\r\n\tUnstoppable progress in the technologies of synthesis of diamond, graphene, and its compounds with stable parameters will provide materials for the industry of devices for integrated, radio, Opto- and quantum electronics and photonics.
\r\n\tIn most electronic and optical properties, diamond and graphene are superior to traditional and perspective semiconductors. It is safe to say that silicon and gallium arsenide are materials for electronics and optoelectronics of the past, gallium nitride and silicon carbide are high-tech today, and diamond and graphene are the future of electronics and photonics.
Many orthodontic patients complain about the physical and social discomfort which is associated with prolonged use of fixed appliances [1]. There are also numerous studies which report that dental and periodontal complications such as apical root resorption, subsequent gingivitis, periodontitis, enamel demineralization, increased levels of dental caries, and open gingival embrasure spaces may occur during orthodontic treatment [2].
\nHowever, a major challenge in orthodontics is to shorten treatment time by avoiding undesirable side effects without compromising treatment outcome. The rate of orthodontic tooth movement is primarily determined by the remodeling of tissues surrounding the roots; this in return is under the control of molecular mechanisms regulating cellular behaviors in the alveolar bone and periodontal ligament [3]. Assuming that the clinician optimized mechanics and cooperation for any patient, the main factor controlling the treatment time and rate will be the patient’s biological response to the orthodontic forces [4, 5]. Therefore, identifying and controlling the cellular regulators are essential to shorten orthodontic treatment time safely.
\nThe concept of accelerating tooth movement has received increased attention recently [6] with the introduction of various clinical techniques; including local injection of cellular mediators [7], physical or mechanical stimuli [8] and surgically assisted orthodontics [9, 10]. Local or systemic pharmaceutical administration and physical or mechanical stimulation methods might not be applicable to daily clinical practice because of their possible side effects and their outcomes that await validation [11]. Over the past decade, the regional acceleratory phenomenon induced by surgical trauma has received emphasis for accelerating orthodontic tooth movement and reducing the treatment time [11]. However, many techniques which are surgically assisted involve considerably high surgical trauma limiting application of the technique currently.
\nA new method which uses micro-osteoperforations (MOPs) to stimulate alveolar bone remodeling without the disadvantages of surgery such as the requirement of corticotomies, cuts in cortical bone, raising split-thickness flap, and decorticating the bone has recently been identified [5, 12]. Animal studies revealed that micro-osteoperforations significantly stimulate expression of inflammatory markers and increase the number of osteoclasts and bone resorption. The increase in bone remodeling contributes to the rise in both rate and magnitude of tooth movement [4]. In addition to the requirement of additional studies, similar results are reported in clinical trials [4, 5].
\nIn this chapter, we focused on the biologic basis of orthodontic tooth movement, accelerated tooth movement techniques and application methods, advantages, disadvantages, effects, and possible side effects of micro-osteoperforations as a new, reliable, repeatable and minimally invasive method for accelerating orthodontic tooth movement.
\nApplication of mechanical forces to teeth causes orthodontic tooth movement as a result of the biological responses of the periodontal tissues. Alveolar bone remodeling includes selective resorption in some areas and apposition in others. The biologic response to orthodontic therapy includes not only the response of the periodontal ligament and alveolar bone but also the response of growing areas which are distant from the dentition. However, it can be stated that tooth movement is primarily a periodontal ligament phenomenon because the alveolar bone response is also mediated by the periodontal ligament [13].
\nThe first step of the biological response to orthodontic force is “tension and compression in the periodontal ligament” which constricts and deforms blood vessels damaging cells in the periodontal tissues. The initial aseptic acute inflammatory response is realized by releasing chemokines and cytokines from localized cells such as osteoblast, fibroblast, and endothelial cells. Most of these cytokines are pro-inflammatory providing the continuity of the inflammatory response by activating osteoclast precursors of periodontal ligament in extravascular range and inflammatory cells. Infiltration of inflammatory cells causes the increase of chemokine and cytokine levels. This enables differentiation of osteoclast precursors to multinucleated giant cells which will realize alveolar bone resorption that is required for tooth movement. The continuity of the existence of anti-inflammatory chemokines and cytokines is essential in order to suppress destructive pro-inflammatory and osteolytic processes [4]. Therefore; the pro- and anti-inflammatory responses of alveolar bone, periodontal ligament, and inflammatory cells to orthodontic force are required to be known in order to develop safe methods to shorten orthodontic treatment period.
\nThe methods which accelerate tooth movement can be classified in three groups:
Chemical applications (local or systemic applications)
Mechanical-physical stimulations
Surgical-assisted techniques [14]
In this method, substances such as prostaglandins, corticosteroids, vitamin D, cytokines, neuropeptides, leukotrienes, nitric oxide, diazepam, and vasoactive medications, which are considered as physiological agents that transform mechanical forces into cellular response, are used to decrease the resistance to the strength applied during tooth movement that occurs within the cells and to change the environmental factors [15, 16].
\nTaking systemic effect rather than being limited to the applied area and affecting other target cells in the body are reported as a common side effect of using these hormones and medications [17]. Therefore, there is no medication treatment which safely accelerates tooth movement [18].
\nIt was reported that stimulating periodontal ligament mechanically or physically can increase alveolar bone remodeling and tooth movement accordingly. Physical methods frequently include equipment-assisted treatment methods [6] such as low-dose laser applications, electromagnetic field, direct electrical current, and vibrational applications. These methods take effect by inducing signal molecules such as receptor activator of nuclear factor-kappa B (RANK), receptor activator of nuclear factor-kappa B ligand (RANKL) pathway, mitogen-activated protein kinase (MAPK), c-fos, and nitric oxide [6, 19].
\nLow-dosage laser applications are reported to increase osteoblastic and osteoclastic activity by stimulating cellular proliferation and differentiation and accelerate orthodontic tooth movement without creating side effects on periodontal ligament [6, 20].
\nIt is also reported that electromagnetic field applications increased levels of a group of enzyme which is responsible from regulating intracellular metabolism and cellular proliferation accordingly by influencing sodium-calcium change speed in cell membrane [21]. Increase in osteoblastic and osteoclastic activity causes an acceleration in the tooth movement. Darendeliler et al. [22] reported that static magnetic field accelerated tooth movement by shortening unproductive period when no tooth movement is observed but the side effect can be a decrease in serum calcium and slight changes in the chemistry of blood.
\nApplying direct electric current is also among tooth acceleration techniques, but its clinical use is asserted as not appropriate due to some complications such as application difficulty, ionic reactions that cause damages in tissues, and replacing of bone tissue with connective tissue [23].
\nResonance vibration and ultrasonic vibration are also among the methods which are used to accelerate tooth movement. Resonance vibration is reported to increase release of peptide which is called RANKL within periodontal ligament and increase tooth movement rate by providing formation, function, and continuity of osteoclasts. Tooth movement can also be accelerated via ultrasonic vibration with the same mechanism but there is a risk that the heat can cause damage in the dental pulp [19].
\nThe most clinically used and predictable option with stable results among the techniques which accelerate tooth movement is the surgical-assisted technique; it is evaluated as a costly invasive method [6]. It is based on the idea that rapid tooth movement can be achieved by increasing the biological response which is formed in periodontal ligament and alveolar bone. Creating an injury in the bone is a potential physical mechanism which provides rapid tissue recovery. Higher regional tissue response during this tissue remodeling/regeneration period is called as regional acceleratory phenomenon (RAP) [24]. Regional acceleratory phenomenon is a complex physiological case in which initially osteoclastic activity and secondly bone density is decreased followed by a rapid osteoblastic activity and a remodeling process. Orthodontic tooth movement acceleration is provided via the increase in cytokine activity around the teeth and decrease in cortical bone resistance and formation of hyalinization tissue by activation of this recovery mechanisms [25]. The advantages of the dentoalveolar surgical intervention in orthodontic treatment of adult patients are reported as: (a) less treatment time, (b) avoidance of potential periodontal complications, (c) favorable direction of growth, and (d) extensive envelope of the tooth movement [26].
\nThey were first used by Heinrich Köle who stated that the basic resistance toward tooth movement was in cortical layer so by applying corticotomies and osteotomies might accelerate tooth movement by breaking the resistance [27]. Köle et al. applied vertical corticotomies between the roots of two adjacent teeth buccally and lingually and horizontal osteotomies subapically as to combine corticotomies buccal-lingually. They theorized that the segments which became “blocks of bone” move as a whole to achieve rapid tooth movement without devitalization in long-term monitoring. Düker et al. also reported that pulpal and periodontal tissues of the teeth which were applied orthodontic force similarly were not damaged in their study on dogs with reference to Köle’s corticotomies [28].
\nAlthough Köle and Düker proposed the opposite, periodontal and pulpal damages can be formed following invasive horizontal subapical osteotomies [29]. Additionally, osteotomy surgery is an invasive intervention with possible complications such as vascular and nerve damages so it is not a widely accepted method [30]. Nonetheless, Köle’s studies pioneered surgery-assisted methods which accelerate tooth movement to be involved in the literature of modern orthodontics.
\nKöle’s horizontal subapical osteotomies were changed with horizontal subapical corticotomies by Gantes et al. [31] and Suya [32] and it was stated that treatment of the cases was completed in almost 50% less period when compared to conventional methods. Gantes et al. [31] reported that overall vitality of the tooth was preserved and none of the patients had a periodontal damage that can be clinically recognized despite minimal root resorptions and gingival recession. Suya [32] asserted that corticotomy-assisted orthodontics had less root resorption and relapse risk and pain when compared to traditional treatments. In a recent study, Uzuner et al. [33] reported that corticotomy-assisted orthodontics increased the rate of tooth movement during canine retraction in 20% ratio and also relative bodily movement was achieved with the corticotomy-combined treatment.
\nThe method was introduced to orthodontic literature by Liou and Huang [34]. Initially, a distractor device which consists of canine and molar bands was applied to the patients by the researchers and following extraction of upper first premolar teeth, surgical preparation phase which consists of two vertical channels formed buccally and lingually toward canine teeth through the extraction socket and a horizontal incision on the base of the extraction socket that connects the channels was completed at the same session. Interseptal bone was not cut mesiodistally during the surgical intervention. Activation was carried out without a need for latent period different from traditional distraction method and distalization of canine teeth was completed in a short period of 3 weeks with minimal anchorage loss. None of the patients suffered from pain and minimal resorption was observed in the roots of canine teeth in the radiographies at the end of procedure. Suggesting to be used especially in orthodontic treatments with primary premolar extraction which has anterior crowded teeth, Liou and Huang [34] associate the periodontal ligament distraction with this method to the distraction which is formed in midpalatal suture during rapid maxillary expansion.
\nThe method was introduced by Kişnişci et al. [35] in 2002. The researchers applied a distraction device before teeth extraction as in periodontal ligament distraction method but a more rigid device was used. Initially, the osteotomy curved apically at a distance of 3–5 mm from the apex of the canine at the same session with the primary premolar tooth extraction as a surgical preparation. Cortical bone which remained in the buccal of the socket after the extraction was carefully removed. Direct distraction was applied by skipping latent period similar to periodontal ligament distraction method. Canine distraction was reported to be completed within 8–12 days without anchorage loss. Root resorption or vitality loss was not observed in the posttreatment evaluations.
\nAlthough a faster canine distalization is achieved with less teeth tilting in dentoalveolar distraction method when compared to periodontal ligament distraction method, it is clear to be a more invasive method [36].
\nThe method which is known as “Wilckodontics” or “periodontally accelerated osteogenic orthodontics” was introduced by Wilcko and Wilcko [9, 37, 38, 39, 40]. According to the researchers, achieving optimal tooth movement is possible by forming a bone layer of 1.5 mm or less on the root surface in the direction of movement in corticotomy-assisted orthodontic treatment. When the force is applied, soft tissue matrix and osteoid islets remaining from the demineralized layer move with the root and remineralized when the orthodontic movement is completed. Wilcko brothers explained the acceleration of tooth movement following corticotomy with demineralization-remineralization period that is generated from rapid osteoclastic activity in alveolar bone in the beginning of “regional acceleratory phenomenon” which was introduced by Frost [24]. According to this mechanism, less resorption and rapid orthodontic tooth movement is achieved as a result of the decrease in alveolar bone density and increased metabolic activity in bone tissue. Thus, the term “movement of bone blocks” which was defined by Köle [27] was replaced with the term “bone matrix transplantation.”
\nWilcko and Wilcko discussed the need for applying a bone graft in order to prevent dehiscences, fenestrations, and relapses which can occur in posttreatment period due to the decrease in alveolar bone density within the cases with buccal move of the roots or thin buccal bones following corticotomy. They proposed to use resorbable bone graft by saturating clindamycin phosphate or platelet-rich plasma and creating circular perforations on the surface of the bone in order to increase blooding of graft material if the cortical bone thickness is sufficient [37]. The applied surgery apart from this procedure is almost the same with Suya procedure [32]. In this technique, bonding and applying forces to teeth is initiated 1 week earlier from the surgical intervention and biweekly orthodontic examinations are recommended.
\nTreatments are completed in three or four times shorter periods with “periodontally accelerated osteogenic orthodontics” method when compared to traditional orthodontic treatments besides its increased root resorption and relapse risks. Its need for additional surgical intervention with an extra cost, possibility of bone loss in alveolar crest, and gingival recession following the surgery and surgical complications such as pain and edema are among the disadvantages of the procedure.
\nThe necessity to remove flaps during corticotomy-assisted orthodontic treatment makes the method invasive, decreasing its acceptability by the patients and clinicians. Therefore, corticision was introduced by Park et al. [41] as an alternative approach for corticotomy procedures. The researchers made the patients rinse their mouth with an antiseptic mouthwash and then placed a stabilized scalpel on the attached gingiva interradicularly as to make an angle of 45–60 with the long axle of root of the teeth and applied cortical incisions via a surgical hammer without removing flaps [42]. Incisions were applied as 2/3 of the roots vertically and in 10 mm depth. Corticision area must be cleaned with physiological saline solution until hemorrhage stops. Park reported that fixed orthodontic treatment of a patient without extraction was completed in a short period of 10 months through this method. Although corticision method is minimally invasive with a short surgical intervention, it is not widely accepted as it is not appropriate to grafting and the surgical technique is disturbing for the patience.
\nIn 2009, Dibart et al. [43] introduced a minimally invasive technique that can be applied by piezosurgical tools, the piezoincision method, which can be carried out without any flap surgery as in corticision method but it allows hard or soft tissue grafting differently. In this method, small piezoelectric incisions are placed in the area from the targeted corticotomy area to periost. Piezoincisions of 3 mm length and depth are applied with the piezosaw without removing mucoperiosteal flap. In this stage, mucoperiosteal flap can be removed as a tunnel and a bone graft in pad form can be replaced if necessary. Sutures are required if grafting is applied, otherwise there is no need for sutures. It was reported that no significant difference was found in terms of tooth movement speed and root resorption in the studies which compare corticotomy-assisted methods with piezoincision method [44].
\nPiezoincision is a practical, minimally invasive, and effective method. Additionally, ultrasonic vibrations which occur during the procedure in piezoincision method also contribute to accelerate tooth movement [3]. Required precautions must be taken before the procedure with patients in high-risk group due to possibility of temporary bacteremia formation risk following the procedure.
\n“Piezopuncture” method, which is applied by using an ultrasonic piezosurgical tool, “piezotome” without gingival incisions in piezoincision method was developed by Kim et al. [45]. In their study on 10 dogs, the researchers created several cortical punctures both buccally and lingually on the mesial and distal sides of the teeth which will be moved and reported that anabolic activity and tooth movement were accelerated at the end of the procedure. Omidkhoda et al. who carried out piezopuncture technique on human reported that tooth movement was accelerated but they observed distal tilt in the canine teeth crowns in their case reports which consist of two cases [46].
\n“Piezopuncture” method also takes part in literature as a method with promising positive results but it must be evaluated by further clinical studies.
\nOrthodontic tooth movement is a biological response which is created by an external force that will prevent the dentofacial complex to be in physiological balance [13]. Orthodontic force creates an aseptic inflammatory response in periodontal tissues. An increase on vascular permeability and cellular infiltration of leucocytes was reported in the early period of orthodontic tooth movement [47]. Along with native cells such as osteoblasts and fibroblasts, migrated immune cells produce inflammatory cytokines that include chemotactic factors, growth factor, monocyte-derived factor, lymphocyte, and colony-stimulating factors [48, 49]. The gingival crevicular fluid of moving teeth includes tumor necrosis factor-α (TNFα), interleukin-1 (IL-1), IL-2, IL-3, IL-6, IL-8, osteoclast differentiation factor, and interferon-γ (IFNγ) [48, 50].
\nOrthodontic tooth movement rate is basically found associated with the rate of bone resorption which is controlled by osteoclast activity [51]. Therefore, any factors which effect activities of osteoclast precursor cells and their transformations into osteoclasts can be assumed to have significant effects on orthodontic tooth movement. There are a lot of researches that report the increase in the activity of inflammatory markers such as chemokines and cytokines as a response to orthodontic forces [5, 25]. It is reported that several cytokines which play role in osteoclast formation and activity such as TNFα, IL-1, and IL-6 are found in gingival crevicular fluid during orthodontic tooth movement [25]. Although the roles of chemokines and cytokines during orthodontic treatment are not clearly known, they are valued as essential mediators for orthodontic tooth movement in terms of their significant roles on differentiation and activity of osteoclast cells [52, 53, 54]. Significant decrease on orthodontic tooth movement rate within the studies in which the effects of these markers are blocked via different techniques such as anti-inflammatory medication or genetic manipulation can be accepted as a proof that these factors are extremely efficient on orthodontic tooth movement rate [55, 56, 57]. Previous studies represent that surgical interventions which cause minor bone traumas increase inflammatory cytokines, bone remodeling, and orthodontic tooth movement acceleration together with regional bone density [24, 58]. Surgery-assisted techniques which are applied in order to accelerate orthodontic tooth movement should be studied under subtitles such as corticotomy and osteotomy techniques, dental distraction technique, perisegmental corticotomy, and piezoincision. Corticotomy-assisted orthodontic treatment increases bone remodeling which accelerates recovery and repair mechanisms and tooth movement rate accordingly by creating a mechanical trauma in cortical bone [59]. Although corticotomy-assisted orthodontic treatment was reported to be an efficient method in accelerating tooth movement, the significance of removing flaps is also stated to cause important postoperative complications [60]. Piezoincision technique, which is a minimally invasive technique that includes piezoelectric incisions without removing flaps, was developed in order to overcome these disadvantages [43]. Piezoincision is known to be an effective method for acceleration of tooth movement but it was reported to have high risks of damaging tooth roots [18]. Surgery-assisted techniques are invasive with disadvantages such as bone loss, postoperative pain, edema and infection, avascular necrosis besides low acceptance rates by the patients [37, 40]. Based on this, the hypothesis that small osteoperforations on cortical bone without removing flaps will increase bone remodeling and tooth movement rate accordingly by stimulating release of inflammatory cytokines minimizing these disadvantages was developed (Figure 1). Micro-osteoperforation is an up-to-date procedure which is promoted as an auxiliary dentoalveolar procedure which can accelerate tooth movement via minimum surgical interventions.
\nMicro-osteoperforations on cortical bone increase bone remodeling and tooth movement rate by stimulating release of inflammatory cytokines.
In their animal study in 2010, Teixeira et al. [25] classified 48 rats, which were applied experimental orthodontic tooth movement, into four groups as one group with only orthodontic forces, a group via application of soft tissue flaps together with orthodontic force, a group that was applied 3 small perforations on cortical plate with soft tissue flaps together and orthodontic force and a control group. The researchers stated that they formed the microperforations in the cortical bone by using a round bur and handpiece. It was observed that at the end of experimental tooth movement period, release of 37 out of the 92 cytokines increased in all experimental groups and 21 of them were at the maximum level in the group which was applied perforation. In addition to that, light and fluorescent microscopy, microcomputed tomography, and immunohistochemistry examinations, which were carried at the end of the experiment, represented a significant increase in osteoclast number which accompanied by generalized osteoporosis and orthodontic tooth rate besides bone remodeling activity [25]. Similar to previous studies, researchers also demonstrated that the increase in bone remodeling was not limited around the loaded teeth but also involved the periodontal structures of the adjacent teeth. The researchers, who argued that the observed effects of osteoperforations on tooth movement can be related to loss in bone structure rather than release of increased inflammatory cytokine, stated that perforations were applied in the smallest amount and number possible and the remaining cortical bone was healthy in order to minimize this possibility. These findings also represent that the perforations that will be applied in order to accelerate tooth movement rate are not necessarily be adjacent to the moved teeth. Stating that inflammation can cause negative effects on periodontium and tooth structure when it is uncontrolled because it is a double-sided injury, it is also reported that applying micro-osteoperforations instead of some surgical interventions such as corticotomy, which are applied for acceleration of tooth movement, can minimize the side effects.
\nTsai et al. [11] applied both micro-osteoperforations and corticision without removing flaps different from the previous studies and evaluated the differences between the procedures in their animal study which was carried out to evaluate the effects of micro-osteoperforations and corticisions on orthodontic tooth movement rate. It was stated that bone and bone mineral densities were significantly decreased when compared to control group and tooth movement rate was increased in both groups without any significant difference. The rise in tooth movement rate in both groups in this study is smaller than the previous studies. The researchers, who stated that there might be a direct proportion between trauma amount and remodeling rate, reported that the difference was resulted from the smaller amount of the trauma as the flap was not removed.
\nIn 2016, Cheung et al. [12] published a study which evaluated the effectiveness of micro-osteoperforations. Mini-implants were used in order to form micro-osteoperforations different from the previous animal studies and the existence of external apical root resorption was evaluated following the procedure. Similar to previous studies, it was observed that there was a decrease on the density and volume of the bone surrounding moved molar teeth compared with the control side besides the acceleration of orthodontics tooth movement on the side where micro-osteoperforations were applied in the split mouth design study with six rats. Histological examinations also showed that new bone formation increased as well as osteoclast numbers on the side with micro-osteoperforations. This is a proof of the existence of osteoclasts-osteoblast coupling formation with decortication. Despite the fact that resorption and new bone formation were represented together, bone fraction volume and bone mineral density was decreased, which shows that resorption was more than new bone formation during tooth movement period. Contrary to conventional theories which assert osteoclast activity is limited to pressure area, the recent studies show that periodontium was remodeled as a single unit [61]. This study also shows that osteoclast rate in all alveolar bone surrounding the moving teeth is clearly on the pressure areas.
\nAlikhani et al. [5] designed a clinical trial to evaluate tooth movement with or without micro-osteoperforations in order to investigate whether this phenomenon occurs in human or not. They called the technique of creating micro-osteoperforations in the bone as “alveocentesis.” In their study, 20 adults were divided into 2 groups as control and experimental groups. Micro-osteoperforations were applied in the experimental group on one side of the maxilla using a disposable micro-osteoperforation device designed for this purpose by Propel Orthodontics (Ossining NY) and the control group did not receive any micro-osteoperforations. Following 28 days of canine retraction period, amount of the tooth movement was measured and also the activity of inflammatory mediators was determined in gingival crevicular fluid with an antibody-based protein assay. Additionally, the presence of pain or discomfort was evaluated with a numeric rating scale. Results of this first clinical trial about micro-osteoperforations in the literature reported significant increase in the levels of inflammatory markers and also 2.3-times rise in the rate of tooth movement with micro-osteoperforations. However, significant pain or discomfort during or after the procedure was not reported by the patients; also, any other complications were not observed.
\nIt was stated that orthognathic surgery, corticotomies (applying several incisions and perforations with removing flaps), piezoincision (creating injury on the bone with small incisions without removing flaps via a piezoelectric device), and even tooth extractions will increase the release of inflammatory markers and bone remodeling by creating injuries similar to micro-osteoperforations on alveolar bone effecting the rate of tooth movement accordingly [5]. Unfortunately, increase of inflammatory marker release cannot continue for a long period of time and a decrease in cytokine activity is observed regardless of the severity of the trauma after 2–3 months [4] which reveals the necessity for repeating the procedure during orthodontic treatment. Therefore, the extraction is suggested to be applied at the same time with major tooth movement for the patients whose tooth is planned to be extracted. There will not be a need for micro-osteoperforation requirement to accelerate tooth movement process as remodeling will speed up. In other words, it would be appropriate to prefer micro-osteoperforations in the treatments without tooth extraction or when extraction is carried out long after the orthodontic treatment because its effects are similar to tooth extraction. It is considered that as the level of trauma increases, inflammatory response will also rise. The rise on tooth movement rate when micro-osteoperforation number is increased can be shown as a proof. It was stated that regional acceleratory phenomenon (RAP) took effect in 1 or 2 days following the surgical intervention and reached its maximum level in 1 or 2 months [9]. Aboul-Ela et al. [59], Al-Naoum et al. [62], and Leethanakul et al. [63] reported that tooth movement speed was high during 2 months following the creation of traumas in cortical layers but it gradually decreased in this period. Alikhani et al. also stated that cytokine activity decreased after 2 months following micro-osteoperforation so they proposed that the procedure shall be repeated after a month break [4]. Micro-osteoperforations are repeatable which can be considered as an advantage because application time can affect the results in all surgically assisted procedures. On the other hand, there is not a clear information on how frequently micro-osteoperforations can be applied in order to achieve an optimum acceleration in tooth movement rate.
\nIn a recent thesis study in Akdeniz University, Faculty of Dentistry, Department of Orthodontics (Antalya, Turkey), efficiency of micro-osteoperforations on molar distalization rate with cervical headgear was evaluated on 3D digital models [64]. About 17 patients whose molar relations were bilateral class II (minimum teeth to teeth) with class I skeletal anomalies or normal or low vertical growth pattern were included in the study which is regarded as the first study to evaluate the efficiency of micro-osteoperforations on molar distalization. Propel device (Ossining, NY) was used to form three micro-osteoperforations—one mesially and two distally—of 1.5 diameter and 5 mm depth on a random molar teeth, in the session where distalization was initiated with cervical headgears in the split-mouth designed study. Micro-osteoperforations were renewed at least twice during the distalization period every 8 weeks in each sample. The procedure continued until class I relationship was achieved on the side where tooth movement was considered to be slower. Studies were carried out on 3D digital models which were taken just before and after molar distalization in order to compare molar distalization rate and tilt and rotation rate in molar teeth. While no significant difference was observed between tilting and rotation rates, it was concluded that on the micro-osteoperforation side, more tooth movement was seen.
\nLee et al. [65], who stated that in the studies which evaluated the efficiency of micro-osteoperforations on orthodontic tooth movement, micro-osteoperforations were generally applied on healthy alveolar bone, planned a study considering that the effects of bone remodeling process that was activated by applying orthodontic tooth movement and micro-osteoperforations on the atrophic ridge could be different. The researchers, who created atrophic alveolar ridge model on eight beagle dogs, evaluated tooth movement rates and atrophic alveolar ridge area on the sides with and without osteoperforations in their study which they planned via split mouth design. Micro-CT based histomorphometry analysis similar to the previous studies suggested that osteoperforations accelerated tooth movement with a decrease in bone density without any differences in atrophic ridge volume. This up-to-date finding can be evaluated as an indicator that the efficiency of micro-osteoperforations on bone remodeling is more related to resorption mechanism and osteoclast activation.
\nIn the literature, there is a limited number of studies which evaluate the effects of micro-osteoperforations on tooth movement in human. Current studies indicate that micro-osteoperforation is a safe method that can accelerate tooth movement but it must be taken into consideration that several factors such as occlusal relations, movement type, applied mechanics, age and gender of the patient, oral hygiene, periodontal illnesses, alveolar bone loss, systemic diseases, and medication use effect tooth movement rate in human. Therefore, the efficiency of micro-osteoperforations must be evaluated with long-term studies in which study groups are standardized as much as possible considering these variable where different tooth movement types (distalization, intrusion, eruption of impacted tooth, etc.) and mechanics are applied containing more sample numbers.
\nMicro-osteoperforation is an up-to-date method among the surgery-assisted techniques of accelerating tooth movement. Therefore, in the literature, there are studies in which different methods are used in order to create MOPs on alveolar bones.
\nWe observe that low-speed handpiece and round bur combinations [11, 25] and mini-implants [12] are used within the animal studies which evaluate effects of MOPs on tooth movement and both methods are accepted as effective. Even if in a limited number of clinical trial; micro-osteoperforations are typically applied with a handheld disposable appliance designed by Propel Orthodontics (Ossining, NY). Propel is an appliance which is designed to apply alveocentesis procedure. The foremost part of the device which is like an orthodontic stainless steel screw is patented, allowing perforation of alveolar bone traumatically over keratinized gingiva and moving mucosa. Contrary to other rotatory devices, Propel was reported to have a slight effect on soft issue. It is a device which enables tissue remodeling and micro-osteoperforations between tooth roots over both stable and moving tissue of 1.5 mm diameter and 3, 5, and 7 mm depth without flap surgery in order to accelerate tooth movement. The appliance has an adjustable length and a light signal that turns on when the clinician achieved desired depth [5, 64]. Micro-osteoperforations, which are applied on the defined depth, reach to medullar bone from cortical bone increasing inflammatory mediators. The device was also reported not to cause soft tissue damage while enabling remodeling process [5].
\nWhile it is not always possible to create homogenous perforations of same size using micro-osteoperforation methods such as round burs, Propel device which is designed in order to form MOPs has not included in routine clinical use yet. Thus, mini-implants are considered more advantageous than other methods as they are included in clinical routine and frequently used by orthodontists for different purposes and easily tolerated by the patients. On the other hand, in the literature, there are limited studies in which mini-implant-facilitated micro-osteoperforations are carried out with human. Aksakalli et al. [66] applied three micro-osteoperforations distal to the canine teeth with miniscrews just before canine distalization period. In their case report, they reported that MOP method with miniscrews accelerated canine distalization in their 14-year-old male patient with class II malocclusion by almost 1.5-fold and also without harmful effects on root and periodontal structures. On the contrary, Alkebsi et al. [67] could not find any differences of anchorage loss, canine rotation, and tipping between the MOP and control sides in their randomized controlled clinical trial where they investigated the effectiveness of miniscrew-facilitated MOPs on the rate of canine distalization.
\nAll of the methods are applied without a need for additional periodontal surgeries which is considered as a significant advantage but additional clinical studies are required in order to evaluate the efficiency of each technique and their advantages and disadvantages over each other in detail.
\nWhen micro-osteoperforations are compared with several surgical techniques, which are proved to accelerate tooth movement, they are considered as more advantageous because they are less invasive with no need for removing flaps eliminating possible side effects of the surgery [4, 5]. Additionally, all techniques which make use of micro-osteoperforation do not include an invasive surgical procedure represent that they are easily applicable in the clinics by the orthodontists and can be added to clinical routine. Patients did not report any pain or discomfort in the clinical studies with micro-osteoperforations which shows that it is easily accepted and tolerated by the patients who are under orthodontic treatment [5, 64]. These advantages also enable the micro-osteoperforations to be periodically repeated until the desired results are achieved [4, 64].
\nThere is a limited number of studies that evaluate patients’ pain and discomfort levels among the clinical studies in which micro-osteoperforations are applied. Alikhani et al. [5] asked their patients to scale their pain and discomfort levels via a numeric rating scale on the day they replaced the device, the day they began canine distalization, 24 h, 7th and 28th days after canine distalization in their study in which they evaluated the effect of micro-osteoperforations on canine distalization. In this scale, which is reported as having high credibility, “0” presents no pain, while “10” stands for the existence of the worst pain. Data analyses showed that the patients had the most pain in 24 h following canine distalization but no significant difference was observed between experimental and control groups. The patients defined a slight and resistible pain on the micro-osteoperforation side which does not require taking painkillers but no statically significant difference was found. The similar feedbacks were taken in Boz’s thesis study in 2018 concluding that micro-osteoperforations did not cause a significant pain or discomfort [64]. In line with these findings, it is possible to state that micro-osteoperforations are easily tolerated by the patients and can be applied to routine clinical use.
\nOrthodontically induced inflammatory root resorption (OIIRR) is included in negative side effects of orthodontic tooth movement as a frequent research subject. Although its etiology and predictors are not fully understood, it is considered to be resulted from complex interaction of individual sensitivity [68], applied mechanics [69, 70], and specific dental predisposition [71]. Orthodontically induced inflammatory root resorption was stated to be related with periodontal ligament remodeling which is a result of the pressure applied to tooth root during tooth movement and removal of hyalinized necrotic tissues after trauma. Excessive pressure that causes ischemic necrosis [72] of periodontal ligament and root resorption related to orthodontic tooth movement is reported to be frequently observed in the areas in which excessive pressure is applied to periodontal ligament [73]. The underlying biological process of both orthodontic tooth movement and root resorption covers local inflammatory response. Animal studies show that many pro-inflammatory cytokines are common in both pathways. Cytokines such as IL-1, TNFα, and chemokines as IL-8 and MCP-1 are known to have significant roles to initiate and ease root resorption process [74]. These inflammatory mediators have significant roles on activation of tooth movement and osteoclast activity [75]. Inhibition of cytokine activity decreases osteoclast and odontoclast rate as well as tooth movement and root resorption [76]. It is known that accelerated tooth movement techniques increase inflammatory cytokine activation.
\nIn the literature, there are several studies that evaluate the effects of accelerated tooth movement and decortication on root resorption [5]. The cytokines which promote inflammation are also reported to activate cementoclasts which cause root resorption increasing root resorption risk accordingly [77]. On the contrary, there are findings in the literature which state that decortication and demineralization of alveolar bone decrease the pressure toward tooth movement enabling an ease for the movement and decreasing root resorption risk accordingly [12]. It was found out that the effects of tooth movement accelerated via corticotomy on orthodontically induced inflammatory root resorption were similar to conventional orthodontic treatment but it was also reported that periapical radiographies may not be reliable for assessing root resorption in two studies which was carried out by evaluation of periapical radiographies [78, 79]. In an animal study which evaluates the effects of corticotomies on tooth movement, it was found out that there were not any differences between control and experimental groups in terms of root resorption [80].
\nIn the literature, there is a limited number of studies which evaluates the effects of micro-osteoperforations on root resorption. Tsai et al. reported in their study in which they compared the efficiency of micro-osteoperforations and corticisions that root resorption creation risk of minor surgical interventions is lower when compared with conventional orthodontic treatments. The hematoxylin and eosin analysis of the researchers showed that micro-osteoperforation-assisted accelerated tooth movement was resulted in decreased root resorption [11]. Similarly, in the study in which Cheung et al. evaluated effects of micro-osteoperforations on experimental tooth movement in rats, root resorption was observed on the MOP application side on the samples which were colored with hematoxylin eosin reporting that 3D volumetric analysis did not show any volumetric difference in the root of upper molar teeth which was moved [12]. Although all findings support the idea that micro-osteoperforations do not increase root resorption risk showing that mini-implants can be safely used for MOP procedures in terms of root resorption, it is clear that there is a need for further supportive studies with increased sample number.
\nCheung et al. [12] included 20 patients whose upper primary premolars are planned to be extracted for orthodontic purposes in their study which is known as the initial clinical study to evaluate the effects of MOPs on OIRR. About 150 g buccal tipping force was applied to premolar tooth which was planned to be extracted and micro-osteoperforations of 5 mm depth were applied to mesial and distal parts of the premolar teeth on the experimental side via Propel device (Propel Orthodontics, San Jose, Calif) evaluating the patient’s opposite side as the control group. Following 28 days of tooth movement period, premolar tooth on both sides was extracted and examined by microcomputed tomography, volumes of root resorption craters were calculated and compared. Volumetric root loss average of the premolar tooth on the side which micro-osteoperforations are applied was found to be 42% more than the premolars on the control side. The researchers represented that the side to be applied micro-osteoperforations was not randomly selected (decision was taken in accordance with the availability of the distance between the roots) and evaluation was carried out following a short-term tooth movement as the limitations of the study and suggested further studies with treatments of longer terms and larger sample numbers. Nonetheless, when the findings of the study are considered, it can be stated that special attention shall be paid on planning micro-osteoperforations with patients who are individually prone to root resorption.
\nAs a result, there are studies which report that micro-osteoperforations can cause positive and negative effects on root resorption. Their relations were not clearly explained so there is a need for further studies.
\n\n
Among several techniques which are defined to accelerate orthodontic tooth movement and treatment periods accordingly, due to numerous studies, surgical techniques that have the most predictable results have been an essential part of modern orthodontics.
Micro-osteoperforations are outstanding as a minimal invasive, easy-to-use, repeatable, and efficient new method that can eliminate some disadvantages of surgery among the defined invasive techniques.
Experimental studies have proved that micro-osteoperforations accelerated bone remodeling process and orthodontic tooth movement accordingly together with an increase in osteoclast number and new bone formation and a decrease on bone volume and density. A limited number of clinical studies also support the findings.
Different techniques are defined to apply micro-osteoperforation in the literature but there is a need for studies that evaluate differences between techniques in order to determine the ideal method.
Further studies are required for the ideal timing and frequency of the application in order to achieve optimum tooth movement acceleration.
Although it is reported that side effects such as pain or root resorption are not observed due to micro-osteoperforations, long-term studies with more samples are required.
I declare that I have no conflict of interest regarding the publication of this chapter.
Traditionally the process of mechanical homogenization has been employed in the laboratory setting for the disruption of animal or plant tissues in preparation for downstream molecular applications [1]. However, in the face of a global pandemic this technology has been adapted to increase efficacy and efficiency in viral detection in a variety of COVID-19 diagnostic workflows [2, 3, 4].
As the global community began to respond to the spread of SARS-CoV-2, the expansion of public health surveillance programs and community testing protocols became critical objectives [5]. However, the need for rapid expansion in testing capacity caused a tremendous strain on the supply chains providing the equipment and reagents traditionally needed for respiratory virus PCR-based testing [6]. As in most cases, necessity drove innovation. Given the large number of research and academic laboratories equipped to assist in PCR testing, many groups began to offer their assistance in processing patient samples while others began examining novel approaches to viral detection which circumvented the supply chain bottle necks. During the development of these novel testing protocols laboratory safety, diagnostic assay sensitivity and specificity became top priority [5, 6, 7]. In an attempt to utilize common laboratory equipment to safely speed up testing efforts, the use of mechanical homogenization was proposed to inactivate the SARS-CoV-2 from nasopharyngeal swabs as a method of increasing safety during processing [2, 3, 4, 8].
In brief, mechanical homogenization is the process of using shearing forces applied via mechanical grinding media and rigorous repetitive motion to dissociates a given sample [1]. The parameters at which a sample is processed will impact the degree to which it is dissociated and the quality of the targeted product for downstream applications [1]. In the case of SARS-CoV-2, the goal of mechanical homogenization was to disrupt the viral envelope while still maintaining the integrity of its RNA [2, 3]. This allowed for a reduction in infective potential in the laboratory setting, while preserving the accuracy of polymerase chain reaction (PCR) based diagnostic assays [2, 3].
Following the initial application of mechanical homogenization to COVID-19 swab-based PCR protocols, this technology was adapted to process saliva samples for both antigen and PCR detection workflows [2, 3, 4]. Through mechanical homogenization, high viscosity saliva samples were sufficiently processed to allow for automation integration, paving the way for the widespread application of this novel methodology [4, 9].
In this chapter we will further explore the applications of homogenization in response to the COVID-19 pandemic and the multiple diagnostic methodologies this technology has been implemented in and its impact on laboratory safety and overall testing efficiency.
During the late spring of 2020, while SARS-CoV-2 was spreading exponentially and uncontrollably across the globe, testing for this disease was focused entirely on RT-qPCR detection of the virus using US CDC or WHO approved primers [5, 10]. The traditional method for these types of RT-qPCR tests involved two major components. First, the process of virus inactivation and RNA extraction completed through a series of chemical reactions that resulted in purified viral RNA from the provided patient sample [5, 6, 10]. The extracted RNA was then utilized in the second half of this method, amplification and detection [5, 6, 10]. Through RT-qPCR, the purified RNA from the patient sample was combined with the preapproved primers for attempted amplification of the targeted genes, indicating the presence or absence of SARS-CoV-2 depending on the level of amplification seen [5, 6, 10]. The RNA amplification was quantified and reported out as a Cq value, with any Cq less than 40 qualifying as a COVID-19 positive sample per the US CDC and WHO guidelines [10].
The necessity of testing drove up demand for all reagents, machines, and plastics utilized in the RT-qPCR testing method, overstressing the supply chain for these products [5, 8, 9]. Additionally, the need for cold storage of reagents involved in the extraction process and the high price tag on the automated machinery needed to complete both the extraction and detection phases of the traditional testing method, furthered the gap between resource challenged areas and the industrialized regions when it came to COVID-19 testing infrastructure [11, 12]. Areas with the capital needed to create multimillion dollar testing facilities were able to do so, improving their public health response to the pandemic, while those lacking that investment and infrastructure were left with reduced testing capabilities [11]. A critical need arose for a cost efficient, yet safe and effective testing methodology that could be implemented in these resources challenged settings [8, 11].
While the utility of mechanical homogenization in COVID-19 testing was already established as an effective adjunct to the extraction process, improving sensitivity through efficient viral lysis, this process was expanded upon in an attempt to remove the extraction process entirely allowing for direct detection of SARS-CoV-2 from lysed patient samples [2, 3]. The direct-to-PCR approach for COVID-19 testing arose out of necessity to reduce the use of costly reagents in a period where the strain on the supply chain made them difficult to come by [2, 3, 8]. Additionally, this proposed method dramatically reduces cost when compared with the fully automated extraction machinery [2, 3, 8].
In the direct-to-PCR method for viral detection, shaker mill mechanical homogenization was proposed to provide sufficient viral lysis off nasopharyngeal swabs to expose adequate amounts of RNA for RT-qPCR detection [2, 3]. This method was shown to lyse greater than 95% of virus off a nasopharyngeal swab, allowing the resultant lysate to be placed directly into the RT-qPCR reaction as denoted in Figure 1 [2, 3].
The direct-to-PCR viral detection methodology using shaker mill homogenization off nasopharyngeal swabs.
Through proof-of-concept testing with a close relative of SARS-CoV-2, human coronavirus 229E (HCoV-229E), and direct comparison studies between the traditional extraction-based method and the direct-to-PCR method, it was shown that the two methods had above a 94% agreeability in the detection of positive samples [2, 3]. Utilizing the direct-to-PCR method diagrammed in Figure 1, shaker mill homogenization was proven to be a viable alternative to the traditional extraction-based method for RT-qPCR detection of SARS-CoV-2 off nasopharyngeal swabs [2, 3].
In addition to the quality of the matched proven efficacy with the traditional, extraction-based methodology, the direct-to-PCR method described utilizing mechanical homogenization also reduces the total cost and time per swab processed [2, 3, 8]. The traditional model for nasopharyngeal swab viral testing cost $10 - $40 USD per swab, when taking into account the extraction kits, automation equipment for extractions, and the RT-qPCR set up [8]. Compared to $3 - $5 USD per swab with the homogenization methodology, given that this workflow does not require additional reagents for viral nucleotide extraction and purification, the only reagent costs are associated with the final RT-qPCR testing [8]. The homogenization equipment utilized in this workflow is sold at a fraction of the cost of the large fully automated extraction machinery.
Along with reducing cost per sample the homogenization workflow reduces the total processing time per sample from approximately 3 hours to 1 hour and 15 minutes [2, 3]. This is accomplished through replacing the extraction and purification steps of the traditional workflow with a 30 sec homogenization step preceding the RT-qPCR [2, 3]. Further supporting the implementation of this workflow into the COVID-19 testing repertoire to assist in increasing access to cost effective and timely viral detection methods that maintain sensitivity and specificity when compared to the traditional testing methodologies [8].
After months of nasopharyngeal swabbing for COVID-19 diagnostic testing, there was a push to look for equally sensitive testing methodologies which provided a more pleasant patient experience during sample collection [4, 6, 9]. By improving the patient experience with testing, the hope was to gain public cooperation with viral surveillance efforts [9, 13]. The high concentration of SARS-CoV-2 particles found throughout the upper respiratory tract led researchers to begin examining the utility of oral swabs or saliva in the current RT-qPCR testing strategies [13, 14].
Saliva samples were shown to have adequate viral loads for reliable RT-qPCR detection, however the high viscosity of the samples made them difficult to pipette preventing the utilization of the fully automated extraction machinery already in place in many large public health testing facilities [9, 13, 14]. Mechanical homogenization in the form of beat beating homogenization was introduced to saliva samples to break up the viscous structure and expose the viral particles [4, 15]. The beat beating strategy utilized ceramic bead media within a 2 mL screw capped sample tube and a mechanical homogenizer to apply rigorous kinetic energy to the saliva sample for 30 seconds to achieve complete dissociation (Figure 2) [4, 15]. It was shown that the kinetic energy transferred from the bead beading media homogenized in a sigmoidal pattern was highly effective in dissociating the sample to allow for pipettable lysate that could then be implemented into fully automated extraction-based PCR testing workflows [1, 4, 15]. With the addition of bead beating homogenization to this workflow, the throughput and sensitivity of the assay were dramatically increased [4, 15]. Prior to the implementation of beat beating homogenization, saliva-based testing demonstrated a sensitivity in the mid to low 80% range and throughput was limited to a few hundred samples per day via manual processing [4, 15]. Currently, saliva-based PCR testing utilizing mechanical homogenization prior to extraction procedures demonstrated a 95% sensitivity and 99% specificity, closely matching that of nasopharyngeal swab-based testing for COVID-19 [4, 13, 14, 15]. Additionally, with the capability of full automation integration, throughput of sample processing increased from hundreds to thousands of samples per day with the utilization of bead beating homogenization equipment [4, 15].
The methodology for saliva-based testing utilizing bead beating mechanical homogenization for adequate sample dissociation and viral lysis followed by RNA extraction for RT-qPCR viral detection.
Given the similar sensitivity and specificity for SARS-CoV-2 testing, with the improvement in patient experience during sample collection, this method was implemented at universities across the state of Georgia as a community surveillance program [4, 15]. The difference in patient experience from obtaining a nasopharyngeal swab versus a saliva sample for weekly surveillance measures dramatically improved community compliance with testing, validating saliva testing as a viable public health surveillance strategy for COVID-19 propagation in a community [4, 6, 13, 14, 15]. Similar entities have now implemented saliva-based testing that utilize front-end mechanical homogenization across the world to improve compliance with public health testing efforts [4, 6, 15].
The United States’ Food and Drug Administration (FDA) has approved the use of antigen testing for the detection of SARS-CoV-2 in the summer of 2020 to increase the national testing capacity [6, 16]. Antigen tests are immunoassays that are commonly used in the diagnosis of respiratory pathogens such as influenza [17]. Antigen test are designed to detect the presence of a specific viral antigen, which is defined as a toxin or other foreign substance which induces an immune response [16, 17]. Antigen test are currently approved for nasopharyngeal swab specimens however studies suggest saliva samples may be just as effective in detecting viral antigens [6, 16, 18]. When compared to PCR test, antigen testing is relatively inexpensive, and most test results are available in 15 minutes or less. Antigen test in general are less sensitive than RT-PCR test as well as other nucleic acid amplification test (NAATs) [19]. Alternatively, RT-PCR can amplify and detect minute levels of nucleic acid that cannot be cultured which in this case suggest the presence of viral nucleic acids does not signify contagiousness [20]. Both antigen and nucleic acid tests are optimal when the patient is at their viral load peek [6, 16, 20]. More data is needed to guide the use of antigen tests on asymptomatic individuals and to determine if those who were at one time diagnosed positive for SARS-CoV-2 remain infectious.
The advantage of antigen testing is its convenience and accessibility in the use screening high-risk congregate settings such as primary or secondary educational environments, as well as correctional facilities [16, 21]. Repeat testing could quickly identify infection, therefore allowing implementation of patient quarantine and other preventive measure. However, health care professionals need to understand the limitations of antigen testing [19, 20]. Specifically, the testing factors and analytical performance characteristics, such as sensitivity, specificity, and accurate positive and negative predicted values. The “Holy Grail” for SARS-CoV-2 testing remains to be RT-PCR or some form of nucleic acid amplification testing [21]. Nucleic acid testing should be used to confirm an antigen test to avoid inconsistent and inaccurate results test performance may vary based on specimen choice, quality of specimen, the presence of transport medium, and the amount of time required for transport [20, 21]. Since antigen test are typically less sensitive than NAAT testing, negative results can occur while RT-PCR tests may return a positive result [19]. This may occur is specimen sample is collected early before symptom onset or late in the infection [19, 20]. The specificity of antigen tests is as high as NAAT testing, reducing the likelihood of false positives [16, 21]. False positive will still occur, particularly in communities where prevalence of infection is low [16, 20, 21]. The CDC recommends testing professionals establish infection prevalence for antigen testing based on a rolling average, using the positivity rate of their own SARS-CoV-2 testing over the previous 7–10 days, while considering the clinical and epidemiological context of the person or community being tested [6, 16].
Despite the debated advantages and disadvantages of antigen testing, the concept of saliva-based antigen testing for SARS-CoV-2 detection gained traction due to the ease of use for the patient and potential for rapid turn around time in laboratory processing to support public health efforts. However, as noted in the previous section on saliva-based PCR testing, working with such a viscous material posed difficulty in automation integration prior to the addition of homogenization into the workflow. Antigen testing faced similar difficulties when using saliva for large scale testing, the viscous patient samples required further processing prior to automation integration.
In an attempt to mitigate variations in saliva viscosities and allow for sample integration into high-throughput liquid handler reliant workflows, several protocols were developed to dissociate the saliva samples while maintaining intact antigen for detection [6, 22]. These protocols recommend various combinations of heating and enzyme digestion; heating greater than 60 degrees centigrade for as long as an hour or incubating with Proteinase K as an enzymatic digestion [23]. Reports have found these techniques to be somewhat effective in permitting antigen detection from saliva samples, however inconsistencies have also been scored [18, 20, 23]. Heating can denature the viral proteins and RNA, rendering them undetectable, and enzymes such as Proteinase K is very costly as well as cause degradation of targeted proteins through excessive digestion [20]. Not to mention the suggested incubation periods as great as an hour extends the amount of time required to have a patients’ result.
Just as with saliva-based PCR testing, homogenization was proposed as a method for efficient sample disruption [24]. Viscosity in homogenized saliva samples has been shown to be greatly reduced to amounts that are similar to those found in water. Allowing for ease in pipetting and increase throughput using automation and liquid handlers [15]. The various forces found in homogenization are only required for small amounts of processing time, as short as 5 seconds per sample without generating any extra heat during the processing, maintaining the integrity of the antigens targeted. In contrast to other proposed methods for saliva processing in antigen detection, additional enzymes are not required, saving costs and without any needed incubation steps, also saving valuable time during testing.
During the COVID-19 global pandemic, safety of all individuals involved in the care of COVID-19 patients as well as laboratory and clinical staff involved in testing for SARS-CoV-2 became a top priority. Given the highly virulent nature of SARS-CoV-2 and the lack of knowledge and treatments we had available, it was essential to neutralize the virus during laboratory testing while preserving the diagnostic capacity of all assays [5]. Employing viral neutralization techniques in the diagnostic workflow was a critical step in increasing the number of facilities available to process COVID-19 patient samples, supporting increased public health testing efforts.
Techniques involving thermal inactivation, chemical neutralization or degradation, enzymatic digestion, and mechanical disruption of samples were all proposed as potential solutions to laboratory safety when handling potential COVID-19 positive patient samples [5, 6]. However, given the global strain on the plastics and chemical reagents needed to complete many of these neutralization steps, the authors felt it was prudent to examine the potential of mechanical sample dissociation in the form of homogenization and its effect on virus neutralization [2, 3, 8]. Ultimately, it was shown that following 30 seconds of homogenization, 98% of the virus in any given sample was inactivated, while still preserving the genetic material for adequate PCR detection [2, 3]. This finding supported expanding the implementation of homogenization in the COVID-19 diagnostic workflow because it could be done both in the laboratory setting, as well as the location of sample collection provided the homogenized sample would be properly refrigerated and transferred for PCR detection within the next 12 hours [2, 3, 4, 15].
The mechanical lysis of the SARS-CoV-2 particles in a potentially infectious sample permitted these samples to be processed in a BSL-2 facility, supporting the expansion of laboratory testing facilities equipped to process COVID-19 samples [2, 3, 8]. Without a proven neutralization step, such as mechanical homogenization, all COVID-19 samples would have to be processed in BSL-3 facilities due to the potential risk of exposure to infectious virus. While it is still recommended that the homogenization procedure occur in a biosafety cabinet within a BSL-2 facility, the procedure provides sufficient viral lysis to improve safety when handling potentially infected patient samples and allows additional laboratories to assist with testing in a cost-effective manner [2, 3, 8, 15].
Mechanical homogenization has proven its utility in the response to COVID-19 through shaker mill and bead beating technologies implemented in a variety of diagnostic workflows [2, 3, 4, 8, 15]. These innovations made possible through effective and efficient viral lysis of SARS-CoV-2 are proving to improve access, speed, and safety while processing patient samples [2, 3, 4, 8, 15]. As the global community continues to push innovation to combat COVID-19, mechanical homogenization should be viewed as one of the many repurposed technologies adapted to assist with the response through improving the safety and efficacy of diagnostic testing in a cost-effective manner.
The authors would like to acknowledge the laboratory interns and personnel which worked so diligently to support the research efforts of this and all other projects in our laboratory; Mr. Brandon Easparro, Ms. Taylor White, and Ms. Akelachi Okparanta. We would also like to thank Mr. Brent Barton for his contribution to our publications through graphics development, including but not limited to, the graphics used in this manuscript. Additionally, we would like to recognize the following researchers for their assistance in procuring the samples needed to conduct the research studies which allowed us to complete this chapter; Drs. Angel Rivera and Maria Nagy of Quorum X Diagnostics (Tucker, GA, USA), Dr. Michael Shannon of The Georgia Tech Research Institute (Atlanta, GA, USA), Dr. John Roback of Emory University School of Medicine (Atlanta, GA, USA), and Dr. Tonney Nyirenda of the University of Malawi College of Medicine (Blantyre, Malawi).
All authors of this chapter are employed by PerkinElmer Inc. in some capacity; however, they have no personal financial incentives in the success or failure of the company, nor was their research referenced in this chapter impacted or influenced by their employment status or any financial incentives. RJ Nash is the owner of Jeevan BioSciences with personal financial interest in the company; however, none of the research conducted for this chapter directly benefited Jeevan BioSciences, nor did his ownership impact the research.
The authors would like to thank Mr. Pete Tortorelli and Mr. Karl Jahn for trusting us enough to support our preliminary research efforts and their continued support of our scholarly activities. Additionally, we would like to acknowledge and thank Ms. Rachel True, Mrs. Rachel Nash, and Mrs. Leah Proctor for their incredible patience, support, and sacrifices made for our research, it does not go unnoticed or unappreciated.
polymerase chain reaction. reverse transcriptase polymerase chain reaction. quantitative reverse transcriptase polymerase chain reaction. US Centers for Disease Control and Prevention. World Health Organization. Food and Drug Administration.
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\\n\\n5.1 IntechOpen has a right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Corresponding Author or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Corresponding Author or any Co-Author (being an individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Corresponding Author or any Co-Author (being a company) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for or enters into any compromise or arrangement with any of its creditors.
\\n\\nIn case of termination, IntechOpen will notify the Corresponding Author, in writing, of the decision.
\\n\\n6. INTECHOPEN’S DUTIES AND RIGHTS
\\n\\n6.1 Unless prevented from doing so by events outside its reasonable control, IntechOpen, in its discretion, agrees to publish the Chapter attributing it to the Corresponding Author and any Co-Author.
\\n\\n6.2 IntechOpen has the right to use the Corresponding Author’s and any Co-Author’s names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Chapter and has the right to contact the Corresponding Author and any Co-Author until the Chapter is publicly available on any platform owned and/or operated by IntechOpen.
\\n\\n6.3 IntechOpen is granted the authority to enforce the rights from this Publication Agreement, on behalf of the Corresponding Author and any Co-Author, against third parties (for example in cases of plagiarism or copyright infringements). In respect of any such infringement or suspected infringement of the copyright in the Chapter, IntechOpen shall have absolute discretion in addressing any such infringement which is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\\n\\n7. MISCELLANEOUS
\\n\\n7.1 Further Assurance: The Corresponding Author shall and will ensure that any relevant third party (including any Co-Author) shall, execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\\n\\n7.2 Third Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\\n\\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
\\n\\n7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\\n\\n7.5 Variation: No variation of this Publication Agreement shall be effective unless it is in writing and signed by the parties (or their duly authorized representatives).
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\\n\\nAny modification to or deletion of a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\\n\\n7.7 No partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Corresponding Author or any Co-Author, nor authorize any party to make or enter into any commitments for or on behalf of any other party.
\\n\\n7.8 Governing law: This Publication Agreement and any dispute or claim (including non-contractual disputes or claims) arising out of or in connection with it or its subject matter or formation shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of or in connection with this Publication Agreement (including any non-contractual disputes or claims).
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The Corresponding Author (acting on behalf of all Authors) and INTECHOPEN LIMITED, incorporated and registered in England and Wales with company number 11086078 and a registered office at 5 Princes Gate Court, London, United Kingdom, SW7 2QJ conclude the following Agreement regarding the publication of a Book Chapter:
\n\n1. DEFINITIONS
\n\nCorresponding Author: The Author of the Chapter who serves as a Signatory to this Agreement. The Corresponding Author acts on behalf of any other Co-Author.
\n\nCo-Author: All other Authors of the Chapter besides the Corresponding Author.
\n\nIntechOpen: IntechOpen Ltd., the Publisher of the Book.
\n\nBook: The publication as a collection of chapters compiled by IntechOpen including the Chapter. Chapter: The original literary work created by Corresponding Author and any Co-Author that is the subject of this Agreement.
\n\n2. CORRESPONDING AUTHOR'S GRANT OF RIGHTS
\n\n2.1 Subject to the following Article, the Corresponding Author grants and shall ensure that each Co-Author grants, to IntechOpen, during the full term of copyright and any extensions or renewals of that term the following:
\n\nThe aforementioned licenses shall survive the expiry or termination of this Agreement for any reason.
\n\n2.2 The Corresponding Author (on their own behalf and on behalf of any Co-Author) reserves the following rights to the Chapter but agrees not to exercise them in such a way as to adversely affect IntechOpen's ability to utilize the full benefit of this Publication Agreement: (i) reprographic rights worldwide, other than those which subsist in the typographical arrangement of the Chapter as published by IntechOpen; and (ii) public lending rights arising under the Public Lending Right Act 1979, as amended from time to time, and any similar rights arising in any part of the world.
\n\nThe Corresponding Author confirms that they (and any Co-Author) are and will remain a member of any applicable licensing and collecting society and any successor to that body responsible for administering royalties for the reprographic reproduction of copyright works.
\n\nSubject to the license granted above, copyright in the Chapter and all versions of it created during IntechOpen's editing process (including the published version) is retained by the Corresponding Author and any Co-Author.
\n\nSubject to the license granted above, the Corresponding Author and any Co-Author retains patent, trademark and other intellectual property rights to the Chapter.
\n\n2.3 All rights granted to IntechOpen in this Article are assignable, sublicensable or otherwise transferrable to third parties without the Corresponding Author's or any Co-Author’s specific approval.
\n\n2.4 The Corresponding Author (on their own behalf and on behalf of each Co-Author) will not assert any rights under the Copyright, Designs and Patents Act 1988 to object to derogatory treatment of the Chapter as a consequence of IntechOpen's changes to the Chapter arising from translation of it, corrections and edits for house style, removal of problematic material and other reasonable edits.
\n\n3. CORRESPONDING AUTHOR'S DUTIES
\n\n3.1 When distributing or re-publishing the Chapter, the Corresponding Author agrees to credit the Book in which the Chapter has been published as the source of first publication, as well as IntechOpen. The Corresponding Author warrants that each Co-Author will also credit the Book in which the Chapter has been published as the source of first publication, as well as IntechOpen, when they are distributing or re-publishing the Chapter.
\n\n3.2 When submitting the Chapter, the Corresponding Author agrees to:
\n\nThe Corresponding Author will be held responsible for the payment of the Open Access Publishing Fees.
\n\nAll payments shall be due 30 days from the date of the issued invoice. The Corresponding Author or the payer on the Corresponding Author's and Co-Authors' behalf will bear all banking and similar charges incurred.
\n\n3.3 The Corresponding Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Chapter worldwide for the full term of the above licenses, and shall provide to IntechOpen upon request the original copies of such consents for inspection (at IntechOpen's option) or photocopies of such consents.
\n\nThe Corresponding Author shall obtain written informed consent for publication from people who might recognize themselves or be identified by others (e.g. from case reports or photographs).
\n\n3.4 The Corresponding Author and any Co-Author shall respect confidentiality rights during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Corresponding Author and any Co-Author are confidential and are intended only for the recipient. The contents may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
\n\n4. CORRESPONDING AUTHOR'S WARRANTY
\n\n4.1 The Corresponding Author represents and warrants that the Chapter does not and will not breach any applicable law or the rights of any third party and, specifically, that the Chapter contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy. The Corresponding Author warrants and represents that: (i) the Chapter is the original work of themselves and any Co-Author and is not copied wholly or substantially from any other work or material or any other source; (ii) the Chapter has not been formally published in any other peer-reviewed journal or in a book or edited collection, and is not under consideration for any such publication; (iii) they themselves and any Co-Author are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) they themselves and any Co-Author have not assigned and will not during the term of this Publication Agreement purport to assign any of the rights granted to IntechOpen under this Publication Agreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\n\nThe Corresponding Author also warrants and represents that: (i) they have the full power to enter into this Publication Agreement on their own behalf and on behalf of each Co-Author; and (ii) they have the necessary rights and/or title in and to the Chapter to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licenses expressed to be granted in this Publication Agreement. If the Chapter was prepared jointly by the Corresponding Author and any Co-Author, the Corresponding Author warrants and represents that: (i) each Co-Author agrees to the submission, license and publication of the Chapter on the terms of this Publication Agreement; and (ii) they have the authority to enter into this Publication Agreement on behalf of and bind each Co-Author. The Corresponding Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each such Co-Author.
\n\nThe Corresponding Author agrees to indemnify and hold IntechOpen harmless against all liabilities, costs, expenses, damages and losses and all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of or in connection with any breach of the aforementioned representations and warranties. This indemnity shall not cover IntechOpen to the extent that a claim under it results from IntechOpen's negligence or willful misconduct.
\n\n4.2 Nothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\n\n5. TERMINATION
\n\n5.1 IntechOpen has a right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Corresponding Author or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Corresponding Author or any Co-Author (being an individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Corresponding Author or any Co-Author (being a company) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for or enters into any compromise or arrangement with any of its creditors.
\n\nIn case of termination, IntechOpen will notify the Corresponding Author, in writing, of the decision.
\n\n6. INTECHOPEN’S DUTIES AND RIGHTS
\n\n6.1 Unless prevented from doing so by events outside its reasonable control, IntechOpen, in its discretion, agrees to publish the Chapter attributing it to the Corresponding Author and any Co-Author.
\n\n6.2 IntechOpen has the right to use the Corresponding Author’s and any Co-Author’s names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Chapter and has the right to contact the Corresponding Author and any Co-Author until the Chapter is publicly available on any platform owned and/or operated by IntechOpen.
\n\n6.3 IntechOpen is granted the authority to enforce the rights from this Publication Agreement, on behalf of the Corresponding Author and any Co-Author, against third parties (for example in cases of plagiarism or copyright infringements). In respect of any such infringement or suspected infringement of the copyright in the Chapter, IntechOpen shall have absolute discretion in addressing any such infringement which is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\n\n7. MISCELLANEOUS
\n\n7.1 Further Assurance: The Corresponding Author shall and will ensure that any relevant third party (including any Co-Author) shall, execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\n\n7.2 Third Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\n\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
\n\n7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\n\n7.5 Variation: No variation of this Publication Agreement shall be effective unless it is in writing and signed by the parties (or their duly authorized representatives).
\n\n7.6 Severance: If any provision or part-provision of this Publication Agreement is or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted.
\n\nAny modification to or deletion of a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\n\n7.7 No partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Corresponding Author or any Co-Author, nor authorize any party to make or enter into any commitments for or on behalf of any other party.
\n\n7.8 Governing law: This Publication Agreement and any dispute or claim (including non-contractual disputes or claims) arising out of or in connection with it or its subject matter or formation shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of or in connection with this Publication Agreement (including any non-contractual disputes or claims).
\n\nLast updated: 2020-11-27
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. 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Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. 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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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Miller, Hayley Wright, Josie Hough and Francesco P.\nCappuccio",authors:[{id:"77507",title:"Dr.",name:"Michelle A",middleName:null,surname:"Miller",slug:"michelle-a-miller",fullName:"Michelle A Miller"}]},{id:"32269",doi:"10.5772/32991",title:"Epidemiology of Insomnia: Prevalence and Risk Factors",slug:"epidemiology-of-insomnia-prevalence-and-risk-factors",totalDownloads:4711,totalCrossrefCites:5,totalDimensionsCites:12,abstract:null,book:{id:"711",slug:"can-t-sleep-issues-of-being-an-insomniac",title:"Can't Sleep? Issues of Being an Insomniac",fullTitle:"Can't Sleep? Issues of Being an Insomniac"},signatures:"Claudia de Souza Lopes, Jaqueline Rodrigues Robaina and Lúcia Rotenberg",authors:[{id:"93493",title:"Prof.",name:"Claudia",middleName:null,surname:"Lopes",slug:"claudia-lopes",fullName:"Claudia Lopes"},{id:"95778",title:"Dr.",name:"Jaqueline",middleName:null,surname:"Robaina",slug:"jaqueline-robaina",fullName:"Jaqueline Robaina"},{id:"95790",title:"Dr.",name:"Lúcia",middleName:null,surname:"Rotenberg",slug:"lucia-rotenberg",fullName:"Lúcia Rotenberg"}]},{id:"32149",doi:"10.5772/29364",title:"Sleep and Pregnancy: Sleep Deprivation, Sleep Disturbed Breathing and Sleep Disorders in Pregnancy",slug:"sleep-and-pregnancy-sleep-deprivation-sleep-disturbed-breathing-and-sleep-disorders-in-pregnancy",totalDownloads:4017,totalCrossrefCites:1,totalDimensionsCites:5,abstract:null,book:{id:"993",slug:"sleep-disorders",title:"Sleep Disorders",fullTitle:"Sleep Disorders"},signatures:"Michelle A. Miller, Manisha Ahuja and Francesco P. Cappuccio",authors:[{id:"77507",title:"Dr.",name:"Michelle A",middleName:null,surname:"Miller",slug:"michelle-a-miller",fullName:"Michelle A Miller"},{id:"119883",title:"Ms.",name:"Manisha",middleName:null,surname:"Ahuja",slug:"manisha-ahuja",fullName:"Manisha Ahuja"},{id:"119885",title:"Prof.",name:"Francesco P",middleName:null,surname:"Cappuccio",slug:"francesco-p-cappuccio",fullName:"Francesco P Cappuccio"}]},{id:"65707",doi:"10.5772/intechopen.82754",title:"Sleep Physiology and Polysomnogram, Physiopathology and Symptomatology in Sleep Medicine",slug:"sleep-physiology-and-polysomnogram-physiopathology-and-symptomatology-in-sleep-medicine",totalDownloads:1240,totalCrossrefCites:3,totalDimensionsCites:5,abstract:"Over recent years, the importance of sleep physiology and pathology has been better understood in terms of correct diagnosis, treatment, prognosis and innovative research of diseases. Sleep disorders are often confused with clinical symptoms of adult and pediatric medical conditions. In medicine, electrophysiological signal recording methods are very important for establishing a correct diagnosis especially in neurological sciences. Polysomnography (PSG) is a golden standard diagnostic method that records electrophysiological signals used for sleep physiology and diseases. When the medical disciplines and diseases that make use of this diagnostic method are considered, its significance becomes clearer. For example, medical disciplines benefiting from PSG are as follows: “Clinical Physiology, Neurology, Ear Nose and Throat, Dentistry, Psychiatry, Pulmonology, Cardiology, Pediatric Neurology, Pediatric Cardiology, Internal Medicine, Neurosurgery, Endocrinology, etc.” The patient groups diagnosed with PSG are as follows: “Sleep Disordered Breathing (Central Sleep Apnea Syndrome, Obstructive Sleep Apnea Syndrome), Obesity, Morbid Obesity, REM Behavior Disorder, Restless Leg Syndrome, Rhythm Disorders, Epileptic Disorders, Insomnia, Insomnia and Headache, Hypersomnia, Narcolepsy, Secondary Hypertension, etc.” Interpretation and understanding electrophysiological signals correctly show us interactions of body systems with sleep physiology and integrated therapeutic approaches to sleep disorders. In conclusion; new approaches to sleep pathophysiology depend on a better understanding and further advancement of polysomnography.",book:{id:"7076",slug:"updates-in-sleep-neurology-and-obstructive-sleep-apnea",title:"Updates in Sleep Neurology and Obstructive Sleep Apnea",fullTitle:"Updates in Sleep Neurology and Obstructive Sleep Apnea"},signatures:"Murat Kayabekir",authors:[{id:"265598",title:"Associate Prof.",name:"Murat",middleName:null,surname:"Kayabekir",slug:"murat-kayabekir",fullName:"Murat Kayabekir"}]},{id:"28107",doi:"10.5772/28521",title:"Chronic Fatigue Syndrome and Viral Infections",slug:"chronic-fatigue-syndrome-and-viral-infections",totalDownloads:3474,totalCrossrefCites:3,totalDimensionsCites:3,abstract:null,book:{id:"953",slug:"an-international-perspective-on-the-future-of-research-in-chronic-fatigue-syndrome",title:"An International Perspective on the Future of Research in Chronic Fatigue Syndrome",fullTitle:"An International Perspective on the Future of Research in Chronic Fatigue Syndrome"},signatures:"Frédéric Morinet and Emmanuelle Corruble",authors:[{id:"74167",title:"Prof.",name:"Frederic",middleName:null,surname:"Morinet",slug:"frederic-morinet",fullName:"Frederic Morinet"},{id:"97755",title:"Dr.",name:"Emmanuelle",middleName:null,surname:"Corruble",slug:"emmanuelle-corruble",fullName:"Emmanuelle Corruble"}]}],mostDownloadedChaptersLast30Days:[{id:"65707",title:"Sleep Physiology and Polysomnogram, Physiopathology and Symptomatology in Sleep Medicine",slug:"sleep-physiology-and-polysomnogram-physiopathology-and-symptomatology-in-sleep-medicine",totalDownloads:1240,totalCrossrefCites:3,totalDimensionsCites:5,abstract:"Over recent years, the importance of sleep physiology and pathology has been better understood in terms of correct diagnosis, treatment, prognosis and innovative research of diseases. Sleep disorders are often confused with clinical symptoms of adult and pediatric medical conditions. In medicine, electrophysiological signal recording methods are very important for establishing a correct diagnosis especially in neurological sciences. Polysomnography (PSG) is a golden standard diagnostic method that records electrophysiological signals used for sleep physiology and diseases. When the medical disciplines and diseases that make use of this diagnostic method are considered, its significance becomes clearer. For example, medical disciplines benefiting from PSG are as follows: “Clinical Physiology, Neurology, Ear Nose and Throat, Dentistry, Psychiatry, Pulmonology, Cardiology, Pediatric Neurology, Pediatric Cardiology, Internal Medicine, Neurosurgery, Endocrinology, etc.” The patient groups diagnosed with PSG are as follows: “Sleep Disordered Breathing (Central Sleep Apnea Syndrome, Obstructive Sleep Apnea Syndrome), Obesity, Morbid Obesity, REM Behavior Disorder, Restless Leg Syndrome, Rhythm Disorders, Epileptic Disorders, Insomnia, Insomnia and Headache, Hypersomnia, Narcolepsy, Secondary Hypertension, etc.” Interpretation and understanding electrophysiological signals correctly show us interactions of body systems with sleep physiology and integrated therapeutic approaches to sleep disorders. In conclusion; new approaches to sleep pathophysiology depend on a better understanding and further advancement of polysomnography.",book:{id:"7076",slug:"updates-in-sleep-neurology-and-obstructive-sleep-apnea",title:"Updates in Sleep Neurology and Obstructive Sleep Apnea",fullTitle:"Updates in Sleep Neurology and Obstructive Sleep Apnea"},signatures:"Murat Kayabekir",authors:[{id:"265598",title:"Associate Prof.",name:"Murat",middleName:null,surname:"Kayabekir",slug:"murat-kayabekir",fullName:"Murat Kayabekir"}]},{id:"67469",title:"Sleep Disorder at High Altitude",slug:"sleep-disorder-at-high-altitude",totalDownloads:823,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"In this chapter, we discuss the occurrence, mechanism, clinical manifestations, outcomes, and managements of a commonly encountered sleep disorder of someone traveling in high altitude for working and sight-seeing. Humans ascending to altitudes above 2500 m usually suffer from substantial disturbances in sleep quality as difficulty in sleep onset, frequent awakenings, respiratory disturbance, and a feeling of drowsiness on the next day. Data obtained from polysomnographic studies demonstrated several variations of sleep architecture in those healthy subjects ascending to high altitude during sleep, including periodic breathing and decreased non-rapid eye movement deep sleep stage 3 and 4 (in new nomenclature N3), which were usually accompanied by and the lowered arterial O2 and restricted ventilation. Hypoxia is most severe during sleep and in correspondence to periodic breathing and sleep disturbance at high altitude. Poor sleep quality impairs cognition and executive abilities at high altitude though it may largely be improved after full time of acclimatization. Evidence-based choices for clinicians to treat sleep disorder at high altitude are relatively scarce at present. Supplemental oxygen and dietary nitrate are effective in alleviating nocturnal hypoxia. There is strong evidence supporting the efficacy and safety of acetazolamide and nonbenzodiazepines in minimizing periodic breathing and improving sleep quality at high altitude.",book:{id:"7076",slug:"updates-in-sleep-neurology-and-obstructive-sleep-apnea",title:"Updates in Sleep Neurology and Obstructive Sleep Apnea",fullTitle:"Updates in Sleep Neurology and Obstructive Sleep Apnea"},signatures:"Fanyi Kong",authors:[{id:"285948",title:"Dr.",name:"Fanyi",middleName:null,surname:"Kong",slug:"fanyi-kong",fullName:"Fanyi Kong"}]},{id:"64983",title:"Cognitive Impairment and Obstructive Sleep Apnea",slug:"cognitive-impairment-and-obstructive-sleep-apnea",totalDownloads:1355,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Obstructive sleep apnea (OSA) is a frequent sleep disorder characterized by repetitive interruption of ventilation caused by partial or complete collapse of the upper airway during sleep. OSA is highly prevalent in the world and it has been associated with cardiovascular disease and cognitive impairment in children and adults. The cognitive impairment in individuals with OSA includes deficiencies in attention and constructional abilities, delayed long-term visual and verbal memory, and executive functions. Although, the pathogenesis of cognitive impairment in patients with OSA is complex and remains incompletely understood, several mechanisms, such as hypoxia, inflammation and sleep fragmentation have been proposed. The aim of this chapter is to describe some findings reported in the literature to explain the association between OSA and cognitive impairment.",book:{id:"7076",slug:"updates-in-sleep-neurology-and-obstructive-sleep-apnea",title:"Updates in Sleep Neurology and Obstructive Sleep Apnea",fullTitle:"Updates in Sleep Neurology and Obstructive Sleep Apnea"},signatures:"Liliana Otero, María del Carmen Figueredo, Alain Riveros-Rivera and Patricia Hidalgo",authors:[{id:"273415",title:"Ph.D.",name:"Liliana",middleName:null,surname:"Otero",slug:"liliana-otero",fullName:"Liliana Otero"},{id:"280824",title:"Dr.",name:"Carmen",middleName:null,surname:"Figueredo",slug:"carmen-figueredo",fullName:"Carmen Figueredo"},{id:"283338",title:"Dr.",name:"Alain",middleName:null,surname:"Riveros",slug:"alain-riveros",fullName:"Alain Riveros"},{id:"283339",title:"Dr.",name:"Patricia",middleName:null,surname:"Hidalgo-Martinez",slug:"patricia-hidalgo-martinez",fullName:"Patricia Hidalgo-Martinez"}]},{id:"71574",title:"Surgical Treatment Options for Obstructive Sleep Apnea",slug:"surgical-treatment-options-for-obstructive-sleep-apnea",totalDownloads:741,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Given the increased prevalence of obstructive sleep apnea (OSA) multiple treatment modalities including medical and surgical have been developed. First-line therapy for most of the people with obstructive sleep apnea (OSA) consists of behavioral modification, including weight loss if appropriate, and positive airway pressure (PAP) therapy. Patients who fail or do not tolerate PAP therapy, treatment options include oral appliances and surgical therapy. Surgical therapies have variable efficacy and are very important tool on OSA management in selected patients. 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He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,institution:{name:"Universidad Católica San Antonio de Murcia",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:2,paginationItems:[{id:"1",title:"Oral Health",coverUrl:"https://cdn.intechopen.com/series_topics/covers/1.jpg",isOpenForSubmission:!0,editor:{id:"173955",title:"Prof.",name:"Sandra",middleName:null,surname:"Marinho",slug:"sandra-marinho",fullName:"Sandra Marinho",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGYMQA4/Profile_Picture_2022-06-01T13:22:41.png",biography:"Dr. Sandra A. Marinho is an Associate Professor and Brazilian researcher at the State University of Paraíba (Universidade Estadual da Paraíba- UEPB), Campus VIII, located in Araruna, state of Paraíba since 2011. She holds a degree in Dentistry from the Federal University of Alfenas (UNIFAL), while her specialization and professional improvement in Stomatology took place at Hospital Heliopolis (São Paulo, SP). Her qualifications are: a specialist in Dental Imaging and Radiology, Master in Dentistry (Periodontics) from the University of São Paulo (FORP-USP, Ribeirão Preto, SP), and Doctor (Ph.D.) in Dentistry (Stomatology Clinic) from Hospital São Lucas of the Pontifical Catholic University of Rio Grande do Sul (HSL-PUCRS, Porto Alegre, RS). She held a postdoctoral internship at the Federal University from Jequitinhonha and Mucuri Valleys (UFVJM, Diamantina, MG). She is currently a member of the Brazilian Society for Dental Research (SBPqO) and the Brazilian Society of Stomatology and Pathology (SOBEP). Dr. Marinho's experience in Dentistry mainly covers the following subjects: oral diagnosis, oral radiology; oral medicine; lesions and oral infections; oral pathology, laser therapy and epidemiological studies.",institutionString:null,institution:{name:"State University of Paraíba",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null},{id:"2",title:"Prosthodontics and Implant Dentistry",coverUrl:"https://cdn.intechopen.com/series_topics/covers/2.jpg",isOpenForSubmission:!0,editor:{id:"179568",title:"Associate Prof.",name:"Wen Lin",middleName:null,surname:"Chai",slug:"wen-lin-chai",fullName:"Wen Lin Chai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRHGAQA4/Profile_Picture_2022-05-23T14:31:12.png",biography:"Professor Dr. Chai Wen Lin is currently a lecturer at the Department of Restorative Dentistry, Faculty of Dentistry of the University of Malaya. She obtained a Master of Dental Science in 2006 and a Ph.D. in 2011. Her Ph.D. research work on the soft tissue-implant interface at the University of Sheffield has yielded several important publications in the key implant journals. She was awarded an Excellent Exchange Award by the University of Sheffield which gave her the opportunity to work at the famous Faculty of Dentistry of the University of Gothenburg, Sweden, under the tutelage of Prof. Peter Thomsen. In 2016, she was appointed as a visiting scholar at UCLA, USA, with attachment in Hospital Dentistry, and involvement in research work related to zirconia implant. In 2016, her contribution to dentistry was recognized by the Royal College of Surgeon of Edinburgh with her being awarded a Fellowship in Dental Surgery. She has authored numerous papers published both in local and international journals. She was the Editor of the Malaysian Dental Journal for several years. Her main research interests are implant-soft tissue interface, zirconia implant, photofunctionalization, 3D-oral mucosal model and pulpal regeneration.",institutionString:null,institution:{name:"University of Malaya",institutionURL:null,country:{name:"Malaysia"}}},editorTwo:{id:"479686",title:"Dr.",name:"Ghee Seong",middleName:null,surname:"Lim",slug:"ghee-seong-lim",fullName:"Ghee Seong Lim",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003ScjLZQAZ/Profile_Picture_2022-06-08T14:17:06.png",biography:"Assoc. Prof Dr. Lim Ghee Seong graduated with a Bachelor of Dental Surgery from University of Malaya, Kuala Lumpur in 2008. He then pursued his Master in Clinical Dentistry, specializing in Restorative Dentistry at Newcastle University, Newcastle, UK, where he graduated with distinction. He has also been awarded the International Training Fellowship (Restorative Dentistry) from the Royal College of Surgeons. His passion for teaching then led him to join the faculty of dentistry at University Malaya and he has since became a valuable lecturer and clinical specialist in the Department of Restorative Dentistry. He is currently the removable prosthodontic undergraduate year 3 coordinator, head of the undergraduate module on occlusion and a member of the multidisciplinary team for the TMD clinic. He has previous membership in the British Society for Restorative Dentistry, the Malaysian Association of Aesthetic Dentistry and he is currently a lifetime member of the Malaysian Association for Prosthodontics. Currently, he is also the examiner for the Restorative Specialty Membership Examinations, Royal College of Surgeons, England. He has authored and co-authored handful of both local and international journal articles. His main interest is in prosthodontics, dental material, TMD and regenerative dentistry.",institutionString:null,institution:{name:"University of Malaya",institutionURL:null,country:{name:"Malaysia"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:54,paginationItems:[{id:"81595",title:"Prosthetic Concepts in Dental Implantology",doi:"10.5772/intechopen.104725",signatures:"Ivica Pelivan",slug:"prosthetic-concepts-in-dental-implantology",totalDownloads:25,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Current Concepts in Dental Implantology - From Science to Clinical Research",coverURL:"https://cdn.intechopen.com/books/images_new/10808.jpg",subseries:{id:"2",title:"Prosthodontics and Implant Dentistry"}}},{id:"80963",title:"Pain Perception in Patients Treated with Ligating/Self-Ligating Brackets versus Patients Treated with Aligners",doi:"10.5772/intechopen.102796",signatures:"Farid Bourzgui, Rania Fastani, Salwa Khairat, Samir Diouny, Mohamed El Had, Zineb Serhier and Mohamed Bennani Othmani",slug:"pain-perception-in-patients-treated-with-ligating-self-ligating-brackets-versus-patients-treated-wit",totalDownloads:22,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Current Trends in Orthodontics",coverURL:"https://cdn.intechopen.com/books/images_new/10780.jpg",subseries:{id:"2",title:"Prosthodontics and Implant Dentistry"}}},{id:"80964",title:"Upper Airway Expansion in Disabled Children",doi:"10.5772/intechopen.102830",signatures:"David Andrade, Joana Andrade, Maria-João Palha, Cristina Areias, Paula Macedo, Ana Norton, Miguel Palha, Lurdes Morais, Dóris Rocha Ruiz and Sônia Groisman",slug:"upper-airway-expansion-in-disabled-children",totalDownloads:35,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Oral Health Care - An Important Issue of the Modern Society",coverURL:"https://cdn.intechopen.com/books/images_new/10827.jpg",subseries:{id:"1",title:"Oral Health"}}},{id:"80839",title:"Herbs and Oral Health",doi:"10.5772/intechopen.103715",signatures:"Zuhair S. 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She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",institutionURL:null,country:{name:"Turkey"}}}]},{type:"book",id:"7139",title:"Current Approaches in Orthodontics",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7139.jpg",slug:"current-approaches-in-orthodontics",publishedDate:"April 10th 2019",editedByType:"Edited by",bookSignature:"Belma Işık Aslan and Fatma Deniz Uzuner",hash:"2c77384eeb748cf05a898d65b9dcb48a",volumeInSeries:2,fullTitle:"Current Approaches in Orthodontics",editors:[{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null}]},{type:"book",id:"7572",title:"Trauma in Dentistry",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7572.jpg",slug:"trauma-in-dentistry",publishedDate:"July 3rd 2019",editedByType:"Edited by",bookSignature:"Serdar Gözler",hash:"7cb94732cfb315f8d1e70ebf500eb8a9",volumeInSeries:3,fullTitle:"Trauma in Dentistry",editors:[{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",institutionURL:null,country:{name:"Turkey"}}}]},{type:"book",id:"7060",title:"Gingival Disease",subtitle:"A Professional Approach for Treatment and Prevention",coverURL:"https://cdn.intechopen.com/books/images_new/7060.jpg",slug:"gingival-disease-a-professional-approach-for-treatment-and-prevention",publishedDate:"October 23rd 2019",editedByType:"Edited by",bookSignature:"Alaa Eddin Omar Al Ostwani",hash:"b81d39988cba3a3cf746c1616912cf41",volumeInSeries:4,fullTitle:"Gingival Disease - A Professional Approach for Treatment and Prevention",editors:[{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. 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