Various agents used in immunotherapy of warts.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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There are five major HPV genera:
The clinical picture of cutaneous warts differs by specific location on the body [2]. Most extragenital warts are benign, and usually clinical diagnosis is adequate, but sometimes additional methods are required especially in atypical, subclinical or dysplastic lesions. Genital lesions are more prone to transform to malignancy, so determining the extent of disease is essential. Examining the wart and scraping off the top layer of the wart to check for signs of dark, pinpoint dots—clotted blood vessels—are common with warts.
Warts can be visualised exceptionally well by dermoscopy, especially the black dots. Dermoscopy is also very useful in terms of differential diagnosis and follow-up [2].
Genital/mucosal lesions remain undetected for a long time; not only that, all lesions may not be clinically evident at a time. Topical application of 3–5% of acetic acid for 3–5 min and followed by examination with 10X hand lens or colposcope is a reasonable accurate diagnostic tool. Lesions will be represented as tiny white papules. The routine use of this procedure to detect mucosal changes attributed to HPV infection is not recommended because the results do not influence clinical management.
Acanthosis, epidermal hyperplasia, papillomatosis, compact orthokeratosis, hypergranulosis, tortuous dermal papillary capillaries, and vertical tiers of parakeratotic cells are the typical histological findings of warts. In the granular layer, cells have coarse keratohyalin granules and vacuoles surrounding wrinkled-appearing nuclei. Koilocytes are pathognomonic.
In situ hybridization is a direct signal detection assay. It preserves the morphological context with HPV DNA signals. It has low sensitivity; however, in recent years, using improved signal-detecting method, sensitivity increased. It is becoming a valuable screening tool for women of age more than 30 years.
Patients who are diagnosed with condylomata need a Papanicolaou (Pap) test of the cervix in accordance with the guidelines of the American College of Obstetricians and Gynaecologists
Computed tomography (CT) or magnetic resonance imaging (MRI) can be used to determine the extent of spread of cervical carcinoma and extensive anogenital papillomatosis that has spread into the pelvis.
Warts are usually self-limiting. Large studies have shown complete spontaneous remission in 42% of patients after 2 months; in 53%, after 6 months; and in 65%, after 2 years [2]. The intact immune system plays the most important role for preventing HPV infection. This can be seen in patients with primary immunodeficiency or in immunosuppressed patients.
HPV-induced warts are the most common skin disorder in organ transplant recipients [3]. Children with recalcitrant extragenital wart may suffer from primary immunodeficiency. It has been shown that immunosuppressed patients experience resolution of treatment-refractory warts once their immune status has improved [4]. The known spontaneous remission of HPV-induced warts, which is attributed to cell-bound mechanisms, underscores the role of the immune system, including an increase in Th1 cytokines and infiltration of T cells (CD4+, CD8+) around the diseased tissue [5].
Guidelines for the management of cutaneous warts have been prepared for dermatologists on behalf of the British Association of Dermatologists [6]. The guideline highlighted the ideal aims of treatment of warts as follows: (i) Removal of wart without recurrence. (ii) Treatment should result with no scars. (iii) Immunity that induced by treatment should be lifelong [5]. The general principles observed in the treatment of warts are the following: (1) There is no need to treat all warts. (2) Treatment indications are pain, interference with function, cosmetic embarrassment and risk of malignancy. (3) All the treatments have success rate not very high (average 60 ± 70% clearance in 3 months). (4) An immune response is usually essential for clearance. Immunocompromised individuals may never show wart clearance. (5) Younger individuals with short duration of illness usually have the highest clearance rates for various treatments [5].
There is a high rate of spontaneous remission, especially in children, so ‘wait-and-see’ approach is feasible in many cases. Regular filing or paring down the hyperkeratotic layer makes the lesion thin and comfortable. Simple measure to limit the spread of lesion should be encouraged. The treatment of warts can be broadly classified into destructive, antimitotic, virucidal, immunotherapy, and some folk and alternative therapies which have recently become popular again.
The goals of wart treatment are to resolve all or a maximum number of warts, make it painless, need only one or a part of a wart treated, only need minimum number of treatments, leave no scar, offer lifetime HPV immunity and be easily available for all patients [7]. The criteria for wart treatment, developed by the American Academy of Dermatology in 1995, [7] include (1) the patient’s desire for therapy; (2) symptoms of pain, bleeding, itching or burning; (3) disabling or disfiguring lesions; (4) large numbers or large sizes of lesions; (5) the patient’s desire to prevent the spread of warts to unblemished skin of self or others; and (6) an immunocompromised condition [6].
The lesions are damaged or removed by different procedures followed by clinical cure. The destructive therapies include surgical removal by curettage and cautery, chemical cautery, cantharidin, cryotherapy, electrocautery, radiocautery ablation, infrared coagulation, photodynamic therapy, and lasers.
Curettage followed by cautery was an early and still widely practiced method of surgical removal of warts. A success rate of 65–85% has been reported in surgical therapy, but scarring and recurrence rate are high (30%), and the sole of the foot is the site where scarring is particularly problematic. Curettage followed by cautery is most commonly used for filiform warts on the limbs and face [8]. Excision is usually to be avoided as scarring is inevitable, and there is frequent chance of recurrence in the scar.
It is keratolytic, reduces the thickness of warts and may also stimulate an inflammatory response. Over-the-counter preparations are available as 17% salicylic acid combined in a base of flexible collodion or as a 40% salicylic acid plaster patch [9]. It is minimally expensive, convenient and reasonably effective, with negligible pain, but results require weeks to months of treatment. Occasionally, contact dermatitis due to colophony may develop, and to avoid systemic toxicity, it should be applied only in limited area. Treatment result with salicylic acid therapy extremely depends on patient compliance. Before pairing or debridement of the dead, hyperkeratotic tissue, wart(s) should be soaked in warm water for 5 min. The salicylic acid preparation should then be applied to the debrided wart [10].
Strong chemicals can destroy tissue. Trichloroacetic acid (
A terpenoid secreted by blister beetles, which is absorbed by lipids in keratinocytes, activates serine proteases and leads to acantholysis [14, 15]. Depending on the amount, concentration, duration of exposure and occlusion, an intraepidermal blister will form and resolve, within a week [16]. The superficial nature of the injury reduces the risk of scarring. One randomised control trial shows that cantharidin is effective, is safe, yields better cosmesis and requires fewer applications than TCA for the treatment of warts when used sufficiently far from mucosal and intertriginous areas. It was also shown to be well tolerated and that patients being treated with Cantharone were significantly more satisfied than those treated with TCA. This may be attributed to less pain during application and during the entire treatment, better cosmetic results and perhaps fewer visits [17].
It is a strong caustic agent that can penetrate deep into tissue, produces chemical burn with escher and is not used routinely for treatment of common wart. Strong (80%) phenol solution for the treatment of common warts showed that phenol was an effective form of treatment for warts. It must be used by a physician and should not be used in extensive areas [18].
Topical tretinoin, although currently recommended for the treatment of acne, has also been reported to be of benefit in plane warts. A study of 25 children with plane warts treated with 0.05% topical tretinoin cream (applied once daily for 6 weeks) was compared with a control group of 25 untreated children. After 12 weeks, clearance of warts was observed in 84.6% of the treated group as compared with 32% of the control group. It was well tolerated with some redness and peeling in 42.3% of the treated group [19].
Photodynamic therapy (PDT) with topical 5-aminolevulinic acid has a good curative effect, especially in recalcitrant facial flat warts [20, 21, 22]. It is unclear, but selective photothermolysis of oxyhaemoglobin within the dilated microvasculature of the warts leads to destruction of capillaries followed by improvement of warts, may be the mechanism of action of this curative effect [23]. Many factors affect the efficacy of PDT, including photosensitizer concentration; solvent type; incubation time; type, dose, and time of irradiation of the light; and the area of exposed parts. ALA gel (10%) was applied topically to lesions and incubated for 3 h. The lesions were irradiated by an LED light of 630 ± 10 nm at dose levels of 60–100 mW/cm. At the 24-week follow-up, the average effective rate was 88.8%, with no recurrences. No significant side effects were reported [24].
Cryotherapy induces cold thermal injury in the lesion. Cryotherapy may have an effect on wart clearance either by simple necrotic destruction of HPV-infected keratinocytes or possibly by inducing local inflammation conducive to the development of an effective cell-mediated response [25]. Dimethyl ether spray, carbon dioxide snow and liquid nitrogen all produce cold thermal damage to the skin. Different types of devices and techniques are used to induce targeted cold injury to warts. Carbon dioxide slush (−79°C) is now less commonly used.
It is in aerosol form, easy to handle and stored in normal room temperature, and its preservation time is very high (nearly 3 years), available in market and easy to buy. As the evaporation temperature reaches −57°, therefore, it is likely to be less effective, and efficacy in inducing tissue temperatures adequate for cell necrosis appears low [26]. But one multicentre RCT on comparing effects of DMEP and LN2 shows that no clinically relevant differences between the efficacy, tolerance and safety of the two cryogenic agents used in primary care were found. The low freezing of DMEP was sufficient for the cryotherapy of benign lesions [27].
Having a temperature of −196°C, the coldest freeze, is the most commonly used method in medical practice. It is very effective in elimination of a large variety of very common benign and premalignant skin lesions (verrucas,
Localised heating with radiofrequency heat generators and surgical excision with radiofrequency electrosurgical knives have been used with moderate success [32, 33].
Radiofrequency ablation is a common mode of treatment, and it involves the principle of tissue destruction with various waveforms of alternating electric current whose frequencies fall within the range of radiofrequency (500–4000 khz) [34]. The overall cure rate for warts with radiosurgery ranges between 33 and 80% depending on the number of sittings and the type of warts [35, 36].
Electrocautery is a form of electrosurgery that utilises galvanic or direct current for generating heat. Although rarely used nowadays in the developed nations, it is still widely used in the developing countries and is considered more effective for treating thicker lesions with an overall success rate of 56–80% [7].
It is an instrument that produces noncoherent infrared light with a spectrum of 400–2700 nm. It has been reported as a cheaper, safer and more easily handled alternative to CO2 laser treatment. Direct application of infrared contact coagulators causes thermal injury to a depth dependent on the duration of exposure [37]. A bulla arises after IRC that may protect the lesion against infection. Cure rate was 66.7% for warts treated with IRC. The instrument allows adjustable tissue necrosis without tissue adhesion and has yielded remissions with a 10.8% recurrence rate [38]. In comparison to electrocoagulation, infrared coagulation produces similar outcomes [37], but it is safer than EC in side effect profile.
The CO2 laser was the initial laser modality used to treat warts and has been used since 1980s [39, 40, 41]. The CO2 laser emits infrared light of wavelength 10,600 nm. It is absorbed by tissue water and results nonselective thermal tissue destruction. The CO2 laser treats warts via two mechanisms. A focused CO2 laser beam used as a scalpel to excise the wart down to the subcutaneous tissue, followed by the base of the wart, which is vaporised by a defocused beam until a clean surgical field is obtained [42, 43, 44, 45]. Cohort studies report that simple and recalcitrant common, palmar, plantar, periungual and subungual warts have been successfully treated with CO2 laser, with response rates ranging from 50 to 100% [40, 43, 46, 47, 48, 49, 50, 51, 52, 53]. Usually, excision by focused mode followed by vaporisation and haemostasis with defocused mode is the common practice. Deeper warts need more passes. Using two to four passes per wart is adequate [46, 47, 48, 49]. CO2 laser treatment may be used for recalcitrant warts but also as a first-line of therapy for warts—mainly in the sole, hands and other parts also [46]. Single verruca lesions usually result better (66.7%) than multiple verruca (62.5%) [46]. It can be used for first-line therapy for periungual and subungual warts. It has been seen that patients with subungual and periungual warts, who have failed previous conventional therapy, respond less than in patients when CO2 laser therapy was given as first line (47.9% compared to 80.0%) [47]. Subungual warts respond better than periungual warts [47]. Usually one or two sessions are adequate [48]. Patients with one session heal earlier than patients with more than one session [48]. Adverse effects include permanent nail matrix damage and scarring, and nail changes such as distal onycholysis and thickening may occur [47, 48, 51]. CO2 laser may also be used as excision tool, with a remission rate of 95.5%, but requires specialised unit [49]. Scarring is a possibility [49]. ‘En bloc’ excision of wart is very much effective [100%] in paediatric age group also with no recurrence, and usually single session is adequate [50]. Many treatment modalities are not feasible in immunosuppressive patients. CO2 laser can be a safe and comparably effective modality of treatment, even in one intervention [51]. Complete excision of the lesional skin with a portion of deeper tissue and 1-mm non-lesional margin leads to the complete clearance of HPV DNA, which leads to very lower recurrence, though chance of scar formation is there. Dressing with artificial dermis leads to less scar formation [52]. Application of Imiquad after CO2 laser in recalcitrant wart reduces or stops recurrences [53]. Vapour produced by CO2 laser with any power density and fluence contains intact papillomavirus DNA. This infected vapour may cause pulmonary infection [54]. Plume produced from laser procedure collected and used as inoculum may produce identical lesions [55]. So, safety precautions during laser surgery may be strictly maintained [55]. It is important to wear surgical masks as it is capable of removing all laser- or electrocoagulation-derived viruses [56], even gas scavenging system to be in use [57]. But a study among CO2 laser surgeons in all the members of American Society of Laser Medicine shows that the plume does not possess enough infectious material to produce significantly more amount of warts in laser surgeons in comparison to population-based common subjects [58]. But, sitewise, CO2 laser surgeons have a greater risk of acquiring nasopharyngeal lesions, especially when they treat genital warts with HPV types 6 and 11 [58]. Scar formation is a known side effect of CO2 lasers, and there are more chances of hypertrophic scar formation if the patient is on cyclosporine for other reasons [59]. In superpulsed CO2 LASERs, the high irradiances and brief duration make possible very precise removal of target lesion volumes and controlled excision. Here, thermal damage is very less leading to less inflammation and less scarring [60].
Non-ablative lasers are largely replacing ablative CO2 lasers as side effects are less, both for patients and clinicians [61]. Er:YAG laser emits 2940 nm wavelength. It is absorbed 12–18 times more efficiently by water containing superficial cutaneous tissue than CO2 laser. At 250 microsecond pulse duration and 5 J/cm2 fluence short pulse, Er:YAG laser ablates 5–20 micrometre of tissue per laser pass, and minimal residual thermal damage that results faster tissue re-epithelialization and less side effects. The disadvantage is intraoperative bleeding [62]. Its mechanism of action in treating warts is through direct ablation of the lesion in the epidermis, layer by layer until normal tissue is visualised. This laser type also has bactericidal effects [61]. Er:YAG laser was tried in all types of common warts—periungual, subungual and plantar warts; complete clearance rate was 68% for plantar warts, 78% for periungual warts and 76% for subungual warts. In patients with extensive involvement, more than one session were needed. Relapse was only in plantar wart patients (17.8%) [62]. Chance of scarring is less in Er:YAG laser [62, 63]. For hard-to-treat palmoplantar warts, a combination of ablative Er:YAG laser and topical 0.5% podophyllotoxin solution yields higher success with complete clearance of 88.6% without any pigmentary changes, wound infection and scarring. Relapse rate is also less [64]. Er:YAG laser procedure can be done without anaesthesia or with topical cream anaesthesia as there is minimal pain, except only in large, very thick plaque in the plantar or palm. The plume contains no viral DNA [65]. Side effects are less with Er:YAG laser, no hyper- or hypopigmentation and no post-operative infection. Healing is very fast, within 7–10 days. Redness persists up to 3 months [66]. In a study of 69 patients with difficult-to-treat warts (periungual or plantar), 72.5% of patients with wart observed complete response (CR) irrespective of the duration of infection with HPV or the age of the patients. Plantar warts were more resistant (13.5% non-responders) than periungual warts (5.9% non-responders), and larger mosaic plantar warts were less sensitive than single warts; 24.0% of patients showed relapse [67]. Wound healing may be assisted/accelerated with LED phototherapy (633 nm). Immediately after Er:YAG ablation, with precise removal of wart tissue, a red LED therapy system is applied (633 nm, 20 min, 96 J/cm2) to the wound and surrounding area, LED system with same parameters were repeated on the second, sixth and tenth post-operative day. On the sixth post-operative day, the wound has shrunk noticeably and is filled with healthy, granulation tissue, and on day 15, the wound healed completely with minimal scarring; recurrence rate was also less (<6%) [68].
Principal emission of Nd:YAG is at 1064 nm, in the infrared range [Nd:YAG produces heat]. Heat therapy depends on the principle that diseased tissue which is being treated is more sensitive to the effects of the elevated temperature than normal tissue and this is less able to recover after heat exposure [69]. Side effects such as coagulation, blister or crusts are less after hyperthermia. Response is excellent (77%), though in 23% of the method failed, and there is no recurrence in 9 months follow-up. Nd:YAG can be used in all types and site warts including periungual, hand and plantar warts [70]. HPV DNA becomes completely absent in hyperthermia-treated wart lesions, in comparison to cryotherapy where 96% wart lesions are positive for HPV DNA by in situ hybridization [71]. The light of the solid state Nd:YAG laser can easily be guided by fibres to tissue and perform good coagulation and homeostatic function, in laryngeal, as well as genital, easily and more precisely. Its continuous suction endures a minimal load of potential infectious laser plume [72]. For therapeutic treatment, Nd:YAG laser can be utilised for genital tract lesion and cervical conization for early neoplasms like dysplasia, carcinoma in situ and microinvasive carcinoma [73, 74]; these are caused by HPV infections. Invasive lasers like CO2 are normally considerably more painful and require longer recovery time, and also side effects like scarring are high. A long pulsed Nd:YAG laser emits 1064 nm wavelength light, in infrared spectrum, in longer wavelength with lower haemoglobin, and melanin absorption coefficients allows deeper delivery of higher energy in hyperkeratotic and thicker epidermis that are assisted with warts [75]. Several studies have evaluated the use of the Nd:YAG laser in the treatment of simple and recalcitrant common, palmoplantar, periungual and subungual warts, with efficacies ranging from 46 to 100% [61, 76, 77, 78]. Laser protocol varied among different studies: spot size between 3 and 7 mm, pulse duration of 1–20 ms, fluence of 100–200 J/cm2, cooling methods, number of pulses between 1 and 8, treatment interval from 2 weeks to 12 months and mean number of treatments between 1.49 and 4.65. In a study of Han et al. [76], 348 patients of all types of simple and recalcitrant common, palmoplantar and periungual warts are treated with Nd:YAG laser (spot size, 5 mm; pulse duration, 20 ms; 200 J/cm2; no cooling; 1–2 pulses). After a mean of 1.49 treatments, wart clearance rate was 96% though there were differences in clearance rates after initial treatment depending on location (72.6% for common warts vs. 44.1% for palmoplantar warts) [76]. For determination of effectiveness and safety of a novel 100 microsecond pulsed 1064 nm Nd:YAG laser in treatment of Verruca vulgaris, low energy (200 mjouls) Nd:YAG, in monthly intervals for 3 months was given to 25 patients with lesion on hands-nineteen patients had complete clearance; with minimal discomfort [61]. At least partial response (50% reduction) in verruca size was noticed in all lesions [61]. Aggressive treatment of hand warts may cause tissue damage. To avoid the tissue damage, a novel modification was tried [77]. Fifty one recalcitrant verrucas were treated with ND:YAG laser; all warts were administered in at least three pulses. The circle of pulses given in that way that the three circles overlapped each other only on the site of verruca- so that highest level of energy reached only to the wart. The adjacent tissue can avoid unintended tissue damage [77]. All lesions subsided, 88.35% lesions in one laser session, remaining patients were required two laser sessions- those lesions were periungual and palmar. There was no recurrence in 12 months follow-up, no major side effects, no nail dystrophy or severe post-treatment scarring. Hyperpigmentation was present in 5.48% patients [77].
Among non-ablative modalities, pulsed dye laser (PDL) can be used for a selective, non-bloody destruction of extragenital and genital warts [79]. It emits a wavelength of 585, which is absorbed by haemoglobin and oxyhaemoglobin [79, 80]. Mechanism of action is unclear, but may be a result of intense heating of dermal vessels that leads to damage of viral DNA-containing keratinocytes. The theory is based on the presence of dilated and congested vessels at the base of most verruca and the mechanism of selective photothermolysis that results in the targetting of haemoglobin by the PDL [80]. The heat and immunological process and the removal of the blood supply to the wart may be the reason for the effectiveness of PDL in verruca therapy, but it is not above controversy [81]. This selective damage to blood vessels, sparing unnecessary damage to healthy adjacent cellular structure, avoids the scarring [82]. The local dermal vascular destruction of the warts stimulates cell-mediated immune response that is important for eradication of viral warts [83]. So, PDL for wart therapy, even in facial wart, is attractive [84] for its efficient and cosmetic resolution [84, 85]. The PDL is usually painless or minimally painful like snapped by a rubber band [86], though some patients complain of severe intraoperative pain [87, 88], so local anaesthesia may be required. Purpura may develop due to sudden burst of wart vasculature—that develops within minutes in the treated areas—which takes 10–14 days to subside spontaneously [88]. Even perianal warts in child patients are also treatable with PDL without any complications and with 100% clearance [89]. Verruca plana lesions on face in Asian (type IV-V skin) clear completely with PDL without producing significant pigmentary and textural complications [90]. Safety is one of the major advantages of this technique [91]. But the absence of any proven superiority over the standard treatments in terms of efficacy, coupled with high costs, means that PDL should only be used as second-line therapy in patients with cosmetic needs [91].
Laser protocols are different in all studies, and variation of results may be for that reason. Different protocols include spot size of 5–10 mm, fluence of 5 j/m2–15 j/m2, pulse duration of 38 ns–1.5 ms, consecutive 2–3 pulses with overlap of 1–2 mm, 1–12 sessions, interval of 2–4 weeks and cooling methods [90, 91, 92, 93, 94, 95, 96, 97, 98]. In immunocompetent children, the overall response rate is 75%, and the remaining 25% had partial clearance, with an average number of treatment for complete clearance to be 3.1—face and perineum are areas most likely to be cleared in one treatment (50 and 20%, respectively) [99, 100]. It is also a more effective therapy especially against those that have not been eradicated by other treatments [101]. Though less, adverse effects are also not very much uncommon, about 8.2% of patients had adverse effects like wound formation (3.8%), residual scarring (2.9%), infection (1.0%) and collapse (0.5%); 63% of patients had excessive pain [97]. But opinion about pain and patient compliance are different in other study [102]. Here only 6.34% of patients classified the method as too painful and withdrew after the first one or two treatments They have concluded that FPDL is safe and effective for the removal or reduction of verrucae vulgares, and requires less patient compliance compared with other treatment options. PDL followed by intralesional Bleomycin gives very good result with complete clearance, even in immunosuppressive patients, though the overall treatment session was high (1.8 vs. 3) [98], but should be aware of common side effects seen such as painful haemorrhagic blistering and superficial ulceration [103].
The KTP laser has been utilised in the treatment of recalcitrant cutaneous warts, and when treated to complete clearance, no recurrence occurred [104].
Glutaraldehyde is a tissue fixative that polymerises keratin. Its effectiveness lies in desiccation of surface virions and resultant reduction of antigenic load [105]. However the mechanism of action of glutaraldehyde against warts has not been clarified precisely. Glutaraldehyde therapy (GA) for warts was first introduced in 1971 [106]. Therapeutic responses with glutaraldehyde in periungual, palmar and plantar warts were 80, 60 and 68.5%, respectively [107]. When GA is buffered by suitable alkalinating agents to a pH of 7.5–8.5, the solution becomes antimicrobially active [108]. The concentration of glutaraldehyde is another consideration for use. Though 2 w/v% is the minimum for antimicrobial activity [108], undiluted high concentration of 25% solution appeared to work faster on warts of all kinds [107]. The benefits of using glutaraldehyde as first-line treatment for warts, especially resistant ones, are the same as those of cryotherapy [107].
Formalin (formaldehyde) is a virucidal agent and has strong disinfectant properties and exerts its effects by causing damage to the upper layers of epidermal cells that contain the virus, thus destroying viruses [28, 109]. Formalin application was effective in 83.3% of patients, but complete disappearance of warts was seen in 11.1% [110]. The most common side effects of formalin include redness, irritation and dryness of skin [111].
Oral antivirals are not a regular treatment modality, but isolated case report about improvement in wart lesion after oral treatment with acyclovir [112], valacyclovir are there. Plantar wart is cleared completely with 1 gm valacyclovir for 60 days [113]. Improvements of wart with intravenous cidofovir in one HIV seropositive patient with complete clearance are available [114]. Nearly total clearance of multiple viral wart with didanosine, stavudine and efavirenz triple antiretroviral therapy in a 34-year-old male homosexual patient was seen, accompanied by a significant improvement in immune status [115]. The observations are not powerful enough to assume causality (instead of a simple casual or placebo effect).
Bleomycin is a chemotherapeutic agent which has an antitumor, antibacterial and antiviral activity which may be related to its ability to bind with deoxyribonucleic acid (DNA), causing bleomycin strand scission and elimination of pyrimidine and purine bases [116]. It selectively affects squamous cell and reticuloendothelial tissue [117]. Bleomycin is not thought to bind directly to HPV [10]. Bleomycin causes acute tissue necrosis that may stimulate an immune response, as evidenced by the fact that it is less effective as a wart treatment in immunosuppressed renal transplant patients [118, 119, 120, 121].
Adverse effects include injection pain and burning, erythema, swelling and pain within 24–72 h after injection before a black thrombotic eschar forms. Local complications after periungual injections are nail loss [122] or dystrophy [123]. Reynaud’s phenomenon in treated fingers, local pigmentation [124] or urticaria [122], even flagellate hyperpigmentation [125] are reported after.
In a systemic review [126], comparing intralesional bleomycin with placebo, the studies have given conflicting results. Intralesional bleomycin was compared with saline or sesame oil; duration was 6 weeks to 3 months. The RCTs in the review favour I/L Bleomycin, and only one study opined placebo to be more effective. The result of wart clearance was between 18 and 94%, but the study showed clearance rate to be 94%, which was not significantly different from the result (73%) achieved by placebo injections of saline. Concentration of 0.5% bleomycin is more effective than concentration of 0.25% or 1% bleomycin. Pain was experienced by most patients, irrespective of doses. In a study of comparison between intralesional Bleomycin and cryotherapy, 0.1% concentration of bleomycin was used [127]. Greater efficacy in clearing warts was shown with intralesional bleomycin than in cryotherapy. The clearance rates of warts for intralesional bleomycin therapy found were 97%, and in 94.9% of patients, all warts treated with bleomycin were cleared. There was significantly less number of treatment sessions, with a mean of 1.38 in case of bleomycin treatment than the cryotherapy where the mean is 3.08.
Podophyllotoxin is a topical antimitotic that is purified from the plant families Coniferae and Berberidaceae (e.g. species of
It results in necrosis when applied to anogenital warts. Only a trained medical professional can apply it, and it cannot be dispensed to a patient. CDC guidelines for anogenital warts, recommended regimens for External Anogenital Warts (i.e. penis, groin, scrotum, vulva, perineum, external anus and perianus), includes patient-applied therapy with podofilox (podophyllotoxin) 0.5% solution or gel—using a cotton swab or finger. This podofilox solution (using a cotton swab) or gel (using a finger) should be applied to anogenital warts twice daily for 3 consecutive days, followed by 4 days of drug interval. If necessary, it can be repeated, for up to four cycles. The total treated area should not exceed 10 cm2, and up to 0.5 ml podofilox should be used per day [131]. If possible initial application should be demonstrated by one healthcare provider for demonstration of proper application and technique and to identify the appropriate warts for treatment. Mild to moderate pain or local irritation might develop after treatment [131].
Podophyllotoxin, the active ingredients of podophyllin, is contraindicated in pregnancy. Though human data not available during application in lactating mother, it is considered as potential toxic. Podophylline, a raw form, is also contraindicated in pregnancy and breastfeeding mother, due to the potential severe myelotoxicity and neurotoxicity in the mother, though no human data available. The American college of Obstetricians and Gynecologists and other sources contraindicated the use of podophyllum agents include the use of podophyllotoxin (podofilox) during pregnancy and in the vagina or cervix at any time [132]. In a randomised comparative study, 60 women with genital warts were treated with either weekly application of 20% podophyllin solution or self-treatment with 0.5% podophyllotoxin cream twice daily for 3 days in weekly intervals. Patients were treated for a maximum of four treatment cycles, and final assessment was carried out after 3 months. Podophyllotoxin cream had a significantly better clearance than podophyllin solution, a primary clearance of was 82% vs 59%. These final clearance decreased to 71% and 48% at the 3-month follow-up, respectively. Total wart clearance was 94% with podophyllotoxin and 74% with podophyllin solution. Podophyllin cream came to as easy to apply and effects significantly better than podophyllin solution. Local side effects were mild to moderate with erythema, and erosion appeared to be higher in the podophyllotoxin group but not so serious to discontinue treatment [133].
This treatment uses the patient’s own immune system to fight the warts. Some types of immunotherapy only target certain cells of the immune system. Others affect the immune system in general. Because of the cumbersome nature of the conventional procedures and a high risk of recurrence, immunotherapy is becoming more and more popular, especially in the treatment of refractory cutaneous and genital warts. These include various topical, intralesional and systemic agents. There are no well-defined criteria or consensus on when immunotherapy should be tried in a patient with warts. Current indications [134] include the following (Table 1).
Recalcitrant warts
Recurrent warts
Extensive warts
Difficult-to-treat areas—periungual and palmoplantar sites
Various agents used in immunotherapy of warts.
Courtesy of Prof Devinder M Thappa and Minu J Chiramel [134].
Imiquimod is a non-nucleoside heterocyclic amine which acts as an immune response modifier that may stimulate cytokines, including interferon-α, interleukin-1, interleukin-6, tumour necrosis factor-α, granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor [135]. In a quantitative systemic review of published randomised control trials, six RCTs were evaluated, and all six studies were conducted in the sitting of home administration after initial professional examination and advice wart locations are genital, both in males and females. Five of the studies are on immunocompetent patients and one study on HIV-positive patients; 90% of the study population are male. Imiquimod was used as 5% cream in 4 trials and 2% cream in one trial, with complete clearance achieved in 51% in imiquimod group but only 6% patients in placebo group. The number needed to treat (NNT) was 2.2 (95% confidence interval 2.0–2.6). At least 50% reduction in wart area occurred in 72% of patients treated with Imiquimod 5% cream and 20% in placebo treated group. The number needed to treat was 1.9 (1.7–2.2). Warts were completely cured and did not recur in 37% (31% to 43%) of patients treated with imiquimod 5%, and 4% (2% to 6%) of patients treated with placebo. The NNT was 3.0 (2.5 to 3.8). Fewer patients were cured with 1% imiquimod in two trials, and for this concentration the NNT was 9.5 (5.9 to 25). Imiquimod 5% cream was significantly more effective than imiquimod 1% cream for complete wart clearance [136]. Common adverse events were localised itching, erythema, burning and erosion or excoriation, there was rarely any withdrawal from study due to these adverse effects. In HIV infected patients with warts, at least 50% reduction of wart area was seen in 38%, and in placebo it was 14%. Adverse events were similar to non-HIV group [137]. It is found to be effective and safe in children and there are reports of safe use in pregnancy [138, 139]. Disadvantages of using imiquimod 5% cream were the high cost and the length of average treatment (9.5 weeks).
The delayed hypersensitivity response against the antigen is the key to clinical response against warts, same as that of the Mw vaccine. It increases the serum levels of IL-12 and decreases the level of IL-4 [147]. One to three doses are administered 1 month apart. In cutaneous warts (common, plantar, and plane warts), there was a resolution rate of 39.7% [148]. Topically applied BCG paste (weekly for 6 weeks) has also been found to be effective in children with common warts and plane warts with 65% resolution [149], and usually there are no side effects. However, another report in India showed a high incidence of flu-like symptoms precluding further doses in 57% of patients, making one question its safety in tuberculosis endemic countries like India [150].
Various types of vaccines and antigens were tried for wart management. Measles, mumps and rubella (MMR) viral vaccine accelerates the clearance of virus and viral infected cells by stimulation of cell-mediated and humoral immunity [151]. In this double-blind RCT, MMR vaccine was tried for three injections in 2-week interval with normal saline as control; 75% of patients had complete clearance, and another 16.6% had more than 50% clearance. There were no side effects, and in 6-month follow-up, there was no relapse [151]. In another study of MMR vaccine, 81.4% of patients had complete clearance; another 10% had partial clearance, in comparison to 27.5% and 15% with saline control [152]. A preliminary, open-label (PPD: purified protein derivative) study to investigate the effectiveness of the tuberculin antigen in the treatment of recalcitrant warts, taking advantage of the vaccination schedule in their country was designed. Three consecutive intralesional tuberculin (5TU PPD RT23-tween 80 solution) injections with 3-week intervals into each target wart, depending on the tuberculin reactivity, were performed. Injections of 0.3, 0.2 and 0.1 mL of antigen were administered to patients with indurations of 5–9, 10–15 and > 15 mm, respectively. Five patients (29.4%) demonstrated complete clearance, five (29.4%) had partial and five (29.4%) minimal response. Some patients showed complete clearance of untreated facial warts also. Patients with initial PPD test site in duration less than 10 mm had no or minimal response [153]. Mumps and
Interferon has been shown to be active against HPV both in vitro and in vivo, to protect murine cells against infection with bovine papillomaviruses and to eliminate extrachromosomal viral DNA from infected cells [164, 165]. In a systematic meta-analysis, the rate of complete response in locally used interferon was 44.4% in comparison to placebo, 16.1%. The complete response rate of systemically used interferon as compared to placebo for treating genital warts had no perceivable discrepancy, for systemically used interferon 27.4% and placebo 26.4%. Both groups had near same recurrence rate (interferon 21.1% vs. placebo 34.2%, p > 0.05). In subgroup analysis, it was noticed that relapse was less in intralesional interferon in comparison to placebo group, but relapse rate were the same in between systemic and placebo groups. Adverse events were mostly mild and transient and could be tolerated [166].
Dietary zinc has profound effects on the human immune system and deficiency leads to reduced immune capacity [167, 168]. It can be given as topical preparation, oral medication or intralesional. Topical preparation as 10% zinc sulphate lotion yields complete clearance in 80% in plane wart [169]; plane warts were seen in 85.7% [170]. Complete clearance noticed in 61% patients after 1 month therapy and 87% after 2 months of therapy with oral zinc sulphate 10 mg/kg/day in a placebo-controlled trial [171]. But it was not the same in other studies, 50% complete clearance with the same dose after 2 months in another open level clinical study [172]. Intralesional 2% zinc sulphate too has been found to induce clearance of warts [173].
H2 blockers, such as cimetidine and ranitidine, have been tried in treatment of warts. They block the type 2 histamine receptors on suppressor T cells and augment cell-mediated immunity [174]. It increases the levels of IFNγ and IL-2 and decreases the levels of IL-18 [175]. It has been used in a dose of 20–40 mg/kg/day for 3–4 months with response rate ranging from 30 to 87% [176, 177]. There is no significant difference between cimetidine and placebo [178], and some author proposed a placebo effect for cimetidine [179].
Levamisole, an antihelminthic agent, is found to have immunomodulatory effects, making it effective in various dermatological disorders including viral warts at a dose of 2.5–5 mg/kg/day for 3 consecutive days every 2 weeks for 4–5 months [180, 181, 182]. The response to levamisole was approximately 60%. Side effects are rash, nausea, abdominal cramps, taste alteration, alopecia, arthralgia and a flu-like syndrome and rarely cause myopathy, leukocytoclastic vasculitis, lichenoid eruptions and leukoencephalopathy [183, 184].
Since 2006, two vaccines against Human papillomavirus (HPV) have been licenced in more than 100 countries [185]. Both vaccines target HPV types 16 and 18, which account for about 70% of all cervical cancer cases, and the quadrivalent vaccine also targets HPV types 6 and 11, associated with 90% of genital warts (GWs) [186]. In Denmark, the quadrivalent HPV vaccine was introduced into the children’s vaccination programme in January 2009 for 12-year-old girls. In 2014 the European Medicines Agency and the World Health Organisation Strategic Advisory Group of Experts recommended a two-dose schedule for 9–13-year-old girls. However, three-dose schedule offers better protection against genital warts than a two-dose schedule in a nationwide study. But, if the dosing interval extends (about six months), the two dose schedule came as effective as three. The quadrivalent HPV vaccine that comprises the L1 protein of HPV types 6, 11, 16 and 18 has been in use on a large scale in countries like Denmark with a decline in the prevalence of genital warts [187]. Similar decline in genital warts has been noticed in the UK and Australia [188, 189].
Autowart inoculation by means of homologous autoimplantation helping to induce specific cell-mediated immunity has been proposed as a treatment option for recalcitrant, extensive and genital wart [190]. About 83 patients with all types of wart lesions were included in a study. At 16 weeks of therapy, 69.5% of patients recovered completely, and more than 75% improvement occurred in another 8.5% patients. No significant complication was documented. There was no recurrence within study period [191]. Another study also had noticed 73.3% total clearance of warts, with a majority of them (91%) within 2 months [190]. Inoculation site infection and post-inflammatory hyperpigmentation and hypopigmentation are the side effects.
Contact sensitizers are a mode of inducing a type IV hypersensitivity reaction, thus making them a form of topical immunotherapy [28]. Diphencyprone (DCP) is the preferred compound. DCP 2% solution is applied after every 10–14 days, on the medial side of upper arm—till there is appearance of local erythema and vesiculation—and this may be repeated up to three times. Warts were then first pared followed by application with stepwise concentration of DCP: 0.01, 0.05, 0.10, 0.25, 0.50, 1.0, 1.5, 2.0, 3.0, 4.0 and 6.0%. Treatments are applied every 1–4 weeks. Resistant palmoplantar warts treated with DCP over 8 years [192] exhibited 88% clearance rate. However, a large percentage of patients developed adverse effects (56%), including painful blistering at the site of sensitization and near warts, pompholyx-like or generalised eczematous eruption, influenza-like symptoms, vesiculation elsewhere due to passive transfer of DCP and inguinal lymphadenopathy. They concluded that patients with recalcitrant palmar, plantar, periungual and digital warts are good candidates for DCP therapy [193].
There are various other agents being tried infrequently in the management of warts.
Historic folk remedies have included many variants.
Duct tape occlusion therapy involves placing a piece of duct tape over the wart. The mechanism of action of this technique still remains unknown [194].
Components of garlic (
Application of paste made of baking powder and castor oil is age old technique for warts.
Herbal preparations such as Echinacea and propolis are reported to boost the immunity when administered orally [196], act as immunomodulators and improve warts.
Sinecatechins are derived from green tea extract (
Glycyrrhizic acid, obtained from the root of
Intralesional injection of 0.2 ml of 15 mg/kg vitamin D3 led to complete resolution [200] in 19 (82.60%) out of 23 patients with palmoplantar warts and 14 (77.77%) of 18 patients with verruca vulgaris.
Numerous varieties of approaches for wart management are there. It is difficult to choose the best wart treatment. It should be determined by type of wart, whether old or new; site; immune status of the patient; pregnancy; the effects and side effects of the wart management procedure; its compliance with patient; and above all the availability of the planned modality of treatment. A rational consideration of all factors can provide an appreciable benefit.
Selenium (Se) benefits for health in human and animal have provided popularity for this chemical element. Selenium is a nutrient for animals since 1957 [1]; thus, it must be part of their diet. However, there are large agricultural areas containing low levels of Se in soil or it is present, but as chemical forms unavailable for plants, consequently these areas are producing vegetables or animal products with low Se contents.
In Brazil, there are some researches indicating that large agricultural areas are located in soils with low Se levels, that is, daily diet Se intake evaluated in people groups from São Paulo, Brazil, presented values below to estimated average requirement values, which shows deficiency of Se in the diets from this region [2]. A research at Rio Grande do Sul, Brazil, also resulted in marginal deficiency of Se in cattle [3]. Both data indicated the possibility of Brazilian soils contain low available Se levels.
The agronomic biofortification of food through field fertilization with Se could be a solution to provide this micronutrient for animals and humans through plants. Plants are able to absorb and incorporate Se to organic compounds as seleno-amino acids. Thus, inorganic Se is converted to organic Se compounds through the plants which can be easily absorbed by the human body and to be available where needed in the body [4]. In some countries, Se fertilization is well established, and it is annually done in New Zealand in which Se along with phosphorus fertilization is applied in pastures [5].
Selenium essentiality for plants is not convinced, but its availability for plants, as well as for the animals, could improve their performance and consequently the human health. For both animals and plants, this element acts as defense through its influence in glutathione peroxidase controlling oxygen reactive species from stress situations [6].
Large knowledge about specific rates, sources, Se dynamic in soils and plants, and even behavior of animal intake in pasture is required for a safe Se fertilization, to ensure food and environmental security. High Se levels available in soils can cause toxicity for plants and animals. Thus, for the beneficial of Se application as fertilizer commonly are required low rates, which raises concerns about risks of super dosages, what can be aggravated by complex dynamic of Se in soil and plants.
Se availability in soil is the first requirement for Se application as fertilizer. Most soils contain low Se levels, including in tropical environments, while the highest contents are found at arid areas characterized by the presence of accumulator plants [7].
Low Se levels were observed in the main eight soil types of Brazil (Table 1). These soils were collected at São Paulo state as well as in plant of
Chemical parameters of fertility in tropical soils and selenium levels in sampled soils at São Paulo state, Brazil.
The contents up to 500 μg dm−3 characterized low Se soils [8], and confirming the relation between soil and plants, the samples of
Besides the Se presence in soil, its availability for plants depends on oxidation state. Selenium is chemically similar to sulfur, but it occurs naturally in four oxidation states, −2 (selenide), 0 (elemental Se), +4 (selenite), and +6 (selenate) [9]; however, sodium selenate is the source recommended for Se fertilizations due its high solubility. Unlike selenate, the mechanism of selenite uptake by plants remains unclear [10].
In weathered soils, there are low nutrient levels; high contents of Fe, Al, and Mn; and high acidity, according to soils analyzed (Table 1). Thus, it is necessary to know the Se dynamic in these soils. A profile of weathered soils analyzed from São Paulo observed low Se levels in soils with higher sand contents (Figure 1) that could indicate leaching potential.
Selenium levels in tropical soil profiles and, respectively, sand contents in sampled soils at São Paulo state, Brazil (unpublished data).
A study of Se adsorption and desorption in soils from Cerrado, Brazil, verified low values of distribution coefficient in soils; thus, Se tended to be more in solution than in the solid phase, and in the most weathered soils, with higher clay and Al and Fe oxide contents, there are the highest affinity for Se, while in sandy and loamy soils, Se tends to be less adsorbed and can therefore be taken up by plants or easily leached, damaging the ecosystem [11].
The low natural levels of Se in soils and its absence in fertilization to crops explain the low contents in food from vegetables [12] and consequently in Brazilian diet, except for northern areas [2]. Although, in a study of hemodialysis patients from north and southeast of Brazil, both patient groups presented low Se plasma levels when compared to recommended values; independently of the region, all patients presented Se deficiency [13].
This information is an alert for necessity to Se fertilization in Brazil. It was incentivized in the 1980s, but its requirement was unsuccessful, while in some countries, it is well stablished already. Applications of Se in areas of low Se bioavailability have been an option with good results to supply this element to plants and, consequently to animals, improving animal performance and nutritional quality of food produced as milk and meat [11], even in environments with no deficiency symptoms [14].
However, toxic potential of selenium requires caution as fertilizer due its complex dynamic nature in soil and plants. Selenium as selenate (SeO42−) is commonly found in alkaline and oxygen soils under high redox conditions (pe + pH > 15), and this oxidation state is predominantly absorbed by plants, while under low and milder redox conditions, species as selenite and selenide predominate [9].
Selenium fertilization must be controlled through safe doses and soil monitoring due to the possibilities of the Se dynamics in soils. Selenate can be easily absorbed by plants; thus, the doses for fertilizations must be carefully calculated, but also it could be leached with possibilities of water contamination.
Low selenate doses required for fertilization is a challenge due to concern for homogeneous application. According to the Selenium-Tellurium Development Association, the best way for Se application is along with other nutrients [15]. There are positive effects in Se application along with phosphorus fertilization [13].
Some technologies involving Se application along with macronutrients as coating became a technique to easy and high quality of application. Urea coated with a mix of boric acid (0.4% B), copper sulfate (0.14% Cu), and sodium selenate applied to
Seed pelletization seems to be a promissory tool to increase Se content in plants. Beneficial effects were observed in the evaluation of seed pelletization with increasing selenite doses on three ryegrass cultivars; however, the authors recommended it to be evaluated under field conditions in Se-deficient soils [17].
Another technology is the slow release of Se fertilizer as Selcote Ultra; however, its application in rates of up 20 g ha−1 Se on an Ultisol soil of Puerto Rico did not increase in the foliage Se concentrations of Guinea grass pastures [18]. According to the authors, the soil and plant interrelationships may be affecting the foliage of Se absorption potential requiring that the effects need future consideration in terms of Se movement in tropical soils.
The establishment of effective and safe rates in tropical environmental still is required and unknown, regardless of the technical method applied to plant enrichment on Se. High Se availability in agriculture soils can cause toxicity to crops, but it is still more concerning if a crop shows accumulator character, i.e., if a crop has capacity to absorb high levels of selenium with no symptoms of toxicity; this could increase the possibilities to cause toxicity for animals or human.
Forage plants are classified as passive accumulators due its ability to contain 10–30 mg kg−1 of Se in dry matter; however, high-quantity animal intake of Se through dry matter intake could induce intoxication [19]. Although the research with
Depending of the soil, excess of Se can be in unavailable forms to plant uptake over time. Soil influence in dynamic and availability of Se was observed by isolation of Selenium rates applied followed by comparing among soils, Arenic Hapludult, Rhodic Hapludox and Typic Hapludoll, which verified differents Selenium content remaining in soil, respectively, 22, 11, and 37 μg dm−3 and 55, 4, and 38 μg dm−3 after
Besides the uptake ability among plants, the difference among soils was evident. This element in soil can be fixed along with iron, complexed in organic matter, or it can be in many oxidation states depending on the pH, oxygen, and microbial activity [7]. These data confirmed different soil capacities to Se adsorption, but it can turn available for plants in pH changes, as frequently occurs with limestone application, a common practice from tropical agriculture areas.
High contents of selenate in soil, for natural or anthropogenic action, can be establish or reestablish for agricultural or livestock, avoiding the poisoning risk of plants, animals, and humans [20]; in these cases, the areas must be isolated for remediation. The use of plants to clean up contaminated soils is a technique known as phytoremediation that offers a less expensive alternative to stripping pollutants directly from the soil [21].
The management of high Se soil also can include sulfur source application. The similarity between Se and S indicates the competition for sulfate transporters of the root plasma membrane [7]. Sulfur application at 600 kg ha−1 as soluble sources such as ammonium sulfate and ferric sulfate reduced damages in productivity and Se uptake by Urochloa grass, while the lower solubility of calcium sulfate resulted in lower effectiveness in reducing Se uptake [20]. Plants used for phytoremediation can be used for mixture in diets of animals or used as composting to application in low Se areas.
The geochemistry of livestock-producing areas should be well understood to mitigate selenium-related disorders in animals [22]. In China, there are areas with selenosis occurrences; in contrast about 70% of China shows Selenium deficiency, as well as there are about 76% countries located in Se-deficient regions where the Se daily intake level is less than recommended [23].
Brazil is a country who owns the largest livestock in pastures; however, the majority of pastures are in marginal areas, under soils of low fertility. Brazil is one of the largest meat producers. In Brazilian food, the highest Se concentrations have been found to animal origin products, while vegetable food showed lower values [12]; however, some studies showed selenium deficiencies also in cattle, except in north areas [24, 25].
Cattle deficiencies have a likely relation between low Se in forage grass or supplements [26]. Thus, Se deficiency keeps as a concern, since this nutrient has been found in low levels in Brazilian diet.
Selenium fertilization could be a solution, but it is not realized in Brazil. Fertilizers containing selenium could support diet supplementation of grazing animals or animals feed with conserved forages (hay and silage), mainly considering Brazilian pasture areas with more than 160 million of hectares [27].
Selenium fertilization in pastures could increase its presence in animal and human diet besides its benefits to animal productivity. Feeding weaned beef calves for 7 weeks with alfalfa hay containing up to 3.26 mg kg−1 Se in dry matter harvested in fertilized fields with Se resulted to increasing whole-blood Se concentrations and body weights depending upon the Se application rate [28].
Grazing Se fertilizer has been shown to be more effective and safe treatment than animal dosing [13]. Selenium intake by ruminants in organic form, especially as selenoamino acids, needs to be release from proteins until through inorganic forms to be metabolized while Se in milk is from organic Se supply or converted by ruminal microorganisms [29].
Experiment with tropical grass has been shown large differences between Se contents in leaves and stem + sheath.
The fast answer of Se fertilization in tropical pastures can be positive to allow the low and safe doses of Se application along with nitrogen rates during rainy season, including for intercropped pastures with legumes. The concerning of intercropped pastures is explained by legume higher ability to produce protein, which can be apparently favorable to Se absorption.
Thus, this fact probably will require lower Se doses for fertilization in intercropped pastures, including caution with palatability and proportion of legumes in pastures. For example, in three different weathered soils carried out in pots, fertilization of 20 g ha−1 Se showed desirable concentrations to legume
High Se contents in leaves from tropical grass and in legumes comprise another fact to be analyzed for Se fertilization rate establishment although with few data. Usually, grass leaves and legumes are preference fractions for cattle according to its intake selective behavior, mainly in tropical pastures due to high accumulation of stem portions and its low digestibility. Selenium is one of few elements absorbed by plants in enough quantities which enable to intoxicate domestic animals [30].
Evaluating in vitro degradability of two cuts of
In superior plants dual effects can be exerted by Se; at low concentrations it acted as an antioxidant, inhibiting lipid peroxidation, whereas at higher concentrations, it was a prooxidant [6]. Applied doses of selenate above 71 g ha−1 Se exceed maximum recommendation of 5 mg kg−1 Se in dry matter of the leaves of
The effect of high Se diet concentration (60–70 μg kg BW−1 d−1) provided from wheat to steers indicated the negative effects of Se level used in this study on productive performance of feedlot which were not expected [25]. Low forage digestibility can contribute to low Se effects in animals, mainly in tropical forages, while high Se content in forage can reduce its digestibility. Undegraded residues from in vitro incubation contained 25–66% of Se from
Selenium fertilization in tropical low Se soils, as Brazil agricultural areas, is an emergent necessity for animal and human health, also could be beneficial for plants. Thus, Se fertilization in pastures is an alternative to collaborate for animal supplementation and human nutritional demands.
Generally, Se quantities required as fertilizer are low, and there are already available technologies to application but is an extremely necessary soil monitoring.
Nevertheless, more researches in tropical environments is required to establishment of Se rates, plants, and animal answers and reduces or even neutralizes toxicity risks, even though the benefits already are known.
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These heuristics are essentially based on a commonly used scheduling theory in Jackson’s extended heuristic. We present basic structural properties of the solutions delivered by Jackson’s heuristic and then illustrate how one can exploit them to build efficient heuristics.",book:{id:"5966",slug:"heuristics-and-hyper-heuristics-principles-and-applications",title:"Heuristics and Hyper-Heuristics",fullTitle:"Heuristics and Hyper-Heuristics - Principles and Applications"},signatures:"Nodari Vakhania",authors:[{id:"202585",title:"Prof.",name:"Nodari",middleName:null,surname:"Vakhania",slug:"nodari-vakhania",fullName:"Nodari Vakhania"}]}],mostDownloadedChaptersLast30Days:[{id:"56264",title:"Heuristics Techniques for Scheduling Problems with Reducing Waiting Time Variance",slug:"heuristics-techniques-for-scheduling-problems-with-reducing-waiting-time-variance",totalDownloads:1709,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"In real computational world, scheduling is a decision making process. 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The paper will describe both approaches in different domain problems.",book:{id:"5966",slug:"heuristics-and-hyper-heuristics-principles-and-applications",title:"Heuristics and Hyper-Heuristics",fullTitle:"Heuristics and Hyper-Heuristics - Principles and Applications"},signatures:"Aleksandra Swiercz",authors:[{id:"203032",title:"Ph.D.",name:"Aleksandra",middleName:null,surname:"Swiercz",slug:"aleksandra-swiercz",fullName:"Aleksandra Swiercz"}]},{id:"55594",title:"Multi‐Objective Hyper‐Heuristics",slug:"multi-objective-hyper-heuristics",totalDownloads:1470,totalCrossrefCites:1,totalDimensionsCites:0,abstract:"Multi‐objective hyper‐heuristics is a search method or learning mechanism that operates over a fixed set of low‐level heuristics to solve multi‐objective optimization problems by controlling and combining the strengths of those heuristics. Although numerous papers on hyper‐heuristics have been published and several studies are still underway, most research has focused on single‐objective optimization. Work on hyper‐heuristics for multi‐objective optimization remains limited. This chapter draws attention to this area of research to help researchers and PhD students understand and reuse these methods. It also provides the basic concepts of multi‐objective optimization and hyper‐heuristics to facilitate a better understanding of the related research areas, in addition to exploring hyper‐heuristic methodologies that address multi‐objective optimization. Some design issues related to the development of hyper‐heuristic framework for multi‐objective optimization are discussed. The chapter concludes with a case study of multi‐objective selection hyper‐heuristics and its application on a real‐world problem.",book:{id:"5966",slug:"heuristics-and-hyper-heuristics-principles-and-applications",title:"Heuristics and Hyper-Heuristics",fullTitle:"Heuristics and Hyper-Heuristics - Principles and Applications"},signatures:"Mashael Suliaman Maashi",authors:[{id:"201702",title:"Dr.",name:"Mashael",middleName:null,surname:"Maashi",slug:"mashael-maashi",fullName:"Mashael Maashi"}]},{id:"55968",title:"On the Use of Hybrid Heuristics for Providing Service to Select the Return Channel in an Interactive Digital TV Environment",slug:"on-the-use-of-hybrid-heuristics-for-providing-service-to-select-the-return-channel-in-an-interactive",totalDownloads:1303,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The technologies used to link the end-user to a telecommunication infrastructure, has been changing over time due to the consolidation of new access technologies. Moreover, the emergence of new tools for information dissemination, such as interactive digital TV, makes the selection of access technology, factor of fundamental importance. One of the greatest advantages of using digital TV as means to disseminate information is the installation of applications. In this chapter, a load characterization of a typical application embedded in a digital TV is performed to determine its behavior. However, it is important to note that applications send information through an access technology. Therefore, this chapter, based on the study on load characterization, developed a methodology combining Bayesian networks and technique for order preference by similarity to ideal solution (TOPSIS) analytical approach to provide support to service providers to opt for a technology (power line communication, PLC, wireless, wired, etc.) for the return channel.",book:{id:"5966",slug:"heuristics-and-hyper-heuristics-principles-and-applications",title:"Heuristics and Hyper-Heuristics",fullTitle:"Heuristics and Hyper-Heuristics - Principles and Applications"},signatures:"Marcos César da Rocha Seruffo, Ádamo Lima de Santana, Carlos\nRenato Lisboa Francês and Nandamudi Lankalapalli Vijaykumar",authors:[{id:"10493",title:"Dr.",name:"Adamo",middleName:null,surname:"Lima De Santana",slug:"adamo-lima-de-santana",fullName:"Adamo Lima De Santana"},{id:"202549",title:"Dr.",name:"Marcos",middleName:null,surname:"Seruffo",slug:"marcos-seruffo",fullName:"Marcos Seruffo"},{id:"202551",title:"Dr.",name:"Nadamundi",middleName:null,surname:"Vijaykumar",slug:"nadamundi-vijaykumar",fullName:"Nadamundi Vijaykumar"},{id:"202552",title:"Dr.",name:"Carlos Renato",middleName:null,surname:"Francês",slug:"carlos-renato-frances",fullName:"Carlos Renato Francês"}]},{id:"55704",title:"Advanced Particle Filter Methods",slug:"advanced-particle-filter-methods",totalDownloads:1565,totalCrossrefCites:2,totalDimensionsCites:6,abstract:"This chapter presents a set of algorithmic methods based on particle filter heuristics. We start with an introduction to particle filters, which covers the main motivation and related works. Then, the generic framework for particle filter algorithm is presented, followed by two important use cases regarding indoor positioning and multitarget tracking; for both problems, modified particle filter algorithms are presented followed by experimental results, implementation remarks, and a discussion. Finally, a short list of conclusion and future work are presented.",book:{id:"5966",slug:"heuristics-and-hyper-heuristics-principles-and-applications",title:"Heuristics and Hyper-Heuristics",fullTitle:"Heuristics and Hyper-Heuristics - Principles and Applications"},signatures:"Roi Yozevitch and Boaz Ben-Moshe",authors:[{id:"203049",title:"Prof.",name:"Boaz",middleName:null,surname:"Benmoshe",slug:"boaz-benmoshe",fullName:"Boaz Benmoshe"},{id:"203051",title:"Mr.",name:"Roi",middleName:null,surname:"Yozevitch",slug:"roi-yozevitch",fullName:"Roi Yozevitch"}]}],onlineFirstChaptersFilter:{topicId:"549",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"June 29th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:32,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:36,paginationItems:[{id:"82195",title:"Endoplasmic Reticulum: A Hub in Lipid Homeostasis",doi:"10.5772/intechopen.105450",signatures:"Raúl Ventura and María Isabel Hernández-Alvarez",slug:"endoplasmic-reticulum-a-hub-in-lipid-homeostasis",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"82409",title:"Purinergic Signaling in Covid-19 Disease",doi:"10.5772/intechopen.105008",signatures:"Hailian Shen",slug:"purinergic-signaling-in-covid-19-disease",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82374",title:"The Potential of the Purinergic System as a Therapeutic Target of Natural Compounds in Cutaneous Melanoma",doi:"10.5772/intechopen.105457",signatures:"Gilnei Bruno da Silva, Daiane Manica, Marcelo Moreno and Margarete Dulce Bagatini",slug:"the-potential-of-the-purinergic-system-as-a-therapeutic-target-of-natural-compounds-in-cutaneous-mel",totalDownloads:10,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82103",title:"The Role of Endoplasmic Reticulum Stress and Its Regulation in the Progression of Neurological and Infectious Diseases",doi:"10.5772/intechopen.105543",signatures:"Mary Dover, Michael Kishek, Miranda Eddins, Naneeta Desar, Ketema Paul and Milan Fiala",slug:"the-role-of-endoplasmic-reticulum-stress-and-its-regulation-in-the-progression-of-neurological-and-i",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}}]},overviewPagePublishedBooks:{paginationCount:32,paginationItems:[{type:"book",id:"7006",title:"Biochemistry and Health Benefits of Fatty Acids",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7006.jpg",slug:"biochemistry-and-health-benefits-of-fatty-acids",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Viduranga Waisundara",hash:"c93a00abd68b5eba67e5e719f67fd20b",volumeInSeries:1,fullTitle:"Biochemistry and Health Benefits of Fatty Acids",editors:[{id:"194281",title:"Dr.",name:"Viduranga Y.",middleName:null,surname:"Waisundara",slug:"viduranga-y.-waisundara",fullName:"Viduranga Y. Waisundara",profilePictureURL:"https://mts.intechopen.com/storage/users/194281/images/system/194281.jpg",biography:"Dr. Viduranga Waisundara obtained her Ph.D. in Food Science\nand Technology from the Department of Chemistry, National\nUniversity of Singapore, in 2010. She was a lecturer at Temasek Polytechnic, Singapore from July 2009 to March 2013.\nShe relocated to her motherland of Sri Lanka and spearheaded the Functional Food Product Development Project at the\nNational Institute of Fundamental Studies from April 2013 to\nOctober 2016. She was a senior lecturer on a temporary basis at the Department of\nFood Technology, Faculty of Technology, Rajarata University of Sri Lanka. She is\ncurrently Deputy Principal of the Australian College of Business and Technology –\nKandy Campus, Sri Lanka. She is also the Global Harmonization Initiative (GHI)",institutionString:"Australian College of Business & Technology",institution:null}]},{type:"book",id:"6820",title:"Keratin",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6820.jpg",slug:"keratin",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Miroslav Blumenberg",hash:"6def75cd4b6b5324a02b6dc0359896d0",volumeInSeries:2,fullTitle:"Keratin",editors:[{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}}]},{type:"book",id:"7978",title:"Vitamin A",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7978.jpg",slug:"vitamin-a",publishedDate:"May 15th 2019",editedByType:"Edited by",bookSignature:"Leila Queiroz Zepka, Veridiana Vera de Rosso and Eduardo Jacob-Lopes",hash:"dad04a658ab9e3d851d23705980a688b",volumeInSeries:3,fullTitle:"Vitamin A",editors:[{id:"261969",title:"Dr.",name:"Leila",middleName:null,surname:"Queiroz Zepka",slug:"leila-queiroz-zepka",fullName:"Leila Queiroz Zepka",profilePictureURL:"https://mts.intechopen.com/storage/users/261969/images/system/261969.png",biography:"Prof. Dr. Leila Queiroz Zepka is currently an associate professor in the Department of Food Technology and Science, Federal University of Santa Maria, Brazil. She has more than fifteen years of teaching and research experience. She has published more than 550 scientific publications/communications, including 15 books, 50 book chapters, 100 original research papers, 380 research communications in national and international conferences, and 12 patents. She is a member of the editorial board of five journals and acts as a reviewer for several national and international journals. 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The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}},{id:"441116",title:"Dr.",name:"Jovanka M.",middleName:null,surname:"Voyich",slug:"jovanka-m.-voyich",fullName:"Jovanka M. 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Animals need to receive a properly balanced diet. One of the new challenges we are now faced with is sustainable animal diets (STAND) that involve the 3 P’s (People, Planet, and Profitability). We must develop animal feed that does not compete with human food, use antibiotics, and explore new growth promoters options, such as plant extracts or compounds that promote feed efficiency (e.g., monensin, oils, enzymes, probiotics). These new feed options must also be environmentally friendly, reducing the Carbon footprint, CH4, N, and P emissions to the environment, with an adequate formulation of nutrients.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11416,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,series:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517"},editorialBoard:[{id:"175762",title:"Dr.",name:"Alfredo J.",middleName:null,surname:"Escribano",slug:"alfredo-j.-escribano",fullName:"Alfredo J. 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