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Temporomandibular joint disorders (TMD) is one of the highly complicated fields in dentistry [1, 2]. It can emerge in various manners at any time during human life with symptoms such as limited mouth opening, pain at TMJ area, pain in masticatory muscles, headache specially around anterior temporal area, sounds emerging from temporomandibular joints, morning soreness, bruxism, clenching, head and neck pains, attrition and/or abfraction of teeth, internal derangement of temporomandibular disks, decreasing of volume in the synovial liquid. Temporomandibular joint disorder is a functional disturbance. Temporomandibular joints, masticatory muscles, teeth, bones and the central nerve system are all involved in TMJ pathology [3, 4, 5, 6]. For many years, clinicians have employed various mechanical tools for diagnosis and to understand the reasons for the problem [7]. Due to the development of the chipset technology and software programming, we have now device-based diagnostic tools, joint vibration analysis, joint tracking measuring mastication analysis, computer-based occlusal analysis devices, and so on [8, 9, 10] available. However, there are still many questions and discussion points about some of the device-based diagnostic techniques [9]. These kind of device-based technologies require studying with a new methodology. Joint vibration analysis, joint tracker and mastication analysis, electromyography, tens devices and finally digital occlusal analysis systems all need new methodologies. That is to say if you have enough knowledge on how to conduct a joint vibration analysis or a digital occlusal analysis, it is possible to collect a lot of useful information with these devices [11, 12, 13, 14].
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All these symptoms are assembled under TMJ pathology [10, 15, 16, 17, 18, 19]. In dentistry, there is no other problem that must be managed in a multidisciplinary fashion like TMJ disorders.
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Occlusal trauma that may occur after restorations is one of the biggest causes of temporomandibular disorders [20, 21, 22, 23]. Dental extraction and orthodontic restorations are also important conditions that cause this discomfort [22, 24, 25, 26, 27].
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A large number of devices and methods are used for diagnosis and treatment of temporomandibular disorder. The reason for this is not only the complexity of the problem but also the demand for the use of noninvasive methods [10, 28, 29, 30, 31].
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For example, if you have enough knowledge about the joint vibration analysis or if you can use digital occlusal analysis properly, you can access very important information about the temporomandibular disorder [17, 32, 33, 34]. In addition, you may also have the opportunity to see and avoid pathology that may be related to joints according to the course of the treatment of the initial chewing pattern of orthodontic treatments [35, 36, 37]. However, it is very important to know how to use these devices, what their capabilities are, and how effective they can be so that it can be done. The predisposing factors of temporomandibular joint disorders can be eliminated before presenting whether all these devices are professionally used [28, 38, 39, 40].
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Nowadays, one of the most widely used diagnostic tools in the examination of the pathology of temporomandibular joints is magnetic resonance imaging (MRI) technique [4, 11, 15]. MRI represents the golden standard among the temporomandibular diagnostic tools [41]. However, its acquisition is more difficult and costly than other diagnostic tools. Moreover, MRI examination of children is very difficult and complicated.
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Craniomandibular dysfunctions are often multistructural [42] and intracapsular problems are one of the most important subjects that have been studied by dentists for a long time [33, 40, 43]. Normally, if there is no problem in a joint, no sound comes from that joint. There is no distortion in the relationship between joint-disk-articular surface. Joint is lined with synovium secreted for lubrication and nutrition. Joints are connected to a common bone, and therefore, they function together. Normal joints produce very little friction and vibration. If there is degeneration in the joint, there is sound in the joint [44, 45, 46, 47]. The sound spectrum may be bigger or less than the human hearing limits. Scientific research has shown that TMJ sounds have been well categorized. Every TMJ sound is like a signature to a problem [48]. Since sound is a pressure energy, it has a particular frequency.
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Another kind of useful information source is spectrum of TMJ sound. TMJ sounds have distinctive characteristics in clinical diagnosis efforts. Additionally, clinical-arthrographic investigations correlate arthrographic characteristics of intracapsular dysfunction of the temporomandibular joint with sound analysis. Sound patterns are reproducible and provide a noninvasive tool for diagnosis and treatment [14, 49].
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In \nFigure 1\n, a graphic illustration screen shows the results of a clinical software that recorded and analyzed sounds emitted from the temporomandibular joint (TMJ) during simple function as a means for differentially diagnosing disorders of the joint. The patient’s mouth opening distance is measured as 45 mm max. The repeated sounds emitted from the left joint peaks at around 43 mm. Spectral analysis of the same patient is shown in \nFigure 2\n.
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Figure 1.
Maximum opening of the mouth is marked as 45 mm; however, there is a crepitation sound in the left joint at 43 mm of opening of the mouth. The crepitation sound was detected at this level in which head of the condyle is almost at the end of the protrusion. The condyle condition may be considered as only some ligament laxity.
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Figure 2.
Spectral analysis considers the problem of determining the spectral content. Differences between energies of left and right joints are very clear. In this case, aggregation place of peak frequency is very close to the max opening limit, intracapsular deterioration has just started and it is only the beginning phase. We may consider this finding as only an MPD syndrome.
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Generally, spectral analysis considers the problem of determining the spectral content (i.e., the distribution of power over frequency) of a time series from a finite set of measurements, by means of either nonparametric or parametric techniques. At JVA Sweep window of \nFigure 2\n, sound energy frequencies of left joint are shown on a time line.
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Sounds due to temporomandibular joint disorders have been studied for a long time and are classified to the particular groups [45, 47, 50, 51, 52]. Very well-known sound frequencies belong to the “click” sound energy (\nFigure 3\n). A 2x zoom view of the click sound is shown in \nFigure 3\n.
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Figure 3.
Click-type TMJ signal, TMJ signal (by) frequency of click sound followed by crepitation sound starts. Crepitation wave is shown on the left TMJ.
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In \nFigure 4\n, max mouth opening is 45 mm, and a click sound is spotted around 30 mm. The click sound is located just before the eminencia.
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Figure 4.
After six cycles of frequencies, average level of the click sound is around 30.4 mm of this patient who has a mouth opening of 45 mm. Location of the click sound is around the anterior part of the glenoid fossa. In this case, crepitation wave followed by the click sound must be considered an aggravation of the problem.
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Another important frequency type is crepitation: (\nFigure 5\n).
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Figure 5.
Crepitation wave is located just before a click frequency. It is located at the opening distance of 33.0 mm, where the patient’s maximum opening distance is 49 mm.
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2. How can we detect Temporomandibular joint sounds?
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We can detect the temporomandibular joint sounds using frequency accelerators. An accelerator is neither a microphone nor an ultrasound; it is a typical sound receptor. In \nFigure 6\n, a typical sound accelerator is shown designed by Bioresearch Inc. (Milwaukee, USA).
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Figure 6.
Research shows that experienced clinicians correctly diagnose the status of the TMJ less than 50% of the time. Inexperience can only increase this margin for error.
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The overall accuracy of clinical testing for TMD, using both auscultation and palpation, is 43% [53]. Vibration sound analysis procedure aids in diagnosis and thus can be helpful in treatment decisions (\nFigure 7\n).
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Figure 7.
Wavelet transform viewer of a patient.
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3. Clinical application of the joint vibration analysis
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Condylar pathology is linked to articular surface degenerations [54]. Joint vibration analysis tests are helpful for the evaluation of the significance of joint sounds and can help us decide whether the condition is a progressive or degenerative one. Research shows that experienced clinicians correctly diagnose the status of the TMJ less than 50% of the time [53].
Click: very short duration with high amplitude peaks,
Click with crepitation: a short duration click followed by multiple low amplitude peaks,
Hard crepitation: short duration, medium or high amplitude multiple peaks in low-frequency range,
Soft crepitation: long duration, low amplitude, multiple peaks that cover the whole frequency range.
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The evaluation can be made according to the data mentioned above or a special table (suggested by Bioresearch Inc., Milwaukee, USA) is shown in \nFigure 8\n, which is useful in clinical practice.
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Figure 8.
Clinical evaluation chart suggested by Bioresearch Inc., Milwaukee, USA.
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The following evaluations can be made with the JAVA analysis data:
DD = Disk displacement without reduction,
DDR = Disk displacement with reduction,
PDDR = Partial disk displacement with reduction,
EDJD = Early degenerative joint disease,
ADvDJD = Advanced degenerative joint disease.
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Subgroups of these main groups can also be reached with the help of additional clinical findings.
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Evaluation study must start with a total integral value found in the chart. Second stage is the maximum mouth opening value of the patient, measured between the distance of anterior lower and upper teeth. Overbite distance must be added to the measured mouth opening value. Lateral deviation distance also must be measured, as it will be evaluated in the examination. To properly assess temporomandibular sounds, joint vibration sounds should be assessed with the patient’s mouth opening and closing movements.
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Joints are located in the glenoid fossa at the maximum occlusion position of mandible and during the opening of the mouth, translation movement is accompanied by rotation movement. Joint vibration analysis must be calibrated with other clinical findings, such as the maximum occlusion position. The patient is said to strike his teeth strongly, so at this moment a big and equal frequency in both side scan be spotted. This is the maximum occlusion position, and other intermediate frequencies indicate deterioration in the joint (\nFigure 9\n).
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Figure 9.
A patient’s JVA record, total integral value has been found after capturing the frequencies of pathological sounds. According to the value of maximum opening distance, total integral value, integral >300 Hz and ratio of >300/<300 Hz value; in this case, “ligament laxity situation” may be considered.
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Case No.1.
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\nPatient D.Y. 24 years old, Female(History of the Patient, translation from her voice record).\n
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\nMy name is D…Y…. Sounds coming from my joint, especially after lunches …. it started 4 months ago, a tooth extracted from here (showing left side her face), I think this is the reason of my problem … I had it treated, because of a problem here….. Dr. xxxx made the extraction procedure, after the extraction great possible, I heard some cracking sounds. I cannot eat. When I eat something I hear a click sounds, I also have headaches.
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“Clinician\'s Question: When you have your headache?”
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Around afternoons, but not too strong, I mean I hear only click sound. It comes from my left side, from my left joint; tooth extraction was made on that side. I have no more pain, only there is click sound “\nclick (click sound)“. Oh! I want to add something more, I am in orthodontic treatment since the last year.
The patient’s JVA data show that the total integral value of the left joint is bigger than the right joint. This value is 47.3 and indicates a problem. Integral>300 Hz value is 7.8 and ratio value is 0.20.
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Figure 11.
Total integral value is 47.3 (see Figure 10), and this value places between the range of 20 and 80. Second step maximum opening mouth is 39 mm, and this value is between the range of 30 and 40. Third step is “integral >300 Hz” value which is 7.8, and it is located in the 3+ area. Finally, we look the value of “ratio” which is 0.20 of this patient, and it is located in the range of 3–5. As a result, “Chronic disk displacement or mild degenerative joint disease (Piper\'s 4b)” must be considered for this patient. Other clinical examination results (extra-oral examination, radiographic findings, etc.) must be combined with the result of JVA.
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We must consider the Left Joint as problem. If we apply the numerical data to JVA flow chart as follows:
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4. JT mastication analysis
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Chronic temporomandibular disorder (TMD) patients, specifically those with severe symptomatology, shows a reorganized activity, mainly resulting in worsening functional performances [55]. Mastication is one of the most important vital functions of human being. Occlusal disorders can cause people to swallow food without chewing enough. Shimshak and DeFuria showed that TMD patients have, on average, 112% more digestive complaints (in terms of the cost of medical treatment) than a comparable normal group [56]. High-level masticatory performance is the main purpose of dental restorative studies. Chewing pattern is linked to occlusal relationship, it may vary with the occlusal model [57, 58]. Studies have focused on two main types of motions:
physiologic (functional) movements which occur during chewing
nonphysiologic movements such as maximal opening/closing or lateral excursions.
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Nonphysiologic movements can be difficult to reproduce (due to conscious actions of the patient) and are questionable indicators of the functional state of the stomatognathic system. During mastication, the angle of the mandible as it approaches occlusion is quite different from that occurring with lateral excursions from centric occlusion. Interferences identified in lateral excursions may or may not represent functional interferences during mastication. For these reasons, chewing motions (which are subconscious, physiologic, and reproducible) are considered to be the most applicable for a clinical classification of TMD [59].
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The fundamental quantity in mastication analysis is the chewing cycle, representing the motion of the mandible from occlusion to open and from open back to occlusion. The turning point (TP) is defined to be the most open position of the mandible in the middle of a chewing cycle. It averages about 2 mm laterally toward the working (chewing) side and normally 16 mm open from centric occlusion. The terminal chewing position (TCP) is defined as the most closed position of the mandible as it approaches occlusion during mastication. There may be a difference between TCP and maximum intercuspal position of between 0 and 5 mm, default value being 0.3 mm. This number determines the vertical thresholds of each chewing cycle in relation to the TCP of each cycle. For example, a value of 2 will cause the start of opening and ending of closing of a given cycle to be positioned a distance of 2 mm below the TCP. The value can range from 0.0 to 5.0 mm (default is 0.3). Swallowing occurs after every 5–10 chewings approximately. Mandible is in maximum intercuspal position during swallowing.
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There are great differences between orthodontically Class I normal occlusion type and Class II malocclusion or Class III malocclusion chewing patterns. When we look at the breakdown of treatments, we can see many changes in the magnitude of chewing. The analysis of the patterns of chewing in the onset of treatment and later in the course of treatment will provide us concrete information on the success of the treatment [59, 60, 61]. Nowadays, though not routinely used, especially the measurement of chewing performance is important in terms of trying to measure the success of the treatment by comparing the values before and after treatment.
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A classic pattern of chewing is basically examined in three parts [62, 63] (\nFigure 12\n):
Opening phase,
Closing phase, and
Occlusal phase.
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Figure 12.
A chewing pattern consists of three different phases: Opening(red), closing (blue) and occlusal phase (0 point in the diagram). From the opening phase to the closing phase, basically there are three parts in one cycle of mastication. Returning from opening phase is called a “turning point.”
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There are various methods and tools for the examination of masticatory movements [34, 48, 64]. These methods can be grouped under three main headings [65]:
Masticatory movement analysis,
Masticatory muscles analysis,
Analysis of mastication product (analysis of the food).
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However, chewing movements may also be useful in investigating temporomandibular disorders [66]. Masticatory analysis history is based on the beginning time of modern dentistry. In early studies, a video recorder has been used for taking serial pictures of chewing pattern. A rounded white paper part was attached to the patient’s chin, and serial pictures were taken from front of the face of the patient. In this system, a magnet attached onto the lower anterior teeth (\nFigure 13\n) and using a software, record video movie of movements of the magnet together with the mandible (\nFigure 14\n).
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Figure 13.
Placing of magnet.
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Figure 14.
Head parts of Bio-JT (Bioresearch Inc., USA).
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To record chewing patterns, a small magnet is placed on the vestibular side of the lower anterior teeth using a sticky wax (\nFigure 13\n). A headgear containing bilateral electromagnetic controller mechanism senses “xyz” position of the magnet within an accuracy of 0.1 mm. After aligning headgear, using its screw movements of the magnet is recorded (\nFigure 14\n). Besides the analysis of mastication, this gear can be used to measure and record the range of motions of the jaw during speech, distance of the freeway space (with extreme accuracy), velocity and bite registrations. We can see exact positions of the mandible if we use this equipment simultaneously together with the joint vibration analysis (JVA).
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The basic parameters of mastication analysis are given as follows:
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5. Starting cycle
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This is the first chewing cycle to display and analyze. The cycles before the designated starting cycle are neglected. Starting cycle is the default cycle. The first few cycles may be disregarded as they are more often inconsistent.
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5.1. Maximum number of cycles to analyze
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The maximum number of chewing cycles are averaged to calculate the average CP. It also determines how many cycles will be taken into account in the sweep and segmented XY views. Maximum number of cycles are variable between 10 and 30 (default value of number of cycles is 15).
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5.2. Occlusal threshold (OT)
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This number determines the vertical thresholds of each chewing cycle in relation to the TCP of each cycle. Occlusal threshold is the start and the end point of a cycle. For example, a value of 1.0 will cause the start of opening and end of closing of a given cycle to be positioned a distance of 1.0 mm below the TCP. The value can range from 0.0 to 5.0 mm. (default is 0.3 mm).
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5.3. Standard deviation limit
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The number of standard deviations is used as a limit when validating cycles. If a given cycle differs from the average of all cycles by more than this amount, it is marked as deviated and not correct. The value can range from 1.0 to 3.0 mm (default is 2.0).
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5.4. What can be read from masticatory analysis?
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There is a sample screen (the record has been taken from the sample record of User Manual of Bioresearch Inc., USA) [94] in \nFigure 15\n:
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Figure 15.
Mastication narrative: The patient chewed a bolus(gum) on the left side, and 15 chewing cycles were used to average the chewing pattern. The average opening time was consistently short at 225 ± 16 ms. The average closing time was consistently short at 232 ± 20 ms. The average occlusal time was consistently short at 240 ± 13 ms. The average cycle time was consistently short at 697 ± 17 ms. The average vertical turning point consistently occurred at 16.5 ± 1.0 mm from centric occlusion. The average anteroposterior turning point consistently occurred at 5.7 ± 0.6 mm from centric occlusion. The average lateral turning point consistently occurred at 2.1 ± 1.1 mm from centric occlusion. The average maximum lateral width of the chewing cycles was consistent at 4.2 ± 0.6 mm.
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The following record is taken from a patient using full denture in the TMD Clinic of Istanbul Aydin University Dentistry Faculty (\nFigure 16\n):
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Figure 16.
Chewing patterns of a CAD-CAM full denture patient.
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In the research, studies of masticatory movements have been focused on following the two main types of motions:
physiologic (functional) movements which occur during chewing
nonphysiologic movements such as maximal opening/closing or maximum lateral excursions-border movements.
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Average physiologic pattern of masticatory movements (\nFigures 15\n and \n16\n) is produced by a healthy stomathognathic system. It is result of a reflex mechanism and controlled by mechanoreseptors and proprioceptors located in periodontal ligaments [67]. Moreover, premature contact in masticatory occlusion may stimulate neural mechanisms in masticatory system (\nFigure 17\n).
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Figure 17.
Discrepancy in masticatory occlusion is a trigger mechanism for the muscle pain dysfunction syndrome. Premature contacts may stimulate neural mechanism in masticatory MPD syndrome will be developed if premature contacts are not removed from the occlusion. We use also T-scan occlusal analysis system to find and remove the premature contacts from masticatory occlusion [68].
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The production of nonphysiologic movements otherwise is very difficult. There is also a quite difference between approaching angle of mandible in mastication and the angle of lateral excursion to the maximum intercuspal position. For these reasons, subconscious, physiologic and reflex chewing motions are considered to be the most applicable for a clinical classification of TMD. Mastication is a physiologic movement, but grinding of an empty mouth is a para-functional movement. Masticatory movements start as a conscious movement and continue as reflex [69, 70]. Physiologic masticatory movements are controlled and protected by the neuromuscular system [67].
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Total quantity in mastication analysis is the chewing cycle, representing the motion of the mandible from occlusion to open and from open, back to maximum masticatory occlusion. The turning point (TP) is defined to be the masticatory open position of the mandible in the middle of a chewing cycle. It averages about 2 mm laterally toward the working (chewing) side and nominally 16 mm open from centric occlusion. The terminal chewing position (TCP) is defined as the most closed position of the mandible as it approaches occlusion during mastication (masticatory occlusion).
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Chewing rhythm is closely related to the patients’ average chewing pattern (ACP). Average values of parts of chewing pattern are as follows:
Opening time is around 250 ms (± 50 ms), (one-third of total chewing cycle approx.)
Closing time is around 220 ms (± 50 ms), (one-third of total chewing cycle approx.)
Occlusion time is around 200 ms (± 50 ms), (one-third of total chewing cycle approx.)
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We must consider a problem regarding to the joints if cycle time, opening, closing and occlusal time have an unusually longer or shorter value than normal.
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Masticatory movements end in an occlusal phase. In an occlusal movement, lower teeth glide on upper teeth’s occlusal surface and stop at top maximum contact position of masticatory movement. This is not a maximum force position because maximum force position is not a functional situation but a conscious action. Maximum top position of masticatory movement can also be named as “reverse turning point” (RTP) of masticatory movement. Upper and lower teeth are contacted slightly, or not any contact, and opening phase of mastication starts from this point. RTP point is illustrated in \nFigure 18\n:
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Figure 18.
Opening phase of mastication starts from reverse turning point.
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Reverse turning position is not a harmful situation. Furthermore, the CNS reflex (Jaw Jerk Reflex) will form an early RTP point and will escape from excessive contact. This point is variable according to the harmonic masticatory movements of mandible. Normally, this neuromuscular behavior will protect the teeth and will not cause a problem in the joints. But if it lasts for a long time, the working side condenses will be under constant overpressure, which will cause the working joint to eventually break down. The early occurrence of the RTP point should be seen as an adverse symptom that should be corrected clinically for joints. EMG records (\nFigures 20\n) of unbalanced muscle force application with the chewing record (\nFigure 19\n) of a person in this situation can be seen below:
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Figure 19.
The chewing record formed by RTP, and the pattern of the chewing movement was also affected.
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Figure 20.
EMG record of a patient with RTP; right temporal and masseter muscles have hyper-activities. Right side of the joint will be under overload. At the beginning, this situation may not be harmful, though in time the condition may lead to impairment of the right-side condyle.
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6. Computerized occlusal analysis
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“To look at the occlusion and to see the occlusion.”
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Occlusion analysis is one of the most complicated and sophisticated areas of dentistry. According to Prof. Dr. Senih Calikkocaoglu1 “Occlusion is a phenomenon related with bones, teeth, muscles and neurons.” It has four main key points:
Mandibular movements: controlled by joints, muscles and neural receptors,
Upper and lower teeth: end point of the movement - like a stopper, System likes a nut-crucker (\nFigure 21\n).
Masticatory muscles: apply force in a harmonized manner,
Neural system: controls the magnitude, duration and direction of forces.
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There are many dental disturbances to be linked to the occlusion: bruxism, attrition, erosion, abfraction, muscle pain dysfunction syndrome, TMJ problems, and so on, are typical examples [5, 13, 24, 61, 71, 72, 73, 74, 75, 76]. Whether these disorders are related to occlusal discrepancies is the subject of occlusal analysis.
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Occlusion analysis is simply the analysis of all contact positions based on the time vector during closing and departing of upper and lower teeth. Occlusal analysis gives to the clinician teeth position, relative force and time data. Additionally, occlusion analysis gives the sequential time and relative force data of occlusion. Occlusal analysis data present potential to make chance of commentary on pathological reasons of stomatognathic system. Occlusal papers and/or another occlusal indicators do not have that kind of ability.
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The most disturbing situation about occlusion in dentistry is premature contact. As a dentist, we make restorations, bridges, crowns, orthodontic treatment, tooth extraction, and so on, and we may change the occlusion. In proprioceptive mechanism, premature contacts detected by mechanoreceptors in the periodontal ligaments may be harmful for teeth and other structures of stomatognathic system. Normally, temporomandibular joints are not affected immediately by this irregularity. During movements of the mandible, the inputs to muscle spindles and Golgi tendon organs change. But their outputs are differently related to their respective inputs [77]. The reflex control of the mandible is of vital importance for the normal masticatory functioning of humans. Excitatory jaw reflexes are responsible for the rapid reaction to external stimuli to the masticatory muscles [67], while inhibitory jaw reflexes protect the system when sudden loads are applied to the muscles. The fine coordination of the mandibular function is the result of the balanced activation of these reflexes together with the activity of the masticatory muscles, the temporomandibular joints and the associated tissues [78]. Premature contacts are one of the most prominent jaw jerk reflex triggers [68]. The jaw jerk reflex is another protection control mechanism of the stomathognathic system, but it has slightly more rapid and more reflex characteristics than the RTP mechanism of the masticatory movements. After the first reaction, the Jaw Jerk Reflex turns to a RTP mechanism [79]. As we mentioned in the Mastication Analysis section of this chapter, if the reasons for the jaw jerk reflex persists for a long time, the working side condenses will be under constant overload and will cause the working joint to break down.
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“Best Occlusion Analysis starts from Temporomandibular Joints” Peter Dawson [75, 80].
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For many years, scientists created many theories on dental occlusion and its links to the occlusal problems and temporomandibular pathology. Occlusal theories have been focused on two principal matters:
Analysis of occlusion using simulation tools and articulators.
Working on the chairside, the computerized occlusal analysis technique.
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There are many advantages in the second method. In-vitro occlusion analysis techniques are extremely difficult and long procedures. The main advantage of the first method is that it does not contain any risks, and dentist can work under very controlled conditions. But there are a lot of question on the details of the procedures; traditionally, more than one visit is required to complete analyzing and treatment. Working on stomatognathic system needs to be considered together with the neuromuscular mechanism. Articulators may be most useful tools for the production of dental restorations, but they cannot simulate the neuromuscular mechanism [81].
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Computerized occlusal analysis systems are the fastest and safest way to check the dental occlusion. If not intervened, all occlusal contacts can be controlled in detail and sequentially together with relative force info. Analysis of the occlusion can be performed under maximum physiological conditions. Each intervention will be perceived by the neuromuscular mechanism, and the movement will not be a physiological function. Computerized occlusal analysis systems give us control of extreme physiologic occlusion [35, 82, 83, 84, 85, 86]. Actually, occlusal papers and similar indicators (wax, powder, shimstock, foil, etc.), which using intraoral indicators, are also not proper materials for occlusal diagnostics [87].
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Because contact “hold” resistance levels are subjective. Therefore, it is a difficult guiding factor to utilize when selecting contacts to adjust the demonstrated variable forces are within occlusal contacts. Because shim stock foil does not mark the selected teeth, the articulating paper markings are the primary guide for the operator when selecting which contact(s) require adjustment.
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It has been advocated in textbooks on occlusion [2, 3, 5, 6, 7] that mark area is a representative of the load contained within the mark. Legends to photographs depicting occlusal adjustment technique end results and paper mark appearance describe that large and dark marks indicate heavy load, and that smaller and light marks indicate lesser loads [5, 6, 7]. Additionally, the presence of many similar sized marks spread around the contacting arches is purported to indicate equal occlusal contact intensity, evenness, and simultaneity [1, 3].
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Though occlusal indicators show prints of the end of the occlusion, they cannot provide important information such as which tooth tubercle is first in occlusion, which one is second or which one is last and the force differences between these points (\nFigures 22\n).
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Figure 21.
The system is like a second class leverage system and is similar to a nuts breaker. Masticatory muscles apply the force in a harmonic manner, joints bear forces which applied by muscles and the neural system controls the magnitude, duration, direction and peak time of that forces.
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Figure 22.
Occlusal indicators such as occlusion paper may first show contacts first followed by consecutive contacts, but we can only see the last picture and not the events that occurred before [88]. Which is first, second and last? Occlusal paper is like a stamp that shows the static photo of a last step.
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Owing to the computer technologies developed in recent years, we now have the chance to examine the intraoral occlusion as detailed as possible.
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Computerized occlusion is the system that can be best examined today without disrupting the neuromuscular mechanism of the occlusion [20, 23, 38, 39, 83]. In this method, dynamic information of all occlusal contacts that occur when the patient closes and opens mouth is recorded digitally. T-Scan computerized occlusal analysis system (COAS) is one of the most advanced devices in the market today (Tekscan Inc., Boston, USA.) It is a unique system that allows the occlusion to be recorded from the beginning to the end.
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COAS basically consists of three main parts as follows:
Sensor,
Hardware: handle and computer,
Software.
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The sensor used in the system is ultra-fine plastic with a thickness of 0.1 mm (0.004 inch). This thin \nFigure 23\n sensor does not change the neuromuscular pattern that defines the occlusion of the patient. When the patient bites the sensor, the mandibular functional movement is not changed. The occlusion phenomenon occurs physiologically and with the neuromuscular orientation of the patient at that time. Thus, the clinician can accurately see the functional occlusion at that time. \nFigure 24\n shows the sensor used in the T-Scan computerized occlusal analysis system.
\n
Figure 23.
The T-scan sensor is an ultra-thin (0.004 inch, 0.1 mm), flexible printed circuit that detects your patient’s occlusal forces. These sensors are made up of 1370 active pressure sensing locations for the large sensor (#2002 for the Novus Handpiece, and #2001 for the Evolution Handle), and 1122 pressure sensing locations for the small sensor (#2502 for the Novus Handpiece, and #2501 for the Evolution Handle). These sensing locations are referred to as “sensing elements” or “sensels.” the “sensels” are arranged in rows and columns on the sensor. Each sensel can be seen as an individual square on the computer screen by selecting the 2D display mode (text is from company user manual, Teksan Inc. USA) [95] (\nFigures 24\n and \n25\n).
\n
Figure 24.
Application of computerized occlusal analysis system. In this case, patient’s stone model was scanned and model’s stl (STereoLithography) data were imported to the T-scan software. The occlusion analysis was performed on the real model’s 3D image.
\n
Figure 25.
Panoramic X-ray of the patient. He has various restorations both the upper and lowers of the posterior area.
\n
Case No.2.
\n
Patient S.S. Age: 68, Male.
\n
The patient with headache around anterior temporal area for approximately 7 years, occurring usually on mornings due to clenching of his teeth. There was a click sound on left TMJ. Radiographic (\nFigure 25\n) and intraoral examination: A remarkable abfraction detected and restored by fillings 3–4 times but the fillings dropped every time.
\n
When the occlusal analysis was performed, disclussion time was found to be 0.48 s (\nFigure 26\n). Premature contacts identified after the evaluation of the occlusion. The premature contacts are eliminated using a fine diamond bur, and the disclussion time was reduced to 0.23 s. (\nFigure 27\n).
\n
Figure 26.
Before occlusal equilibration.
\n
Figure 27.
After occlusal equilibration.
\n
After equilibration of occlusion, composite restorations were performed on teeth with abfraction. For the next month, the patient was given another follow-up appointment. When he arrives a month later for his follow-up appointment; filling restorations are still standing. There was no headache, and the click sound was gone.
\n
T-Scan records of before and after the occlusal stabilization of the patient are given as follows:
\n
In the computerized occlusal analysis software, the graphic arc dimensions are automatically adjusted according to the size of the anterior teeth in routine clinical trials. (\nFigure 28\n).
\n
Figure 28.
Central teeth dimensions are determinative; after the mesiodistal distance of the central teeth is entered, the dimensions of the other teeth are automatically calculated and the dental arch is formed.
\n
Figure 29.
Computerized Occlusion Analysis is currently the most powerful method of TMD clinics for treatment of patients with muscle pain dysfunction syndrome.
\n
However, if you need an in detail work and you need to see the occlusion in maximum precision you can choose to work with STL (STereoLithography) data. The great advantage of this method is that the tooth copies can be loaded automatically and individually. All teeth sizes are the same with the real dimensions. In this technique, upper and lower stone models are digitally scanned with an STL data ability scanner, and output data in the STL format are uploaded on the computer. Now, the clinician is able to analyze the occlusion in the real dimensions and locate the possible premature contacts precisely. (\nFigure 29\n).
\n
Computerized occlusal analysis is currently the most powerful method of TMD clinics for the treatment of patients with muscle pain dysfunction syndrome [23, 68, 89, 90]. Especially with JAVA, it is now frequently used in clinical routine. Computerized occlusal analysis allows us to perform the following treatments [91]:
\n
Muscle pain dysfunction syndrome can be removed very quickly,
Splint dependence at unbalanced anterior dislocations can be minimized,
Allows for occlusion stabilization in full mouth restorations [84],
Allows to keep occlusal stress within physiological limits in implant prosthetic studies [7].
\n
The impact of occlusal forces on teeth is variable. Occlusal derangements in physiological limits are absorbed with the buffer ability of periodontal ligaments [92]. However, impact of premature contacts on periodontium is like jigging, and this effect causes the enlargement of the alveolar space of teeth causing the teeth to loosen in alveolar space [93]. Therefore, it seems important to remove the occlusal traumas without causing any disruption on temporomandibular joints.
\n
\n\n',keywords:"JVA, T-Scan, chewing pattern, mastication, temporomandibular disorders, MPDS",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/59089.pdf",chapterXML:"https://mts.intechopen.com/source/xml/59089.xml",downloadPdfUrl:"/chapter/pdf-download/59089",previewPdfUrl:"/chapter/pdf-preview/59089",totalDownloads:1562,totalViews:495,totalCrossrefCites:1,totalDimensionsCites:1,totalAltmetricsMentions:0,impactScore:1,impactScorePercentile:62,impactScoreQuartile:3,hasAltmetrics:0,dateSubmitted:"January 5th 2017",dateReviewed:"November 16th 2017",datePrePublished:null,datePublished:"February 28th 2018",dateFinished:"January 30th 2018",readingETA:"0",abstract:"Temporomandibular joint disorder (TMJ) is a complex and multifactorial functional disorder. Best approach in the treatment of TMJ disorders needs in detail proper diagnostic study. Joint vibration analysis (JVA) device, a new age technology and one of the most important diagnostic tools, is used for detecting intra-articular sound vibrations. Every type of vibration in different frequencies shows us the status of joint. Evaluation can be made after analyzing the results applying to a diagram. Like Combining of the sound vibration diagnostic techniques with other examination methods may be very meaningful in efforts of treating TMJ problems. Another diagnosis method is the evaluation of chewing movements. Best chewing efficiency is the most important purpose of masticatory system. Final product is a very important indicator for the efficiency of the mastication, and chewing pattern. T-Scan digital occlusal analyzing system is another important occlusal diagnostic instrument. Digital occlusal analysis system is currently the most powerful method of TMD clinics for treatment of patients with muscle pain dysfunction syndrome. Digital occlusal analysis system allows us to perform the MPDS treatments, splint and occlusal rehabilitation. The three important diagnostic systems are described in this chapter.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/59089",risUrl:"/chapter/ris/59089",book:{id:"6025",slug:"temporomandibular-joint-pathology-current-approaches-and-understanding"},signatures:"Serdar Gözler",authors:[{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",fullName:"Serdar Gözler",slug:"serdar-gozler",email:"serdargozler@aydin.edu.tr",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",institution:{name:"Istanbul Aydın University",institutionURL:null,country:{name:"Turkey"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. How can we detect Temporomandibular joint sounds?",level:"1"},{id:"sec_3",title:"3. Clinical application of the joint vibration analysis",level:"1"},{id:"sec_4",title:"4. JT mastication analysis",level:"1"},{id:"sec_5",title:"5. Starting cycle",level:"1"},{id:"sec_5_2",title:"5.1. Maximum number of cycles to analyze",level:"2"},{id:"sec_6_2",title:"5.2. Occlusal threshold (OT)",level:"2"},{id:"sec_7_2",title:"5.3. Standard deviation limit",level:"2"},{id:"sec_8_2",title:"5.4. What can be read from masticatory analysis?",level:"2"},{id:"sec_10",title:"6. Computerized occlusal analysis",level:"1"}],chapterReferences:[{id:"B1",body:'\nBuescher J. Temporomandibular joint disorders. In: Am Fam Physician [Internet]. Elsevier; 2007 [cited 2016 Dec 15]. pp. 1477-1482. Available from: http://linkinghub.elsevier.com/retrieve/pii/B9780323045742500144\n\n'},{id:"B2",body:'\nScrivani SJ, DAS K, Kaban LB. Temporomandibular disorders. New England Journal of Medicine. 2008:2693-2705\n'},{id:"B3",body:'\nYuasa H, Kino K, Kubota E, Kakudo K, Sugisaki M, Nishiyama A, et al. 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Comparative Biochemistry and Physiology - A Molecular and Integrative Physiology. 2001:207-219\n'},{id:"B71",body:'\nFerreira LA, Grossmann E, Januzzi E, de Paula MVQ, Carvalho ACP. Diagnosis of temporomandibular joint disorders: Indication of imaging exams. Brazilian Journal of Otorhinolaryngology. 2016;82(3):341-352\n'},{id:"B72",body:'\nCooper BC, Kleinberg I. Relationship of temporomandibular disorders to muscle tension-type headaches and a neuromuscular orthosis approach to treatment. Cranio – Journal of Craniomandibular Practice. 2009;27(2):101-108\n'},{id:"B73",body:'\nYamada K, Hanada K, Fukui T, Satou Y, Ochi K, Hayashi T, et al. Condylar bony change and self-reported parafunctional habits in prospective orthognathic surgery patients with temporomandibular disorders. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2001;92(3):265-271\n'},{id:"B74",body:'\nBaldini A, Nota A, Cozza P. The association between occlusion time and Temporomandibular disorders. Journal of Electromyography and Kinesiology. 2015;25(1):151-154\n'},{id:"B75",body:'\nDawson PE. A classification system for occlusions that relates maximal intercuspation to the position and condition of the temporomandibular joints. The Journal of Prosthetic Dentistry. 1996;75(1):60-66\n'},{id:"B76",body:'\nWieckiewicz M, Boening K, Wiland P, Shiau Y-Y, Paradowska-Stolarz A. Reported concepts for the treatment modalities and pain management of temporomandibular disorders. Journal of Headache Pain [Internet]. 2015;16(1):106. Available from: http://www.thejournalofheadacheandpain.com/content/16/1/106\n\n'},{id:"B77",body:'\nWindhorst U. Muscle proprioceptive feedback and spinal networks. Brain Research Bulletin. 2007;73(4-6):155-202\n'},{id:"B78",body:'\nPalla S. Trigger points as a cause of Orofacial pain. Journal of Musculoskeletal Pain. 2004;12(3-4):29-36\n'},{id:"B79",body:'\nKurose M, Yamamura K, Noguchi M, Inoue M, Ootaki S, Yamada Y. Modulation of jaw reflexes induced by noxious stimulation to the muscle in anesthetized rats. Brain Research. 2005;1041(1):72-86\n'},{id:"B80",body:'\nDawson PE, Rinchuse DJ, Rinchuse DJ, Kandasamy S. Evidence-based versus experience-based views on occlusion and TMD [4] (multiple letters). American Journal of Orthodontics and Dentofacial Orthopedics. 2005;128(2):150-152\n'},{id:"B81",body:'\nPanigrahi D, Satpathy A, Patil A, Patel G. Occlusion and occlusal indicating materials. 2015;1(4):23-26\n'},{id:"B82",body:'\nRuge S, Quooss A, Kordass B. Variability of closing movements, dynamic occlusion, and occlusal contact patterns during mastication. International Journal of Computerized Dentistry. 2011;14(2):119-127\n'},{id:"B83",body:'\nQadeer S, Yang L, Sarinnaphakorn L, Kerstein RB. Comparison of closure occlusal force parameters in post-orthodontic and non-orthodontic subjects using T-scan(R) III DMD occlusal analysis. Cranio [Internet]. 2016;9634(April):1-7. Available from: http://dx.doi.org/10.1080/08869634.2015.1122277\n\n'},{id:"B84",body:'\nGözler S. Courtesy of Dr Serdar Gözler. In: Erdemir U, Yildiz E, editors. Esthetic and Functional Management of Diastema: A Multidisciplinary Approach [Internet]. 1st ed. Istanbul: Springer; 2015. p. 35. Available from: https://books.google.com/books?id=FawvCwAAQBAJ&pgis=1\n\n'},{id:"B85",body:'\nKürklü D, Yanikoglu N, Gözler S. Oklüzal Analiz Metodları ve T-scan. Atatürk Üniv Diş Hek Fak Derg. 2009;19(1):55-60\n'},{id:"B86",body:'\nSuit SR, Gibbs CH, Benz ST. Study of gliding tooth contacts during mastication. Journal of Periodontology [Internet]. 1976;47(6):331-334. Available from: http://www.ncbi.nlm.nih.gov/pubmed/1064720\n\n'},{id:"B87",body:'\nCarey J, Craig M, Kerstein R, Radke J. 2_EPA articulating paper study presentation. The Open Dentistry Journal. 2007;1(1):1-7\n'},{id:"B88",body:'\nCarey JP, Craig M, Kerstein RB, Radke J. Determining a relationship between applied occlusal load and articulating paper mark area. Open Dentistry Journal [Internet]. 2007;1:1-7. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2581523&tool=pmcentrez&rendertype=abstract\n\n'},{id:"B89",body:'\nSolow RA. Customized anterior guidance for occlusal devices: Classification and rationale. The Journal of Prosthetic Dentistry. 2013;110(4):259-263\n'},{id:"B90",body:'\nThumati P, Thumati R. The effect of disocclusion time-reduction therapy to treat chronic myofascial pain: A single group interventional study with 3 year follow-up of 100 cases. Journal of Indian Prosthodontic Society [Internet]. 2016;0(0):0. Available from: http://www.j-ips.org/preprintarticle.asp?id=176529\n\n'},{id:"B91",body:'\nClark JR, Evans RD. Functional occlusion: I. A review. Journal of Orthodontics. 2001;28:76-81\n'},{id:"B92",body:'\nKaribe H, Ogata K, Hasegawa Y, Ogihara K. Relation between clenching strength and occlusal force distribution in primary dentition. Journal of Oral Rehabilitation. 2003;30(3):307-311\n'},{id:"B93",body:'\nDaegling DJ, Hylander WL. Occlusal forces and mandibular bone strain: Is the primate jaw “overdesigned”? Journal of Human Evolution [Internet]. 1997;33(6):705-717. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9467777\n\n'},{id:"B94",body:'\nBiopak User Guide, Ver.7. 9275 N. 49th Street, Suite 150 Milwaukee, WI 53223 USA: BioResearch Associates, Inc.; 2011\n'},{id:"B95",body:'\nT-Scan User Manual (Help File in T-Scan Software 9.1). 307 West First Street. South Boston, MA 02127–1309: Tekscan, Inc; 2015\n'}],footnotes:[{id:"fn1",explanation:"Prof. Dr. Senih Calıkkocaoglu, Retired from Dentistry Faculty of Istanbul University, died in the year of 2016."}],contributors:[{corresp:"yes",contributorFullName:"Serdar Gözler",address:"serdargozler@aydin.edu.tr",affiliation:'
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1. Introduction
1.1 History of photodynamic therapy
The therapeutic properties of light were observed already in ancient Greece, Egypt, and India. However, they were not widely used for many centuries [1]. The history of modern photodynamic therapy (PDT) dates back to 1900, when Oscar Raab discovered the toxic properties of the dye acridine red on Paramecium spp. [2]. He and his supervisor, Hermann von Tappeiner, noticed a positive effect of illumination on the toxic activity of this dye. In his later work, von Tappeiner and his colleagues applied this approach to inactivation of bacteria [3] and to treatment of skin cancer [4]. In 1909, von Tappeiner introduced the term “Photodynamic Action” and showed that oxygen is essential for this procedure [5]. PDT has been studied and developed as an anticancer therapy for a long time and was approved by the Food and Drug Administration in the 1990s for various applications in this area of medicine [6, 7, 8]. The antimicrobial properties of this approach were unfairly forgotten for several decades. However, interest in antibacterial PDT has been rekindled and is continuously increasing because multidrug resistance of pathogenic microorganisms has become a serious threat to public health. Photodynamic antibacterial chemotherapy (PACT) has become a promising approach for combating bacterial infections, which are resistant to modern antibiotics.
1.2 Photosensitizers and their mechanism of action
PACT is based on the exposure of bacteria to photosensitive compounds—photosensitizers (PSs). When a PS located in the bacteria or on the bacterial surface is exposed to light (usually visible), it transfers from its low-energy ground state to an excited singlet state. Return of the PS to its ground state is accompanied by either emission of fluorescence or transition of the PS to a longer-living, higher-energy triplet state (PS*) via intersystem crossing. The PS* in turn reacts with surrounding molecules to form free radicals and hydrogen peroxide (Type I reaction) or transfers its energy to molecular oxygen to produce singlet oxygen and other highly reactive oxygen species (ROS; Type II reaction) [9, 10]. Type I and Type II reactions occur simultaneously, and the ratio at which they occur depends on both the PS type and the surrounding conditions. A detailed description of the photosensitization process can be found in the recent reviews of Castano et al. [11] and Cieplik [10]. ROSs formed in this process oxidize biomolecules, damage the cell membrane, and ultimately lead to cell death [12]. PACT usually proceeds predominantly through Type II processes. However, since Gram-negative bacteria are more susceptible to OH. radicals than to singlet oxygen, the Type I reaction may be more efficient against such microorganisms [13, 14].
1.3 Photosensitizers for PACT
Hundreds of compounds are currently available for mediating PDT in various areas of medicine, where some have been shown to be suitable for antimicrobial applications. PSs employed for medical uses should be a single pure compound, stable at room temperature and inexpensive. The PS must have a strong absorption peak in the visible spectrum between 600 and 900 nm and should possess a high-triplet quantum yield that will provide high production of ROS upon illumination. It should not be toxic in the dark (especially to mammalian cells), mutagenic or carcinogenic [15, 16, 17, 18]. In addition, when talking about PACT, it is very important that the PS will display preferential association with bacteria, accumulate within the cells, or bind to the bacterial cell envelope [14, 19].
PSs can generally be assigned to several chemical classes: tetrapyrroles (which include porphyrins, chlorins, bacteriochlorins, and phthalocyanines), synthetic dyes (phenothiazinium salts, Rose Bengal, squaraines, etc.), and naturally occurring compounds (such as riboflavin or curcumin). Cyclic tetrapyrroles present the most well-known class of clinically relevant PSs used mostly for anticancer applications [20]. This structure can be found naturally in such important biomolecules such as haem, chlorophyll, and bacteriochlorophyll. Unlike other types of PSs, most tetrapyrroles (except for bacteriochlorins) are more likely to react by a Type II reaction with the creation of singlet oxygen [16], whereas bacteriochlorins act via a Type I mechanism. Other well-known antimicrobial agents are phenothiazinium-based synthetic dyes, including methylene blue (MB) and toluidine blue O (TBO), which also act as anticancer agents in PDT. These structures can be synthesized more easily than tetrapyrroles but possess high-dark toxicity compared to other PSs [15, 21]. Another representative of synthetic dyes, Rose Bengal (RB), has already been used successfully in antimicrobial and anticancer applications for a long time [16]. Photodynamic active compounds isolated from plants arouse particular interest. These natural compounds include curcumin, extracted from the rhizomes of Curcuma longa, which was found effective in eradicating oral pathogens [22]. Another representative of this group is hypericin isolated from St. John’s wort, which exhibits photodynamic activity against Gram-positive and Gram-negative bacteria. Detailed descriptions of all PS classes can be found in the reviews published by Hamblin and colleagues [15, 16].
2. Photosensitizer activation modes
2.1 Dark activity
The name photosensitizer implies the need for illumination in order to activate PS molecules and trigger their action. However, PSs possess some so-called “dark activity” even in the absence of illumination, leading to cell death in the dark [23, 24, 25, 26, 27, 28, 29]. This feature depends on the PS concentration and manifests itself in different ways for various PSs.
Shrestha demonstrated dark toxicity of RB against Gram-positive Enterococcus faecalis. Exposure of the cells to 10 μM RB in the absence of illumination for 15 min led to a 0.5 log10 reduction in cell concentration [26]. Furthermore, a marked dark toxicity of RB against clinical isolates of Gram-negative Pseudomonas aeruginosa was observed by Nakonieczna [27]. Brovko compared the activity of various PSs against several types of microorganisms and noted high dark toxicity of RB, as well as of phloxine B against Gram-positive Bacillus sp. and Listeria monocytogenes (more than 5 log10 reduction in the bacterial concentration after 30 min of treatment with the dye) [30]. The toxicity of malachite green in the dark against the same microorganisms was very low (<0.1 log10 reduction in concentration after 30 min of treatment with the dye). High concentrations (>500 μg/mL) of acriflavin neutral in the absence of light were significantly toxic to E. coli (more than 6 log10 reduction in concentration after 30 min of treatment with the dye, both under illumination and in the dark). However, illumination significantly enhanced its toxic effect against other tested microorganisms [30].
In our studies, we also noted the dark toxicity of various PSs against different types of bacteria (Figures 1,2, Table 1). Figure 1 shows the effect of various RB concentrations on S. aureus in the absence of light. The number of living cells decreases with increasing RB concentration in the dark. Table 1 shows a comparison between dark and light toxicity of three PSs—malachite green oxalate (MGO), RB, and safranin O. The effect of MGO in the dark was the strongest, and a 0.87 μM concentration of MGO was sufficient for inhibiting the growth of S. aureus. The dark activity of RB and safranin O is noticeably weaker, and the minimal inhibitory concentrations (MIC) for these PSs against S. aureus are more than 100-fold higher. Figure 2 shows that S. aureus cells were completely destroyed by RB at a concentration of 5 μM and MB at 30 μM under illumination. These PSs also showed a cytotoxic effect when applied at the same concentrations in the dark, where MB reduced the bacterial concentration by one and RB by two orders of magnitude.
Figure 1.
Effect of RB concentration on its cytotoxic activity. S. aureus cells at the initial concentration of 104 CFU mL−1 were incubated for 3 min in dark conditions at various concentrations of RB. After the incubation, bacteria were tested by viable count. Error bars present standard deviations.
Figure 2.
SACT and PACT effect of MB on S. aureus. In SACT experiments, the cells at 108 CFU mL−1 concentration were incubated with (a) 5 μM RB or (b) 30 μM MB in the ultrasonic bath for 1 h in the dark. In PACT experiments, the cells were illuminated for 15 min by 1.6 mW cm−2 white light under the same conditions but without sonication. After the treatment, bacteria were tested by viable count. Error bars present standard deviations.
Photosensitizer
MIC, μM
Dark
Illumination
Malachite green oxalate
0.87
0.15
Rose Bengal
128
2
Safranin O
89
23
Table 1.
The MIC values of water-soluble PSs in the dark and under illumination. About 3 × 104 CFU mL−1 of S. aureus were treated by malachite green oxalate, Rose Bengal, and Safranin O at doubled dilutions, illuminated at room temperature by white light of 1.6 mW cm−2 intensity for 1 h, and incubated overnight in the dark by shaking at 37°C.
Figure 3.
Effect of RB at the 10 μM concentration under activation by radio waves at various frequency ranges on eradication of S. aureus at the initial cell concentration of 4.4 × 104 CFU mL−1 in the dark. Error bars present standard deviations.
2.2 Illumination
Although PSs are known to possess a certain dark activity, illumination noticeably increases their cytotoxic effect [6, 14]. An example of the difference in antibacterial activity of different PSs with and without illumination is shown in Table 1. In this experiment, the MIC of three PSs was determined for the bacterium S. aureus in the dark and after 1 h of illumination. As a result of illumination, the MIC of the examined PSs decreased approximately 6-fold for MGO, 64-fold for RB, and 4-fold for Safranin O.
The main light sources used today for activation of PSs are lasers, light-emitting diodes (LED), and gas discharge lamps (GDL) [10, 31, 32]. There is no absolute advantage of one of these light sources over the others. The choice of light source depends on the specific application. Laser is a high-intensity monochromatic source. It can be easily coupled to a single optical fiber and installed on different lighting devices. LED lamps are cheaper and provide a wide emission spectrum. GDLs are also cheaper than lasers—both in acquisition and in maintenance and have a wide emission spectrum. However, GDLs transmit more heat to the illuminated area than lasers and LEDs, which can lead to tissue damage. In general, the emission spectrum and light intensity are more important for the excitation of a specific PS than the particular light source type [10, 31, 32].
2.3 Sonodynamic excitation of photosensitizers
Illumination is undoubtedly the easiest and most effective way to activate PSs. However, its use is restricted, due to limited penetration of visible light into tissues. There is an ongoing search for alternative methods of PS excitation in the dark in order to overcome this problem. Ultrasonic activation seems to be attractive as an alternative to illumination. As with light activation, ultrasound can be selectively focused on a specific area, thus activating only PS molecules located in the affected area. Ultrasound can also easily penetrate into tissues, which opens prospects for its application in treatment of internal lesions and infections, without the need for invasive devices [33, 34]. Ultrasonic irradiation of PSs initiates the formation of highly active cytotoxic species—ROS and free radicals—which lead to the death of pathogenic cells. It was found that some well-known PSs also have sonosensitizing properties. Among them are porphyrins [35], RB [36, 37], chlorin e6 derivative, photodithazine [36], and curcumin [38]. Several studies found sonodynamic therapy (SDT) to be the promising treatment in various forms of cancerous tumors [39, 40, 41, 42, 43]. Sonodynamic therapy is also offered as treatment for atherosclerosis [44]. The applicability of sonodynamic antimicrobial chemotherapy (SACT) for the treatment of infectious diseases has been confirmed by various research groups [33, 34]. We have previously demonstrated the effectiveness of RB activated by ultrasonication for eradication of Gram-positive S. aureus and Gram-negative E. coli [29, 45, 46]. The effectiveness of SACT in inactivation of S. aureus by two other sensitizers—curcumin [38] and hematoporphyrin monomethyl ether [35]—was also reported. Alves et al. have recently reported on effective destruction of Candida albicans by photodithazine and RB in the dark under the ultrasonic excitation. A significant synergistic effect of the combination between PDT and SACT for combatting C. albicans biofilms was also found [36].
Figure 2 demonstrates the effect of ultrasonic activation that we showed on the antibacterial activity of two PSs—RB (Figure 2a) and MB (Figure 2b)—against S. aureus compared to photodynamic activation. Figure 2a shows that 15 min of sonication reduces the number of living cells by almost two orders of magnitude, from 2 × 108 to 4 × 106 CFU mL−1. RB alone applied in the dark causes a two orders of magnitude decrease in the cell concentration. However, sonication in the presence of 5 μM RB exerts a much stronger effect, reducing the cell concentration by 5 orders of magnitude. It should be noted that RB at the same concentration under illumination by visible light of 1.6 mW cm−2 fluence causes complete eradication of S. aureus cells, whereas light alone does not cause any significant harm to these cells. However, MB applied under sonication at the concentration causing complete destruction of S. aureus cells in the light did not eradicate microbial cells more than sonication alone (Figure 2).
2.4 Activation of photosensitizers by radio waves
Another possible way for activating PSs in the dark is by using nonionizing radiofrequency electromagnetic waves. The ability of radiofrequency waves to heat human tissue has been known for a long time and has already been applied for local destruction of cancerous tumors [47, 48]. The effectiveness of this method can be significantly improved by using suitable sensitizers, which can be targeted to the affected area and activated by means of radiofrequency radiation for selective destruction of cells. Tamarov et al. proposed the use of crystalline silicon-based nanoparticles as sensitizers induced by 27 MHz radiofrequency waves for effective treatment of Lewis lung carcinoma in vivo [48]. Another approach involved using gold nanoparticles, which were heated by an electric field using 13.56 MHz radiofrequency, and effectively destroyed human pancreatic cancer cells in vitro [49]. The same frequency was used in other studies to activate fullerene [50] and transferrin [51] and to eradicate cancer tumors in vitro and in vivo. A possible mechanism of radiosensitization, according to Tamarov et al. [48] and Chung et al. [51], may be thermal activation of sensitizers by hyperthermia, caused by dissipation of electromagnetic energy, which leads to thermal damage of cancer cells.
In our studies, we tested the possibility of using radiofrequency radiation to sensitize PSs in order to destroy microorganisms [29]. For this purpose, we irradiated S. aureus cells in physiological saline alone and in the presence of RB with radio waves at different frequencies—from 1 to 20 GHz. S. aureus cells in physiological saline in the dark (without RB and without radiation), S. aureus cells treated with radio waves (in the absence of RB), and S. aureus cells in the presence of RB, but not exposed to radio waves, were used as controls. Radiofrequency radiation alone did not significantly affect the survival of S. aureus. RB in the dark applied at the same concentration did not lead to any decrease in the bacterial concentration. However, exposure of S. aureus cells to radio waves in the presence of RB markedly reduced the number of live microorganisms. The rate of cell damage depended on the radio wave frequency. The most significant effect was observed in the frequency range of 9–12 GHz, where in the presence of RB, only 4.5% of the cells survived (Figure 3). For comparison, irradiation of cells treated by RB with radio waves in the frequency range of 1–3 GHz caused only a 40% reduction in the number of live cells.
To the best of our knowledge, our work was the first attempt to sensitize a PS by radio waves for destruction of bacteria. This topic naturally necessitates a broader and deeper study to understand the mechanisms of excitation and the possibilities of applying this method. The most likely mechanism of RB excitation by radio waves is conversion of electromagnetic energy into heat, which causes activation of RB, followed by energy transfer to dissolved oxygen and the formation of ROS, affecting the cells. We assume that when PSs are exposed to radiofrequency radiation, they actually behave like thermosensitizers excited by heat instead of light [29].
2.5 Chemiluminescent and bioluminescent excitation of photosensitizers
Another approach to overcoming the limitations of PACT in the treatment of deep infections is to replace the external light source by chemo- or bioluminescent light. Bioluminescence is a well-known phenomenon occurring in biological systems as a result of oxidation reactions of luciferins catalyzed by luciferases. This property is inherent in various microorganisms, worms, and insects, and the luciferins and luciferases of different organisms can be completely different. Bioluminescence is considered as a type of chemiluminescence, i.e., luminescence originating in the course of a chemical reaction. Bio- and chemiluminescence systems are used in various fields of medicine, pharmaceuticals, and bioanalytics [52, 53].
One of the well-studied and most effective chemical reactions involving light emission is oxidation of luminol [52, 54, 55]. Most applications of this reaction are associated with treatment of cancers [55, 56, 57]. Use of chemiluminescence as a light source for PACT has not been studied as extensively. Ferraz and colleagues evaluated the potential of chemiluminescent-excited photogem in killing S. aureus cells [58]. Our group demonstrated the effectiveness of chemiluminescent photodynamic antimicrobial therapy (CPAT) for destruction of S. aureus and E. coli by exposing these bacteria to the photosensitizer MB in the presence of luminol [46, 59, 60]. The results presented in Figure 4 show that the rate of growth inhibition by MB increased in the presence of luminol compared to untreated cells or to cells exposed in the dark to MB only.
Figure 4.
Effect of chemiluminescent photodynamic antimicrobial treatment (CPAT) on the viability of S. aureus and E. coli. Cells were incubated with MB at 25 μM concentration in the presence of 0.7 mM luminol. After the treatment, bacteria were tested by viable count. Error bars present standard deviations.
The dark effect of MB discussed in the above “Dark Activity” section can be seen in Figure 4, where the exposure of S. aureus and E. coli to 25 μM MB in the dark reduced the number of live cells by about 10-fold. Luminol alone had no toxic effect on the tested microorganisms. However, when combined with MB, it reduced the number of surviving bacteria by two additional orders of magnitude for S. aureus and 1.5 orders of magnitude in the case of E. coli. Thus, the use of chemiluminescence may expand the capabilities of PDT, allowing the use of PSs for the treatment of internal organs.
3. Encapsulation of photosensitizers in liposomes
Since PSs are usually inactive in the absence of excitation, focusing the beam of light, ultrasound or radio wave radiation on the affected area is the easiest way to achieve selective action of a PS. However, surrounding healthy tissues may also be affected by the PS, even under such focused processing. It is therefore very important to target the treatment directly to the infected site. Highly biocompatible and low immunogenic liposomes can serve as carriers for targeted delivery of PSs encapsulated into liposomes to the infected site [61, 62, 63].
Liposomes are spherical multi- or unilamellar vesicles consisting of phospholipids (e.g., phosphatidylcholines) with an internal hydrophilic cavity. They vary in composition, size, charge, and number of layers and can encapsulate and deliver both hydrophilic and hydrophobic compounds, which can be retained in the water core of liposomes or be encapsulated in the phospholipid bilayer, respectively. A variety of methods have been developed for the production of liposomes with a controlled size and special properties. The most widely used method for producing liposomes is hydration of thin lipid films. In this case, lipids with or without active substances are dissolved in an organic solvent, which is evaporated on a rotary evaporator, producing a thin film on a flask wall. The lipid film is then rehydrated by an aqueous phase. Membrane extrusion and sonication methods are most commonly used for control of liposome size [64]. Advanced strategies for liposome preparation include charging the liposomes, attaching the ligands such as antibodies or lectins to their surface, or altering the physiological conditions such as increasing the temperature or changing the pH in the target tissues to produce heat-sensitive or pH-sensitive liposomes [65]. The works of Ghosh, Li, Bulbake, Abu Lila, and Alavi summarize the latest developments in the field of liposome design and optimization, including passive and active targeting, extended circulation, building multifunctional liposomes, and so on [62, 63, 64, 65, 66].
There exist several methods for PS encapsulation into liposomes (Figure 5). Hydrophilic PSs (e.g., MB, RB, or photofrin) are dissolved in aqueous buffer and are included into the internal cavity of liposomes. Hydrophobic compounds (such as temoporfin and bacteriochlorin a) are integrated in the phospholipid bilayer [62, 67]. Several groups have shown that encapsulation of PSs in liposomes improves their effectiveness against cancer in vivo. Back in 1983, Jori and colleagues reported that hematoporphyrin and its derivatives incorporated into liposomes on the basis of dipalmitoyl-phosphatidyl-choline are effective for systemic delivery of PSs to tumors in rats [68]. Enhancement of the photodynamic effects of photofrin encapsulated in a liposome carrier was later demonstrated on a human glioma implanted in rat brain [69]. A variety of PSs (temoporfin, zinc phthalocyanine, benzoporphyrin derivative monoacid, etc.) in various liposomal formulations, such as dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylglycerol, dioleoylphosphatidylcholine, and others, were found to be effective on HT29 and Meth A tumor models in vivo [62]. However, the only clinically approved liposomal PS drug to date is Visudyne, developed by QLT in Vancouver, and produced by Novartis AG, Switzerland. This formulation is produced from a derivative of benzoporphyrin monoacid encapsulated in unilamellar dimyristoylphosphatidylcholine/egg phosphatidylglycerol liposomes. The liposomes in this drug not only dissolve the lipophilic PS for intravenous administration but also contribute to its enhanced absorption in tumor tissues [62, 64].
Figure 5.
Schematic representation of a liposome with PS entrapped in the internal aqueous phase and within the external phospholipid bilayer.
Liposomal PS preparations are suitable for antibacterial applications. This approach ensures the delivery of the compound at a higher concentration, thus increasing the cytotoxicity of the drug. In addition, the local use of liposomal preparations provides a slow release of active components, which helps prolong their effect in infected tissues. In Gram-negative bacteria, fusion between liposomes and the outer cell membranes leads to the delivery of concentrated liposome contents directly into the cytoplasm [70, 71, 72]. In Gram-positive bacteria, the PS is probably released when liposomes interact with the external peptidoglycan and diffuse through the cell wall [72, 73, 74]. Various researchers have demonstrated the effectiveness of liposomal formulations of various PSs against Gram-positive and Gram-negative microorganisms and also against fungal infections in vitro and in vivo. Ferro et al. showed high efficacy of porphyrin incorporated into cationic liposomes against S. aureus, compared to the free drug [75, 76]. Tsai also showed an increase in the bactericidal efficacy of hematoporphyrin against a number of Gram-positive bacteria, including S. aureus, as a result of its incorporation into liposomes [77]. Yang proved the efficacy of chlorine e6 encapsulated in cationic liposomes against susceptible and drug-resistant clinical isolates of C. albicans both in vitro and for infected burn wounds in vivo [78].
In our studies, we tested the effect of different PSs in different liposome formulations on Gram-positive and Gram-negative bacteria. Figure 6 presents a comparison between the MICs of free and dipalmitoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol liposome-encapsulated MB and NR against S. aureus (Figure 6a) and E. coli (Figure 6b).
Figure 6.
MIC values of free and liposome encapsulated MB and NR determined against (a) S. aureus and (b) E. coli. Liposomes were prepared from dipalmitoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol at 15 mg/mL total lipid concentration by sonication for 10 sec. Bacteria at 3 × 104 CFU mL−1 concentration were treated by MB and NR at doubled dilutions, illuminated at room temperature by white light of 1.6 mW cm−2 intensity for 1 h, and incubated overnight in the dark by shaking at 37°C. Error bars present standard deviations.
As can be seen from the results, incorporation into liposomes significantly increased the antibacterial activity of MB and NR. Following encapsulation, the MIC of MB decreased by approximately 2-fold and that of NR by about 1.4-fold for both tested microorganisms (Figure 6). We tested the effect of liposome composition on the delivery of these PSs to cells and determined the conditions for efficient use of encapsulated PSs [74].
In addition, we tried to apply liposomal forms of PSs to CPAT by encapsulating not only PSs in liposomes but also luminol and introduced to activate PSs in sites inaccessible to external lighting [59]. We monitored the survival of the cells following their exposure to either liposomal MB or luminol, as well as to liposomes containing both compounds together (Figure 7) when the experiments were carried out in the dark.
Figure 7.
Chemiluminescent photodynamic antimicrobial treatment effect on the viability of S. aureus and E. coli. Cells were incubated with 25 μM MB liposome (lip) encapsulated together with 0.7 mM luminol (LM). After the treatment, the bacteria were tested by viable count. Error bars present standard deviations.
It can be seen (Figure 7) that luminol itself did not lead to cell damage. MB in the liposomal form exhibited certain dark activity, similar to that in a free form discussed in the “Dark Activity” section. The addition of luminol to MB liposomes markedly increased its antibacterial activity toward S. aureus and E. coli. Liposomes were not targeted in this study. Targeting of liposomes can lead to an additional increase in the efficiency and specificity of this technique.
4. Immobilization
New prospects of using PSs are opened by the immobilization of PSs onto a solid phase. This approach may allow repeated or continuous use of PSs. PSs can be immobilized by adsorption and covalent bonding onto solid supports and by ionic bonding to ion-exchange resins or incorporation into polymer films. The photodynamic properties of immobilized PSs are reported to be retained for a long time [79, 80, 81, 82, 83]. PSs studied in the immobilized form include RB, MB, and TBO; the porphyrin derivatives 5,10,15,20-tetrakis (p-hydroxy phenyl) porphyrin, 5,10,15,20-tetrakis (p-aminophenyl) porphyrin, and zinc (II) phthalocyanine tetrasulfonic acid; and the ruthenium salts tris (4,4′-diphenyl-2,2′-bipyridine) ruthenium (II), tris (4,7-diphenyl-1,10-phenanthroline) ruthenium (II), tris (1,10-phenanthrolinyl-4,7-bis (benzenesulfonate) ruthenate (II), and tris (4,40-dinonyl-1,10-phenan throline) ruthenium (II). Solid supports applied for immobilization of PSs include polyethylene, polypropylene, polystyrene, polycarbonate, polymethyl methacrylate, polyester isophthalic resin, silicone, cationic nylon, porous silicones, poly (vinylidene difluoride), cellulose membranes, and chitosan [82, 83, 84, 85, 86, 87, 88]. Immobilized PSs demonstrated antibacterial properties against Gram-negative and Gram-positive bacteria in batch and continuous regimes and under reuse. Immobilized PSs were found more stable and resistant to photobleaching than in a free form [82, 86, 88].
Our group immobilized PSs in polymers using several techniques. The first method included mixing solutions of PSs in chloroform with solutions of polymers in the same solvent, followed by evaporation of the solvent, which yielded thin polymeric films with homogeneously incorporated PSs. This technique was applied to RB and MB immobilized onto polystyrene, polycarbonate, and polymethyl methacrylate [88, 89, 90]. In all cases, the obtained polymer films showed high antibacterial activity against Gram-positive and Gram-negative bacteria when exposed to an external source of white light. However, since this method involves using an organic solvent, it cannot be considered environmentally friendly. The second method is based on dissolution of PSs in a melted polymer under extrusion and does not require any additional chemical reagents [91]. The photosensitizers RB, Rose Bengal lactone, MB, and hematoporphyrin were immobilized in polyethylene and polypropylene using this method. The antibacterial efficiency of immobilized PSs obtained as polymeric strips and beads was tested against S. aureus and E. coli in batch and continuous regimes under white fluorescent light. All immobilized PSs significantly reduced the concentration of the tested microorganisms, up to their complete eradication [91].
Another immobilization technique was based on polymerization of silicon in the presence of RB as the photosensitizer. Silicon tablets produced by this method contained evenly distributed RB that was not bound to the support by covalent bonds [29]. The antibacterial activity of the immobilized RB was tested under illumination and using ultrasonic activation in the dark (Figure 8). Figure 8 demonstrates the effect of immobilized RB on S. aureus cells when subjected to ultrasound in the dark. Silicone alone did not affect the microorganisms with and without sonication. However, the number of alive cells in samples subjected to immobilized RB under sonication decreased with sonication time and decreased by more than three orders of magnitude after 10 min of treatment.
Figure 8.
Antibacterial activity of silicon-immobilized RB (5% w/w) under ultrasonic treatment in the dark. Control—S. aureus cells treated by ultrasound only. After the treatment, bacteria were tested by viable count. Error bars present standard deviations.
Further development of immobilization methods and different PSs and polymers may expand the possibilities of this approach and yield the applications in various fields, such as the production of antibacterial surfaces and water disinfection.
5. Conclusions
Numerous studies show that photodynamic antibacterial chemotherapy is a powerful tool for killing microorganisms. Since this method requires external illumination, it can be successfully applied only to the treatment of local superficial skin and oral cavity infections. Development of new modes of PS excitation by ultrasound, radio waves, chemiluminescent, and bioluminescent light opens new prospects for their use in treating internal infections. Encapsulation of PSs in liposomes may solve the problem of using hydrophobic PSs with poor solubility in the aqueous phase. It can also provide delivery of a concentrated PS directly to the target site, thus increasing efficiency and reducing side effects of the treatment. Immobilization of PSs in a solid phase enables using them repeatedly or in a continuous mode. It can be assumed that PSs have a good potential for various clinical and nonclinical applications.
Acknowledgments
This work was supported by the Research Authority of the Ariel University, Ariel, Israel.
Conflict of interest
The authors declare no conflict of interest.
\n',keywords:"photodynamic therapy (PDT), photodynamic antimicrobial chemotherapy (PACT), photosensitizer (PS), chemiluminescent antimicrobial chemotherapy (CPAT), sonodynamic antimicrobial chemotherapy (SACT), targeted drug delivery, liposomes, immobilization",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/69306.pdf",chapterXML:"https://mts.intechopen.com/source/xml/69306.xml",downloadPdfUrl:"/chapter/pdf-download/69306",previewPdfUrl:"/chapter/pdf-preview/69306",totalDownloads:877,totalViews:0,totalCrossrefCites:3,dateSubmitted:"June 10th 2019",dateReviewed:"September 4th 2019",datePrePublished:"September 30th 2019",datePublished:"July 1st 2020",dateFinished:"September 28th 2019",readingETA:"0",abstract:"Increasing resistance of bacteria to antibiotics is a serious worldwide problem, and to combat resistant bacteria, new antibacterial approaches are to be developed. One alternative to traditional antibiotic therapy is photodynamic antimicrobial chemotherapy (PACT). PACT is based on excitation of photosensitizers (PS) capable of transferring the absorbed light energy to dissolved molecular oxygen causing generation of reactive oxygen species, which irreversibly damage bacterial cell components. The overall efficiency of PACT has been proven for Gram-positive and Gram-negative bacteria. The effectiveness of PACT can be increased by encapsulation of PS in liposomes providing more concentrated delivery of PS, enhanced cytotoxicity, improved pharmacokinetic properties, sustained release, and prolonged action of the PS. For continuous and reusable application, PS can be immobilized in polymers. Chemiluminescence, sonodynamic treatment, and radiofrequency irradiation allow to perform excitation of PS in the dark without external illumination, opening prospects for combating internal infections. Combination of PS with antibiotics can gain a synergistic effect, allowing in some cases to overcome the resistance of bacteria to antibiotics.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/69306",risUrl:"/chapter/ris/69306",signatures:"Faina Nakonechny and Marina Nisnevitch",book:{id:"8997",type:"book",title:"Microorganisms",subtitle:null,fullTitle:"Microorganisms",slug:"microorganisms",publishedDate:"July 1st 2020",bookSignature:"Miroslav Blumenberg, Mona Shaaban, Abdelaziz Elgaml",coverURL:"https://cdn.intechopen.com/books/images_new/8997.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83880-188-5",printIsbn:"978-1-83880-187-8",pdfIsbn:"978-1-83880-363-6",isAvailableForWebshopOrdering:!0,editors:[{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"23436",title:"Dr.",name:"Marina",middleName:null,surname:"Nisnevitch",fullName:"Marina Nisnevitch",slug:"marina-nisnevitch",email:"marinan@ariel.ac.il",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Ariel University",institutionURL:null,country:{name:"Israel"}}},{id:"307858",title:"Dr.",name:"Faina",middleName:null,surname:"Nakonechny",fullName:"Faina Nakonechny",slug:"faina-nakonechny",email:"fainan@ariel.ac.il",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Ariel University",institutionURL:null,country:{name:"Israel"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_1_2",title:"1.1 History of photodynamic therapy",level:"2"},{id:"sec_2_2",title:"1.2 Photosensitizers and their mechanism of action",level:"2"},{id:"sec_3_2",title:"1.3 Photosensitizers for PACT",level:"2"},{id:"sec_5",title:"2. Photosensitizer activation modes",level:"1"},{id:"sec_5_2",title:"2.1 Dark activity",level:"2"},{id:"sec_6_2",title:"2.2 Illumination",level:"2"},{id:"sec_7_2",title:"2.3 Sonodynamic excitation of photosensitizers",level:"2"},{id:"sec_8_2",title:"2.4 Activation of photosensitizers by radio waves",level:"2"},{id:"sec_9_2",title:"2.5 Chemiluminescent and bioluminescent excitation of photosensitizers",level:"2"},{id:"sec_11",title:"3. Encapsulation of photosensitizers in liposomes",level:"1"},{id:"sec_12",title:"4. Immobilization",level:"1"},{id:"sec_13",title:"5. 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Department of Chemical Engineering, Biotechnology and Materials, Ariel University, Ariel, Israel
Department of Chemical Engineering, Biotechnology and Materials, Ariel University, Ariel, Israel
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Open Access Funding
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For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
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Indexing and listing across major repositories, see details ...
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Dissemination and Promotion
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*These prices do not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT as long as provision of the VAT registration number is made during the application process. This is made possible by the EU reverse charge method.
\n\n
Services included are:
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An online manuscript tracking system to facilitate your work
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Personal contact and support throughout the publishing process from your dedicated Author Service Manager
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Assurance that your manuscript meets the highest publishing standards
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English language copyediting and proofreading, including the correction of grammatical, spelling, and other common errors
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XML Typesetting and pagination - web (PDF, HTML) and print files preparation
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Discoverability - electronic citation and linking via DOI
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Permanent and unrestricted online access to your work
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What isn't covered by the Open Access Publishing Fee?
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If your manuscript:
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\n\t
Exceeds the number of pages defined by the publishing guidelines, an additional fee per page may be required
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If a manuscript requires Heavy Editing or Language Polishing, this will incur additional fees.
\n
\n\n
Your Author Service Manager will inform you of any items not covered by the OAPF and provide exact information regarding those additional costs before proceeding.
\n\n
Open Access Funding
\n\n
To explore funding opportunities and learn more about how you can finance your IntechOpen publication, go to our Open Access Funding page. IntechOpen offers expert assistance to all of its Authors. We can support you in approaching funding bodies and institutions in relation to publishing fees by providing information about compliance with the Open Access policies of your funder or institution. We can also assist with communicating the benefits of Open Access in order to support and strengthen your funding request and provide personal guidance through your application process. You can contact us at funders@intechopen.com for further details or assistance.
\n\n
For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
\n\n
Added Value of Publishing with IntechOpen
\n\n
Choosing to publish with IntechOpen ensures the following benefits:
\n\n
\n\t
Indexing and listing across major repositories, see details ...
\n\t
Long-term archiving
\n\t
Visibility on the world's strongest OA platform
\n\t
Live Performance Metrics to track readership and the impact of your chapter
\n\t
Dissemination and Promotion
\n
\n\n
Benefits of Publishing with IntechOpen
\n\n
\n\t
Proven world leader in Open Access book publishing with over 10 years experience
\n\t
+5,700 OA books published
\n\t
Most competitive prices in the market
\n\t
Fully compliant with OA funding requirements
\n\t
Optimized processes that assure your research is made available to the scientific community without delay
\n\t
Personal support during every step of the publication process
\n\t
+184,650 citations in Web of Science databases
\n\t
Currently strongest OA platform with over 175 million downloads
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H. Gulrez, Saphwan Al-Assaf and Glyn O Phillips",authors:[{id:"58120",title:"Prof.",name:"Saphwan",middleName:null,surname:"Al-Assaf",slug:"saphwan-al-assaf",fullName:"Saphwan Al-Assaf"}]}],mostDownloadedChaptersLast30Days:[{id:"35255",title:"Mechanical Transmissions Parameter Modelling",slug:"mechanical-transmissions-parameter-modelling",totalDownloads:7279,totalCrossrefCites:1,totalDimensionsCites:2,abstract:null,book:{id:"1982",slug:"mechanical-engineering",title:"Mechanical Engineering",fullTitle:"Mechanical Engineering"},signatures:"Isad Saric, Nedzad Repcic and Adil Muminovic",authors:[{id:"101313",title:"Prof.",name:"Isad",middleName:null,surname:"Saric",slug:"isad-saric",fullName:"Isad Saric"}]},{id:"68505",title:"Research Design and Methodology",slug:"research-design-and-methodology",totalDownloads:24813,totalCrossrefCites:7,totalDimensionsCites:16,abstract:"There are a number of approaches used in this research method design. The purpose of this chapter is to design the methodology of the research approach through mixed types of research techniques. The research approach also supports the researcher on how to come across the research result findings. In this chapter, the general design of the research and the methods used for data collection are explained in detail. It includes three main parts. The first part gives a highlight about the dissertation design. The second part discusses about qualitative and quantitative data collection methods. The last part illustrates the general research framework. The purpose of this section is to indicate how the research was conducted throughout the study periods.",book:{id:"8511",slug:"cyberspace",title:"Cyberspace",fullTitle:"Cyberspace"},signatures:"Kassu Jilcha Sileyew",authors:[{id:"292841",title:"Ph.D.",name:"Kassu",middleName:null,surname:"Jilcha Sileyew",slug:"kassu-jilcha-sileyew",fullName:"Kassu Jilcha Sileyew"}]},{id:"67558",title:"Polymerase Chain Reaction (PCR): Principle and Applications",slug:"polymerase-chain-reaction-pcr-principle-and-applications",totalDownloads:10511,totalCrossrefCites:6,totalDimensionsCites:15,abstract:"The characterization of the diversity of species living within ecosystems is of major scientific interest to understand the functioning of these ecosystems. It is also becoming a societal issue since it is necessary to implement the conservation or even the restoration of biodiversity. Historically, species have been described and characterized on the basis of morphological criteria, which are closely linked by environmental conditions or which find their limits especially in groups where they are difficult to access, as is the case for many species of microorganisms. The need to understand the molecular mechanisms in species has made the PCR an indispensable tool for understanding the functioning of these biological systems. A number of markers are now available to detect nuclear DNA polymorphisms. In genetic diversity studies, the most frequently used markers are microsatellites. The study of biological complexity is a new frontier that requires high-throughput molecular technology, high speed computer memory, new approaches to data analysis, and the integration of interdisciplinary skills.",book:{id:"7728",slug:"synthetic-biology-new-interdisciplinary-science",title:"Synthetic Biology",fullTitle:"Synthetic Biology - New Interdisciplinary Science"},signatures:"Karim Kadri",authors:[{id:"290766",title:"Dr.",name:"Kadri",middleName:null,surname:"Karim",slug:"kadri-karim",fullName:"Kadri Karim"}]},{id:"62059",title:"Types of HVAC Systems",slug:"types-of-hvac-systems",totalDownloads:12245,totalCrossrefCites:8,totalDimensionsCites:14,abstract:"HVAC systems are milestones of building mechanical systems that provide thermal comfort for occupants accompanied with indoor air quality. HVAC systems can be classified into central and local systems according to multiple zones, location, and distribution. Primary HVAC equipment includes heating equipment, ventilation equipment, and cooling or air-conditioning equipment. Central HVAC systems locate away from buildings in a central equipment room and deliver the conditioned air by a delivery ductwork system. Central HVAC systems contain all-air, air-water, all-water systems. Two systems should be considered as central such as heating and cooling panels and water-source heat pumps. Local HVAC systems can be located inside a conditioned zone or adjacent to it and no requirement for ductwork. Local systems include local heating, local air-conditioning, local ventilation, and split systems.",book:{id:"6807",slug:"hvac-system",title:"HVAC System",fullTitle:"HVAC System"},signatures:"Shaimaa Seyam",authors:[{id:"247650",title:"M.Sc.",name:"Shaimaa",middleName:null,surname:"Seyam",slug:"shaimaa-seyam",fullName:"Shaimaa Seyam"},{id:"257733",title:"MSc.",name:"Shaimaa",middleName:null,surname:"Seyam",slug:"shaimaa-seyam",fullName:"Shaimaa Seyam"},{id:"395618",title:"Dr.",name:"Shaimaa",middleName:null,surname:"Seyam",slug:"shaimaa-seyam",fullName:"Shaimaa Seyam"}]},{id:"70315",title:"Some Basic and Key Issues of Switched-Reluctance Machine Systems",slug:"some-basic-and-key-issues-of-switched-reluctance-machine-systems",totalDownloads:1238,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Although switched-reluctance machine (SRM) possesses many structural advantages and application potential, it is rather difficult to successfully control with high performance being comparable to other machines. Many critical affairs must be properly treated to obtain the improved operating characteristics. This chapter presents the basic and key technologies of switched-reluctance machine in motor and generator operations. The contents in this chapter include: (1) structures and governing equations of SRM; (2) some commonly used SRM converters; (3) estimation of key parameters and performance evaluation of SRM drive; (4) commutation scheme, current control scheme, and speed control scheme of SRM drive; (5) some commonly used front-end converters and their operation controls for SRM drive; (6) reversible and regenerative braking operation controls for SRM drive; (7) some tuning issues for SRM drive; (8) operation control and some tuning issues of switched-reluctance generators; and (9) experimental application exploration for SRM systems—(a) wind generator and microgrid and (b) EV SRM drive.",book:{id:"8899",slug:"modelling-and-control-of-switched-reluctance-machines",title:"Modelling and Control of Switched Reluctance Machines",fullTitle:"Modelling and Control of Switched Reluctance Machines"},signatures:"Chang-Ming Liaw, Min-Ze Lu, Ping-Hong Jhou and Kuan-Yu Chou",authors:[{id:"37616",title:"Prof.",name:"Chang-Ming",middleName:null,surname:"Liaw",slug:"chang-ming-liaw",fullName:"Chang-Ming Liaw"},{id:"306461",title:"Mr.",name:"Min-Ze",middleName:null,surname:"Lu",slug:"min-ze-lu",fullName:"Min-Ze Lu"},{id:"306463",title:"Mr.",name:"Ping-Hong",middleName:null,surname:"Jhou",slug:"ping-hong-jhou",fullName:"Ping-Hong Jhou"},{id:"306464",title:"Mr.",name:"Kuan-Yu",middleName:null,surname:"Chou",slug:"kuan-yu-chou",fullName:"Kuan-Yu Chou"}]}],onlineFirstChaptersFilter:{topicId:"1",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82385",title:"Cyclodextrins as Bricks for Tuning Polymer Properties",slug:"cyclodextrins-as-bricks-for-tuning-polymer-properties",totalDownloads:1,totalDimensionsCites:null,doi:"10.5772/intechopen.105688",abstract:"Cyclodextrins are natural cyclic oligosaccharides with a cone shape delimiting a hydrophobic cavity. The rims of cyclodextrins can be functionalized in order to improve their properties. Based on this, cyclodextrins can be linked to polymer chains, which further allows the tuning of the polymer properties. This review describes the methods of polymer functionalization with cyclodextrins and highlights the changes in the physicochemical properties of these materials. This chapter is focused on polymers in solution and in gel states. Cyclodextrin-based polymers are evaluated by various physicochemical methods, such as rheology, calorimetry, and spectroscopy (electron paramagnetic resonance, fluorescence, nuclear magnetic resonance (NMR), Fourier transform infrared (FT-IR), etc.). Both natural and synthetic polymers are considered in this chapter.",book:{id:"11901",title:"Cyclodextrins - New Perspectives",coverURL:"https://cdn.intechopen.com/books/images_new/11901.jpg"},signatures:"Ludmila Aricov, Anca Ruxandra Leontieș, Iulia Matei and Gabriela Ioniță"},{id:"82443",title:"Phase Noise in OFDM",slug:"phase-noise-in-ofdm",totalDownloads:0,totalDimensionsCites:0,doi:"10.5772/intechopen.105551",abstract:"Orthogonal frequency division multiplexing (OFDM) technique provides high data rate with high spectral efficiency for operating close to the Shanon capacity bounds. With the advantages of simple channel equalization, robustness against frequency selectivity of the channel, and efficient implementation, this is a widely deployed technique. Orthogonal frequency division multiplexing access (OFDMA), the multiple access technique using OFDM, has the great potential for providing high spectral efficiency due to its integrated space-frequency and multiuser diversity. Besides all the advantages, OFDM/A is very susceptible to transceiver’s impairments such as phase noise (PHN), carrier frequency offset, and in-quadrature phase imbalance effect. Phase noise is the random fluctuation in phase of the sinusoidal waveform used for frequency up/down conversion of baseband signals to/from RF (radio frequency). This occurs due to the inherent imperfections of oscillators used for this purpose. This chapter addresses the orthogonal frequency division multiplexing/multiple access system performance under the impact of transceiver oscillator phase noise.",book:{id:"10990",title:"Multiplexing - Recent Advances and Novel Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10990.jpg"},signatures:"Kamayani Shrivastav"},{id:"82360",title:"Development and Usage of Electronic Teaching Technologies for the Economic Training of Students in a Technical University",slug:"development-and-usage-of-electronic-teaching-technologies-for-the-economic-training-of-students-in-a",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.105610",abstract:"In this chapter, the experience of the Department of Economic Theory in the development and use of electronic technologies in teaching economic theory for students of technical directions is described. The necessity of electronic testing in the context of the concept of practice-oriented teaching has been substantiated. The stages of development and structure of electronic testing are presented. The process of forming the base of test tasks is described. The structure of the software is stated. The experience of approbation and application of testing technology is presented. The influence of electronic testing technology on teaching methods is shown. The issues of electronic support of business games are considered. Electronic technologies are considered as a necessary and essential element in the organization and implementation of business games developed at the department. An assessment of the impact of electronic testing and electronic support of business games on the quality of the educational process is given.",book:{id:"11170",title:"Quality Control",coverURL:"https://cdn.intechopen.com/books/images_new/11170.jpg"},signatures:"Valeryi Semenov"},{id:"82348",title:"Biochar Development as a Catalyst and Its Application",slug:"biochar-development-as-a-catalyst-and-its-application",totalDownloads:1,totalDimensionsCites:null,doi:"10.5772/intechopen.105439",abstract:"Biochar is a carbon-rich pyrogenic material that is made from carbon-neutral sources (i.e., biomass). It offers key strategies for carbon capture and storage (CCS) as well as being an environmentally friendly means of soil amendment. The recent recognition of biochar as a versatile media for catalytic applications has prompted preliminary research into biochar’s catalytic capacity and mechanistic practices via various routes. This chapter provides a review of biochar production technologies, biochar’s catalyst development, and its application in various catalytic processes as well as descriptions of the benefits and drawbacks of the various applications currently available. The characteristics of biochar-based catalysts, challenges of effective application of this catalyst system, emerging application, prospects, and future work consideration for effective utilization of biochar-based catalysts were presented.",book:{id:"11537",title:"Biochar - Productive Technologies, Properties and Application",coverURL:"https://cdn.intechopen.com/books/images_new/11537.jpg"},signatures:"Stephen Okiemute Akpasi, Ifeanyi Michael Smarte Anekwe, Jeremiah Adedeji and Sammy Lewis Kiambi"},{id:"82418",title:"Bayesian Networks for Decision Support in Emergency Response: A Model for Missing Person Investigations",slug:"bayesian-networks-for-decision-support-in-emergency-response-a-model-for-missing-person-investigatio",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.105047",abstract:"The successful operation of Emergency services (Police, Fire, Medical Emergency) relies heavily upon Information Systems and particularly Decision Support Systems. Missing person cases consume resources from the already overstretched resources of Police Forces. Such cases predominantly come from at-risk groups such as children in care, people suffering from depression, or elderly people suffering from dementia. This chapter reviews current practices used for missing person cases and describes a decision support model based on Bayesian networks.",book:{id:"11068",title:"Contemporary Issues in Information Systems - a Global Perspective",coverURL:"https://cdn.intechopen.com/books/images_new/11068.jpg"},signatures:"Denis Reilly"},{id:"82437",title:"Water Availability for the Environmental Flow in Two Rivers of Mexico under Climate Change",slug:"water-availability-for-the-environmental-flow-in-two-rivers-of-mexico-under-climate-change",totalDownloads:0,totalDimensionsCites:0,doi:"10.5772/intechopen.104881",abstract:"Adaptation to climate change requires, among others, the modification of river flow regimes to account for the change in household, agricultural, industry, and energy water consumption as well as their short/medium/long-term socioeconomic impact. In this study, the comparative analysis of the variation of the precipitation in relation to the availability of water in the Yautepec and Cuautla rivers in Morelos, Mexico, for the previous period and subsequent period is carried out, to determine the change in the availability of water in the ecosystem. In winter (February), an increase in rainfall on the Yautepec and Cuautla River was observed, where annual seasonal agriculture and Pine and Oyamel forest are the characteristic vegetation. In autumn (October), a decrease in precipitation takes place. The flows in some regions do not coincide with the increase in the percentage of precipitation (Oaxtepec and Las Estacas Stations) and point out the synergistic effect of the human use of the water resource and the effects of climate change. On Ticumán Station, the depletion of the flow only can be associated with the use of the resource by human influence. The modifications caused by alteration of a river’s flow regime and climatic change must be studied through comparative multidisciplinary studies that give to decision-makers the design of environmental flows.",book:{id:"11532",title:"River Basin Management - Under a Changing Climate",coverURL:"https://cdn.intechopen.com/books/images_new/11532.jpg"},signatures:"Rebeca González-Villela, Alfonso Banderas Tarabay and Marco Mijangos Carro"}],onlineFirstChaptersTotal:803},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"June 11th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). In addition to a number of research articles, he has written two books, Computational Intelligence: An Introduction and Fundamentals of Computational Swarm Intelligence.",institutionString:null,institution:{name:"Stellenbosch University",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",isOpenForSubmission:!0,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. 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In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. 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