\r\n\tOver the years, the concept of maintenance became more comprehensive, reducing fault occurrence and increasing industrial system availability. Besides, reliability, safety, and criticality requirements were associated with the system or equipment under analysis. Maintenance strategies or schemes can be classified as corrective (run-to-break), preventive (time-based), and predictive (condition-based maintenance). Corrective maintenance is only performed after an occurrence of a fault. Therefore, it involves unexpected breakdowns, high costs, changes in the production chain, and it could lead to catastrophic events. Preventive maintenance and interventions occur based on a scheduled maintenance plan or the equipment's mean time between failures. Although it is more effective than corrective maintenance, unexpected failure may still occur by preventing most failures. Additionally, the process cost is still high, especially the costs associated with labor, inventory, and unnecessary replacement of equipment or components.
\r\n\tOn the other hand, predictive maintenance analyses the equipment condition so that a possible fault can still be identified at an early stage. Predictive maintenance aims to identify a machine anomaly so that it does not result in a fault. Such maintenance involves advanced monitoring, processing, and signal analysis techniques, which are generally performed non-invasively and, in many cases, in real-time. In the case of machines or processes, these techniques can be developed based on vibration, temperature, acoustic emission, or electrical current signal monitoring. It should be noted that monitoring such signals or parameters to verify the operating condition is called condition monitoring. Condition monitoring aims to observe the machine's current operational condition and predict its future condition, keeping it under a systematic analysis during its remaining life. In this sense, a fault condition can be detected and identified from systematic machine condition monitoring. A diagnosis procedure can be established, whereby properly investigating the fault symptoms and prognosis.
\r\n\t
\r\n\tThis book will aim to merge all these ideas in a single volume, aggregate new maintenance experiences, apply new techniques and approaches, and report field experiences to establish new maintenance processes and management paradigms.
\r\n\t
Ménière’s disease (MD), also called idiopathic endolymphatic hydrops, is one of the most common causes of dizziness originating in the inner ear. The typical clinical manifestations are frequent spontaneous vertigo, fluctuating sensorineural hearing loss, tinnitus, and/or aural fullness. Vertigo is typically the most debilitating symptom, and control of vertiginous episodes is the primary goal of therapeutic interventions for most patients.
There are numerous available therapeutic options for MD including conservative treatments with dietary modifications, oral medication, procedural treatments with intratympanic therapies, and surgical treatments. A failure of conservative therapy often introduces the need for a more aggressive therapy on the treatment algorithm.
Surgical intervention or intratympanic aminoglycosides can be used in patients with intractable vertigo, which, ideally, should control the vertigo while preserving the hearing level and balance. The side effects of aminoglycosides are well-know. The risks of vestibular and cochlear toxicity are mainly related to types of aminoglycosides, route of administration, duration of the therapy, total or cumulative dose, individual susceptibility, renal function, patient’s age, etc.
In 1948, Fowler [1] first used systemic streptomycin to treat vertigo attacks in patients with intractable MD. The results showed that vertigo attacks could be well controlled, but treatment carried the risks of bilateral vestibulopathy, nephrotoxicity, and unpredictable results. In 1957, Schuknekt [2] may have been the first to use intratympanic streptomycin to alleviate vertigo attacks in patients with unilateral intractable MD, and it was firstly named “chemical labyrinthectomy”. Intratympanic gentamicin (ITG) for the treatment of severe vertigo was reported by Lange [3]. The initial approach was complete vestibular ablation to control the vertigo. However, with this approach, the hearing was at a greater risk. Over the past decades, the pharmacological mechanisms of aminoglycosides have been progressively studied in depth and clinical trials have been extensively developed.
At present, intratympanic injection of gentamicin is probably the most effective non-surgical treatment to eradicate vertigo in MD and is gradually gaining popularity in the worldwide. Compared with the treatment regimen decades ago, several modifications for ITG treatment have emerged regarding the concentration of the gentamicin solution, the frequency of injections, and the method of delivery. In this chapter, the history, background, and progression of ITG treatment for MD are discussed, as well as the basic science, therapeutic method, treatment efficacy, indications, contraindications, and complications.
Aminoglycosides are highly potent, broad-spectrum antibiotics and are widely used by various routes of injection to treat serious infections caused by Gram-negative bacteria (e.g.,
Streptomycin, which was discovered in 1944, is the first aminoglycoside antibiotic in human history and was thereafter marked by the successive introduction of a series of milestone compounds (kanamycin discovered in 1957, gentamicin in 1963, and neomycin in 1970s) which definitively established the usefulness of this class of antibiotics for the treatment of Gram-negative bacillary infections. From the 1960s to 1970s, aminoglycosides were widely used, but due to their serious ototoxicity and nephrotoxicity, their systemic application was limited, and they were gradually fading out of the ranks of first-line drugs. At the beginning, the most common side effect of streptomycin used by intravenous injection was temporary imbalance without vertigo or nystagmus. Higher systemic doses increased the chance of permanent imbalance and, occasionally, deafness. These early observations led to animal and cadaver studies which confirmed the vestibulotoxic and cochleotoxic effects of high-dose streptomycin.
Based on its vestibulotoxicity, streptomycin foremost unveiled its potential in the treatment of vestibular diseases. In 1948, about 4 years after streptomycin was discovered, Fowler [1] first used systemic streptomycin to treat vertigo attacks in patients with intractable MD which was refractory to traditional medical treatment. He and others used between 2 and 4 g of intramuscular streptomycin per day in patients with unilateral or bilateral MD, typically until onset of severe imbalance, and reported that vertigo attacks could be well controlled without loss of hearing. Often, and especially with higher dosing, vertigo control was accompanied with the troubling symptoms of permanent, severe imbalance, and oscillopsia.
In 1957, Schuknecht [2] may have been the first to use intratympanic streptomycin to alleviate vertigo attacks in patients with unilateral MD that was uncontrolled by traditional medical management. He conceived of this idea after noting that intratympanic formalin will readily pass into the inner ear and prevented post-mortem degeneration of the inner ear membranous structures in patients. He correctly theorized that streptomycin could also pass into the inner ear and devised a cat animal model that demonstrated clinical and pathologic vestibulotoxicity with intratympanic streptomycin. Based on these results, he devised a clinical trial of intratympanic streptomycin administration to patients with uncontrolled unilateral MD. He administered variable amounts of streptomycin (between 0.125 and 0.5 g), either hourly or over 4 hours, over a variable amount of days. The first group of three patients who received 1 or 2 days of treatment achieved only brief control of their vertigo, but did not lose any hearing. Subsequently, an additional group of five patients received streptomycin for 3 days or longer. These patients had permanent resolution of their vertigo episodes, but at the cost of deafening the ear. Schuknekt coined the term “chemical labyrinthectomy” to describe this phenomenon. He concluded that intratympanic streptomycin at the therapeutic dosage failed to preserve hearing, and should only be considered for patients who are not good surgical candidates, but would otherwise be proper candidates for inner ear ablation [2].
With the administration of intratympanic aminoglycosides, chemical ablation of the inner ear via systemic administration of aminoglycosides fell into disfavor due to the side effects of bilateral vestibulopathy, nephrotoxicity, and unpredictable results. However, choosing which kind of aminoglycoside for intratympanic injection has gradually changed. In 1977, Lange [3] appears to be the first to have used IT administration of gentamicin. He reported about 55 patients suffering from severe unilateral MD, seen over a period of 3–10 years. Patients were treated with intratympanic administration of streptomycin or better, gentamicin. The medication was given using a plastic tube inserted behind the annulus within the transmeatal approach, and 0.1 ml gentamicin (earlier streptomycin) was instilled every 5 hours until the first signs of inner ear reaction (nystagmus or vertigo) appeared. In 90% of the cases, vertiginous attacks ceased after therapy, and hearing was preserved in 76%.
Entering the 1990s, intratympanic gentamicin had gained widespread popularity in the treatment of MD. Compared with streptomycin, ITG for treatment of MD provided equivalently excellent vertigo control while showing a lower incidence of hearing loss in early clinical data. Gentamicin gained popularity over streptomycin and gradually came to be the drug of choice for chemical ablation of inner ear.
In 1993, Nedzelski et al. [5] studied 50 patients with unilateral MD by treatment of microcatheter administration of streptomycin over a 5 h treatment, 4 treatments within 48 hours, and the rate of vertigo control was up to 96%; only 24% of his patients experienced various degrees of hearing loss. Although streptomycin was being used in the study, he advocated for using gentamicin instead for its theoretical reduction of cochleotoxicity.
Beck and Schmidt [6] reported on their 10 years of experience with intratympanally applied streptomycin and gentamicin in the therapy of MD. They theorized that the dosage might be a critical factor for hearing preservation with vertigo control. Aminoglycosides could be titrated to impede the secretory epithelium of the vestibular apparatus without destroying the sensory cells, thus achieving vertigo control while maintaining caloric response, that is, vestibulo-ocular reflex. More importantly, risk of deafness could potentially be eliminated. By reducing the dosage delivered and titrating, they were able to achieve excellent rates of vertigo control (92%) while also achieving respectable hearing preservation rates (15% hearing loss with no cases of deafness).
During the same era, around the early 1990s, two schools of thought emerged in an effort to standardize ITG treatment, dubbed the “shotgun” approach, and the “low-dose” approach. The shotgun approach, championed by Nedzelski and others [5], was characterized by daily IT injections to a fixed endpoint or to a clinical threshold that heralded damage to the inner ear. Proponents of this approach attempted to achieve adequate vestibular ablation for long-term vertigo control. The low-dose approach, championed by Magnusson and others [7], was characterized by weekly IT injections, also to a fixed endpoint or to clinical effect. Proponents of this approach tried to achieve vertigo control while minimizing damage to hearing and potentially preserving the caloric response as well.
Today, intratympanic injection of gentamicin is probably the most effective non-surgical treatment to eradicate vertigo in MD. Yet, it is an ablative method that carries a non-negligible risk of hearing loss. Currently, gentamicin is usually instilled via IT injection or through a tympanostomy tube to the round window niche. These injections are repeated over a variable amount of time, typically between daily to weekly injections, until a clinical endpoint is achieved or until there is a decline in hearing. No consensus has been reached so far on the overall dosage, dosing methods, timing of delivery, treatment duration, clinical endpoint of therapy, or concentration of gentamicin. Both clinical evidence and basic science models should be further studied to scientifically elicit the most effective and safe regimen.
Aminoglycoside antibiotics have a well-documented history of cochleotoxic and vestibulotoxic effects. Administration of intratympanic aminoglycoside antibiotics to patients with MD is based on the notion that the patient’s vestibular symptoms are due to the damaged and distorted vestibular signals emanating from their ear and that they are better off with no signal than with a damaged and distorted signal. The objective of ITG is to weaken vestibular signals in the Ménière’s ear to the point at which they are no longer strong enough to generate a vertigo attack. Ideally, aminoglycosides would act to reduce vestibular function, and thus alleviate the patient’s symptoms of vertigo, while preserving hearing. The degree to which a drug is cochleotoxic or vestibulotoxic differs among aminoglycosides. Gentamicin and streptomycin, for instance, are reported to be more vestibulotoxic. Other aminoglycosides, such as amikacin, are considered to be relatively more cochleotoxic and thus are not used transtympanically. The best evidence for this is the simple clinical observation that patients undergoing systemic gentamicin or streptomycin therapy experience vestibulopathy much more commonly than hearing loss. This feature has been used by otologists to control the vestibular symptoms of MD, initially provided through systemic delivery by Fowler [1] and subsequently through IT injections by Schuknecht [2, 8]. Use of streptomycin has been largely replaced by gentamicin which is thought to be more selectively vestibulotoxic and better able to preserve residual hearing in patients with unilateral MD refractory to medical management [9, 10].
Within the bony labyrinth, several studies have investigated the trafficking and distribution of aminoglycosides, finding different patterns of distribution dependent upon the dose, duration, and route of administration. IT-injected aminoglycosides appear to gain access to the inner ear via the oval window and the round window [11, 12], and uptake either by passive diffusion or by endocytosis [13, 14]. Salt et al. recently quantified diffusion of gentamicin through the oval (35%) versus the round window (57%) [12, 15]. Access to these membranous structures is however uncertain, partly due to their variable permeability in individuals, resulting in unpredictable drug exposure of the inner ear [16, 17, 18]. Similar mechanisms of cellular trafficking (active diffusion and endocytosis) have been proposed in the transport of aminoglycosides into cells of the inner ear [19].
Once the drug crosses the oval window and the round window, the situation becomes more complex and the precise mechanism by which aminoglycosides exert their toxic effects on hair cells is unknown, to date. Previous animal studies showed that in the cochlea, sensory hair cells, the spiral ligament including the stria vascularis, and spiral ganglion cells had a very early uptake of gentamicin. Similarly, hair cells, dark cells, and vestibular ganglion cells are the primary targets in the vestibular system. This may demonstrate that gentamicin most likely diffuses across the inner ear membranes, readily achieving concentrations within the scala vestibuli, cochlear duct, and vestibule and then exerts its cellular toxicity.
Multiple mechanisms, including disruption of calcium-dependent cytokine production resulting in the damage to hair cell membrane integrity, increased superoxide production, hair cell transduction blockage, glutamate decarboxylase inhibition, ornithine decarboxylase inhibition, and free radical damage, all have been developed to explain aminoglycosides’ direct toxicity to hair cells [10, 20, 21]. While most cells of the inner ear demonstrate aminoglycoside penetration, several studies have identified preferential loss of the hair cells at the basal turn of the cochlea over the apical hair cells and vestibular type I hair cells over their type II counterparts [22, 23, 24, 25, 26]. Direct damage to the spiral ganglion has also been observed [27] and histologic studies in rhesus monkeys suggest relative sparing of the maculae [28].
In parallel to previous findings, several studies have demonstrated that direct application of gentamicin into the vestibular labyrinth also causes greater loss of type I versus type II vestibular hair cells [29, 30]. Recently, Lyford-Pike et al. [26] used the animal model, chinchilla, to provide the evidence that the selective loss of type I hair cells assuredly occurred because these cells preferentially accumulate gentamicin acutely after intratympanic administration. Type II hair cells and supporting cells concentrate substantially less gentamicin. These results might theoretically ameliorate the more profound symptom of vertigo (driven by type I hair cells) while preserving cochlear function.
Aminoglycosides may also act to inhibit production of endolymph, restoring the balance between endolymphatic and perilymphatic pressure. This would also act to alleviate all symptoms of endolymphatic hydrops. Additionally, aminoglycosides are theorized to cause selective damage to the cells of the cochlear stria vascularis and planum semilunatum in the cristae ampullae of the semicircular canals, which are involved in ionic regulation and endolymph production [31]. It is also known that gentamicin utilizes the cellular machinery of endolymph production to traffic into the inner ear after systemic administration [32]. The theory that vestibular dark cells and, thus, endolymphatic flow, are the targets by which aminoglycosides alleviate vertigo is of significant clinical interest because it suggests that it is not necessarily important to ablate the vestibule to achieve vertigo control in MD. This idea can explain why patients with intact caloric responses can still achieve significant vertigo control after intratympanic aminoglycoside administration.
In conclusion, direct toxicity to vestibular hair cells and direct toxicity to the endolymph producing apparatus might be the two major mechanisms of action by ITG. Most importantly, gentamicin has been proved to be more vestibulotoxic than cochleotoxic in humans. The inner ear toxicity of gentamicin might follow an order. Secretory dark cells of the vestibule might be the first to be damaged, followed by the vestibular neuroepithelium and the afferent vestibular fibers, and finally, the hair cells of the organ of Corti are destroyed [33, 34].
Ménière’s disease is manifested by episodic vertigo, tinnitus, aural fullness, and fluctuating hearing loss. The treatment of patients with MD is usually directed at the most disabling symptom, which is the debilitating vertigo. MD treatment protocols typically measure vertigo control according to AAO-HNS Committee on Hearing and Equilibrium guidelines for grading vertigo severity [35]. Often, clinical trials also attempt to assess other disease sequelae such as hearing loss, tinnitus, and aural fullness.
As a well-known relapsing-remitting disease, it is rather difficult to accurately evaluate the efficacy of ITG in treatment of MD. Firstly, the natural history of remission and exacerbation of symptoms make evaluation of the effectiveness of treatment remarkably difficult. Commonly, vertigo attacks can improve without treatment of any kind as periods of remission are not uncommon. Thus, a clinical trial without controls will not account for this finding. Another difficulty is that clinical researchers attempt to show hearing preservation with IT gentamicin protocol, but hearing tends to worsen over time in MD regardless of treatment. Finally, the variable nature of MD with fluctuation in levels of hearing and even frequency and severity of vertigo can make clinical trials difficult.
To date, there have only been a few interventional randomized controlled trials investigating the true efficacy of ITG in the treatment of MD. In 2004, the first prospective, double-blind, randomized clinical trial of intratympanic gentamicin versus intratympanic buffer solution (placebo) in patients with active MD was reported by Stokroos et al. [36]. They performed ITG injections with buffered gentamicin (30 mg/ml) every 6 weeks until the vertigo complaints disappeared (12 patients received gentamicin versus 10 for placebo), outcome measures included the number of vertiginous spells, degree of sensorineural hearing loss, labyrinthine function, and labyrinthine asymmetry. Compared to the placebo group, topical gentamicin provided a significant improvement in the number of vertiginous attacks per year at follow up which varied between 6 and 28 months. There was no statistically significant change in hearing or other outcomes in two groups. However, hearing had a tendency to deteriorate in the placebo-treated patients, due to the natural course of the disease, which suggests that early treatment with topical gentamicin may preserve residual sensorineural hearing in active MD.
In 2008, Postema et al. [37] reported another prospective, double-blind, randomized, placebo-controlled trial associated with ITG therapy for control of vertigo in unilateral MD. They used weekly injections of 0.4 ml of gentamicin (30 mg/ml). A total of 4 injections were given through a ventilation tube (16 patients received gentamicin and 12 received a placebo). The results showed that gentamicin treatment resulted in a significant reduction of the score for vertigo complaints (including vertigo severity) and the score for perceived aural fullness. They also noted that a small increase in hearing loss (average of losses at 0.5, 1, 2, and 4 kHz: 8 dB HL) was measured in the gentamicin group.
In 2016, Patel et al. [38] performed a randomized, double-blind, comparative effectiveness trial of intratympanic methylprednisolone (n = 30) versus gentamicin (n = 30) in patients with refractory unilateral MD. Patients were randomly assigned (1:1) to two intratympanic methylprednisolone (62.5 mg/ml) or gentamicin (40 mg/ml) injections given 2 weeks apart, and were followed up for 2 years. In the methylprednisolone group, complete vertigo control (Class A) was achieved in 21/30 patients (70%) compared to 25/30 (83.3%) in the gentamicin group. After methylprednisolone, 22 patients (78.5%) experienced an improved functional level score and 8 patients (28.7%) better pure-tone hearing and speech discrimination. There were also reductions for tinnitus, dizziness, and aural fullness. Fifteen patients (50%) required further courses of methylprednisolone. Two patients were deemed treatment failures and were assigned ITG treatment. The study showed no significant difference between the methylprednisolone and gentamicin for the control of vertigo, total number of injections, number of patients with relapsing vertigo, or the amount of pain from injection but better speech discrimination after methylprednisolone.
Based on the above prospective, double-blind, randomized controlled clinical trials, intratympanic gentamicin, as a medically ablative method, seems to be the most effective non-surgical treatment to eradicate vertigo in intractable MD, but with a potential risk of hearing loss. However, there is no consensus on the treatment protocol of ITG, especially for the concentration of gentamicin, dosage in each application, number of injection, and the time interval between two doses.
In the over 40 years of clinical trials in the treatment of MD by ITG, the majority are case series without controls, mainly because of the significant difficulties in conducting the randomized controlled clinical trials or case/control trials [33]. In earlier studies, the highest rate of vertigo control was reported with daily injections or multiple titrations. On the other hand, considerable hearing loss was experienced in several studies. Moller et al. [39] treated 15 patients with disabling MD with daily injections for periods ranging from 3 to 11 days. They achieved 93.4% of vertigo control, but also 33.4% of hearing loss. They reported that none of the patients were responsive to caloric stimulation. Laitakari [40] reported 90% of vertigo control and 45% of hearing loss in 20 patients who had daily ITG for a minimum of 3 consecutive days. Parnes and Riddell [41] reported 41.7% worsening of the hearing in their group of patients who received three daily injections within 4 days. Murofushi et al. [42], using several daily injections, reported hearing loss in 30% of cases. Corsten et al. [43] reported 81% vertigo control but 57% hearing loss in patients (n = 21) who had gentamicin instillation 3 times a day for 4 consecutive days. Kaplan et al. [44] reviewed the 10-year long-term results of 114 patients treated with gentamicin instillation 3 times a day for 4 consecutive days. They achieved 93.4% of vertigo control and 25.6% of hearing loss.
In the early 2000s, regarding patients with hearing deterioration and even those becoming deaf, there was a discussion about reducing the gentamicin dose or performing the application at longer intervals. Daily titration methods were abandoned. Transtympanic gentamicin therapy was modified to weekly or monthly intervals as “needed” or “on demand” to reduce the symptoms of MD, aiming to maintain cochlear as well as vestibular function. Harner et al. [45] reported a very high rate of vertigo control with preservation of hearing in 43 patients. There were no patients with changes in cochlear function and ablation of the labyrinth. All patients received one injection, and half of them received a repeat injection 1 month after therapy. Minor [46] used gentamicin on weekly intervals until the development of spontaneous nystagmus, head-shaking nystagmus, or head thrust sign. Vertigo was controlled in 91% of the patients, and profound hearing loss only occurred in 1 patient. Atlas and Parnes [47] reviewed the outcomes of 83 patients who received weekly injections. They reported hearing loss in 17% of the patients, with vertigo control in 84%. Martin and Perez [48] reported vertigo control in 83.1% of the patients and hearing loss in 15.5% of them after gentamicin at weekly intervals. De Beer et al. [49] reported 15.8% with hearing loss and 80.7% with vertigo control after, between 1 and 10, intratympanic injections at a minimum interval of 27 days. Casani et al. [50] reported 12% hearing loss after a maximum of 2 injections of gentamicin and 81% vertigo control.
Most recently, Vlastarakos et al. [51] published a systematic review looking at sustained-release delivery of IT gentamicin (dynamic-release versus sustained-release vehicles). Dynamic release (microcatheter at the round window) was found to provide satisfactory vertigo control in 89.3% (70.9% reporting complete control). Sustained-release preparations (gentamicin-soaked wick/pledget) provided 82.2% satisfactory control in the pool of patients (75% with complete control). In patients receiving sustained-release preparations, complete hearing loss was reported in 31.1% patients with another 23.3% of patients experiencing partial hearing loss. This adverse change in hearing was unacceptably high, reinforcing the suggestion of using a sustained-release vehicle only in patients who had failed IT gentamicin injections previously or those without serviceable hearing.
Commonly, intratympanic injection under otoscope or microscope is a simple and recommendable technique. The desired amount of gentamicin is injected over the round window through the posterosuperior quadrant of the tympanic membrane. There are two common doses of gentamicin for injection. The standard intravenous preparation of gentamicin is 40 mg/ml, which can be buffered with 8.4% sodium bicarbonate so that discomfort on injection is reduced. A total of 1.5 ml of gentamicin mixed with 0.5 ml of sodium bicarbonate at these concentrations will produce a final concentration of 26.6 mg/ml gentamicin. Approximately 0.3–0.5 ml of solution is usually adequate to bathe the round window in solution. Typically, patients will remain lying flat with the injected ear up for 10 min to 1 h. This procedure is generally well tolerated by patients, who should be told to expect brief pain on injection, followed by possible vertigo or disequilibrium. Warming the medication can help in this regard (preventing a cold caloric response).
Based on the combination of current clinical practice, basic science models, and results from clinical trials, low drug dose and long interval between injections, mainly in order to reduce the risk of deafness, are reasonably encouraged. The low dose method involves using 1–2 injections of gentamicin and waiting a month or 2 weeks between injections. The rate of vertigo control may be up to 80–90%, with no significant side effects. The second injection is given only if there has been a vertigo spell 2 weeks prior. In other words, instead of titrating to the onset of damage to the vestibular system, the criterion is a positive effect on the disease. Occasionally, a third dose is given.
In short, whatever technique is used, the goal is to apply gentamicin to the round window in sufficient concentration and over a sufficient amount of time that it achieves a therapeutic effect while avoiding both local and systemic side effects, especially hearing loss.
Not all patients with MD can be treated with ITG. Based on the international consensus on treatment of MD obtained from the IFOS meeting 2017 [52], MD should be treated with a step-by-step therapy. The first line of treatment includes the medical conservative treatment, such as dietary modification and oral medicine. After this line of treatment, 80% of patients with MD are cured or in remission. When the vertigo of MD fails to be controlled by the first-line treatment for more than 6 months, it will be regarded as intractable MD. Then the second line is the IT injections, mainly IT steroids as a conservative treatment and ITG in the case of IT steroid failure, and preferentially in patients with hearing impairment. After the second line treatment, 90–95% of the total patients are cured or in remission. The third line is the surgical, either conservative or destructive, treatment. For unilateral intractable MD with serviceable hearing (i.e., speech reception threshold better than 50 dB HL and speech discrimination score of more than 50%) in the treated ear, treatment protocol with an injection repetition not shorter than 1 week between adjacent injections or one with injections on a monthly basis as “needed” is preferred. These methods provide the same level of vertigo control yet offer better preservation of hearing functions [33].
The best indication for ITG treatment appears to be the control of vertigo in profound hearing loss or non-serviceable ears, in which speech reception threshold is worse than 50 dB HL and speech discrimination score less than 50% [53, 54]. Under these scenarios, there is no need to consider the risk of deafness, and titration methods or multiple injections on a daily basis are preferred, since these methods have significantly elevated incidence of hearing loss [33]. Transmastoid labyrinthectomy has traditionally been offered for non-serviceable ears in patients with MD. This method has been the gold standard, and it is very effective in eradication of vertigo in more than 94% of patients. In comparison, ITG therapy provides a minimally invasive ambulatory substitute with low morbidity and fewer side-effects, which is also very cost effective to manage vertigo in these MD patients with non-serviceable ears [53].
Another important indicator is the control of vertigo in patients who have failed endolymphatic sac surgery. Marzo and Leonetti [55] have shown the effectiveness of ITG therapy for patients who have failed endolymphatic sac surgery, thus reducing the need for vestibular neurectomy in those with intractable disease.
To be allergic and hypersensitive to aminoglycosides are two absolute contraindications for ITG. It is worth noting that patients who carried the mitochondrial mutation of the gene MT-RNR1 (mitochondrially encoded 12S ribosomal RNA) are hypersensitive to aminoglycosides. A single injection of aminoglycosides results in complete and definitive deafness in subjects with this mutation [56]. A systematic genetic screening of MD patients is highly recommended to prevent the occurrence of bilateral deafness. The treatment is intended for the abolition of vestibular function; thus, administration of gentamicin must be done carefully in the elderly, who have difficulty attaining vestibular compensation, in patients with complications, or in those with bilateral MD. Taking also into consideration the fact that individual’s drug sensitivity depends on their genetic background, investigation of appropriate drug levels according to evidence-based medicine remains a future task.
The complications of ITG treatment are primarily bi-fold: one is the risk caused by drug toxicity of gentamicin, the other is the risk caused by intratympanic injection. Undoubtedly, the main risk of ITG treatment for vertigo is the sensorineural hearing loss and associated prolonged disequilibrium and ataxia, which are common complaints after this treatment. Less common side effects include local hemorrhage, allergic response and tympanic membrane perforation (especially in an irradiated or otherwise damaged tympanic membrane), local discomfort, inflammation, otitis media or externa, and transient vertigo caused by a caloric reflex effect from the instilled fluid [38, 57]. It is also critical to educate all patients who are given intratympanic aminoglycosides that bilateral permanent hearing loss is possible, even from one single unilateral injection.
Intratympanic injection of gentamicin is probably the most effective non-surgical treatment to eradicate vertigo in MD. But it is also an ablative method that carries a non-negligible risk of hearing loss. Gentamicin has been proved to be more vestibulotoxic than cochleotoxic; direct toxicity to vestibular hair cells and direct toxicity to the endolymph producing apparatus might be the two major mechanisms of action. To date, no consensus has been reached on the dosage, dosing methods, timing of delivery, treatment duration, clinical endpoint of therapy, and concentration of gentamicin. However, based on the combination of current clinical practice, basic science models, and results from clinical trials, low drug dose and long intervals between injections are reasonably recommended. The application of gentamicin-induced vestibular ablation has minimized the number of more invasive procedures such as unilateral labyrinthectomy and vestibular neurectomy. In comparison with surgery, the vertigo control is comparable, the overall cost is reduced, and complications are limited. ITG in treating intractable MD has gradually become a prevalent therapy during the past decades. However, to administer ITG treatment, multiple factors should be comprehensively considered including patient selection, pharmacological mechanism, drug dose, the interval of administration, complications, indications, and contraindications.
The authors thank Alisa Hetrick for her comments on an earlier version of the article.
The authors declare no competing financial interest.
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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. 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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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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:null},{id:"243698",title:"Dr.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:null,institution:null},{id:"7227",title:"Dr.",name:"Hiroaki",middleName:null,surname:"Matsui",slug:"hiroaki-matsui",fullName:"Hiroaki Matsui",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Tokyo",country:{name:"Japan"}}},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"338222",title:"Mrs.",name:"María José",middleName:null,surname:"Lucía Mudas",slug:"maria-jose-lucia-mudas",fullName:"María José Lucía Mudas",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}}]}},subseries:{item:{id:"10",type:"subseries",title:"Animal Physiology",keywords:"Physiology, Comparative, Evolution, Biomolecules, Organ, Homeostasis, Anatomy, Pathology, Medical, Cell Division, Cell Signaling, Cell Growth, Cell Metabolism, Endocrine, Neuroscience, Cardiovascular, Development, Aging, Development",scope:"Physiology, the scientific study of functions and mechanisms of living systems, is an essential area of research in its own right, but also in relation to medicine and health sciences. The scope of this topic will range from molecular, biochemical, cellular, and physiological processes in all animal species. Work pertaining to the whole organism, organ systems, individual organs and tissues, cells, and biomolecules will be included. Medical, animal, cell, and comparative physiology and allied fields such as anatomy, histology, and pathology with physiology links will be covered in this topic. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. 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