\r\n\tTo viable rural development has a vital role for rural communities. In the design of policies to be successful that affect them rural people have to decide and implement. According to this, it is a critical point to involve the poor and disadvantaged, along with related stakeholders, agricultural and rural development. Hence, for the sustainable development by international initiatives and all other institutions were searched and to be present the agricultural and related research results. To help support the effort, various governmental and non-governmental agencies established fundings for sustainable rural development research and fostered the development of human well-being goals in rural areas via national and international initiatives. In this context, most efforts resulted in successful cases. This book will intend to provide the reader with a comprehensive overview of the theory, approaches, strategies, and cases, and key elements and challenges of sustainable development, and Bioeconomy, Green and Circular economy for sustainability, and UN SDGs-Agenda 2030 and EU Green Deal.
\r\n
\r\n\tI believe that this work will be fundamental in the field of SDG, and it will be a guiding, idea-generating key for researchers, practitioners, rural community, and policy decision-makers, and I hope that together we will establish sustainable rural life and development around the world. \r\n\t
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He has been a visiting scientist for Postdoc, at Leibniz Hannover University, Institute of Horticultural Economics. He is a member of the Turkish Agricultural Economics Association, and Association for International Agricultural and Extension Education, Society of Agricultural Economics, Scientific Committee Member of the Turkish Foundation for Combating Soil Erosion.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"170206",title:"Prof.",name:"Dr. Orhan",middleName:null,surname:"Özçatalbaş",slug:"dr.-orhan-ozcatalbas",fullName:"Dr. Orhan Özçatalbaş",profilePictureURL:"https://mts.intechopen.com/storage/users/170206/images/system/170206.png",biography:"Dr. Orhan Özçatalbaş graduated from Çukurova University Agricultural Faculty at Adana, Turkey in 1986 and completed his PhD in Agricultural Economics in the same institution in 1994. 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1. Introduction
The International Continence Society (ICS)/International Urogynecological Association (IUGA) defines overactive bladder (OAB) as urgency with or without urge incontinence (UUI), associated with urinary frequency and nocturia in the absence of pathological (e.g. UTI, stones, bladder tumor) and metabolic factors (e.g. diabetes) [1]. The diagnosis is made by exclusion. Whether there is nerve damage or not, OAB might be classified as neurogenic or idiopathic. The prevalence of OAB is 11.8% with no significant difference between male and female and the incidence increases with age [2]. The prevalence of OAB in adults aged ≥18 years was 16% in men and 16.9% in women in the USA, and in adults aged ≥40 years, it was 15.6% for men and 17.4% for women in Europe. In Asia, the prevalence of OAB was lower, but it was still 6.0% with no differences between male and female [3].
As a result, proper understanding and management of OAB is mandatory to improve patients’ quality of life and decrease its socioeconomic burden. Behavioral therapy, bladder retraining, and pelvic floor exercise represent the first line of management of OAB. Pharmacotherapy is the second line of treatment. Anticholinergics and β3 agonists have been shown to be clinically effective in people with OAB [4]. Yet, it has many side effects such as dry mouth, dry eyes, constipation, blurred vision, dyspepsia, urine retention, and reduced cognitive function, which limit their use especially in elderly. More than 70% of patients discontinue medication within 6 months to 3 years due to side effects [5]. Refractory OAB (ROAB) develops when both behavioral therapy and oral medications become no longer effective [5]. The AUA/SUFU guidelines describe ROAB as a failure of behavioral therapy after 8–12 weeks and failure of at least one anticholinergic agent used for 4–8 weeks [6]. ROAB has an unknown prevalence rate, but it is not uncommon among the OAB population [7]. Third-line treatment should be considered when patients fulfill the ROAB diagnostic criteria. Sacral neuromodulation (SNM) and Botulinum neurotoxin-A (BoNT-A) have been recently demonstrated to be successful, with success rates reaching up to 60% and 70%, respectively [6].
BoNT-A is frequently used for cosmetic purposes and is used to treat strabismus, blepharospasm, muscle dystonia, hyperhidrosis, and migraine [8]. Carpenter was the first to prove that botulinum neurotoxin inhibits bladder contractility in rats in 1967. In 2011, BoNT-A was licensed for the treatment of urine incontinence (UI) caused by neurogenic overactive detrusors. The US Food and Drug Administration (FDA) approved it for the treatment of OAB in 2013 [9].
2. Pathophysiology and management of OAB
OAB is a chronic condition of urgency, frequency, nocturia with or without UUI. It is sub-classified into dry and wet type based on the absence or presence of the UUI. The exact cause of OAB is not well-understood. The pathophysiology varies between neurogenic, myogenic, or idiopathic factors [10]. The imbalance between the excitatory and inhibition neural pathway to the bladder is one of the underlying mechanisms. Also, the increased sensitivity of bladder muscle receptors and muscarinic receptor upregulation plays a role in OAB pathophysiology [11]. Another potential cause is the myogenic dysfunction secondary to structural or functional alteration of the detrusor smooth muscle. Idiopathic detrusor instability of undetermined underlying cause is another mechanism [10].
Proper history taking and at least a 3-day bladder diary are indicated for initial evaluation of patients in order to quantify OAB symptoms. Urodynamic evaluation is essential for establishing the diagnosis. The hallmark urodynamic feature of OAB is detrusor overactivity (DO). Yet, it may not be demonstrated in some patients due to the inability to reproduce symptoms during the urodynamic [12]. It is worth mentioning that urodynamic diagnosis has no proven predictive value for the treatment response [13]. And EAU guidelines recommended against routine urodynamic evaluation before starting the first line of treatment for uncomplicated OAB [14].
The first line of management is conservative treatment in the form of lifestyle modification (fluid restriction, decrease caffeine intake, weight reduction, and stop smoking), behavioral therapy, bladder retraining, timed voiding, and pelvic floor muscle exercise [14]. Bladder retraining and timed voiding work by setting a target time for using the toilet before it patient should not void. Once this is achieved the time can be lengthened. Thus the central control can be re-learned as in infancy. Pelvic floor muscle training; described by Kegel, aims at strengthening and rehabilitating the pelvic floor muscle, increasing its tone, and increasing urethral resistance [15].
The second recommended line of treatment is pharmacotherapy. It can be initiated together with conservative treatment or postponed till the failure of conservative treatment based on the OAB symptoms severity. The EAU and AUA guidelines recommended anticholinergics and β3 agonists as a pharmacological treatment of OAB [6, 14]. Anticholinergics are competitive muscarinic receptors antagonists. They prevent cholinergic muscarinic receptors activation in the urinary bladder and consequently reduce spontaneous detrusor muscle activity during the filling phase and decrease detrusor pressure. Many anticholinergics have been used in clinical trials and none proved to be superior to the others in OAB management. Dose escalation may be appropriate in certain patients and increases the response [16]. The efficacy of anticholinergics varies between 50% and 75%. They help to reduce urgency and UUI episodes along with reducing frequency of micturition. However, adherence to anticholinergic treatment is low and decreases over time because of lack of efficacy, adverse events, and/or cost and a significant number of patients will stop anticholinergic agents within the first 3 months [17, 18].
When anticholinergics are ineffective, non-tolerated, or contraindicated, β3 agonist (mirabegron) can be used. It activates the β-3 adrenergic receptor in the detrusor muscle in the bladder, which leads to muscle relaxation and an increase in bladder capacity helping the bladder to fill and store urine. Yet, it is not free of side effects. Tachycardia, hypertension, dyspepsia, palpitations, atrial fibrillation, joint swelling, rash, and pruritus were reported with mirabegron use [19].
Patients who are refractory to behavioral and pharmacologic therapy should be properly reevaluated. If the diagnostic criteria of ROAB are fulfilled, a third-line treatment should be offered. Third-line therapy recommended by guidelines is intradetrusor injection of BoNT-A or sacral neuromodulation [6, 14].
3. Mechanism of action of botulinum neurotoxin
Botulinum toxin is a neurotoxin derived from Gram-positive, spore-producing bacteria (Clostridium botulinum). The bacteria produce seven serotypes (A–G) of botulinum toxin each with different antigenic profiles and biochemical actions; however, they all have a similar pharmacological effect [20]. Botulinum toxin types A (BoNT-A) and B (BoNT-B) have been developed for clinical use. BoNT-A has the longest duration of action which makes it more suitable for clinical use.
BoNT-A is synthesized as a single polypeptide chain (150 kDa) which is cleaved into a light chain (50 kDa) and a heavy chain (100 kDa) held together by a fragile disulfide bond and noncovalent bonds. The available formulations of BoNT-A are BOTOX (onabotulinumtoxin A) (Allergan, United States), Dysport (abobotulinumtoxin A) (Ipsen, United Kingdom), and Xeomin (incobotulinumtoxin A) (Merz, Germany). Each formulation of BoNT-A has its own dosing regimen which is not interchangeable. BOTOX is most commonly used followed by Dysport (the former is five times more potent than the latter) [20].
Although fibroblast growth factor receptor 3 has been mentioned as a potential BoNT-A receptor, two forms of BoNT-A cell-surface receptors have been identified: gangliosides and the synaptic vesicle-associated protein 2 (SV2) family [21]. BoNT-A’s heavy chain attaches to SV2 on the nerve terminals’ surface, followed by endocytic internalization of the toxin within the nerve terminal. The toxin is broken within the synaptic vesicle after translocating into the cytoplasm, leaving the light chain of BoNT-A as the actual active moiety. BoNT-A light chain can then cleave synaptosome-associated protein (SNAP25) off the SNARE proteins, a complex protein that when intact forms the core of the neuroexocytosis machinery. This disrupts the fusion of neurotransmitter-containing vesicles with the neuronal cell membrane, inhibiting neurotransmitter release [22].
SV2-immunoreactive and SNAP25-immunoreactive nerve fibers are found in the sub-urothelium and muscle layer of the human bladder, but not in the urothelium. Almost all parasympathetic nerves express SV2 and SNAP25, while only about half of sensory and sympathetic nerves do [23]. Cleaved SNAP25 is the final product of the BoNT-A light chain’s enzymatic activity. It is regarded as an appropriate marker of BoNT-A’s action and, thus, an essential target in future research [24].
3.1 Motor effect of BoNT-A
Intradetrusor injection of BoNT-A temporarily blocks the presynaptic vesicular release of acetylcholine (ACh) at the neuromuscular junction of the parasympathetic nerves supplying the detrusor muscles and decreases detrusor pressures and phasic contractions in both idiopathic and neuropathic bladders. However, patients also report a significant decrease in urgency and hence, it is hypothesized that botulinum toxin also modulates the sensory pathways [20].
3.2 Sensory effects of BoNT-A
BoNT-A suppresses bladder sensations by processes unrelated to its effects on ACh release. Transient receptor potential vanilloid subfamily 1 (TRPV1) and P2X3 immunoreactive fibers can be seen throughout the sub-urothelium of the human bladder [25]. BoNT-A injection reduces TRPV1 and P2X3 activity in sensory nerve fibers with subsequent reduction in the frequency of urgency episodes [26]. Also, intravesical BoNT-A injections have been demonstrated to reduce ATP and neurotrophin release from urothelial cells and increase NO release [27]. ATP has been shown to play a role in the pathophysiology of OAB by mediating the sense of bladder fullness [27].
4. Techniques of administration of BoNT-A
Intradetrusor injection of BoNT-A should be offered to carefully-selected and thoroughly-counseled patients with ROAB not responding to the previous two lines of treatment. Patients should be able and willing to maintain close follow-up and frequent PVR estimation and accept the possibility of self-catheterization [6].
Patients should be given enough written and verbal peri-procedure instructions, as well as information regarding urinary tract infection (UTI) and urine retention. Prophylactic antibiotics are recommended for all patients and continue for 1–3 days postoperatively. Urinalysis should be performed before the procedure to rule out active infection. Administration of intradetrusor BoNT/A injections has been described in an office setting under local anesthesia or in the operating room with regional or general anesthesia using a flexible or rigid cystoscopy.
For idiopathic detrusor overactivity typically 100–200 units of BOTOX (diluted in 20 mL of normal saline) or 750–1000 units of Dysport have been used. BOTOX 100 U is licensed in Europe to treat OAB with persistent or refractory UUI in adults of both genders [14]. Similarly, the AUA guidelines recommended 100 U of BOTOX as a third-line of treatment of OAB [6].
There is no consensus on the ideal injection technique. The location of injections, the depth of injections, the number of injection sites, and the volume at each site vary in literature. Kuo et al. looked back at injection sites and discovered that success rates were the same whether they were in the bladder body alone, the trigone alone, or the bladder body and trigone together [28]. In a subsequent meta-analysis of OAB patients, no significant differences in efficacy between trigonal sparing and non-trigonal sparing injection techniques were found with short-term cure rates of 52.9% and 56.9%, respectively [29].
The injection depth varies as well and is influenced by the length of the needle tip (available tips range between 2 and 8 mm) used for injections. Some authors added a trace amount of indigo carmine or methylene blue to the injection solution to facilitate observation of the procedure and assessment of drug distribution [30]. Even among the same surgeons, there is likely to be some variation, and no study has determined whether sub-urothelial or intradetrusor injection is preferable. However, intradetrusor injections, as opposed to submucosal injections, with sparing of the trigone are favored. Again, there is no consensus on the number of injection sites and the dilution of the toxin but generally, 20 sites are injected and the volume per injection is usually 0.5–1 mL (Figure 1) [31].
Figure 1.
Illustrate the technique of intra-detrusor injection of BoNT-A.
4.1 Precautions during injection
Botox is a vacuum-dried protein that must be refrigerated. The vials must be reconstituted with preservative-free saline before injection, and the combination can be kept at 2–8°C for up to 24 h.
It’s worth noting that the product contains human albumin, which should be disclosed due to some patients’ reactions to it [31].
To avoid protein denaturation, avoid rapid shaking of the vial when preparing the combination. Developing an institutional method for labeling syringes containing botulinum toxin dilutions is a significant practical consideration, especially if nurses or other personnel are engaged in its preparation [31].
Because the thickness of the detrusor muscle varies with the grade of bladder filling, puncturing the muscle appears to be very easy, especially at high bladder filling grades. Furthermore, the bladder wall between trabeculation bars might be quite thin and easily perforated. A suburothelial injection may be a viable option.
5. Efficacy of BoNT-A injection in ROAB
In a multicenter double-blinded randomized trial compared the efficacy of 50, 100, and 150 U onabotulinum toxin A to placebo in OAB patients, at 3 months >50% improvement in urgency and UUI was reported by 37% of the 50 U patients, 68% of 100 U patients and 58% of 150 U. Only the 100 U groups was statistically significant compared to the placebo group. Frequency was statistically significant, reduced in 100 and 150 U groups and complete continence at 3 months was significantly greater in the 100 U group (55%) and the 150 U group (50%) compared to the placebo group (11%). At five-months post-treatment, these differences were maintained [32].
A phase III trial randomized 557 OAB-wet patients; whose symptoms were not responded to anticholinergics to receive bladder wall injections with BoNT-A (100 U) or saline. At week 12, in patients treated with BoNT-A, UUI episodes were halved and the number of micturitions reduced by more than two. A total of 22.9% of the patients in the BoNT-A arm were fully dry, against 6.5% in the saline arm [33]. Tincello and colleagues published the results of the RELAX study including 240 women with refractory OAB to compare 200 U BoNT-A and placebo injections. At 6 months, voiding frequency, urgency, and incontinence episodes per day were significantly reduced in patients receiving BoNT-A injection. Continence was also significantly higher in the treatment group (31% vs. 12%, p = 0.002) with subsequent statistically significant improved patients’ QOL [34].
In early systematic review assessing the efficacy and safety of botulinum toxin in the management of OAB, Anger et al. reported that BoNT-A treatment improved incontinence episodes and patients’ QOL scores, as shown by a 15-point drop in Urinary Distress Inventory scores compared to placebo-injected patients [35]. In a recent systematic review and network meta-analysis, BoNT-A (100 U) had associated with the greatest reductions in urinary incontinence (UI) episodes, urgency episodes, and micturition frequency, and the highest odds of achieving decreases of 100% and ≥50% from baseline in UI episodes/day. In comparison to other pharmacotherapies, BoNT-A was more superior in reduction of UUI episodes, urgency, and frequency and was associated with higher odds of achieving a 100% and ≥50% decrease in UUI episodes/day than most other treatments in the network [36].
Moreover, pre-treatment with BoNT-A improved patients’ response to anticholinergic treatment. One hundred pre-treated patients with intravesical injections of 100 IU of BoNT-A and the effect faded, were randomized to receive 10 mg solifenacin and placebo for 12 weeks. After 12 weeks of follow-up, all overactive bladder symptom score items, including the total score, had improved significantly (P < 0.0001) in solifenacin group. Also, urodynamic parameters including frequency and amplitude of detrusor contractility and detrusor leak point pressure decreased significantly with increased cystometric capacity and improved incontinence quality of life parameters with solifenacin re-treatment [37]. This was explained by the possibility that repeated BoNT-A injections increased bladder capacity and restored the normal numbers and function of M3 receptors, potentially restoring patients’ responsiveness to anticholinergic drugs [37]. This was based on the clinical findings and immunohistochemical assays which evidenced that BoNT-A injections could restore the number and efficacy of intra vesical urothelial and suburothelial receptors [38].
The effects of BoNT-A injection last for 4–10 months (mean 6 months). The median time to request re-treatment in the pooled analysis of the two RCTs was 24 weeks [33, 39]. Follow-up over 3.5 years showed the consistent or increasing duration of effect for each subsequent injection, with a median of 7.5 months [14].
Intradetrusor injection of BoNT-A is still an invasive procedure and associated with a considerable incidence of adverse events. The local side effects include pain, UTI, bleeding, no benefit, need for further injections, need for temporary self-catheterization. The generalized side effects include flu-like symptoms, dry mouth, and malaise. Bauer et al. focused on side effects with botulinum toxin injection and reported that 54% of patients reported at least one side effect [40]. The side effects included urinary retention (8.9%), gross hematuria (17.9%), UTI (7.1%), dry mouth (19.6%), dysphagia (5.4%), impaired vision (5.4%), eyelid weakness (8.9%), arm weakness (8.9%), and leg weakness (7.1%). However, symptoms other than urinary retention and UTI were transient and resolved without the need for further treatment [40].
The reported rate of UTI ranged from 3.6% to 54.5% from different RCTs [6] and some reported increased rates of UTI with increases in the dose [41].
Increased PVR and the need for self-catheterization is not uncommon adverse event after botulinum toxin injection. The rate of urinary retention in published studies ranges from 5.4 to 43%, depending on how retention is defined [6, 20, 33, 39]. An interim analysis of a long-term extension study found that the proportions of patients requiring CIC remained stable at 4.6%, 4.1%, and 4.7% after one to three BoNT A treatment cycles, respectively [20]. The onset of urinary retention usually coincides with the onset of clinical efficacy, which occurs between 5 and 10 days after injection and the duration of retention varies, with some patients only requiring CIC for a few days, while others require CIC for the duration of the drug’s effects [42, 43, 44]. Multivariate analysis revealed that preoperative PVR ≥ 100 ml and preoperative bladder capacity were associated with postoperative urinary retention for the first BoNT-A treatment. Preoperative PVR, BoNT-A units injected, and retention after the first injection were all associated with an increased rate of postoperative retention in those who received a second BoNT-A treatment [45].
Mild hematuria is expected to occur transiently after the procedure due to the injection technique, but severe hematuria requiring intervention or hospitalization for bladder irrigation occurs infrequently [44]. Not all patients benefit from treatment, and many patients discontinue injections outside of clinical trials due to a lack of efficacy or intolerable side effects, such as the need for catheterization [43].
7. Botulinum toxin versus SNM for ROAB
The choice between both BoNT-A and SNM for the management of ROAB is influenced by many factors. BoNT-A is a straightforward day case or outpatient procedure, which could be performed with local anesthesia or intravenous sedation. But it is still an invasive procedure. Also, due to the self-limited duration of action, reinjection every 6 months may be necessary. Whereas, SNM is more complex that necessitates a two-step procedure. However, its effect can last for 4–6 years or even longer. Currently, SNM associated risk of injury and surgical complexity are more tolerable due to the standardized and popularity of the technique. As a result, patients may prefer treatment with a longer duration [46]. Safety and effectiveness are critical factors to consider when making a decision. Efficacy and safety of BoNT-A injection and SNM are often assessed using successful treatment rates (symptoms of OAB improvement >50%) and adverse events, respectively. In A multicenter randomized trial that compared the 2-years outcome of BoNT-A and SNM, no difference in mean UUI episodes reduction was found (p = 0.15), with no differences in UUI resolution, ≥75% or ≥50% UUI episodes reduction [46]. Others reported that SNM had a better success rate than BoNT-A after 6 months of follow-up [47]. In a recent systematic review, no significant difference was found in successful treatment between BoNT-A and SNM at 6 months after procedures [48].
The injection of BoNT-A is associated with a significant rate of side effects, particularly urinary retention. Local discomfort and infection are prevalent in SNM and are easily managed. As a result, compared to SNM, BoNT-A injection has a safety disadvantage. Both options have opposing viewpoints on their efficacy.
The suggestion would be reconsidered if we introduced cost-effectiveness. BoNT-A injection would be a cost-effective choice over a two-year period. The results of the ROSETTA randomized trial identified that two-year costs were higher for sacral neuromodulation than for BoNT-A and persisting through 5 years [49]. While at 10 years, SNM provides a considerable possibility of symptom and quality-of-life improvement and is more cost-effective compared to BoNT-A [50]. As a result, in the long run, SNM would be the better alternative.
In the case of the non-responder who was initially treated with SNM or BoNT-A injection, we do not know whether we can switch to another therapy or how effective it will be. BoNT-A can be used in SNM non-responders with a success rate of 43.4% but is associated with a high long-term discontinuation rate (55%) [51].
Furthermore, the success rate in ROAB patients who used SNM therapy after failed BoNT-A therapy was 58.5%. There was no significant difference between ROAB patients who chose SNM as replacement therapy after failed BoNT-A therapy and those who used SNM therapy as first (Table 1) [52].
Sacral neuromodulation (SNM)
Botulinum toxin (BoNT-A)
Mechanism of action
SNM mainly functions in the central nervous system:
Somatic afferent nerve activates the centralinhibitory pathway.
Visceral sensory nerve activates the central inhibitory pathway
On peripheral nerve: activate the motor nerve pathway
BoNT-A mainly acts on the peripheral nervous system.
BoNT-A can inhibit neurotransmitter release not only from efferent but also possibly from afferent nerve terminals.
Decline the neurotransmitter release in the presynaptic membrane.
Reduces receptors expression in the postsynaptic membrane.
Improves the sensation of the bladder by decreasing ATP in the sub-urothelium.
Central effect:
BoNT-A Impairs the sensory fibers terminals in the spinal cord dorsal horn.
Compared to medications
Superior
Equal
Undesirable events
Low incidence
Higher incidence, especially UTI and urine retention
Long term stability
Long term 80% stability
Short term stability 70% of patients drop out
Satisfaction
High maintained satisfaction
Short-term satisfaction
Re-treatment
Less
Repeated in a less than a year
Cost effectiveness
Long term cost effective (5 and 10 years)
Short-term cost effective (2 years)
Table 1.
Comparison of the sacral neuromodulation and botulinum toxin treatment.
8. Future perspectives
As mentioned before, intra-detrusor injection of BoNT-A is still an invasive procedure that requires anesthesia and is associated with specific complications especially UTI and urine retention. Also, the efficacy and safety of intra-detrusor injection are sensitive to injection volume and depth, and this issue has motivated researchers to study injection-free modes of drug delivery into the bladder [53]. Therefore, intravesical instillation rather than injection of BoNT-A seems to be a sound idea. Nevertheless, BoNT-A delivery to the bladder tissue after intravesical instillation is hampered by toxin degradation by urine proteases, dilution by urine at the time of instillation, and poor uptake due to the urothelium impermeability, which results from the watertight barrier located at the umbrella cells in the superficial layers of bladder urothelium that are augmented by glycosaminoglycan and uroplakins [54].
To overcome this barrier, intravesical instillation of BoNT-A formulated with liposome (lipo-botulinum toxin) to enhance its absorption was evaluated in two studies; one pilot study and a 2-center, double-blind, randomized, placebo-controlled trial. After 1-month, lipo-botulinum toxin instillation was associated with a statistically significant reduced urinary frequency and urgency; however, the treatment did not reduce UUI episodes. Furthermore, onabotulinum toxin complexed with liposomes did not result in urinary retention [55, 56].
Another method tested was to add a chemical agent that enhances drug delivery into the bladder tissue. Dimethyl sulfoxide (DMSO) is an organic solvent that has been used to facilitate the delivery of several anticancer drugs into animal bladders. Petrou et al. studied 25 women with ROAB that were given BoNT-A (300 U) mixed with 50% DMSO. Efficacy and toxicity were assessed at baseline, 1 and 3-months after treatment. The median number of UUI episodes decreased at 1 month (p = 0.004) and then increased back at 3 months. Also, a significant reduction in symptom scores from baseline was noted. The Impact Questionnaire short form improved from 13 to 7 at 1 month (p = 0.007), and the Urogenital Distress Inventory improved from 10 to 5 at 1 month (p = 0.003). No serious side effects or urinary retention were noted [57].
Kodama et al. stated that low energy shock waves (LESWs) increase tissue permeability and drug delivery into cells by the shear force generated by the movement of liquid relative to cells, which temporarily affects the permeability of the plasma membrane. So, it can deliver macromolecular drugs into the cell cytoplasm without toxicity [58]. In the OAB-rat model, intravesical instillation of BoNT-A plus LESW group showed statistically significant lower amplitude.
(p = 0.001) and lower frequency of detrusor contractions (p = 0.01). Histologically, combined treatments significantly reduced submucosal edema and inflammatory cell infiltrate scores. Moreover, BoNT-A plus LESW significantly increased tissue expression of antioxidant marker (superoxide dismutase) and suppressed oxidative stress marker (malondialdehyde) and inflammatory cytokines (tumor necrotic factor-α and interleukin-6) [59].
In preliminary clinical study, including 15 patients with ROAB, Intravesical instillation of 100 IU of BoNT-A was done followed by LESWs (3000 shocks over 10 min) exposure to the suprapubic area was tested. Patients were followed-up by urine analysis, urine culture, PVR, and Overactive Bladder Symptom Score (OABSS) at 1, 2, and 3 months. Patients showed statistically significant improvements in all OABSS domains and the total score after 1 and 2 months of treatment (P < 0.05). Whereas, only the nocturia domain remained significantly improved after 3 months (P = 0.02). Seven (46.6%) and 12 (80%) patients were totally dry at 1 and 2 months, respectively. Also, treated patients had no significant increase in PVR throughout the study period (P > 0.05), and none of the patients required clean intermittent catheterization [60].
Further research to optimize the procedure of injection to be less invasive, more effective, and improve the injection-free mode is mandatory and expected in the near future.
9. Conclusion
Intravesical injections of BoNT-A have been approved as third-line treatment for OAB after the failure of behavioral and pharmacotherapy with successful short-term outcomes.
Repeated injections should be put into consideration during decision-making and patient counseling.
Intravesical BoNT-A injections are associated with a significant rate of adverse events (such as increased post-void residual volume, acute urinary retention, and UTI); thus, informed consent must be given before treatment.
No consensus on the standard injection technique and dose of BoNT-A in ROAB.
Approaches to optimize the procedure techniques; to be less invasive, more effective, and with less side effects, improve the injection free mode and improve its outcome to be more durable are mandatory future perspectives.
Conflict of interest
Authors have no conflict of interest to disclose.
\n',keywords:"botulinum neurotoxin, overactive bladder, refractory overactive bladder, outcomes",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/80381.pdf",chapterXML:"https://mts.intechopen.com/source/xml/80381.xml",downloadPdfUrl:"/chapter/pdf-download/80381",previewPdfUrl:"/chapter/pdf-preview/80381",totalDownloads:81,totalViews:0,totalCrossrefCites:0,dateSubmitted:"November 26th 2021",dateReviewed:"December 24th 2021",datePrePublished:"February 8th 2022",datePublished:null,dateFinished:"February 7th 2022",readingETA:"0",abstract:"Botulinum neurotoxin has been approved for use in different urologic disorders, especially overactive bladder (OAB). OAB is highly prevalent, with a relevant impact on patients’ quality of life and the available health resources. The prevalence of OAB is 11.8% with no significant difference between male and female. Botulinum neurotoxin is now approved as a treatment of choice for refractory overactive bladder (ROAB) after the failure of behavioral and pharmacological therapy. It is associated with improvement of urgency and urge urinary incontinence in 60–70% of patients. Yet the effect is not long-standing and fades out in a mean of 6-months duration and repeated injection is warranted. Moreover, its associated side effects are not uncommon, especially urinary tract infection and urine retention. New modifications have been studied to make it less invasive, effective, and tolerable by the patients through injection-free mode. The subject to be explained in the book chapter is the role of botulinum neurotoxin in ROAB, including the mechanism of action, different types of botulinum toxin used, the accepted dose, associated side effects, and comparison of the outcome to other available treatment modalities. In addition, a close look at the new accepted approaches for intravesical administration of botulinum toxin in the bladder will be done.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/80381",risUrl:"/chapter/ris/80381",signatures:"Mohamed H. Zahran, Ali Abdel Raheem, Ibrahim Alowidah and Diaa-Eldin Taha",book:{id:"11328",type:"book",title:"Botulinum Toxin - Recent Topics and Applications",subtitle:null,fullTitle:"Botulinum Toxin - Recent Topics and Applications",slug:null,publishedDate:null,bookSignature:"Associate Prof. Suna Sabuncuoglu",coverURL:"https://cdn.intechopen.com/books/images_new/11328.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80355-229-3",printIsbn:"978-1-80355-228-6",pdfIsbn:"978-1-80355-230-9",isAvailableForWebshopOrdering:!0,editors:[{id:"270856",title:"Associate Prof.",name:"Suna",middleName:null,surname:"Sabuncuoglu",slug:"suna-sabuncuoglu",fullName:"Suna Sabuncuoglu"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Pathophysiology and management of OAB",level:"1"},{id:"sec_3",title:"3. Mechanism of action of botulinum neurotoxin",level:"1"},{id:"sec_3_2",title:"3.1 Motor effect of BoNT-A",level:"2"},{id:"sec_4_2",title:"3.2 Sensory effects of BoNT-A",level:"2"},{id:"sec_6",title:"4. Techniques of administration of BoNT-A",level:"1"},{id:"sec_6_2",title:"4.1 Precautions during injection",level:"2"},{id:"sec_8",title:"5. Efficacy of BoNT-A injection in ROAB",level:"1"},{id:"sec_9",title:"6. Botulinum toxin injection-related adverse events",level:"1"},{id:"sec_10",title:"7. Botulinum toxin versus SNM for ROAB",level:"1"},{id:"sec_11",title:"8. Future perspectives",level:"1"},{id:"sec_12",title:"9. Conclusion",level:"1"},{id:"sec_16",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Abrams P, Artibani W, Cardozo L, Dmochowski R, van Kerrebroeck P, Sand P. International Continence Society. Reviewing the ICS 2002 terminology report: the ongoing debate. Neurourol Urodyn. 2009;28(4):287. 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DOI: 10.1016/j.urology.2012.12.021'},{id:"B26",body:'Apostolidis A, Popat R, Yiangou Y, Cockayne D, Ford AP, Davis JB, et al. Decreased sensory receptors P2X3 and TRPV1 in suburothelial nerve fibers following intradetrusor injections of botulinum toxin for human detrusor overactivity. J Urol. 2005;174(3):977-982; discussion 982-3. DOI: 10.1097/01.ju.0000169481.42259.54'},{id:"B27",body:'Yiangou Y, Facer P, Ford A, Brady C, Wiseman O, Fowler CJ, et al. Capsaicin receptor VR1 and ATP-gated ion channel P2X3 in human urinary bladder. BJU Int. 2001;87(9):774-779. DOI: 10.1046/j.1464-410x.2001.02190.x'},{id:"B28",body:'Kuo HC. Bladder base/trigone injection is safe and as effective as bladder body injection of onabotulinumtoxinA for idiopathic detrusor overactivity refractory to antimuscarinics. Neurourol Urodyn. 2011;30(7):1242-1248. DOI: 10.1002/nau.21054'},{id:"B29",body:'Davis NF, Burke JP, Redmond EJ, Elamin S, Brady CM, Flood HD. 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Therefore, greenhouse gas emissions and contaminated effluent are environmental problem. The most of the governments in the world warn all the industrial sectors containing textile manufacturing to be careful about environmental pollution. Increasing in public awareness of environment and competitive global market forces the textile industry to manufacture textile products environmentally. Environmental pollution in textile wet processes can be reduced by four main ways. They are process optimization (reducing in water, chemical energy consumption, and time loss), use of ecofriendly chemicals, reuse of water, and new technologies like ozone and plasma technologies, transfer printing, enzymatic processes, etc. This chapter is about the use of ozone in the textile industry.",book:{id:"7431",slug:"textile-industry-and-environment",title:"Textile Industry and Environment",fullTitle:"Textile Industry and Environment"},signatures:"Ayşegül Körlü",authors:[{id:"255885",title:"Dr.",name:"Ayşegül",middleName:null,surname:"Körlü",slug:"aysegul-korlu",fullName:"Ayşegül Körlü"}]}],mostDownloadedChaptersLast30Days:[{id:"66213",title:"Utilization of Cotton Spinning Mill Wastes in Yarn Production",slug:"utilization-of-cotton-spinning-mill-wastes-in-yarn-production",totalDownloads:1895,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Efficient use of natural resources and utilization of recoverable wastes are getting more and more important day by day since recovering wastes have both economic and environmental benefits. As the source material costs constitute the majority of the yarn production costs, decreasing raw material costs provide considerable advantages for spinners. From the point of textile manufacturing, various production wastes can be reused in textile industry. In each step, from ginning (for cotton fibers) to end product formation, recyclable/recoverable waste materials are generated. However, mainly polyester products are recycled (r-PET) and used again in textile industry by 100% or in blends with other man-made or natural fibers. Compared to research on r-PET, recovered cotton fibers inspired interest recently. The main objective of this study is to fill the gap in the literature via investigating the properties of the yarns produced with recovered cotton wastes, generated in different sources. For this purpose, spinning mill waste types were selected. In this experimental study, different waste types (card waste, blowroom waste, and fabric waste) and blending ratios were used. As a conclusion, the effect of waste type and blend ratio on the physical and mechanical properties of the yarns and the fabrics, produced with virgin and waste cotton fibers, were analyzed.",book:{id:"7431",slug:"textile-industry-and-environment",title:"Textile Industry and Environment",fullTitle:"Textile Industry and Environment"},signatures:"Tuba Bedez Ute, Pinar Celik and Memik Bunyamin Uzumcu",authors:[{id:"292303",title:"Dr.",name:"Pinar",middleName:null,surname:"Celik",slug:"pinar-celik",fullName:"Pinar Celik"},{id:"292576",title:"Dr.",name:"Tuba",middleName:null,surname:"Bedez Ute",slug:"tuba-bedez-ute",fullName:"Tuba Bedez Ute"},{id:"292577",title:"Dr.",name:"Memik Bunyamin",middleName:null,surname:"Uzumcu",slug:"memik-bunyamin-uzumcu",fullName:"Memik Bunyamin Uzumcu"}]},{id:"65473",title:"Sustainable Production Methods in Textile Industry",slug:"sustainable-production-methods-in-textile-industry",totalDownloads:1935,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"The textile industry is part of the industries that continuously harm the environment because of the high water consumption and the presence of various pollutants in the wastewater. Wastewater treatment is lacking or includes only physical treatment in underdeveloped and developing countries due to installation and operating costs of a treatment plant. As a result, a broad spectrum of hazardous and toxic substances, such as (azo) dyes, heavy metals, acids, soda, and aromatic hydrocarbons, pollute precious sources of clean water, in which untreated water is discharged. The main solution to this problem is to reduce the treatment cost. For this purpose, the process should be optimized to reduce the amount of water and chemicals. In this chapter, first studies on the reference document (BAT) referred by the European Council are reviewed. Minimizing production costs, obtaining high-quality products, and reducing the amount and the pollutant content of wastewater are complex problems that cannot be solved by the conventional optimization methods. Therefore, nonconventional optimization methods applied on the textile processes are also reviewed from the latest studies in the literature.",book:{id:"7431",slug:"textile-industry-and-environment",title:"Textile Industry and Environment",fullTitle:"Textile Industry and Environment"},signatures:"Miray Emreol Gönlügür",authors:[{id:"288485",title:"Dr.",name:"Miray",middleName:"Emreol",surname:"Gönlügür",slug:"miray-gonlugur",fullName:"Miray Gönlügür"}]},{id:"64003",title:"Chemical and Tinctorial Aspects Related to the Reuse of Effluents Treated by Ozonation in Dyeing Processes",slug:"chemical-and-tinctorial-aspects-related-to-the-reuse-of-effluents-treated-by-ozonation-in-dyeing-pro",totalDownloads:803,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The purpose of this chapter is to study the interactions that are established between inorganic auxiliaries and the by-products of contaminants present in effluents coming from dyeing operations during oxidation treatment processes using ozone, and the influence of auxiliaries and by-products on the behavior of dyes in subsequent dyeing processes using the treated water. Carrying the treatment until the complete elimination of the contaminants present in it is a very expensive operation. Because of this, it is chosen to discolor and reuse the spent dyebaths treated as many times as possible to take advantage of the water and the inorganic salts contained therein. The variable composition of the dyebaths involves kinetic aspects during the treatment, which is important to take into account in the design of the process. Various by-products are already generated from the beginning of the treatment, which will have an influence on the following stages of the same treatment process, as well as on the kinetics of the dyeing processes carried out using the treated water and on the results obtained in such dyeing processes. All this will depend on the chemical and dyeing class to which the dyes used during the subsequent dyeing processes belong.",book:{id:"7431",slug:"textile-industry-and-environment",title:"Textile Industry and Environment",fullTitle:"Textile Industry and Environment"},signatures:"Pablo Colindres Bonilla",authors:[{id:"259209",title:"Dr.",name:"Pablo",middleName:null,surname:"Colindres Bonilla",slug:"pablo-colindres-bonilla",fullName:"Pablo Colindres Bonilla"}]},{id:"66171",title:"Phase Change Materials for Textile Application",slug:"phase-change-materials-for-textile-application",totalDownloads:1709,totalCrossrefCites:5,totalDimensionsCites:7,abstract:"The objective of this chapter is to determine which of the existing PCM families are more suitable for textile thermoregulation while proposing new solutions. Indeed, many of these materials are either limited by their overall enthalpy of phase change or by their thermal window. 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\r\n\tTransforming our World: the 2030 Agenda for Sustainable Development endorsed by United Nations and 193 Member States, came into effect on Jan 1, 2016, to guide decision making and actions to the year 2030 and beyond. Central to this Agenda are 17 Goals, 169 associated targets and over 230 indicators that are reviewed annually. The vision envisaged in the implementation of the SDGs is centered on the five Ps: People, Planet, Prosperity, Peace and Partnership. This call for renewed focused efforts ensure we have a safe and healthy planet for current and future generations.
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\r\n\tThis Series focuses on covering research and applied research involving the five Ps through the following topics:
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\r\n\t1. Sustainable Economy and Fair Society that relates to SDG 1 on No Poverty, SDG 2 on Zero Hunger, SDG 8 on Decent Work and Economic Growth, SDG 10 on Reduced Inequalities, SDG 12 on Responsible Consumption and Production, and SDG 17 Partnership for the Goals
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\r\n\t2. Health and Wellbeing focusing on SDG 3 on Good Health and Wellbeing and SDG 6 on Clean Water and Sanitation
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\r\n\t3. Inclusivity and Social Equality involving SDG 4 on Quality Education, SDG 5 on Gender Equality, and SDG 16 on Peace, Justice and Strong Institutions
\r\n
\r\n\t
\r\n
\r\n\t4. Climate Change and Environmental Sustainability comprising SDG 13 on Climate Action, SDG 14 on Life Below Water, and SDG 15 on Life on Land
\r\n
\r\n\t
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\r\n\t5. Urban Planning and Environmental Management embracing SDG 7 on Affordable Clean Energy, SDG 9 on Industry, Innovation and Infrastructure, and SDG 11 on Sustainable Cities and Communities.
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\r\n\tThe series also seeks to support the use of cross cutting SDGs, as many of the goals listed above, targets and indicators are all interconnected to impact our lives and the decisions we make on a daily basis, making them impossible to tie to a single topic.
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Currently, he is a professor of Orthodontics. He holds a Certificate of Advanced Study type A in Technology of Biomaterials used in Dentistry (1995); Certificate of Advanced Study type B in Dento-Facial Orthopaedics (1997) from the Faculty of Dental Surgery, University Denis Diderot-Paris VII, France; Diploma of Advanced Study (DESA) in Biocompatibility of Biomaterials from the Faculty of Medicine and Pharmacy of Casablanca (2002); Certificate of Clinical Occlusodontics from the Faculty of Dentistry of Casablanca (2004); University Diploma of Biostatistics and Perceptual Health Measurement from the Faculty of Medicine and Pharmacy of Casablanca (2011); and a University Diploma of Pedagogy of Odontological Sciences from the Faculty of Dentistry of Casablanca (2013). 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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:"19",type:"subseries",title:"Animal Science",keywords:"Animal Science, Animal Biology, Wildlife Species, Domesticated Animals",scope:"The Animal Science topic welcomes research on captive and wildlife species, including domesticated animals. 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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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