in alleviating several aliments in the traditional medicine and folk uses. In modern medicine, they provided lead compounds for the production of medications for treating various diseases from migraine up to cancer. Secondary plant metabolites are classified according to their chemical structures into various classes. In this chapter, we will be presenting various classes of secondary plant metabolites, their distribution in different plant families and their important medicinal uses.",book:{id:"6302",slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Rehab A. Hussein and Amira A. El-Anssary",authors:[{id:"212117",title:"Dr.",name:"Rehab",middleName:null,surname:"Hussein",slug:"rehab-hussein",fullName:"Rehab Hussein"},{id:"221140",title:"Dr.",name:"Amira",middleName:null,surname:"El-Anssary",slug:"amira-el-anssary",fullName:"Amira El-Anssary"}]},{id:"77433",title:"Extraction of Bioactive Compounds from Medicinal Plants and Herbs",slug:"extraction-of-bioactive-compounds-from-medicinal-plants-and-herbs",totalDownloads:1266,totalCrossrefCites:2,totalDimensionsCites:5,abstract:"Human beings have relied on herbs and medicinal plants as sources of food and remedy from time immemorial. Bioactive compounds from plants are currently the subject of much research interest, but their extraction as part of phytochemical and/or biological investigations present specific challenges. Herbalists or scientists have developed many protocols of extraction of bioactive ingredients to ensure the effectiveness and the efficacy of crude drugs that were used to get relief from sickness. With the advent of new leads from plants such as morphine, quinine, taxol, artemisinin, and alkaloids from Voacanga species, a lot of attention is paid to the mode of extraction of active phytochemicals to limit the cost linked to the synthesis and isolation. Thus, the extraction of active compounds from plants needs appropriate extraction methods and techniques that provide bioactive ingredients-rich extracts and fractions. The extraction procedures, therefore, play a critical role in the yield, the nature of phytochemical content, etc. This chapter aims to present, describe, and compare extraction procedures of bioactive compounds from herbs and medicinal plants.",book:{id:"10356",slug:"natural-medicinal-plants",title:"Natural Medicinal Plants",fullTitle:"Natural Medicinal Plants"},signatures:"Fongang Fotsing Yannick Stéphane, Bankeu Kezetas Jean Jules, Gaber El-Saber Batiha, Iftikhar Ali and Lenta Ndjakou Bruno",authors:[{id:"224515",title:"Dr.",name:"Fongang Fotsing",middleName:null,surname:"Yannick Stéphane",slug:"fongang-fotsing-yannick-stephane",fullName:"Fongang Fotsing Yannick Stéphane"},{id:"227816",title:"Dr.",name:"Bankeu Kezetas",middleName:null,surname:"Jean Jules",slug:"bankeu-kezetas-jean-jules",fullName:"Bankeu Kezetas Jean Jules"},{id:"227817",title:"Prof.",name:"Lenta Ndjakou",middleName:null,surname:"Bruno",slug:"lenta-ndjakou-bruno",fullName:"Lenta Ndjakou Bruno"},{id:"349790",title:"Prof.",name:"Gaber",middleName:null,surname:"El-Saber Batiha",slug:"gaber-el-saber-batiha",fullName:"Gaber El-Saber Batiha"},{id:"357350",title:"Dr.",name:"Iftikhar",middleName:null,surname:"Ali",slug:"iftikhar-ali",fullName:"Iftikhar Ali"}]},{id:"26491",title:"Homeopathy: Treatment of Cancer with the Banerji Protocols",slug:"homeopathy-treatment-of-cancer-with-the-banerji-protocols",totalDownloads:54048,totalCrossrefCites:1,totalDimensionsCites:2,abstract:null,book:{id:"542",slug:"a-compendium-of-essays-on-alternative-therapy",title:"A Compendium of Essays on Alternative Therapy",fullTitle:"A Compendium of Essays on Alternative Therapy"},signatures:"Prasanta Banerji and Pratip Banerji",authors:[{id:"79939",title:"Dr",name:"Prasanta",middleName:null,surname:"Banerji",slug:"prasanta-banerji",fullName:"Prasanta Banerji"},{id:"79943",title:"Dr.",name:"Pratip",middleName:null,surname:"Banerji",slug:"pratip-banerji",fullName:"Pratip Banerji"}]},{id:"54028",title:"Chemical Composition and Biological Activities of Mentha Species",slug:"chemical-composition-and-biological-activities-of-mentha-species",totalDownloads:7474,totalCrossrefCites:13,totalDimensionsCites:46,abstract:"The genus Mentha L. (Lamiaceae) is distributed all over the world and can be found in many environments. Mentha species, one of the world’s oldest and most popular herbs, are widely used in cooking, in cosmetics, and as alternative or complementary therapy, mainly for the treatment of gastrointestinal disorders like flatulence, indigestion, nausea, vomiting, anorexia, and ulcerative colitis. Furthermore, it is well documented that the essential oil and extracts of Mentha species possess antimicrobial, fungicidal, antiviral, insecticidal, and antioxidant properties. The economic importance of mints is also evident; mint oil and its constituents and derivatives are used as flavoring agents throughout the world in food, pharmaceutical, herbal, perfumery, and flavoring industry. To provide a scientific basis for their traditional uses, several studies have been conducted to determine the chemical composition of mints and assess their biological activities. This chapter describes the therapeutic effects and uses of Mentha species and their constituents, particularly essential oils and phenolic compounds; some additional biological activities will also be considered.",book:{id:"5612",slug:"aromatic-and-medicinal-plants-back-to-nature",title:"Aromatic and Medicinal Plants",fullTitle:"Aromatic and Medicinal Plants - Back to Nature"},signatures:"Fatiha Brahmi, Madani Khodir, Chibane Mohamed and Duez Pierre",authors:[{id:"193281",title:"Dr.",name:"Fatiha",middleName:null,surname:"Brahmi",slug:"fatiha-brahmi",fullName:"Fatiha Brahmi"},{id:"199693",title:"Prof.",name:"Khodir",middleName:null,surname:"Madani",slug:"khodir-madani",fullName:"Khodir Madani"},{id:"199694",title:"Prof.",name:"Pierre",middleName:null,surname:"Duez",slug:"pierre-duez",fullName:"Pierre Duez"},{id:"203738",title:"Prof.",name:"Mohamed",middleName:null,surname:"Chibane",slug:"mohamed-chibane",fullName:"Mohamed Chibane"}]}],onlineFirstChaptersFilter:{topicId:"991",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:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:106,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:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{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"}}}},{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"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"June 11th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). In addition to a number of research articles, he has written two books, Computational Intelligence: An Introduction and Fundamentals of Computational Swarm Intelligence.",institutionString:null,institution:{name:"Stellenbosch University",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",isOpenForSubmission:!0,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. 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In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"26",title:"Machine Learning and Data Mining",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",isOpenForSubmission:!0,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. 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Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,series:{id:"11",title:"Biochemistry"}}},seriesLanding:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"June 29th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:318,numberOfPublishedBooks:32,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",fullName:"Abdulsamed Kükürt",profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",institutionString:null,institution:{name:"Kafkas University",institutionURL:null,country:{name:"Turkey"}}},{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/110940",hash:"",query:{},params:{id:"110940"},fullPath:"/profiles/110940",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()