Advantages and disadvantages of various types of MIS in Gynecology.
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
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In addition, composite processes aimed at strengthening the metal and polymeric materials for various environmental conditions have been incorporated, while advances in the extraction process for purification of tri-n-butyl phosphate (TBP)/inositol hexaphosphate (IP6) have been discussed in detail.",isbn:"978-1-83962-957-0",printIsbn:"978-1-83962-956-3",pdfIsbn:"978-1-83962-964-8",doi:"10.5772/intechopen.87885",price:119,priceEur:129,priceUsd:155,slug:"material-flow-analysis",numberOfPages:112,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"79b0d74806f8e2b5104b9b3aa283c92b",bookSignature:"Sanjeev Kumar",publishedDate:"September 29th 2021",coverURL:"https://cdn.intechopen.com/books/images_new/10055.jpg",numberOfDownloads:1380,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:0,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"July 1st 2020",dateEndSecondStepPublish:"July 22nd 2020",dateEndThirdStepPublish:"September 20th 2020",dateEndFourthStepPublish:"December 9th 2020",dateEndFifthStepPublish:"February 7th 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"296040",title:"Dr.",name:"Sanjeev",middleName:null,surname:"Kumar",slug:"sanjeev-kumar",fullName:"Sanjeev Kumar",profilePictureURL:"https://mts.intechopen.com/storage/users/296040/images/system/296040.jpg",biography:"Dr. Sanjeev Kumar has been working as an assistant professor in the Department of Mechanical Engineering at the National Institute of Technology, Raipur, India, since August 2021. Prior to this position, he served as Senior Researcher at CDL-IPE, Technical University of Vienna, Austria, from June 2018 to July 2021. Dr, Kumar also served as a Postdoc Researcher on the FWF project at IMAT, TU Graz, Austria, from May 2017–April 2018. He obtained his Ph.D. and MTech degrees in Welding Metallurgy from IIT Roorkee, India, while also obtaining a BTech in Mechanical Engineering from AKGEC-GZB UPTU, Lucknow, India. His primary research interest is welding, thermomechanical processing, and material design. He has published one book and more than thirty-eight research papers in recognized international journals, conferences, and books.",institutionString:"National Institute of Technology Raipur",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"TU Wien",institutionURL:null,country:{name:"Austria"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"14",title:"Materials Science",slug:"materials-science"}],chapters:[{id:"76839",title:"Plastic Deformation Behavior in Steels during Metal Forming Processes: A Review",doi:"10.5772/intechopen.97607",slug:"plastic-deformation-behavior-in-steels-during-metal-forming-processes-a-review",totalDownloads:408,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The plastic deformation occurs in steels during metal forming processing such as rolling, forging, high-pressure torsion, etc. which modify mechanical properties of materials through the grain refinement, and the shape change of objects. Several phenomena in the scope of plastic deformation, such as hardening, recovery, and recrystallization are of great importance in designing thermomechanical processing. During the last decades, a focus of research groups has been devoted particularly to the field of metals processing of steel parts through plastic deformation combined with specific heat treatment conditions. In this review chapter, the current status of research work on the role of plastic deformation during manufacturing is illuminated.",signatures:"Sanjeev Kumar and Erwin Povoden-Karadeniz",downloadPdfUrl:"/chapter/pdf-download/76839",previewPdfUrl:"/chapter/pdf-preview/76839",authors:[{id:"296040",title:"Dr.",name:"Sanjeev",surname:"Kumar",slug:"sanjeev-kumar",fullName:"Sanjeev Kumar"},{id:"328965",title:"Prof.",name:"Erwin",surname:"Povoden-Karadeniz",slug:"erwin-povoden-karadeniz",fullName:"Erwin Povoden-Karadeniz"}],corrections:null},{id:"74159",title:"Explosive Welding Process to Clad Materials with Dissimilar Metallurgical Properties",doi:"10.5772/intechopen.94448",slug:"explosive-welding-process-to-clad-materials-with-dissimilar-metallurgical-properties",totalDownloads:114,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Explosive welding is a solid-state process, which is an advanced form of joining two metal plates with dissimilar metallurgical properties, irrespective of the differences in physical and chemical properties. In this process, high pressure of explosive is used to accelerate one metal plate over another to form the bimetallic product. The pressure needs to be sufficiently high and for enough length of time to achieve inter-atomic bonds. During the explosive welding process, a jetting phenomenon occurs at the collision point which cleans the top oxide layer over metals and leaves the virgin surfaces that help in the joining process. The metals are joined without losing their pre-bonded properties with higher bond strengths than the strength of the weaker parent material. There are various critical factors such as explosive type, mass of explosive, stand-off distance, type of plate material, velocity of detonation etc. which affect the bond quality. Researchers mainly play with all these parameters to bring out the best characteristics of the bimetallic product that can be used for the desired applications such as heat exchanger, pressure vessels etc.",signatures:"Bir Bahadur Sherpa and Reetu Rani",downloadPdfUrl:"/chapter/pdf-download/74159",previewPdfUrl:"/chapter/pdf-preview/74159",authors:[{id:"327230",title:null,name:"Bir Bahadur",surname:"Sherpa",slug:"bir-bahadur-sherpa",fullName:"Bir Bahadur Sherpa"},{id:"331924",title:"Ms.",name:"Reetu",surname:"Rani",slug:"reetu-rani",fullName:"Reetu Rani"}],corrections:null},{id:"73621",title:"Influence of Annealed Aluminum Properties on Adhesion Bonding of Cold Sprayed Titanium Dioxide Coating",doi:"10.5772/intechopen.94097",slug:"influence-of-annealed-aluminum-properties-on-adhesion-bonding-of-cold-sprayed-titanium-dioxide-coati",totalDownloads:248,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"It is well known that cold spraying ceramic materials can be difficult because cold spraying requires plastic deformation of the feedstock particles for adhesion to the substrate. The challenge lies in the difficulty of plastically deforming hard and brittle ceramic materials, such as TiO2. Previous studies have reported the possibility of cold spraying thick pure TiO2 but the bonding mechanism of cold sprayed TiO2 is not fully understood. The factor like substrate condition as oxide film thickness and mechanical properties may also affect cold spray deposition but not fully understood in cold spraying ceramic. The aim of the present research is to investigate the correlation between the oxide thickness and substrate deformation with the adhesion strength of cold-sprayed TiO2 coatings toward the bonding mechanism involved. Relevant experiments were executed using Al 1050, subjected to various annealing temperatures and cold-sprayed with TiO2 powder. The results indicate a decreasing trend of coating adhesion strength with increasing annealed substrate temperature from room temperature to 400°C annealed. Metallurgical bonding is pronounced as bonding mechanism involved between TiO2 particle and annealed 1050 substrate.",signatures:"Noor Irinah Omar, Motohiro Yamada, Toshiaki Yasui and Masahiro Fukumoto",downloadPdfUrl:"/chapter/pdf-download/73621",previewPdfUrl:"/chapter/pdf-preview/73621",authors:[{id:"327297",title:"Ph.D. Student",name:"Noor Irinah",surname:"Omar",slug:"noor-irinah-omar",fullName:"Noor Irinah Omar"}],corrections:null},{id:"75852",title:"Anisotropic Mechanical Properties of 2-D Materials",doi:"10.5772/intechopen.96598",slug:"anisotropic-mechanical-properties-of-2-d-materials",totalDownloads:257,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"While prior reviews and research articles focused on the various synthetic routes and microstructural controls of 2D nanomaterials as well as their functional applications, this chapter discloses the anisotropic behaviors of 2D materials and puts emphasis on the mechanical anisotropy of three distinct 2D materials, namely graphene, MoS2 and Al alloy coating, representative of carbon, inorganic and metallic 2D crystalline materials. Except for the relatively low interlayer cohesive stress, the in-plane anisotropy of the former two materials classes is subjected primarily to the hexagonal structure of the unit cells of the graphene and MoS2. The anisotropy of metallic thin films with high-density grain boundaries with preferential directionality, rendered by the non-equilibrium synthetic methods, results from both the conventional Taylor factor and the directionality of the grain boundaries. Despite 2D materials’ wide spectrum of applications, such as electronics, energy devices, sensors, coating etc., the mechanical anisotropy could be critical for certain mechanical applications, such as friction, and provide instructions on the durability, reliability and property optimization in the various applications of different 2D materials.",signatures:"Qiang Li",downloadPdfUrl:"/chapter/pdf-download/75852",previewPdfUrl:"/chapter/pdf-preview/75852",authors:[{id:"336293",title:"Dr.",name:"Qiang",surname:"Li",slug:"qiang-li",fullName:"Qiang Li"}],corrections:null},{id:"76597",title:"Development of LDPE Crystallinity in LDPE/Cu Composites",doi:"10.5772/intechopen.97725",slug:"development-of-ldpe-crystallinity-in-ldpe-cu-composites",totalDownloads:220,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter summarizes the study of the filler (ie copper) effect on LDPE phasic composition in LDPE/Cu composites prepared in solution. During this research work, a particular effort is focused on the use of DSC under non-standard conditions. Therewith, the presence of copper microparticles has a great effect on the network phase than on the crystalline long-range-order phase of LDPE structure. Furthermore, LDPE phasic composition in absence and presence of copper microparticles is investigated by FTIR spectroscopy followed by a spectral simulation of the band that appeared at 720 cm−1 corresponding to the CH2. Anywise, the two-phase model confirmed that no variation is observed of LDPE phase composition for all copper contents into LDPE/Cu films. However, with the three-phase model the orthorhombic phase fraction was found to be constant compared to the fraction of amorphous and that of network phase were found to increase and decrease respectively with increase in the copper particle load in the film. Overall, the thermal and structural behavior of LDPE in presence of copper particles allows this type to be used as phase change materials (PCMs) by adding a paraffin fraction in the LDPE/Cu composite. An update of the most relevant work carried out in the field of phasic characterization of polyethylene is presented in this chapter.",signatures:"Makki Abdelmouleh and Ilyes Jedidi",downloadPdfUrl:"/chapter/pdf-download/76597",previewPdfUrl:"/chapter/pdf-preview/76597",authors:[{id:"337600",title:"Prof.",name:"Abdmouleh",surname:"Makki",slug:"abdmouleh-makki",fullName:"Abdmouleh Makki"},{id:"337825",title:"Dr.",name:"Ilyes",surname:"Jedidi",slug:"ilyes-jedidi",fullName:"Ilyes Jedidi"}],corrections:null},{id:"76005",title:"Study of the Equilibrium of Nitric Acid with a Solution of TBP/IP6",doi:"10.5772/intechopen.96992",slug:"study-of-the-equilibrium-of-nitric-acid-with-a-solution-of-tbp-ip6",totalDownloads:133,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The behavior of the tri-n-butylphosphate (TBP) for a Liquid–liquid extraction (LLE) system is well known. To establish a new LLE system, the calculation of the equilibrium to establish an extraction system of TBP and inositol hexaphosphate (IP6) needs to be done. First, the change in the activity coefficient of TBP/IP6 related to the activity of water and TBP/IP6 concentration in the H2O–TBP/IP6–dodecane system, then the degradation of nitric acid in the system should be evaluated to assess the equilibrium. The proposed system consists of a solution of 30% of TBP and 10% of IP6 in nitric acid and dodecane. As main results, we discussed the value of the dissociation degree of nitric acid, the molar and volumetric fractions, the molar activity of the organic and aqueous phases and activities coefficients.",signatures:"Munoz Ayala Israel and Vera Roberto Carlos",downloadPdfUrl:"/chapter/pdf-download/76005",previewPdfUrl:"/chapter/pdf-preview/76005",authors:[{id:"319219",title:"Dr.",name:"Vera",surname:"Roberto Carlos",slug:"vera-roberto-carlos",fullName:"Vera Roberto Carlos"},{id:"320981",title:"Dr.",name:"Muñoz",surname:"Ayala Israel",slug:"munoz-ayala-israel",fullName:"Muñoz Ayala Israel"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"6320",title:"Advances in Glass Science and Technology",subtitle:null,isOpenForSubmission:!1,hash:"6d0a32a0cf9806bccd04101a8b6e1b95",slug:"advances-in-glass-science-and-technology",bookSignature:"Vincenzo M. 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\r\n\tThis book deals with three hot topics related to the synthesis, applications, and technologies of carbon nitride. The introductory chapter deals with the synthesis and Photocatalytic properties of graphitic carbon nitride. The other chapters will cover many topics, such as Graphitic carbon nitride for high capacity hydrogen storage and synthesis and characterization of carbon nitride as coating and activation materials for organic pollutants degradation. In addition, the book will cover, Nano Composites of graphitic carbon nitride for luminescence and photocatalytic applications, Graphitic carbon nitride as catalyst support in fuel cells and water electrolyzers, and Graphitic carbon nitride composite as semiconductors and photocatalytic fibers. The new approaches such as graphitic carbon nitride-based nanocomposites, graphitic carbon nitride from melamine and uric acid, and synthesis of metal-free ultrathin graphitic carbon nitride sheet will be the synthesis for photocatalytic degradation of organic dyes. This book will encourage readers, researchers, and scientists to look further into the frontier topics of carbon nitride and open new possible research paths for further novel development.
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He is a permanent member of the American Chemical Society and member of the Arab Society of Forensic Sciences and Forensic Medicine.",coeditorOneBiosketch:"Dr. Saleh S. Alarfaji is the chairman of the chemistry department at King Khalid University (KKU). He got his MSc in computational chemistry from Murray State University (MSU, USA) and Ph.D. from the University of Nottingham.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"145209",title:"Prof.",name:"Nasser",middleName:"S",surname:"Awwad",slug:"nasser-awwad",fullName:"Nasser Awwad",profilePictureURL:"https://mts.intechopen.com/storage/users/145209/images/system/145209.jpg",biography:"Dr. Nasser Awwad received his Ph.D. in inorganic and radiochemistry in 2000 from Ain Shams University . Nasser Awwad was an Associate Professor of Radiochemistry in 2006 and Professor of Inorganic and Radiochemistry in 2011. He has been a Professor at King Khalid University, Abha, KSA, from 2011 until now. Prof Awwad has edited four books (Uranium, New trends in Nuclear Sciences, Lanthanides, and Nuclear Power Plants) and he has co-edited two books (Chemistry and Technology of Natural and Synthetic Dyes and Pigments and Biochemical Analysis Tools). He has also published 137 papers at ISI journals. He has supervised 4 Ph.D. and 18 MSc students in the field of radioactive and wastewater treatment. He has participated in 26 international conferences in South Korea, the USA, Lebanon, KSA, and Egypt. He has reviewed 2 Ph.D. and 15 MSc theses. He participated in 6 big projects with KACST at KSA and Sandia National Labs in the USA. He is a member of the Arab Society of Forensic Sciences and Forensic Medicine. He is a permanent member of the American Chemical Society, and a rapporteur of the Permanent Committee for Nuclear and Radiological Protection at KKU. 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From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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The major change and innovation of this surgery was to entry inside the abdomen avoiding large incisions on the skin, without affecting the surgical result and safety. The first description of minimal invasive approach as part of an endoscopy is attributed to Phillip Bozzini in 1805, who has visualized the urethral mucosa with a simple tube and candle light. Pantaleoni in 1869 has performed the first gynecologic procedure identifying uterine polyps. In 1910, in Sweden Hans Christian Jacobaeus performed the first Laparoscopy using a Nitze cystoscope. Heinz Kal, a German physician was revolutionary when developing laparoscopy into a diagnostic and surgical procedure in the early 1930’s. The use of gaseous distention with lithotomy Trendelenburg position was firstly conceived by a French gynecologist Raoul Albert Charles Palmer a pioneer of Gynecologic Laparoscopy. The use of “cold light” and fiberoptics were landmark innovations in the endoscopy development. These outriders of endoscopic surgery as well as several other scientists and physicians have led the crucial groundwork that has enabled modern gynecology surgeons to perform laparoscopy on a routine basis, with a variety of energy systems under increasingly ergonomic and efficient conditions. Over time variants of the conventional laparoscopic technique have been developed to improve post-operative pain, cosmetic results and minimized trauma to tissue. (Minilaparoscopy, LESS, NOTES). In addition, since the 1980s surgical robots have been developed to address the limitation of laparoscopy in term of two dimensional visualization, incomplete articulation of instruments and ergonomic limitations. The Da Vinci System developed by the Stanford Research Institute along with the Defense department comprises of three components: a surgeon’s console, a patient-side cart with four robotic arms manipulated by the surgeon (one to control the camera and three to manipulate instruments), and a high-definition three-dimensional (3D) vision system. Articulating surgical instruments are mounted on the robotic arms, which are introduced into the body through cannula. The need for remote interventions led to create a project by the National Aeronautics and Space Administration (NASA) in 1970s and funded by the Defense Advanced Research Project Administration (DARPA), for astronauts and soldiers in battlefields. Surgical robotics were first used in 1985 in neurosurgery; applications soon followed in urology (1988), orthopedics (1992) and gynecology (1998). It is important to notice that both traditional laparoscopic and robotic surgery have been widely adopted prior to emergence of data supporting efficacy and safety, because of its clear advantages compared to conventional surgery.
The patient is placed in a supine lithotomy position. Trendelenburg position is typically used to properly visualize the pelvis by displacing the bowel loops in the superior abdominal quadrants. The correct positioning of the patient plays a crucial role in the laparoscopic technique in terms of neurologic injury, ergonomic surgeon positioning, and adequate access to the vagina, if necessary. The patient’s legs are placed in booted stirrups and it is important to maintain moderate flexion at the knee and hip with minimal abduction or external rotation at the hip. The buttocks should be a few centimeters beyond the edge of the table to allow uterine manipulation. To prevent migration in Trendelenburg position there are different methods: egg-crate foam directly beneath the patient, a vacuum-beanbag mattress, or shoulder braces. A variety of uterine manipulators are available to displace the uterus to facilitate access to pelvic structures. To manipulate the vaginal cuff, for women without uterus, a sponge stick can be positioned in the vagina.
To date, numerous studies have shown the superiority of minimal invasive surgery over laparotomy in terms of perioperative complications, hospitalization and quicker return to normal activity. On the other hand it was initially evident that there was a longer operating time and steeper learning curve for the laparoscopic technique. Today a greater surgical experience of surgeons and innovation of instrumentation have enabled a time overlap of most surgical procedures. In addition, a careful assessment of the patients (comorbidities, BMI and body habitus, patient’s surgical history, type of pathology: size, shape, and mobility) to allow an appropriate safe and efficient procedure is crucial.
The laparoscopic technique uses a laparoscope that is introduced into the abdomen by means of small incisions on the skin (into or near the umbilicus) and that projects the images on an external screen. The laparoscope consists of a camera and a light source. Thanks to the gas insufflation inside the abdominal cavity, the operating space is increased for better visualization of the operating field and instruments. To date we have a wide range of laparoscopic instruments that mimic the ones used in conventional laparotomy. Two or three additional accesses are required for most surgical procedures. In gynecological surgery, usually the ancillary trocars are placed 2 cm medial and cranial to the lateral iliac spines, lateral to the inferior hypogastric artery [1, 2, 3, 4, 5].
Laparoscopes range from 1.8 mm to 12 mm in diameter having a distal end available in different angles. The 0-degree telescope is most commonly used and provides a straightforward view. While in contrast, a 30-degree fore-oblique lens allows for visualization in a large frontal view. Light is introduced through the laparoscope with a fiber optic cable powered by a light source. The camera unit consists of camera head, cable and camera control. The image resolution is dependent on the number of pixels on the chip. Most laparoscopic cameras have 250,00 to 380,000 pixels. Newer developments include the use of voice-activated, wireless systems designed to provide central control over operating room devices using either a microphone or a movable touch-pad screen.
Laparoscopy, as well as other endoscopic techniques, is based on two concepts that make it quite different from the open approach. These are triangulation and the fulcrum effect. Triangulation is a fundamental principle for endoscopic surgery as it allows to perceive the position of the instruments in three-dimensional space by sensing the position of our upper joints and arms across our chest together with visualization of the instrument tips (Figure 1). In fact, it is quite challenging to assess the distance or depth of the tip of a long instrument held in one hand. However, when a second instrument is used, the human brain can process the operative field visualized in the monitor with an impressive accuracy. Fulcrum effect is called the phenomenon where a handle movement of an instrument towards one direction is followed by a tip movement in the exact opposite direction. The tissue acts as a fulcrum or pivotal point. The tip movements ability and the right force needed to perform it, depends on the distance of the middle sign of the length of the instrument from the pivotal point according to the rules of physics (rule of moments). In other words, if more than 50% of the instrument length is beyond the fulcrum point, the tip movements are forceless and with a greater spectrum of movements (Figure 2) compared with the position when most of the instrument length is below the contact with the tissue.
Triangulation principle: the instrument will converge from different angles avoiding crossing and collision.
Fulcrum effect: the abdominal wall, where the trocars are inserted, work as a fulcrum for the laparoscopic instruments. By moving the handle of the instrument to the left, through the fulcum effect, the tip of the same instrument will move to the right.
Gynecologic laparoscopic entry is commonly at or through the umbilicus. The traditional technique is to blindly pass a sharp Veress needle, at the umbilicus, insufflate, and then to pass a sharp trocar. Other closed technique entry, such as direct trocar entry, the radially expanding access system and open techniques are widely used. The method by which incisions are made to introduce the laparoscope may influence the likelihood of complications of the first step (injury to surrounding blood vessels or the bowel). However, a recent systematic Cochrane review comparing groups of patients undergoing laparoscopy with different entry technique, concludes that evidence is insufficient to show whether there were differences between groups in the rate of failed entry, vascular injury, or visceral injury, or in other major complications with the use of an open-entry technique in comparison to a closed-entry technique [6].
In general, complications of laparoscopy include nerve injury, vascular injuries, gastrointestinal injuries, trocar site hernia and urinary tract injury. Successful laparoscopy, just as in laparotomy, requires adequate visualization of the operative field and safe retraction of non-target tissues. An inability to displace bowel out of the pelvis, such as in morbidly obese women, and indistinct events such as acute intra-abdominal hemorrhage, may prompt a conversion to laparotomy. Poor candidates for laparoscopy are those with ventilatory problems, severe cardiorespiratory problems or elevated intracranial pressure as well as patients who cannot tolerate steep Trendelenburg or peritoneal insufflation.
Minilaparoscopy uses smaller abdominal incisions than contemporary laparoscopy and refers to the use of instruments and port sites of 5 mm or less. The 5 mm laparoscopes show high resolution and transport enough energy to properly illuminate the surgical field. These smaller port sites may be used for camera and/or accessory instruments (Figure 3). Although minilaparoscopy has been studied more extensively in general surgery and urology applications in gynecology have been described since 1991. A 3-mm incision was made for visualization with a plastic sheath. Two additional 3-mm incisions were used for accessory instruments to aid in adhesiolysis, biopsy of endometriosis, and laser myomectomy. The use of smaller instruments enhances the chance of decreased incisional pain, less need for post-operative opioid pain medication, shortened recovery time, minimization of tissue trauma, and provides a more favorable cosmetic outcome. One of the advantages that arise from minilaparoscopy in comparison with other forms of MIS is that it uses the same operating techniques, patient positioning, and instrument configuration as conventional laparoscopy. Few studies have shown contradictory results concerning operation time. No difference was proven in postoperative complications such as infection, conversion to laparotomy, reoperation, hospital readmission, estimated blood loss, and venous thrombosis although the literature in that field is still scarce [7]. Minilaparoscopy is an intriguing alternative to traditional laparoscopy and may gradually prove to be even superior.
Standard laparoscopy/Minilaparoscopy illustration: 3–4 entry sites are used on the abdomen for insertion of the instruments. The instruments will converge from different angles and will neither collide nor cross.
Laparoendoscopic single-site surgery (LESS), which is also called single-port surgery or single-incision laparoscopy is a procedure in which all instruments are inserted through a single skin incision, normally at the umbilicus (Figure 4). The first reported case of LESS was a gynecological procedure (tubal sterilization) performed by Wheeless in 1969. Approximately 20 years later, Pelosi et al. reported the first case of hysterectomy through LESS [8]. Currently, LESS is used in different surgical fields (general surgery, gynecology, urology). Compared with conventional laparoscopy, LESS shows substantial technical differences in procedure which, however, continue to be improved. These include: loss of triangulation and depth perception because the camera and working instruments are parallel to each other, limited extra-abdominal working space and decreased field of view due to suboptimal instrument or camera position. For this reason a specialized training is needed to minimize these limits, but for surgeons experienced with standard laparoscopic techniques, adopting LESS seems to be feasible and safe. Essentially the advantage of this technique over the multiport laparoscopy would lie in the improvement of cosmesis, less pain, and decreased incisional morbidity. Recent data in gynecological surgery do not support the added of advantages of LESS over MLS. From an analysis of six randomized controlled trials (RCTs), conducted by Schmitt et al. in 2017 in patients undergoing LESS or MLS for adnexal pathology, there were no differences in length of hospital stay, blood loss, postoperative pain, and cosmetic outcomes [9]. In summary, the choice of LESS depends to a large extent on the skills and preferences of the surgeon after a thorough assessment of the morbidity of the patient and her pathology.
Laparoendoscopic single-site surgery (LESS): a single port access is used and through this port, laparoscope and instruments are inserted. The instruments will cross at the umbilicus and will collide inside the abdomen.
Natural orifice transluminal endoscopic surgery (NOTES) has emerged as the newest concept of MIS (Minimally invasive Surgery) as an experimental alternative to conventional laparoscopy which provides an access to the peritoneum traversing a “natural” orifice (stomach, bladder, vagina, or rectum) with a multichannel endoscope [10]. When the procedure involves only transluminal access it is coined “pure” NOTES, compared with “hybrid” NOTES, which refers to a procedure performed through a natural body orifice with transabdominal assistance. The key technical elements in a NOTES procedure are access via a hollow viscus, performance of the desired maneuver once in the target cavity, and closure of the port upon exit. The choice of the entry site depends on the topography of the organ that must be subjected to surgery, considering a good visualization and proper manipulation of the instruments. For example, the trans-gastric pathway is appropriate for lower abdominal and pelvic procedures, while a trans-vaginal approach is preferable for upper abdomen organs. The conceptual bases that led to the development of NOTES have been the potential benefits of an incision of a viscus compared to the skin, the decrease in the risk of post-operative hernias and the obvious cosmetic result. On the other side, there are some limitations: many of the current instruments in use today are difficult to maneuver when the uterus is retroflexed. Furthermore, a thorough closure of the viscerotomy is crucial to avoid bacterial contamination of the peritoneal cavity and abscess formation.
Of all the approaches, presently the transvaginal access to NOTES is the most common and seems to be the safest and most feasible for clinical application (Figure 5). Transvaginal NOTES (vNOTES) has been used for several operations other than cholecystectomy and appendectomy in humans. Potential complications of this approach include: dyspareunia, infertility, rectal and urinary injury. In 2012, Ahn et al. demonstrated firstly the feasibility and safety of vNOTES in gynecologic surgeries, which represented the key milestone in the evolution of NOTES [11]. The innovative and positive aspects of natural orifice surgery in gynecology include the lack of abdominal incisions, less operative pain, shorter hospital stay, improved visibility, and the possibility to skip lysis of adhesion to reach the pelvic cavity. However, for patients with severe adhesion and obliteration in the pouch of Douglas, vNOTES may be a contraindication due to higher risk of rectal injury. To date, two studies compared the surgical outcomes of vNOTES with conventional laparoscopic technique in gynecologic surgery. Both studies demonstrated that vNOTES could be safely performed for benign and large ovarian tumors and vNOTES might offer superior operative outcomes including blood loss, operating time and length of stay, compared to conventional laparoscopic technique [12, 13]. It seems obvious that sexual dysfunction may be an essential reservation of the females. Surprisingly, a study about transvaginal surgery has showed no problems of sexual intercourse and almost no cases of dyspareunia in a long-term follow-up [14]. The transvaginal peritoneal access for a gynecologist might not cause stress because of being familiar with the pelvic anatomy. Although transvaginal NOTES represents one of the most important innovations in surgery since the advent of laparoscopy, there are still technical limitations that must be overcome before the widespread use of this approach.
Transvaginal natural orifice transluminal endoscopic surgery (vNOTES). An incision is made in the posterior vaginal fornix through which camera and instruments are inserted in the abdominal cavity.
Similar to laparoscopy, robotic surgery uses abdominal ports to create pneumoperitoneum to expand the operative field and to introduce the endoscopic instruments. The most known and currently the only commercially available system is the Da Vinci System (Figure 6). The patient is placed in the standard low dorsal lithotomy position with the legs supported in stirrups. One or two surgeon consoles are used to control robot arm movement. A separate robot column is positioned by the bedside and serves as the base for the four robotic arms. One of these arms controls the laparoscope while the other arms hold the robotic instruments. If port sites in addition to the basic four are needed, an assistant surgeon can operate by the patient bedside through one or two additional laparoscopic accessory ports. Port placement for robotic surgery is unique in that ports must be placed with a minimum interval distance of 8 cm. This makes sure that robot arms do not collide with each other and with any accessory port. Importantly, the depth of the inserted trocar in the abdomen is marked by a black ring around the cannula in order to adjust the right fulcrum during the operation. Robotic surgery presents significant technical advantages and some disadvantages compared with conventional laparoscopy. Advantages include 3D visualization of the operative field, mechanical improvement (instrument with seven degrees of freedom of movement), stabilization of instruments within the surgical field, and improved ergonomics. Disadvantages are mainly lack of tactile perception, increased cost, increased operating room time, large size of the devices and risk of mechanical failure. However, the robotic procedure is very useful and decisive in complex surgical procedures where extensive demolition is necessary with consequent restoration of the anatomy. In particular, the Endo Wrist technology is able to overlap with open techniques facilitating the execution of complex maneuvers even for the less experienced. Certainly, surgical simulation, tele-mentoring and telepresence surgery are potential novel benefits of robotic technology. Through robotic surgery most gynecological surgical interventions can be safely performed with an increased comfort for the operator as compared with conventional laparoscopy. However, randomized studies have not demonstrated the superiority of this technique compared to conventional laparoscopy and a clear indication of its use. Moreover, in comparison to conventional laparoscopy the learning curve for becoming proficient in robotic surgery is less steep and has allowed a smooth transition to minimally invasive surgery for many gynecologists [15, 16, 17, 18, 19, 20]. Last but not least, a newer Single Port Robot is currently available although not yet FDA approved for gynecologic procedures.
Robotic surgery set up. It includes 3 components. A surgeon’s console, a patient-side cart with four robotic arms manipulated by the surgeon (one to control the camera and three to manipulate instruments), and a high-definition three-dimensional (3D) vision system. Articulating surgical instruments are mounted on the robotic arms, which are introduced into the body through cannulas.
As it comes clear, nowadays there are various available minimally invasive techniques in the field of gynecology, each of them presenting specific advantages and disadvantages as shown below in Table 1.
Laparoscopy | Minilaparoscopy | LEES | Notes | Robotic Surgery | |
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Advantages: |
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Disadvantages: |
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Advantages and disadvantages of various types of MIS in Gynecology.
The term ergonomics derives from 2 Greek words: “Ergon” that means work and “nomos” that means law. In simple words it describes the science that prepares the worker to best fit his job by developing his working environment and necessary tools by offering the maximum favorable conditions [21]. Usually, when we talk about safety in the OR, anyone might be automatically thinking of safety concerning the patient and not the safety of medical and paramedical staff. Despite the proven safety and efficiency for patients, the development of laparoscopy came with exclusive ergonomic risks such as instrument length and handle design, inappropriate monitor position, and excessively high operating tables. Work-related musculoskeletal injuries and disorders are extremely common in the surgical staff with specific risk situations present in open, laparoscopic, vaginal, and robotic surgery. Needless to point out, that surgeon’s safety has received scarce consideration, throughout the passage from laparotomy to MIS. Studies have shown that, despite significant impact of surgeon injury on productivity and career longevity, surgeons seldom and almost never report work-related injuries to the hospitals, building up a tendency of silent suffering. Although surgical ergonomics guidelines do exist, most surgical staff is not aware of guidelines, while targeted surgical ergonomics training is rare.
Work-related musculoskeletal disorders (WMSDs) as being the official term of this emerging phenomenon contribute immensely to reduced productiveness and job absenteeism. According to the guidelines, behaviors such as repetitions, application of more than 30% of strength, excess body segment positioning, prolonged static posture, use of vibration equipment and exposure to cold shall be averted. Given all that, it comes clear that WMSDs have the highest prevalence in the group of surgeons [22]. These sometimes inevitable movements could have important consequences to the admittedly long career life of a surgeon. Therefore, evidence based ergonomics training protocols should be available and become a compulsory part of residency programs to all teaching hospital around the world as it is well known, in the medical life but as well as in other scenarios bad habits hardly dissolve.
The importance of ergonomics in the field of laparoscopy cannot be over-emphasized. Studies have shown that ergonomics awareness and structured training can reduce chronic pain among surgeons as well as suturing time. The commonest sites of injury include the neck, back, shoulder, elbow, and wrist. This is no surprise as in comparison to conventional open surgery, in laparoscopy the surgeon presents prolonged static posture with no dynamic movements of the body resulting in decreased blood supply in the muscles and consequently elevated lactic acid and toxins in the blood circulation due to anaerobic metabolism. Moreover, redundant internal rotation of shoulder and deviation of elbow and wrist are more common in laparoscopy and have a huge impact in the mechanism of strain of the described regions. Risk factors for WMSDs include physician’s traits such as younger age, shorter stature, female sex, smaller glove size, and higher volume, as well as higher patient BMI. On the other hand, protective factors include ergonomics awareness and training, excessive practice and higher surgeon age. Monitor position is a key component in laparoscopic surgery. Ergonomically, the ideal monitor position for laparoscopy is with the monitor image at or within 25 optimal degrees below the horizontal plane of the eye at a distance of approximately 60 cm. The same height, at which the video monitor used to be set for surgeons of different heights, has been demonstrated to be the underlying cause of neck pain and spondylosis in high-volume laparoscopic centers in the first decade after the onset of MIS in routine clinical practice [22, 23, 24].
Robotic surgery offers certain improvements in ergonomics such as greater degrees of freedom, motion scaling, tremor reduction, and 3-D immersive optics. Robotic equipment permits performance of fine tasks without the ‘arcing’ motions characteristic of conventional laparoscopy. Overall pain with robotics is decreased in comparison to open surgery and laparoscopy. Nevertheless, recent studies have questioned this demonstrated ergonomic advantage of robotics as McDonald et al. in 2017 concluded that robotic procedures were associated with more discomfort, stiffness and fatigue in a survey study of 350 surgeons [25]. Another study by Franasiak et al. has shown that approximately 45% of robotic surgeons experienced WMSDs while an impressive percentage of 26% showed to have experienced permanent damage. As resulted by the same study none of the observed surgeons reported injury to institutions while less than 17% of the total number had formerly received appropriate ergonomics training [26]. Given the rapidly emerging field of robotics in gynecologic surgery it comes clear that more solid evidence is needed in order to make safe comparisons between the ergonomic limitations of robotics versus laparoscopy [27].
Artificial intelligence (AI) and augmented reality have been steadily permeating the healthcare field and are expanding into gynecology. Although virtual artificial intelligence systems are still lacking in gynecology, gynecologic surgery has already integrated augmented reality (AR) technology into the operating room. For instance, cervical cancer models using AI have been used to foresee survival after surgery [28]. Over the past decade, gynecologic surgery has incorporated augmented reality in the form of computer-assisted or robotic platforms to close the native gap between open and minimally invasive surgical skills [29]. A.I applications range from simple prognostic tools to more complex models that incorporate clinical data, imaging, and histopathology to contribute into the optimal therapy decision. Various researchers argue that artificial intelligence is superior to traditional regression models in predicting outcomes. Another example of augmented reality in surgery is projecting preoperatively obtained radiologic images to the operating field during surgery to allow surgeons to understand the anatomical relationship between pathologic and healthy organs. Real time detection of the ureter during surgery is currently experimentally tested for eventual future use [30]. 3D printing is already reality in many centers and it permits advanced preoperative surgical planning and as a result minimizes potential injury. The most applicable example is by understanding the variation in uterine myomas where parameters such as size, location, and depth vary a lot and as a result 3D printing could guide the gynecologist to achieve an outstanding level of pre-op planning [31]. A recently published case report has had success in mapping endometriosis nodules with spatial organ involvement preoperatively with a 3DP model [32].
Virtual simulators have been recently utilized in training gynecologic surgeons for laparoscopic and robotic surgery. The simulator’s efficacy has been assessed through published studies and has been shown to improve basic and advanced laparoscopic skills in all training levels. Novice residents improved their speed of execution, accuracy, and maintenance of horizontal view, while senior residents shortened their speed of execution. Virtual simulators could be incorporated into compulsory residency training as tools for practicing coordination and precision [33]. Hopefully we will reach to a point where as in aviation, it could become a requirement for novice trainees to practice and demonstrate adequate mastery of minimally invasive surgical skills before boarding on real surgery.
In conclusion, endoscopic approach remains the best choice in most of gynecological interventions. Despite the continuous groundbreaking advances in the medical technology concerning gynecologic procedures, the standard laparoscopic approach remains the universal king of the endoscopic gynecologic surgery. In everyday clinical practice, the final decision of the preferred technique depends on different variables: surgeon experience with the proposed technique, patient’s characteristics and desire and finally costs. In particular, surgical costs can be divided into equipment costs and operating room time and surgical staff has to be more familiar with these costs as there is evidence that when surgeons are well informed and educated about operating room outlay, the cost of the procedure decreases. Moreover, the cost differential between robotic and laparoscopic hysterectomy decreases as surgeon and hospital volume increase [34]. For example, in selected cases such as hysterectomies for large uteri greater than 750 gr, robotic surgery has been shown to have cost-effective benefits compared to laparoscopic hysterectomy [35]. Minilaparoscopy, LESS and NOTES gave new perspectives to the minimal invasive conception, however despite of specific important flaws they are not frequently used into clinical practice up to date. Laparoscopic training as well as reduction of robotic-assisted technology costs by expanded use seem to be the constant for the future of minimal access surgery in the field of gynecology.
The authors declare no conflict of interest.
The growth of cells in a controlled artificial environment isolated from their natural habitat is referred to as cell culture [1]. It is a significant tool used widely to study cell and molecular biology, screening drugs and toxicity analysis, the role of a particular gene in a disease, and cancer research. Due to their unique properties, they also have been tuned for screening and developing biopharmaceutical compounds such as vaccines and recombinant proteins. One of the major advantages of using cell culture is the homogenous and reproducible data generated [2].
Drug discovery is a lengthy and time-consuming process that undergoes several stages of testing and optimization. This encompasses identification of the target, lead discovery, pre-clinical validation, and clinical trials [3]. Therefore, it is very pertinent to obtain information about the biological activity, biochemical mechanisms, toxicity, and off-target interactions of drug molecules leading to the early stages of drug discovery.
Two-dimensional (2D) cell culture was introduced many decades ago that has been the major type of cell culture technique in numerous fields. This traditional approach has been extensively used for drug screening due to its relatively inexpensive feature and convenience to use. However, the issue of mimicking the
Simplified sketch of 2D cell culture (a) and 3D cell culture (b).
Recently there has been an upsurge of interest towards three-dimensional (3D) cell culture in biomedical research and drug development processes due to its high-throughput accuracy and refined
Cytotoxicity assays are commonly used for
Assays based on metabolism generally include the 3-(4,5-dimethythiazol2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and its alternatives such as 2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide (XTT),3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS) and sulforhodamine B (SRB) assay. Due to rapid, quantitative, versatile, and highly reproducibility of MTT, it is widely used in large-scale, anti-tumor drug-screening program. MTT is a quantitative colorimetric assay that quantifies the reduction of yellow tetrazolium dye by mitochondrial succinate dehydrogenase to purple insoluble formazan crystals by the NADPH dependent cellular oxidoreductase enzymes [12]. The crystals are dissolved in an appropriate solvent. The absorbance is then recorded using a spectrophotometer to analyze the cell viability wherein the crystals get accumulated in the viable cells due to their impermeability to the cell membrane.
ATP Bioluminescence Assay is used to measure the ATP level that is well regulated in the metabolically active live eukaryotic cells as compared to the dead cells wherein the ATP level falls due to the activity of ATPases. This assay includes a luciferase enzyme that utilizes energy from ATP that converts luciferin into oxyluciferin and thus produces luminescence. Therefore, luminescence could be used to measure the ATP level. Assays based on the release of enzymes are more significant as they measure the products released by the dead cells [13].
Assays based on the release of enzymes include Lactate dehydrogenase(LDH) leakage assay involving the formation of pyruvate from lactate in the presence of LDH with simultaneous reduction of NAD to NADH that alters the absorbance at 340 nm [14]. Research in cancer and cell biology is greatly dependent on
Cell migration is well known for its significant role in embryonic morphogenesis, cancer invasion and metastasis, immune responses, tissue formation, and angiogenesis [19]. Mainly, cell migration is of two types; single-cell migration and collective cell migration. Single-cell migration is regulated by cytoskeletal activity without cell-to-cell interactions with neighboring cells. This type of migration is important for embryonic development, immune response, and in the early stages of metastasis. On the other hand in the collective cell migration, the group of cells retains their cell to cell interactions as well as collective polarity. Wound healing assay or scratch assay is a 2D
Another assay involving the response of single cells to various chemo-attractants is the transwell assay or the Boyden Chamber assay. This assay can be used for both adherent and non-adherent cells wherein the cells are placed in a serum-free medium on one side of a porous membrane and analyzed on the basis of the cell’s ability to migrate through the pores to the other side. Cell migration can be quantified by counting the cells that have traversed through the membrane towards the higher concentration of chemoattractant [21]. A drawback of this assay is visualizing the cells and their morphology while migrating through pores due to the transitive state of cells [22].
Cancer is one of the most frightful diseases in both developing and developed countries and imparts a major health burden to the society. Tumorigenicity is the tendency of the cultured cells to form tumors. The two common
Colony forming assay is performed using the soft agar method. The basic steps involved in this assay are treating the cell monolayer in the flask, seeding the required number of cells on the agar and incubate for 1–3 weeks, fixing and staining the colonies and finally observing the colonies under the stereomicroscope [23]. Another
Cell migration is an important process in biology where the cells changes and reaches their destination within a proper environment, in order to execute their respective function. It is a normal physiological process that takes place in nearly all forms of organisms. However, changes or deregulation of any kind in the pattern of cell migration or invasion are an indication of pathological conditions including inflammatory diseases and cancer metastasis, with the latter being the most explored one [21]. There are various biological methods that are commonly employed in the scientific community to study the above-mentioned events in depth namely, the cell culture wound-healing assay, the transwell migration, and invasion assay, individual cell-tracking assay, and spreading assay. These assays aim to provide relevant information pertaining to the pattern of cell migration or its response to chemoattractant(s).
It is the simplest of all methods in determining the migration of whole-cell masses altogether. Going further in detail, it can be used to interpret individual cell’s morphological characteristics and phenotypes during migration. Measuring the closed distance compared to the control over regular intervals of time shows specific migration changes or phenotype that was unknown in the past [26].
The transwell migration and invasion assay are used to determine the capability of single cells to respond to various chemoattractant(s) including chemokines, growth factors, lipids, or nucleotides. It also contributes to assessing differential cell migration due to the over-expression of a receptor. It also identifies and characterizes the key regulators participating in cell migration [26].
Conducting single-cell tracking and its live imaging under appropriate conditions adds to the overall advantage of cell migration assay. The software includes a time-lapse video-microscopy protocol comprising of post-processing tracks of the cell populations with single-cell resolution. It greatly helps to understand the cell biology and lineage progression of distinct cell populations [27].
In this type of assay, the spreading process of individual cells is seen and recorded with the help of Differential Interference Contrast microscopy (DIC). The spreading state is recorded every 5 seconds with a Charge-Coupled Device (CCD) of the camera, producing high-quality grayscale images. The process of taking images could extend to several hours [28].
Antibodies, one of the major elements of the immune system are the glycoproteins produced by the immunoglobulins; B-cells provide protection against invading pathogens. The antibodies are highly specific and selective, thus have been used as an extraordinary tool in bioengineering and biomedical research for many years. The antibodies are majorly classified into two categories, Monoclonal Antibodies (mAbs) and Polyclonal Antibodies (pAbs) are based on their origin from the lymphocytes. mAbs are produced by only B lymphocyte or B cells and are monospecific. Due to this property, they possess high specificity and affinity towards a single epitope of an antigen whereas pAbs are produced by different B-cells and possess different affinities for multiple epitopes of a specific antigen. Since mAbs are highly specific, they are produced on a large scale through culturing of antibodies-producing cells widely known as ‘Hybridomas’, which are commonly derived from mice, and the method is known as ‘Hybridoma Technology [29].
Hybridoma technology was discovered and developed by two eminent scientists, Georges Kohler and Cesar Milstein in 1975 and is considered to be one of the biggest breakthroughs. It has proved to be a robust, effective, and successful methodology employed in the field of biotechnology and biomedical research that solely deals with mAb isolation. The B cells go through the antibody maturation process in the germinal centers of secondary lymphoid tissues (for example, lymph nodes, spleen, tonsils, and Peyer’s patches). Upon proliferation, certain mutations are experienced by the B cells, specifically in the genes encoding the variable region of the antibodies that helps in the selection for high-affinity tight binding to the corresponding antigen. The overall resulting antibodies by B cells consist of a natural pairing of the light chain and variable heavy chain genes with constant region genes. This region contains Class Switch Recombination (CSR) differentiates from the hybridoma technology in which CSR is absent [29].
Following are the steps employed for the production of monoclonal antibody by hybridoma technology.
The mouse/mice is/are immunized every 2–3 weeks with red blood cells taken from sheep in order to produce the B cells. These antibodies are isolated from the spleen cells of mice.
After the process of immunization, the blood samples are taken from the mouse to determine the serum antibody titer. When the titer reaches the optimal level, the mouse is boosted by injecting antigen 3 days prior to fusion with myeloma cells [30].
Fusion of isolated spleen cells (limited life span) with tumor lymphocytes (immortal) with the help of PEG (Polyethylene Glycol) leads to the development of hybridomas with an unlimited life span.
Hybridomas are grown in a selective medium containing Hypoxanthine, Aminopterin and Thymidine (HAT). Aminopterin present in the media blocks pathway for nucleotide synthesis, making the cells dependent on the alternative pathway which is not evident in myeloma cells.
The cells are screened and chosen or selected for production of antibodies with the desired specificity.
The cells are cultured and used for the production of large quantities of antibodies [31].
The cells are frozen and stored for future use in therapeutics.
Gene, the fundamental biological unit of heredity that constitutes an ordered sequence of nucleotides present in chromosomes. The functional aspect of a gene is to encode a protein or RNA molecule inherited from parents such as texture and color of the hair and eyes. Any kind of alterations/mutations in a gene sequence can lead to abnormal functionality of the genes. Gene therapy is a modern type of experimental technique in the medical field which involves rectifying the non-functional or malfunctioning of genes by replacing them with healthy and functional genes. Several approaches have been implemented by researchers in terms of correcting a mutated gene with a healthy copy of the gene or by inactivating the mutated gene causing disease. It has been widely studied for various diseases such as immune deficiency, blood disorders, eye problems, metabolic disorders, regeneration of nerve cells, and cancer [32]. The first case of gene therapy was discovered in the 1990s whereby a functional Adenosine Deaminase (ADA) gene was incorporated in the white blood cells of the patient, replacing the non-functional ADA [33]. This application led to interesting results with the immune systems and hence, was considered the most reliable technique.
There are two main methods for gene therapy such as-
The strategy of gene therapy has been applied to this disease in order to improve the advanced symptoms of PD. Gene therapy was applied to transfer ‘Glutamic Acid Decarboxylase (GAD), a chemical produced by a gene into the basal ganglia. GAD showed an increased amount of a neurotransmitter called as Gamma-Aminobutyric Acid (GABA), responsible for inhibiting brain signals and decreasing activity in the nervous system Decreased GABA activity leads to certain brain-related disorders [34].
AD and other frontotemporal dementias (FTDs) are caused by the accumulation of amyloid-β peptide (Aβ) and protein tau in the brain. It is characterized by having memory loss, difficulty in learning and communicating along with the inability to organize things. The use of recombinant Adeno-Associated Viruses (rAAVs) has provided new ways for studying AD and other related neurological disorders [35]. Such strategies or approaches have added novel dimensions to medical treatments.
Cystic fibrosis is a disease known to affect the lungs primarily. Its symptoms include inflammation, airway obstruction leading to respiratory tract infection and deformity. Insertion of the Cystic Fibrosis Transmembrane Regulator (CFTR) gene directly into the epithelium cells of the respiratory tract bear the capability to lessen the symptoms but not totally cure the disease in patients suffering from cystic fibrosis [36].
Cell-based therapy is one of the most important and well-known forms of all treatments in the fields of modern science & medicine. It is not only a curative option for treating deadly or threatening diseases but is also making ‘Regenerative Medicine’ the most vital technique in health care with the specific goal of replacing diseased cells, tissues or organs and thereby restoring their normal function(s) [4]. Over the years, there has been a gush of interests and work done in understanding the potential of stem cells. They are the cells found naturally in the living bodies, characterized by two defining properties of eternal self-renewal and the propensity to differentiate into an adult cell type. There are three main types of stem cells: Totipotent (a cell developing into a healthy organism independent of the permissive environment), Pluripotent (a cell developing into any type of adult cell) and Multipotent (a cell developing into a limited type of cell) [37].
Following is the account of different stem cells used for the treatment of various diseases:-
Reportedly, pluripotent cells have been used successfully to treat animals per se. Animals diagnosed with diabetes are incorporated with cells containing insulin responsive to glucose levels. Additionally, the treatment of the animals suffering from acute spinal cord injury and visual impairment is performed with myelinated neurons and retinal epithelial cells, respectively. Researchers are still conducting studies with the use of pluripotent stem cells to cure several disorders such as Parkinson’s disease, muscular dystrophy and heart failure.
The stem cells created artificially from normal adult somatic cells through co-expression of genes and factors are known as Induced Pluripotent Stem Cells (iPSCs). These are important for maintaining the characteristic properties of Embryonic Stem (ES) cells. Some reports have stated the successful use of iPSCs in conditions like Parkinson’s disease, spinal muscular atrophy, cardiac diseases, blood disorders, diabetes, amyotrophic lateral sclerosis, Huntington’s disease, and familial dysautonomia.
The multipotent stem cells derived from bone marrow (Hematopoietic stem cells) have been used in the 1960s to treat cancer conditions like leukemia, myeloma and lymphoma. Mesenchymal stem cells with the capability of forming whole joints in mouse models have been used regenerating bone and cartilages form. Curing heart ailments are still under clinical trial.
Spurred by the recent advent in cell culture technologies, three-dimensional (3D) cell culture is paving the way in promoting tissue organization and cell differentiation by triggering tissue-based diseased microenvironment. An ideal 3D cell culture system generally composed of tightly bound tissues that involve cell–cell fluent interaction almost mimicking the extracellular matrix (ECM) that is highly dynamic and includes scaffolds of cells in a fluid that enhances them to differentiate (Table 1). The key parameter of a 3D culture environment is the ability to organize the spatial arrangement of cells with other surrounding cells along with physical constraints [8]. This significant approach has gardened great focus on understanding complex cellular biology and their responses by validating mammalian tissue studies via linking the gap between
Approach | Merits | Demerits |
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3D Spheroids |
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Organ-on-a-chip |
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Merits and demerits of different 3D cell culture techniques.
Organ type | Incorporated cell types | Organ-specific properties | Ref. |
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Lung | Primary lung alveolar epithelial cells |
| [76, 77] |
Primary lung endothelial cells |
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Human vascular endothelial cells |
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Human alveolar epithelial cells | |||
Skin | Peripheral perfusion fluid (PPF) |
| [79] |
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Liver | Hepatic cell lines |
| [80] |
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Kidney | Human podocytes Glomerular endothelial cells |
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Human-derived renal proximal tubule epithelial cells |
| [82] | |
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Heart | Cardiomyocytes |
| [83, 84] |
Pancreas | Human pancreatic beta-cell line |
| [85] |
Summary of recent organ-on-a-chip models.
3Dspheroids or multi-cellular aggregates are spherical micro-sized cellular constructs that are produced from numerous gamuts of cell types, originally from scaffold-free systems. The most characteristic features of 3D spheroids are the ability to recapitulate a cell’s typical physiological behavior, cellular heterogeneity, gene expression, cell–cell signaling, and structural architecture with respect to cell–cell contact [10]. Various types of 3Dspheroids include embryonic bodies, tumor spheroids (spheres of different tumorcells), hepatospheres (spheres of hepatic cells), neurospheres (spheres of different cell types of the central nervous system (CNS)) and mammospheres (spheres of mammary glands) [38]. An ideal 3D spheroid constitute ECM components such as proteoglycans, laminin, collagen, fibronectin, tenascin, and glycosaminoglycans [39] which tightens the spheroid density with close ECM-cell and cell–cell anchors eventually increase interstitial fluid pressure (IFP). Depending on the primary amount of cells seeded, the size of spheroid increases with an elevation in cell number, oxygen, and nutrient gradients equivalent to the tissue of interest [5]. Alongside, the different techniques enabling spheroid cultures are illustrated further.
Hanging drop technique is a non-scaffold method wherein a drop of media containing cells are suspended inversely on the lid of the culture dish (bottom-less and open) such that there is no surface provided for the cells and tend to hang. This attempt forms a cluster called spheroid at the tip of the droplet when cultured for a longer period [40]. Spheroids formed through hanging drop cultures have fetched considerable stance in cell culture technology with 100% reproducibility owing to ubiquitous applications in cancer research [41], toxicity testing in hepatocytes [42], and constructing cardiac spheroids [43]. Another method involves the use of a liquid overlay that eases the formation of aggregates and commercially produced as low adhesion plates. These spheroid microplates contain either hydrophilic or hydrophobic coating with V-shaped bottom and allow mild attachment to the surface such that the cells tend to self-aggregate and form spheroid. Unlike the hanging drop technique, low adhesion plates generate one spheroid per plate that signifies its importance for multicellular culture. This ensures a medium-throughput screening that requires no modification in spheroid formation [44]. Spheroids can also be cultured with the use of magnetic nanoparticles with the application of the magnetic field. The process is called magnetic cell levitation that is highly applied to produce spheroids of mesenchymal stem cells and tissue engineering [45, 46]. An
Organoids refer to the primary cultures derived from cell aggregates through
Cancer cell lines have emerged as an eminent tool for comprehending complex physiology of cancers. The cell cultures have eased the outlook in preclinical research to understand the process of disease, morphological changes occurring in tissue, gene function, cell biology and tissue engineering [58]. They have evolved with immense features of offering homogenous samples without any sort of modification and variations. However, a big leap was noted when monolayer cell cultures (2D) obtained from solid tumors were incapable of mimicking the structural elements of tumor microenvironment. Thusly, 3D cancer cell culture models have placed an enduring platform recently whereby ECM in 3D construct is same as that of original cell culture and imparted knowledge of predicting tumor response to treatment [59]. The application of 3D cell culture models of tumors have ought to manifest typical properties of tumor microenvironment such as gene and protein expressions, morphology, angiogenesis, malignancy and invasiveness. From this standpoint, 3D tumor cell culture models scintillate anticancer therapeutics and cancer drug discovery. To date, a vast content of literature owes the significance of these 3D co-cultures models in varying applications. In a study, tumor-associated macrophages (TAM) or cancer-associated fibroblasts (CAF) and gelatin hydrogel microspheres (GM) have been applied to produce cancer co-culture models from different cancer cells including HepG2 (liver), MCF-7 (breast) and WA-hT (lung) in order to inspect sustained release of drugs. They induced metastatic proteins involved in epithelial-mesenchymal transition (EMT) with transforming growth factor-β1 (TGF-β1) and reported elevation in N-cadherin and Vimentin proteins with deceleration in E-cadherin protein [58]. Recently, cancer co-culture models evinced interest in numerous approaches such as 3D breast cancer co-culture models obtained from MCF-7, MRC-5 and MDA-MB-231 tumor cells were used in investigating radiation-induced fibrosis [59], tumor-associated fibroblast differentiation [60] and development of immunotherapies [61], 3D lung cancer co-culture models derived lung squamous carcinoma and Non-Small Cell Lung Cancer Cells (NSCLC)fromTUM622, A549 and Colo699 tumor cells were utilized to explore tumor-stroma interactions [62, 63], 3D renal cancer co-culture models formed from Caki 1 (skin metastasis derived) and ACHN (pleural effusion derived) were sought for determining the efficacy of produced 3D models in stem cell physiology research and drug toxicity screening [64]. 3D colon cancer co-culture models acquired from LS 174 T, HCT 116, Colo205, MCF7, SW480, SW620, CCD-18Co, Caco-2, HT-29, and H446 have also been used to explore tumor-stroma interactions [65].
Organ-on-a-chip is a biomimetic system that uses fabrication of computerized microchips and microfluids consisting of living cells, mimicking the natural environment of organs from which it is been created. There are several factors that made organ chips be listed in “Top Ten Emerging Technologies” in the World Economic Forum [75] such as shear force, tissue-boundaries, concentration gradients, tissue–organ interactions and cell patterning. Organ chips have intensified in the field of drug therapeutics for their ability of high throughput screening. Table 2 summarizes the recent researches carried out using various organ chips. These organ chips use microtechnology that provides nutrients to the cells for their better growth and proliferation. Microfluids are one such component that has been used in various studies for efficient treatment in drug sensitivity testing [86]. Talking of this notion, a microfluidic chip was produced in order to monitor and document real-time impedimetric biosensor changes. Other organ-on-a-chip models such as blood–brain barrier chips have been developed to represent the
Animal models used in laboratories have been greatly avoided due to the fact that they are costly and require a large number of laborers. This approach was replaced by the use of
Drug discovery is a lengthy and time-consuming process that undergoes several stages of testing and optimization. This encompasses identification of the target, lead discovery, pre-clinical validation, and clinical trials [3]. Due to the constant failure of drugs in Phase II and Phase III clinical trials, there has been constant pressure on the pharmaceutical industry to seek more novel drugs with lower side effects and cost-effectiveness. 3D cell culture has emerged as a significant high-throughput system that has uplifted the standards of cell culture [93]. Specifically, spheroids are considered the most reliable model for testing drugs in various diseases because of their capability of resembling the natural environment of original tissue [93]. The spatial organization of spheroids in different layers of cells leads to cellular death by forming reactive oxygen species [94]. In the case of investigating the effect in 3D spheroids, fluorescence microscopy plays a key role in determining pharmaceutical dispersion within spheroids (eg-doxorubicin and epirubicin) [95]. The capital importance of any drug testing involves cell-based assays that are efficient enough and easily reproducible compared to expensive animal models. Cell-based assays have shaped the physiological relevance of 2D cultures [96]. While the reaction may vary from technique to technique such as cell viability, proliferation, signaling and migration and drug to drug for achieving better sensitivity. It is now broadly accepted that compared to 2D cultures, 3D models serve the resemblance of the natural environment of original tissue efficiently and differently in 3D environments. Research has nested stance on novel 3D culture technologies that impart functional basis of tissues such as spheroids and organoids [97]. A study used 3D hydrogel-based model for the determination of drug sensitivity in HepG2 cell lines by comparing cytotoxicity effect with cytotoxicity (CT50) and lethal dose (LD50) values [98]. Organoid 3D models also aid as a resourceful tool for modeling neurodevelopmental disorders [98]. Microfluidic chips have also been utilized in drug sensitivity testing whereby a study elaborated its efficacy in lung cancer which was in combination with stromal cell lines [98]. Evaluation of absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the drug is primarily examined in
Therapeutic proteins production using human cell lines has greatly influenced different medical areas including biopharmaceutical research and vaccine production. Mammalian cell lines prove futile in protein production due to their likelihood of possessing post-translational modifications (PTMs) achieved from recombinant proteins that are in accordance with the endogenous human proteins. These cell lines show exquisite specificity to produce similar proteins to those in humans naturally synthesized, an advantage over mammalian expression systems [99]. One of the most routinely and high yields of proteins production is performed by using cell-based expression systems such as Chinese hamster ovary (CHO) a cell line that constitutes major advances such as accomplishment of gene amplification, specific productivity, better selection strategies, and devising greater expression units and advanced hosts. CHO cells have established their safety profile for 20 years from the production of its first recombinant biotherapeutic protein in 1986 [100]. Other human cell lines such as BHK-21 cells are used for the generation of few coagulation factors such as factor VIII [101]. There are two vital human cell lines namely, HEK293 and HT-1080 that are used to manufacture licensed products of human PTMs. The advancement in protein-based drug development and technologies has driven more towards the therapeutic proteins market that comprises of sales of these therapeutic proteins. The methods that are involved in the production of these proteins are pegylation, glycoengineering, albumin fusion, Fc-fusion, product purity, targeting, and functionality of therapeutic protein drugs. Few examples of therapeutic protein drugs which has been produced using protein engineering technologies and approved by the Food and Drug Administration (FDA) from the past five years are imiglucerase, Belimumab, alfa, coagulation factor IX recombinant human and albiglutide [102]. A French pharmaceutical company named Sanofi accomplished a great achievement of strengthening its R&D strategy with the best proprietary therapeutic proteins production pharmaceutical company, Ablynx, for a nanobody technology platform.
In particular, a plethora of research studies have shed light on the fact that in spite of the availability of advanced organ-on-chip technologies and bioengineered 3D models, the application is limited by drug companies due to their relatively novel approach which is more likely requires to undergo further validation and characterization. Moreover, 3D cell culture models with high-throughput screening in combination with high-content leads to the identification of clinically relevant compounds. However, still many difficulties are being faced as 3D cell cultures do not meet certain criteria in the drug discovery process with regard to size, morphology, complexity, and protocol for assaying. It requires ample standardization and optimization to extract successful specific phenotypes for drug screening. Thus, there are few 3D models that are constrained for their restricted access due to limited permeability. Following the advances in protein therapeutics, more improvements in generating sophisticated therapeutic protein products will be developed for better futuristic research.
Authors thanks, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Tathawade, Pune, for providing necessary facilities. This work was supported by Dr. D. Y. Patil Vidyapeeth seed grant (DPU/14/2016, dated 06/01/2016).
There are no conflicts of interest.
2D | Two-dimensional |
3D | Three-dimensional culture |
Aβ | Amyloid-β peptide |
ADMET | Absorption, distribution, metabolism, excretion and toxicity |
ADA | Adenosine Deaminase |
AD | Alzheimer’s disease |
ARDS | Acute respiratory disease syndrome |
CAF | Cancer-associated fibroblasts |
CCD | Charge-Coupled Device |
CFTR | Cystic fibrosis transmembrane regulator |
CHO | Chinese hamster ovary |
CNS | Central nervous system |
CSCs | Cancer stem cells |
CT50 | Cytotoxicity 50 percent |
CSR | Class Switch Recombination |
DIC | Differential Interference Contrast microscopy |
ECM | Extracellular matrix |
ES | Embryonic Stem |
EMT | Epithelial-mesenchymal transition |
FTDs | Frontotemporal dementias |
GABA | Gamma-Aminobutyric Acid |
GAD | Glutamic Acid Decarboxylase |
GM | Gelatin hydrogel microspheres |
HAT | Hypoxanthine, Aminopterin, Thymidine |
IFP | Interstitial fluid pressure |
iPSCs | Induced pluripotent stem cells |
LDH | Lactate dehydrogenase |
LD50 | Lethal dose 50 percent |
MTT | 3-(4,5-dimethythiazol2-yl)-2,5-diphenyl tetrazolium bromide |
MTS | 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium |
MDC | Microfluidic Diffusion Chamber |
mAbs | Monoclonal Antibodies |
NAD | Nicotinamide adenine dinucleotide |
NADH | Reduced nicotinamide adenine dinucleotide |
NADPH | Nicotinamide adenine dinucleotide phosphate |
NSCLC | Non-Small Cell Lung Cancer Cells |
pAbs | Polyclonal Antibodies |
PDX | Patient-derived xenograft |
PD | Parkinson’s Disease |
PPF | Peripheral perfusion fluid |
PTMs | Post-translational modifications |
rAAVs | Adeno-Associated Viruses |
SRB | Sulforhodamine B |
TAM | Tumor-associated macrophages |
TGF-β1 | Transforming growth factor-β1 |
TME | Tumor microenvironment |
XTT | 2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide. |
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Telling personal stories, such as talking about your day or recounting what happened in the playground, is essential for communication and establishing relationships. However, due to their language impairments, people with aphasia (PWA) and children with developmental language disorder (DLD) often have problems with everyday discourse which impact on their lives more widely. While improvement in language skills is supported by speech-language pathology (therapy), it tends to focus on smaller linguistic components, such as single words and sentences. This chapter outlines how speakers construct discourse in everyday situations and focuses on the meanings that people use discourse to convey, as well as the lexical and grammatical resources they use to convey these meanings. Current methods for discourse analysis will be outlined and key developments in narrative discourse production therapy will be reviewed.",book:{id:"5957",slug:"advances-in-speech-language-pathology",title:"Advances in Speech-language Pathology",fullTitle:"Advances in Speech-language Pathology"},signatures:"Lucy T. Dipper and Madeleine Pritchard",authors:[{id:"201158",title:"Dr.",name:"Lucy",middleName:null,surname:"Dipper",slug:"lucy-dipper",fullName:"Lucy Dipper"},{id:"208542",title:"Dr.",name:"Madeleine",middleName:null,surname:"Pritchard",slug:"madeleine-pritchard",fullName:"Madeleine Pritchard"}]},{id:"70186",doi:"10.5772/intechopen.90173",title:"Computational Model for the Construction of Cognitive Maps",slug:"computational-model-for-the-construction-of-cognitive-maps",totalDownloads:734,totalCrossrefCites:5,totalDimensionsCites:7,abstract:"The chapter considers an option for solving the problem of storing data in the Web environment and providing an access to the data, taking into account their semantics, i.e., in accordance with the nature of the tasks solved by users of different classes. The proposed solution is based on the use of presentation of the data in the form of semantic networks. As the main technical tool for describing access methods, the chapter proposes cognitive maps (CMs), which can also be considered as semantic networks of special type. When access is done, the presentation of information consistent with the semantic description of the user is provided. The suggested method of constructing CMs is based on the intensional logic. The solution is presented in the form of a computational model, which provides for the construction of CM’s dependence on the parameter. The proposed method of parametrization makes it possible to take into account the semantic characteristics of users of various classes. Some CM constructions for problem domain description are presented. A method for semantically oriented naming of CMs is proposed. The method is based on building of a functor of special type.",book:{id:"7311",slug:"cognitive-and-intermedial-semiotics",title:"Cognitive and Intermedial Semiotics",fullTitle:"Cognitive and Intermedial Semiotics"},signatures:"Larisa Yu. Ismailova, Sergey V. Kosikov and Viacheslav E. Wolfengagen",authors:[{id:"299703",title:"Dr.",name:"Larisa",middleName:"Yusifovna",surname:"Ismailova",slug:"larisa-ismailova",fullName:"Larisa Ismailova"},{id:"299704",title:"Prof.",name:"Viacheslav",middleName:null,surname:"Wolfengagen",slug:"viacheslav-wolfengagen",fullName:"Viacheslav Wolfengagen"},{id:"299711",title:"Mr.",name:"Sergey V.",middleName:null,surname:"Kosikov",slug:"sergey-v.-kosikov",fullName:"Sergey V. Kosikov"}]},{id:"56698",doi:"10.5772/intechopen.70107",title:"Risk Factors for Speech-Language Pathologies in Children",slug:"risk-factors-for-speech-language-pathologies-in-children",totalDownloads:1573,totalCrossrefCites:2,totalDimensionsCites:5,abstract:"Risk factors are understood to encompass “aspects of individual behavior or lifestyle, environmental exposure, hereditary or congenital characteristics that are associated with a health related condition”. These are conditions that increase the chances of the child presenting speech-language disorders and that can be avoided, controlled, or treated. Risk is defined as the chance of a child exposed to certain factors (environmental or biological) to acquire or develop speech-language disorders. The objectives of the present study were: to identify the risk factors for speech-language disorders in children up to five years of age and to verify the relationship between risk factors and speech-language diagnostic hypotheses. The aspects of being male gender, prematurity, shyness, being an only child or youngest child, presenting deleterious oral habits, having a family history of speech-language disorders, and use of licit or illicit drugs during pregnancy seem to be the factors that should draw the attention of the health professionals in child development. Therefore, the monitoring of children who have these risk factors should be performed in order to promote the necessary stimulation and the construction of healthy environments.",book:{id:"5957",slug:"advances-in-speech-language-pathology",title:"Advances in Speech-language Pathology",fullTitle:"Advances in Speech-language Pathology"},signatures:"Daniela Regina Molini-Avejonas, Laís Vignati Ferreira and Cibelle\nAlbuquerque de La Higuera Amato",authors:[{id:"38599",title:"Prof.",name:"Daniela",middleName:null,surname:"Molini-Avejonas",slug:"daniela-molini-avejonas",fullName:"Daniela Molini-Avejonas"},{id:"204612",title:"Prof.",name:"Cibelle",middleName:null,surname:"Amato",slug:"cibelle-amato",fullName:"Cibelle Amato"},{id:"210543",title:"Ms.",name:"Laís",middleName:null,surname:"Ferreira",slug:"lais-ferreira",fullName:"Laís Ferreira"}]}],mostDownloadedChaptersLast30Days:[{id:"56698",title:"Risk Factors for Speech-Language Pathologies in Children",slug:"risk-factors-for-speech-language-pathologies-in-children",totalDownloads:1576,totalCrossrefCites:2,totalDimensionsCites:5,abstract:"Risk factors are understood to encompass “aspects of individual behavior or lifestyle, environmental exposure, hereditary or congenital characteristics that are associated with a health related condition”. These are conditions that increase the chances of the child presenting speech-language disorders and that can be avoided, controlled, or treated. Risk is defined as the chance of a child exposed to certain factors (environmental or biological) to acquire or develop speech-language disorders. The objectives of the present study were: to identify the risk factors for speech-language disorders in children up to five years of age and to verify the relationship between risk factors and speech-language diagnostic hypotheses. The aspects of being male gender, prematurity, shyness, being an only child or youngest child, presenting deleterious oral habits, having a family history of speech-language disorders, and use of licit or illicit drugs during pregnancy seem to be the factors that should draw the attention of the health professionals in child development. Therefore, the monitoring of children who have these risk factors should be performed in order to promote the necessary stimulation and the construction of healthy environments.",book:{id:"5957",slug:"advances-in-speech-language-pathology",title:"Advances in Speech-language Pathology",fullTitle:"Advances in Speech-language Pathology"},signatures:"Daniela Regina Molini-Avejonas, Laís Vignati Ferreira and Cibelle\nAlbuquerque de La Higuera Amato",authors:[{id:"38599",title:"Prof.",name:"Daniela",middleName:null,surname:"Molini-Avejonas",slug:"daniela-molini-avejonas",fullName:"Daniela Molini-Avejonas"},{id:"204612",title:"Prof.",name:"Cibelle",middleName:null,surname:"Amato",slug:"cibelle-amato",fullName:"Cibelle Amato"},{id:"210543",title:"Ms.",name:"Laís",middleName:null,surname:"Ferreira",slug:"lais-ferreira",fullName:"Laís Ferreira"}]},{id:"56385",title:"Formulaic Language: The Building Block of Aphasic Speech",slug:"formulaic-language-the-building-block-of-aphasic-speech",totalDownloads:1837,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Aphasia is a condition that may appear when parts of the brain (Broca’s or Wernicke’s area) responsible for language production and processing are damaged. In most cases, patients have the left side of their brain affected. Thus, formulaic language remains intact in most cases. During speech therapy, this can be a solid base to build on. Formulaic language consists of formulas that are fixed phrases, stereotypes that behave as a single-unit lexical item. They have a significant role in language acquisition and fluent discourse production. These ready-made parts of speech are stored in the long-term memory. Studies suggest that the processing of formulaic language engages right hemisphere areas of the brain. Due to their language impairment, people with aphasia often have a lower quality of life, consequently social and professional integration for them being problematic. The investigation of preserved patterns, such as formulaic language and impairments related to different aspects of discourse, may provide insights both for clinical practice and for cognitive science, therefore, facilitating a more efficient approach to treatment.",book:{id:"5957",slug:"advances-in-speech-language-pathology",title:"Advances in Speech-language Pathology",fullTitle:"Advances in Speech-language Pathology"},signatures:"Annamária Győrfi",authors:[{id:"200880",title:"Dr.",name:"Annamaria",middleName:null,surname:"Gyorfi",slug:"annamaria-gyorfi",fullName:"Annamaria Gyorfi"}]},{id:"72178",title:"Cognitive Semiotics and Conceptual Blend: A Case Study from The Crying of Lot 49",slug:"cognitive-semiotics-and-conceptual-blend-a-case-study-from-em-the-crying-of-lot-49-em-",totalDownloads:703,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Cognitive semiotics has been defined by the linguist Jordan Zlatev as “the need to unify or at least to ‘defragment’ our world-views, the need to come to terms with increasingly higher levels of dynamism and complexity”. If we consider, as it is clear from the second cognitive revolution, when embodiment claimed its leading role, that meaning emerges from the constant interaction of body-brain-environment, we need to redefine the field that asks “what is meaning and how does it emerge.” New theories about metaphors as neural nodes and image schemas would shed light over the emergence of meaning in human communication, and, to do so, the study of conceptual blends as essential cognitive tools and as an integrative theory should be put in the center of the debate. In words of Brandt and Brandt, “blends occur as signs and are therefore a natural subject of cognitive semiotics”. Here, we will represent the emergence of meaning in a blend from the highly dynamic and complex narrative The Crying of Lot 49 by Pynchon and propose a conceptual story (or mental space sequence of the story) of the mentioned blend.",book:{id:"7311",slug:"cognitive-and-intermedial-semiotics",title:"Cognitive and Intermedial Semiotics",fullTitle:"Cognitive and Intermedial Semiotics"},signatures:"Marta Silvera-Roig",authors:[{id:"302728",title:"Dr.",name:"Marta",middleName:null,surname:"Silvera-Roig",slug:"marta-silvera-roig",fullName:"Marta Silvera-Roig"}]},{id:"56266",title:"Discourse: Assessment and Therapy",slug:"discourse-assessment-and-therapy",totalDownloads:3063,totalCrossrefCites:7,totalDimensionsCites:9,abstract:"Discourse is essential for interaction and for the expression of ideas, feelings and opinions. Telling personal stories, such as talking about your day or recounting what happened in the playground, is essential for communication and establishing relationships. However, due to their language impairments, people with aphasia (PWA) and children with developmental language disorder (DLD) often have problems with everyday discourse which impact on their lives more widely. While improvement in language skills is supported by speech-language pathology (therapy), it tends to focus on smaller linguistic components, such as single words and sentences. This chapter outlines how speakers construct discourse in everyday situations and focuses on the meanings that people use discourse to convey, as well as the lexical and grammatical resources they use to convey these meanings. Current methods for discourse analysis will be outlined and key developments in narrative discourse production therapy will be reviewed.",book:{id:"5957",slug:"advances-in-speech-language-pathology",title:"Advances in Speech-language Pathology",fullTitle:"Advances in Speech-language Pathology"},signatures:"Lucy T. Dipper and Madeleine Pritchard",authors:[{id:"201158",title:"Dr.",name:"Lucy",middleName:null,surname:"Dipper",slug:"lucy-dipper",fullName:"Lucy Dipper"},{id:"208542",title:"Dr.",name:"Madeleine",middleName:null,surname:"Pritchard",slug:"madeleine-pritchard",fullName:"Madeleine Pritchard"}]},{id:"56414",title:"Evidence for Speech Sound Disorder (SSD) Assessment",slug:"evidence-for-speech-sound-disorder-ssd-assessment",totalDownloads:1608,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Comprehensive studies on aspects related to the assessment of different biomedical parameters (acoustic and laryngeal signs and oral airflow amplitude), as well as parameters for speech disorders, articulation rate, speech inconsistency, and speech stimulability, are essential for better professional practice and to understand misarticulations in children with speech sound disorders (SSDs). Different equipments that enable noninvasive collection and analysis of data have become more common in speech-language pathology practice. Studies recently conducted by our research group have emphasized the evaluation of auditory-perceptual processing by means of assessments of central auditory processing, electrophysiology of hearing—considering that pure-tone, speech audiometry, and tympanometry are routinely used with children during the diagnostic phase and motor speech production performed by acoustic analysis of speech, electroglottography, aerodynamic measures, and ultrasound tongue imaging. This chapter presents the recent advances observed in studies with Brazilian-Portuguese speakers aiming to improve the assessment of speech sound disorders and to understand better the relationship between the different processing mechanisms involved in speech.",book:{id:"5957",slug:"advances-in-speech-language-pathology",title:"Advances in Speech-language Pathology",fullTitle:"Advances in Speech-language Pathology"},signatures:"Haydée Fiszbein Wertzner, Danira T. Francisco, Tatiane F. Barrozo\nand Luciana O. Pagan-Neves",authors:[{id:"204570",title:"Prof.",name:"Haydée",middleName:null,surname:"Wertzner",slug:"haydee-wertzner",fullName:"Haydée Wertzner"},{id:"204572",title:"MSc.",name:"Danira",middleName:null,surname:"Francisco",slug:"danira-francisco",fullName:"Danira Francisco"},{id:"204573",title:"MSc.",name:"Tatiane",middleName:null,surname:"Barrozo",slug:"tatiane-barrozo",fullName:"Tatiane Barrozo"},{id:"204574",title:"Dr.",name:"Luciana",middleName:null,surname:"Pagan-Neves",slug:"luciana-pagan-neves",fullName:"Luciana Pagan-Neves"}]}],onlineFirstChaptersFilter:{topicId:"238",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81605",title:"Primary Progressive Aphasia (PPA)",slug:"primary-progressive-aphasia-ppa",totalDownloads:12,totalDimensionsCites:0,doi:"10.5772/intechopen.104291",abstract:"Primary progressive aphasia (PPA) is a rare neurological condition that affects an individual’s ability to communicate. PPA is a syndrome characterized by a ‘progressive worsening of language with preservation of the activities of daily living and evidence of relatively normal non-verbal abilities on neuropsychological testing’. It commonly appears initially as a disorder of speaking (an articulatory problem) progressing to nearly total inability to speak in its most severe stage, while comprehension remains relatively preserved. This chapter provides an overview of the characteristic features of PPA, its classification, assessment, and rehabilitation options.",book:{id:"10889",title:"Aphasia Compendium",coverURL:"https://cdn.intechopen.com/books/images_new/10889.jpg"},signatures:"Yashaswini Channabasave Gowda and Hema Nagaraj"},{id:"79833",title:"A Comprehensive Overview of Broca’s Aphasia after Ischemic Stroke",slug:"a-comprehensive-overview-of-broca-s-aphasia-after-ischemic-stroke",totalDownloads:105,totalDimensionsCites:0,doi:"10.5772/intechopen.101560",abstract:"Aphasia denotes an acquired central disorder of language, which alters patient’s ability of understanding and/or producing spoken and written language. The main cause of aphasia is represented by ischemic stroke. The language disturbances are frequently combined into aphasic syndromes, contained in different vascular syndromes, which may suffer evolution/involution in the acute stage of ischemic stroke. The main determining factor of the vascular aphasia’s form is the infarct location. Broca’s aphasia is a non-fluent aphasia, comprising a wide range of symptoms (articulatory disturbances, paraphasias, agrammatism, anomia, and discrete comprehension disorders of spoken and written language) and is considered the third most common form of acute vascular aphasia, after global and Wernicke’s aphasia. It is caused by a lesion situated in the dominant cerebral hemisphere (the left one in right-handed persons), in those cortical regions vascularized by the superior division of the left middle cerebral artery (Broca’s area, the rolandic operculum, the insular cortex, subjacent white matter, centrum semiovale, the caudate nucleus head, the putamen, and the periventricular areas). The role of this chapter is to present the most important acquirements in the field of language and neurologic examination, diagnosis, and therapy of the patient with Broca’s aphasia secondary to ischemic stroke.",book:{id:"10889",title:"Aphasia Compendium",coverURL:"https://cdn.intechopen.com/books/images_new/10889.jpg"},signatures:"Dragoș Cătălin Jianu, Tihomir V. Ilic, Silviana Nina Jianu, Any Docu Axelerad, Claudiu Dumitru Bîrdac, Traian Flavius Dan, Anca Elena Gogu and Georgiana Munteanu"},{id:"79482",title:"The Importance of Aphasia Communication Groups",slug:"the-importance-of-aphasia-communication-groups",totalDownloads:151,totalDimensionsCites:1,doi:"10.5772/intechopen.101059",abstract:"Chronic aphasia is linked to poor functional recovery, depression, and social isolation. In the exploration of the above factors, the role of aphasia communication groups has evolved. Aphasia communication groups for stroke survivors with chronic aphasia and their communication buddies are gaining clinical importance. Communication buddies can be family members, friends, carers, health professionals, and speech and language therapy students who serve as communication facilitators for each group member. Group members share experiences on stroke and aphasia by using technology/tablets and the total communication approach. The benefits or outcomes of group involvement are measured by assessment of functional communication, individual self-ratings of the impact of aphasia on communication, and quality of life after stroke. The use of the communication buddy system, total communication approach, and systematic evaluations enables therapists to measure the effectiveness and efficacy of communication groups in terms of functional communication, social inclusion, and quality of life.",book:{id:"10889",title:"Aphasia Compendium",coverURL:"https://cdn.intechopen.com/books/images_new/10889.jpg"},signatures:"Marina Charalambous and Maria Kambanaros"},{id:"79728",title:"Imaging of Vascular Aphasia",slug:"imaging-of-vascular-aphasia",totalDownloads:98,totalDimensionsCites:0,doi:"10.5772/intechopen.101581",abstract:"Brain imaging is essential for the diagnosis of acute stroke and vascular aphasia. Magnetic resonance imaging (MRI) is the modality of choice for the etiological diagnosis of aphasia, the assessment of its severity, and the prediction of recovery. Diffusion weighted imaging is used to detect, localize, and quantify the extension of the irreversibly injured brain tissue called ischemic core. Perfusion weighted imaging (from MRI or CT) is useful to assess the extension of hypoperfused but salvageable tissue called penumbra. Functional imaging (positron emission tomography (PET), functional MRI (fMRI)) may help predicting recovery and is useful for the understanding of language networks and individual variability. This chapter is meant to review the state of the art of morphological and functional imaging of vascular aphasia and to illustrate the MRI profiles of different aphasic syndromes.",book:{id:"10889",title:"Aphasia Compendium",coverURL:"https://cdn.intechopen.com/books/images_new/10889.jpg"},signatures:"Loïc Duron, Augustin Lecler, Dragoș Cătălin Jianu, Raphaël Sadik and Julien Savatovsky"},{id:"79364",title:"Contributions of Linguistics to the Study of Aphasias: Focus on Discursive Approaches",slug:"contributions-of-linguistics-to-the-study-of-aphasias-focus-on-discursive-approaches",totalDownloads:88,totalDimensionsCites:0,doi:"10.5772/intechopen.101058",abstract:"The chapter aims to present and discuss the contributions of Linguistics to the study of aphasias, especially regarding the power of discursive theories to subsidize language assessment and therapeutic follow-up with aphasic individuals. Jakobson, in 1956, based on Saussure’s approach and on Luria’s neuropsychological theory, was the first scholar to call for the participation of linguists in this field, once “aphasia is a problem of language”. Nonetheless, aphasia does not disturb only linguistic formal levels – phonetical-phonological, syntactic, lexical-semantic –, but also pragmatic and discursive aspects of language that are constitutive of meaning processes involved in the social use of language. Unfortunately, more traditional approaches to language assessment and to the follow-up work are exclusively based on metalinguistic tasks, which do not take into consideration the subjective and contextual aspects of language functioning. The experience we have acquired over more than thirty years within the field of Neurolinguistics has shown that qualitative longitudinal researches – mainly case studies – are a privileged locus to seek for evidences of how the linguistic levels are impacted in the several forms of aphasia. Such understanding, in turn, favor the therapeutic work towards more contextualized activities, in order to help the individuals to reorganize their linguistic-cognitive processes.",book:{id:"10889",title:"Aphasia Compendium",coverURL:"https://cdn.intechopen.com/books/images_new/10889.jpg"},signatures:"Rosana do Carmo Novaes-Pinto and Arnaldo Rodrigues de Lima"},{id:"79198",title:"Treatment Approaches for Word Retrieval Deficits in Persons with Aphasia: Recent Advances",slug:"treatment-approaches-for-word-retrieval-deficits-in-persons-with-aphasia-recent-advances",totalDownloads:131,totalDimensionsCites:0,doi:"10.5772/intechopen.100828",abstract:"Word retrieval deficit is found to be one of the most persistent symptoms reported among the constellation of symptoms exhibited by persons with aphasia (PWAs). This deficit restraints the persons with aphasia to perform with ease across day-to-day conversations. As a consequence, PWAs fail to communicate their desired ideas or thoughts. Word retrieval is an intricate process as it entails various levels of processing. In addition, word retrieval breakdown can occur at multiple levels (semantic level or lexical-semantic level, or phonological level). Thus, there is a need for speech-language pathologists (SLPs) to treat this deficit through effective treatment approaches. In recent decades, semantic feature analysis, verb network strengthening treatment, and phonological component analysis have received greater focus and importance in treating word retrieval deficits. Many studies confirmed that the use of these treatment approaches on PWAs possesses a pivotal role in remediating word retrieval deficits.",book:{id:"10889",title:"Aphasia Compendium",coverURL:"https://cdn.intechopen.com/books/images_new/10889.jpg"},signatures:"Deepak Puttanna, Akshaya Swamy, Sathyapal Puri Goswami and Abhishek Budiguppe Panchakshari"}],onlineFirstChaptersTotal:7},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:8,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:286,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:9,numberOfPublishedChapters:101,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:11,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:1,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:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:null,scope:"