\r\n\tOver the years, the concept of maintenance became more comprehensive, reducing fault occurrence and increasing industrial system availability. Besides, reliability, safety, and criticality requirements were associated with the system or equipment under analysis. Maintenance strategies or schemes can be classified as corrective (run-to-break), preventive (time-based), and predictive (condition-based maintenance). Corrective maintenance is only performed after an occurrence of a fault. Therefore, it involves unexpected breakdowns, high costs, changes in the production chain, and it could lead to catastrophic events. Preventive maintenance and interventions occur based on a scheduled maintenance plan or the equipment's mean time between failures. Although it is more effective than corrective maintenance, unexpected failure may still occur by preventing most failures. Additionally, the process cost is still high, especially the costs associated with labor, inventory, and unnecessary replacement of equipment or components.
\r\n\tOn the other hand, predictive maintenance analyses the equipment condition so that a possible fault can still be identified at an early stage. Predictive maintenance aims to identify a machine anomaly so that it does not result in a fault. Such maintenance involves advanced monitoring, processing, and signal analysis techniques, which are generally performed non-invasively and, in many cases, in real-time. In the case of machines or processes, these techniques can be developed based on vibration, temperature, acoustic emission, or electrical current signal monitoring. It should be noted that monitoring such signals or parameters to verify the operating condition is called condition monitoring. Condition monitoring aims to observe the machine's current operational condition and predict its future condition, keeping it under a systematic analysis during its remaining life. In this sense, a fault condition can be detected and identified from systematic machine condition monitoring. A diagnosis procedure can be established, whereby properly investigating the fault symptoms and prognosis.
\r\n\t
\r\n\tThis book will aim to merge all these ideas in a single volume, aggregate new maintenance experiences, apply new techniques and approaches, and report field experiences to establish new maintenance processes and management paradigms.
\r\n\t
Wounds normally heal in finely balanced, efficient, and ordered sequence of repair events distinguished by four distinct, but overlapping, phases: Hemostasis, Inflammation, Proliferation and Remodeling [1, 2]. These coordinated cellular and molecular events involve numerous processes such as cell proliferation, migration and differentiation. All of these processes demand a continued and efficient supply of oxygen and nutrients, due to the increased cellular biosynthetic activities. Following wounding, the altered microenvironment, such as the reduced oxygen supply, initiates the release of factors by epidermal cells, fibroblasts, macrophages and vascular endothelial cells, all of which stimulate neo-vascularization. The secreted factors include vascular endothelial cell growth factor (VEGF), fibroblast growth factor (FGF) and transforming growth factor (TGF)-β. VEGF is believed to be the most prevalent, efficacious, and long-term signal that is known to stimulate angiogenesis in wounds. TGF-β, especially TGF-β1, is also a key cytokine that regulates the production and secretion of elastin and collagen [3]. Fibroblasts, which attach to fibrin and integrin cables, produce and secrete collagen and elastin that become cross-linked, forming the dermal extracellular matrix (ECM). This allows the restoration of the structure and function to the injured tissue [4, 5].
Chronic wounds or “hard to heal wounds” are characterized by extensive loss of the integument, clear necrosis, or signs of circulation impairment either localized or more extensive, usually in the limbs, or in pressure areas, leading to extensive loss of substance. Chronic wounds seem to be detained in one or more of the phases of wound healing, and some chronic wounds may never heal or may take years to do so. These wounds have lost the fine balance needed for wound repair, leading to chronic non-healing ulcers, associated with morbidity and mortality due to tissue inflammation and infection [6]. Chronic wounds are usually associated with systemic pathologies [7] that cause ischemia, a restriction in blood supply to tissues. Ischemia occurs in diabetic patients due to atherosclerosis as well as microangiopathic disease [8], in chronic venous ulcers due to chronic venous insufficiency [9], in patients with autoimmune disease or under immunosuppressive drug therapy due to vasculitis [10] and in pressure sores due to necrosis of the integument [11]. Chronic wounds cause patients severe emotional and physical stress and create a significant financial burden on patients and the whole healthcare system. Chronic wounds require special attention and wound care.
Copper is an essential mineral involved in many of the physiological processes in all body tissues [12, 13], including the skin and integumentary system [14]. Many of the finely balanced wound healing repair mechanisms are dependent on their interaction with copper (thoroughly reviewed in [6]). This includes, Platelet-derived growth factor (PDGF), involved in the hemostasis phase of wound healing, [15, 16]; VEGF and angiogenin, key growth factors that stimulate angiogenesis, an essential process during the Proliferation Phase [17, 18, 19, 20, 21, 22, 23]; secretion of collagens (types I, II, and V), HSP-47 and elastin fiber components (elastin, fibrillins) by dermal fibroblasts during the Proliferation and Remodeling Phases [16, 24, 25]; activity of Lysyl oxidase (LOX) needed for efficient extracellular matrix (ECM) protein cross-linking between elastin and collagen [26]; stabilization of the skin ECM once formed [27, 28]; modulation of integrins by differentiated keratinocytes during the Remodeling phase [29], and Matrix metalloproteinases (MMPs, mainly MMP-1, MMP-2, MMP-8, MMP-9) and the serine proteases (human neutrophil elastase, HNE) are the major groups of proteases involved in the wound healing process. It is thus not surprising that copper chelation delays wound closure [30]. Copper is also a cofactor of superoxide dismutase, an antioxidant enzyme found in the skin that inhibits cellular oxidative effects, such as membrane damage and lipid peroxidation and protects against free radicals [19]. Copper is also a cofactor of tyrosinase, a melanin biosynthesis essential enzyme, responsible for skin and hair pigmentation.
Infections of the wound may delay wound healing, cause wound deterioration and even cause failure of healing [31]. This may occur through several different mechanisms: consistent and high production of inflammatory mediators, metabolic wastes and toxins; tissue hypoxia; causing hemorrhagic and fragile granulation tissue; reducing fibroblast number and total collagen production; and interfering with reepithelization [32, 33]; reducing the available nutrients and oxygen needed by the host cells and causing neutrophils to be in an activated state producing cytolytic enzymes and free oxygen radicals [34]. In chronic wounds bacteria may be covered by biofilm and be protected from the host defenses and develop antibiotic resistance [31]. Thus, reducing the microbial contamination of wounds increases the capacity of the wound to heal.
Copper is also a needed mineral for the normal function of microorganisms [35]. However, the microorganisms need to carefully control the intracellular copper levels. This is since copper under anaerobic condition is found in the highly reactive cuprous form (Cu1+), and as such it can readily react with the microbial proteins, causing disruption of the protein structures by forming thiolate bonds with iron–sulphur clusters [36]. Thus, above an exposure to a certain concentration of copper, microorganisms cannot cope with the excess copper and are killed [37, 38]. Several mechanisms for the potent biocidal activity of copper have been proposed, which include alteration of proteins and inhibition of their biological assembly and activity; plasma membrane permeabilization; and membrane lipid peroxidation [37]. In contrast to the resistant microbes that have evolved to antibiotics in less than 50 years of use, tolerant microbes to copper are extremely rare even though copper has been a part of the earth for millions of years. This lack of resistance to copper may be explained by the capacity of copper to damage in parallel many key factors in micro-organisms [37].
Copper oxide impregnated wound dressings, hereafter called COD, have been cleared for treatment of acute and chronic wounds, including diabetic ulcers, pressure sores, and venous ulcers, by the USA FDA, EU and other regulatory bodies worldwide. The COD are soft, single use wound dressings composed of an absorbent highly absorbent needle punch layer and one or two external non-binding nonwoven orange polypropylene layers. All layers are impregnated with copper oxide microparticles. The orange external layer(s) is intended to be in contact with the wound bed. The wound dressings are provided with or without an adhesive contour, sterile, in a sterilization pouch (Figure 1). The non-adhesive wound dressings can be cut, trimmed or fold over according to the size and shape of the wound. The dressings can be used up to 7 days or until they are completely soaked with wound exudate.
Copper oxide impregnated wound dressings. The COD are composed of an absorbent layer and one or two external layers. The dressings are provided (a) with or (b) without an adhesive contour. The external layer (c, orange layer) is a non-adherent polypropylene layer placed in contact with the wound bed, which allows the passage of the wound exudates into the internal layer (c, beige layer) that absorbs the wound exudates. COD with two external layers (d) are more appropriate for application in wound cavities and deep wounds. All layers are impregnated with copper oxide microparticles (e, white dots) that endow them with potent biocidal properties.
The COD exert potent wide spectrum antimicrobial efficacy (>4 log reductions), including when the dressings are completely soaked with wound exudate surrogate for 7 days, as demonstrated by us and by independent laboratories using the AATCC Test Method 100. Furthermore, the potent antimicrobial efficacy is maintained even after 7 consecutive microbial inoculations for 7 consecutive days (Figure 2). The antimicrobial efficacy was demonstrated against the following microorganisms:
Continuous antimicrobial efficacy of COD even after 7 consecutive bacterial inoculations. Duplicate COD were inoculated with ~1 x 105
Antimicrobial efficacy comparison between the COD and commercially available silver dressings. The wound dressings were inoculated with ~106 (left panel) and 4x104 (right panel) MRSA CFU. After 1 hour of incubation at 37 °C the bacteria were recovered from the dressings and their viability was determined.
The capacity of copper to enhance faster closure of full-thickness wounds was demonstrated in several wound animal models, [30, 39, 40], including in diabetic mice [41].
The capacity of the COD to directly enhance repair of chronic wounds by supplying
A phenotype similar to diabetes type 2 in mice is achieved via a homozygous point mutation on the leptin receptor gene (LEPR) in the hypothalamus. Genetically engineered diabetic mice (db/db) show significant wound-healing impairment compared to wild-type mice [42]. Full-thickness single skin wounds were inflicted under sterile conditions on the dorsum of each animal followed by continuous dermal application of either COD or identical dressings without copper on the entire wound test site. Histological analysis of skin specimens taken from the diabetic mice treated with the COD 6, 12 and 17 days after wounding demonstrated a normal wound- healing process, including epidermal regeneration and granulation tissue formation, with numerous new blood vessels, chronic inflammatory infiltrate, generation of new hair follicles and sebaceous glands, and fibroplasia [41].
The very clear increase in angiogenesis in the copper treated mice was confirmed by immunohistochemistry staining using the Von Willebrand Factor that stains capillaries. Analysis of mRNA expression levels in the wound sites of 84 genes using real-time PCR gene-array analysis together with immunohistochemistry staining revealed the upregulation of several angiogenic factors, such as Vascular endothelial growth factor (VEGF). Based on the analysis performed a molecular mechanism was suggested in which a redox between cuprous oxide and cupric oxide generates hypoxia that induces the upregulation of Hypoxia-inducible factor-1alpha (Hif-1α) in the dermal layer, apparently in macrophages [41]. The upregulation of Hif-1α then induces a chain of events, depicted in Figure 4, which lead to endothelial cell migration and proliferation, production of new blood capillaries (angiogenesis), immune cell recruitment, fibroblast migration, intense metabolism, increased secretion of extracellular matrix proteins, and increased epithelialization.
Molecular mechanisms of enhanced wound healing by COD. (based on the model published in ref. [
The following cases illustrates the ability of COD to affect infection reduction, angiogenesis and granulation tissue formation, as well as epithelial tissue formation, in hard to heal wounds. In addition, we describe cases of reduction of post-operative swelling and better post-surgery scar formation. All photos are published in the book with the patients’ consent.
Fifty-seven years old male, with history of non-insulin-dependent diabetes mellitus (NIDDM), suffering from ulcers in both feet, mainly on the right side (Figure 5a). The etiology was mainly due to vasculitis type reaction (acute leukocytoclastic vasculitis), with minor large arteries involvement (for which angiographic intervention with percutaneous opening of the superficial femoral artery was carried out). The patient was treated with high dose steroids, immunosuppressive medication (Azathioprine, Imuran) and broad-spectrum antibiotic treatment. The patient right foot worsened with development of necrosis mainly in the medial toes, with the infection spreading to involve the tendons and the plantar fascia. Deep ulcers were present over the medial aspect of the heel and the lateral aspects of the foot (Figures 5a and b).
Clearance of infection, induction of granulation and epithelialization of necrotic wounds. a. Ulcers colonized with
The patient underwent surgery to debride the wound including 1st and 2nd ray amputation. Cultures taken at surgery yielded
Trans-tibial amputation deemed to be the next step. WBC count was 18,000, which was an improvement from previous higher levels, and the CRP was 3.0 (normal <0.5). However, since the patient’s overall condition was stable, it was decided to continue only with local wound care with COD. The dressings were placed deep in the plantar-fascial part of the amputation wound, on the edges of it and on the ulcers (Figure 5d and e). The dressings were replaced twice a week. Prontosan® irrigation was recommended during dressing change. No supplemental antibiotic was given.
The foot condition improved gradually. The superficial semi-necrotic ulcer at the heel and lateral aspect of the foot showed gradual absorption of the necrotic tissue, granulation and epithelization (Figures 5f–i). The main amputation wound, with large area and volume and inner cavity of 6–7 cm, gradually filled with granulation tissue (Figure 5g). The granulation tissue seemed to affect the necrotic tissue with autolysis (self-debridement, Figure 5i). New epithelium gradually covered the healing wounds (Figure 5g and h). Microbial culture, taken from the necrotic tissue three months after cessation of antibiotic administration, did not yield pseudomonas, although normal non-pathogenic colonizing bacteria were identified.
After 5 months of COD treatment, the medial and lateral wounds were closed (Figure 5j and k). The main wound was partially closed and the rest of the wound was with pink to red granulation tissue (Figure 5l).
The powerful ability of COD to promote epithelization is illustrated in the following case of a 71 years old man with NIDDM and diabetic neuropathy. The patient had osteomyelitis of the calcaneus, which necessitated extensive debridement of the heel and the infected calcaneus bone. The wound did not heal and the calcaneus broke through area of weakness due to the missing bone, thus creating a rocker deformity. Repeated surgery with debridement of the soft tissue, correction of the foot alignment and fixation with Steinman pins was carried out (Figure 6a and b, 1-week post-surgery). At surgery and thereafter the wound was dressed with COD, which was changed weekly. While relatively rapid granulation seemed to fill the depth and walls of the large cavity, normal looking skin began crawling from the side surface into the depth of the wound. Figure 6c, taken 3 weeks post-surgery demonstrated epithelization beginning at the superficial wall of the cavity (arrows). This phenomenon is further demonstrated in the photos taken at 7, 8 weeks (Figure 6d and e), 3.5- and 4.5-months post-surgery (Figure 6f and g). The corresponding x-rays at 4.5 months are shown in Figure 6h and i.
Epithelization of a rocker deformity related plantar deep wound. The patient had resection of infected calcaneal bone with correction and stabilization of ensuing rocker deformity with Steinman pins. COD was applied at surgery. a. one week following surgery the deep calcaneal wound is evident’ without signs of infection. b. X-ray showing the inserted Steinman pins. The missing plantar calcaneal bone and the deep soft tissue void underneath can be seen. c. Three weeks post-surgery, following the use of the COD, skin began crawling from the side surface into the depth of the wound. Further coverage of the wound granulation tissue with epidermal tissue is seen after 7 weeks (d), 8 weeks (e) and 3.5 months (f) of COD treatment, resulting in 95% complete closure of the wound at 4.5 months (g). h and i. lateral foot and Axial calcaneal X-rays of the foot 4.5 months after surgery. Although large soft tissue void is prominent, it is filled with practically normal looking skin that crawled in. During all this period the foot was treated solely with COD.
62-year-old man suffered from degenerative changes of the 1st metatarsophalangeal joint (Hallux Rigidus) and metatarsalgia. The forefoot deformities included hallux valgus Interphalangeus, subluxed lesser MTPJ’s, hammer 2nd toe and Bunionette deformity (Figure 7a). Surgery included cheilectomy of the first metatarsal head, Akin-Moberg osteotomy of the base of the proximal phalanx of the big toe, Weil osteotomies of the 2nd and 3rd metatarsals, Chevron osteotomy of the 5th metatarsal and PIPJ arthrodesis to correct the 2nd hammer toe (Figure 7b). The later was fixed with Kirschner wires (KW) and so was the 5th metatarsal. The 2nd and 3rd metatarsals were fixed with a screw and the bog toe proximal phalanx osteotomy was secured with absorbable suture. The foot was dressed with COD immediately after surgery with first dressing change after 3 weeks. At that time, surgical wounds were without any sign of infection or inflammation (Figure 7c). Despite having 4 metatarsal osteotomies and one toe arthrodesis in any of these sites, there was no swelling to the degree that normal skin wrinkles could be observed (Figures 7c-e). This is in contrast to the usual significant swelling that is observed for several months after foot osteotomies.
Reduction of swelling after forefoot surgeries and osteotomies. a. Forefoot deformities in a 62-year-old man. Hallux valgus, hammer second toe, subluxed 2nd and 3rd metatarsophalangeal joints and Bunionette deformity are observed. b. X-ray image taken 2 months after surgery demonstrates osteotomy of the base of the proximal phalanx of the big toe, Weil osteotomies of the 2nd and 3rd metatarsals, Chevron osteotomy of the 5th metatarsal and PIPJ arthrodesis of the 2nd hammer toe (arrows). c. Clinical photo of the foot at first dressing change three weeks after surgery (COD dressings were applied during surgery). Surgical wounds are without any sign of inflammation and lack of swelling and skin wrinkles can be seen. The tip of the KW’s fixing the 2nd toe and the 5th metatarsal are seen and marked with red arrows (the second toe KW is wrapped with plaster to prevent accidental pullout) d. Oblique view of the same foot at the same visit after stitches removal demonstrates clearly the reduction of swelling. e. Clinical photos taken at 5 weeks post-surgery. Skin wrinkles and no swelling is again evident.
Reduction of scar formation may be difficult to prove or demonstrate since the final surgical incision healing is a function of surgical technique as well as the patient own tendency to produce hypertrophic scar or even keloid. We have therefore elected to present the reduced scar formation in two cases of bunion surgery. Figures 8 and 9 with unexpected rapid healing in one patients and very good healing despite basic tendency to hypertrophic scar in another patient.
The first one is a 20-year-old healthy woman who had bunion surgery which included Chevron type osteotomy of the 1st metatarsal and fixation with KW (Figure 8a). The surgical incision and the KW’s are seen at two weeks post-surgery (clinical photos and x-rays, (Figure 8a and b). The KW’s were removed at 4 weeks. By that time nice healing of the surgical incision seems to have taken place (Figure 8c and d). At 7-weeks post-surgery, the osteotomy has healed and clinical appearance is satisfactory (Figure 8e and f). The surgical scar is very delicate (Figure 8g). A comparison between the original incision and its appearance after 7-weeks shows that ~80% of the incision scar is not observed even in high resolution and magnification photography (Figures 8h–j). This implies that either direct epithelization has occurred or remodeling of the scar took place. The superb cosmetic results at 7-weeks seems to be beyond a “successful case” and we attribute it to the beneficial effect of copper oxide on wound healing.
Reduction of scar formation – Case Report 1. a. Bunion surgery that included Chevron type osteotomy of the 1st metatarsal and fixation with two KW’s. b. X-Ray of the foot following surgery. c. Surgical incision appearance at two weeks post-surgery. d. Surgical incision appearance at four weeks post-surgery. e. X-Ray of the foot at 7 weeks post-surgery. f. Clinical appearance of the foot at seven weeks post-surgery. g. Surgical incision appearance at seven weeks post-surgery. h. Enlargement of the surgical site at seven weeks post-surgery. Comparison between the scar appearance after 7 weeks (i) and 2 weeks (j) post-surgery shows that most of the scar has disappeared and was not detectable even at high magnification (h).
The second case is of a 49-years-old healthy woman who underwent bilateral hallux valgus surgery, which included distal first metatarsal osteotomy, fixed with KW’s and Weil ostetomies of the 2nd (+ 3rd) metatarsals (Figure 9a). The feet were dressed with COD. Two weeks post-surgery swelling was minimal and even skin wrinkles could be seen (Figure 9b). One year post surgery the foot position is very good (Figure 9c and d). The dorsal incision scarring is minimal (Figure 9d), the medial scar on both feet is hardly visible (Figure 9e and f). The patient said she has a tendency to create hypertrophic scars, for example a scar following open reduction and internal fixation of elbow fracture 25 year ago (Figure 9g).
Reduction of scar formation – Case Report 2. a. X-ray of both feet showing 1st and 2nd metatarsal osteotomy due to hallux valgus and metatarsalgia. b. Surgical incision appearance at 2 weeks post-surgery. c. X-ray and d. photographs of both feet one-year post-surgery showing successful foot positioning. e. Surgical incision appearance of right foot one-year post-surgery. f. Surgical incision appearance of right foot one-year post-surgery. g. Hypertrophic scar 25 years post-surgery due to elbow fracture.
Copper is a natural mineral, which is an essential element of nutrition due to its role in many of the physiological processes in all body tissues [12, 13]. We have reviewed the beneficial effect of copper in wound healing based on abundant basic science research as well as our cumulative experience with the use of COD. Copper has been known for its antimicrobial properties including against all common wound pathogens and resistant bacteria. Similar properties are attributed to silver. Indeed, silver-containing wound dressings are widely used in wound treatment to reduce the risk of wound and wound-dressing contamination [43]. It is desirable, of course, to have a wound dressing that also promotes wound healing. Previous research has shown the beneficial effect of copper on skin and integumentary system [14] as well as on wound healing in diabetic mice [41]. The mechanism by which copper exerts its positive roll has been shown to be through up-regulating the level of Hif-1α, which is a key protein in tissue generation, especially in conditions of ischemia, like in hard to heal wounds. In this regard copper differs from silver, which exerts the opposite effect on wound healing, probably by downregulating Hif-1α [44]. Therefore, the usefulness of silver-based dressing in promoting wound healing is questionable, among others due to cellular toxicity [45, 46].
However, since copper has potent biocidal properties [37], but in contrast to silver, is an indispensable trace element extremely well metabolized by the human body [12], we hypothesized that it could substitute silver in wound dressings. This would be justified for the goal of reducing bio-contamination. But, even more importantly, are the key roles copper plays in skin generation and angiogenesis. We further hypothesized that the inability of wounds to heal in individuals with compromised peripheral blood supply (e.g., with vascular diseases or diabetics), is partially due to low levels of copper in the wound site [47]. We suggested that by using a copper oxide-containing wound dressing we would slowly release
Based on the above, we prepared wound dressings containing copper oxide (COD, Figure 1). The COD, which possess potent biocidal properties (Figures 2 and 3), were found to be safe in animal studies, showing no skin irritation and no local damage to open wounds or systemic pathological alterations in a porcine full-thickness wound model (unpublished data). Indeed, the risk of adverse reactions due to dermal contact with copper is extremely low [48, 49]. Furthermore, wounds inflicted in diabetic (db/db) mice under sterile conditions and kept covered throughout the study with sterile wound dressings demonstrated a statistically significant enhancement of wound closure when the dressings contained copper oxide [41]. Enhanced wound healing was nearly that anticipated from wild-type mice, where similar full-thickness dorsal skin wounds reach complete closure 7–10 days earlier than in db/db mice [50]. In contrast, commercially-used silver-containing wound dressings did not accelerate wound healing in this model [41]. Following the clearance of the COD to be used clinically, we have found, as described in some representative cases in the article, the significantly better results obtained with the COD than SOC dressings, including silver-based wound dressings.
The demonstrated cases (Figures 5–9) show the several effects of COD on different stages and aspects of wounds healing. The effects were reduction of colonized bacteria and superficial infection, as well as increased granulation and epithelization, as demonstrated in Figure 5. Figure 6 shows rapid epithelization of normal looking plantar skin into the cavity underneath the calcaneus. In addition to wound closure, we see in Figures 7–9 improved healing process on primary closed clean surgical incisions, which expresses itself in improved scar formation and reduces swelling.
Due to the effect of COD on the various stages of wound healing, we now often use the COD continuously during the various phases of wound treatment. For example, we apply them on debrided wounds after partial foot amputation due to diabetic foot infection (instead of povidone-iodine or chlorine based dressings), and as healing progresses, we use them to assist in filling the wound with granulation tissue (for example, instead of using Negative Pressure Wound Therapy (NPWT)). Once the wound has filled with new tissue, we use the COD to help epithelization until full wound closure is achieved.
Another advantage of COD is the few dressing changes it needs, usually once or twice weekly. This makes it convenient to the patient and savvy for the health care system. In the hospital, COD may replace chlorine-based dressings (e.g. Eusol or Daikin solutions), which needs changes 2–3 times daily, and thus reduce the workload on the nursing staff as well as diminishing the risk of spreading resistant bacteria and cross contamination in the Ward.
Additional studies are needed to further elucidate the exact mechanisms by which copper stimulates wound healing. It is clear, however, that copper directly or indirectly stimulates many factors, some of which are impaired in diabetics and are important for keratinocytes and fibroblasts proliferation, epithelization, collagen synthesis, extracellular matrix remodeling and angiogenesis. Indeed, by utilizing COD dressings on chronic wounds, which had failed to heal or healed slowly with other well-recognized wound care protocols, we found improved wound healing kinetics and wound closure in most patients.
As demonstrated by the murine diabetic model [41], the positive effect of the copper oxide-containing dressings is not related solely to its potent biocidal properties, but to the direct stimulation of wound repair. No adverse events were recorded with the use of the copper dressings and all patients showed positive response to its application. Thus, copper dressings appear to hold significant promise in the clinician’s ongoing struggle to heal both acute and chronic wounds. Additional randomized, controlled studies should be conducted to further validate the efficacy of topically applied copper oxide-impregnated dressings.
Vitamin K is a family of natural products, comprises vitamin K1 (phylloquinone), vitamin K2 (methylnaphthoquinones/menaquinones-MK) and vitamin K3 (menadione). These are structurally methylated napthoquinones possess isoprene side chain (vitamin K1 & vitamin K2) and they vary in the extent of isoprene side chain, in terms of number of isoprene units and its level of saturation [1, 2, 3, 4, 5]. However, these structural changes are apparently simple, but needs exist in its specific stereochemistry to exhibit their biological functions. These are the fat-soluble compounds and pertains to a class of lipoquinones [6]. Vitamin K2 are varied on the basis of number of isoprene units present in the side chain and they denoted as MK-n (n – number of isoprene units; Figure 1). The vitamin K2 if contains saturated isoprene units referred as MK-n(m-H2), wherein m is a roman numeral represents isoprene unit number in the side chain which underwent reduction. Among the two natural forms of vitamin K, vitamin K1 presents in green leafy vegetables, for example, kale, collard greens, turnip greens, iceberg lettuce, broccoli, spinach, and brussels sprouts. The Vitamin K2 presents naturally in eggs, meet, fermented foods (natto, cheese, yogurt and sauerkraut) also present in bacteria, for example, MK-9 is found in mycobacterium with nine isoprene units and also its reduced derivative at second isoprene unit MK-9(II-H2) could be active as electron transport agent in [3, 7]. In humans, these menaquinones display several biological properties, including facilitating blood coagulation [8, 9]. In bacteria, these molecules assisting the synthesis of ATP through transport of electrons between the membrane-bound protein complexes and thus acting as electron acceptors and donors in the respiratory electron transport [10, 11]. Vitamin K and its analogues could not synthesize by mankind/animals. So, its required to supply an adequate amount through the dietary sources.
Structures of vitamin K.
Naturally, bacteria producing different variants of vitamin K. Among the aerobic bacteria, most of its Gram-negative bacteria contain ubiquinone as the sole quinone, whereas the menaquinone is the only quinone presents in aerobic Gram-positive bacteria. But, in the case of anaerobic bacteria, irrespective of whether it is Gram-positive or Gram-negative, it produces benzoquinones (ubiquinone), naphthoquinones (menaquinones; MK-n), demethylmenaquinones (DMK-n) [12]. The Gram-negative bacteria, such as,
Structures of vitamin K2 (MK-n) & DMK-n.
These menaquinones have prenyl side chains with all-
Cox and Gibson discovered in 1964, shikimate was present in menaquinone of
a) Sequential formations in the biosynthesis of menaquinones; b) the preliminary precursors in MK-n biosynthesis.
Shikimate pathway for the synthesis of menaquinones is presented in Figure 4. Shikimate was proposed to converted initially into chorismite before its incorporation into menaquinone [15]. In
Biosynthetic pathway of Menaquinone molecules.
In 1939, Fieser [33], Binkley [34], and Almquist [35] were reported initially the synthesis of vitamin K1 independently. The condensation reaction of either menadione/2-methyl-1,4-naphthohydroquinone with natural phytol in the presence of oxalic acid or zinc dust in acetic acid produce vitamin K1 (Figure 5).
The first synthesis of vitamin K1.
The initial synthetic approaches were generally proceeding through the usage of Friedel-Craft alkylation’s for introducing the side chains through its coupling to menadions, which led to the generation of mixture of isomers at the Δ2 position and produced
Grignard reagent mediated synthesis of MK-1.
In addition, Organocuprates were also being used to the synthesis of vitamins K’s. Menaquinone and phylloquinone are synthesized by Chenard group, from the reaction of Gilman based bisketals of quinone substrate with allyl halides and it afforded high yields and good stereoselectivity at the Δ2 position of the vitamin K (Figure 7). The quinone bromide underwent metalation to produce the corresponding cuprate, and its reactivity was varied with different electrophilic substrates (RX). Among the tested electrophilic substrates, if the electrophilic group is small enough (allyl bromide) then the two alkyl groups of cuprate reagent were being used being transferred in the reaction. If the reaction with bulkier electrophilic halide (for example benzyl chloride/bromide, cyclohexanecarbonyl acid chloride), cuprate can transform only one alkyl group [40]. Syper group synthesized protected forms of MK-1 and MK-2 in appreciable yields through the coupling reaction of prenyl bromide and geranyl bromide with 2-bromo-3-methyl-1,4-dimethoxynaphthalene [41]. Generally, these organometallics (Grignard reagents, organocuprates and organolithiums) mediated synthesis of vitamin K required the usage of protected quinones to avoid the side reactions. Unprotected quinones could also give the vitamin k synthesis through their direct coupling with organostannates [42] and organisilanes [43].
Menaquinone analogs synthesized by organocuprates.
Tso and group developed an efficient and conceptually distinguished one-pot protocol to the synthesis of vitamin k, wherein the 3-substituted isobenzofuranone was treated with a base, the generated quinone methide which underwent an anionic [4 + 2] cycloaddition reaction with the alkenyl phenyl-sulfone (dienophile) and that was being synthesized from the corresponding allyl phenylsulfone and various prenyl bromide (RBr). Finally, the vitamin K was produced by the elimination of sulfone from the intermediate. This method was very compatible to the synthesis of phylloquinone and different menaquinone variants MK-1, MK-2 and MK-9 about 60–65% yields (Figure 8) [44].
Methide annulation to a one-pot synthesis of vitamin K.
In 2015, Mal et al., extended this protocol to the synthesis of menadione derivatives (MK-n molecules) by a base mediated reaction of 3-substituted phthalide with methyl methacrylate [45]. The yield of the reaction was verified in this reaction with various leaving groups, such as - methoxy, phenyl sulfonyl, isonitrile, thiophenyl, and nitrile. The nitrile leaving group in the substrate was found to be the best suitable one for the reaction. The 3-nitrilephthalide is to be a menadione auxiliary to the reaction of MK-n variants (Figure 9). The reaction was proceeds through a base mediated anionic driven annulation of 3-nucleofugal phthalides with α-alkyl/aryl acrylates followed by demethoxycarbonylation. If the polyprenyl acrylates are to be the substrates, then various analogs of menadione were being produced (MK-n).
Anionic annulation of 3-nucleofugal phthalides to the synthesis of vitamin K.
Side chain functionalization methods were also being developed to the synthesis of vitamin K analogs. These derivatized vitamin K are received a great deal of interest to reveal the structure activity relationship studies (SAR). These analogs were also proved to be as inhibitors of vitamin K dependent carboxylase and vitamin K epoxide reductase [46]. The side chain stereochemistry is very essential to exhibit the biological activity, as the
Snyder and group during their sustained efforts to retain the stereochemistry of
Enolate alkylation of menadiols to MK-n synthesis.
However, these enolyte alkylations were successful but not very practical. To accomplish the practical methods, Snyder group developed transmetallation method for the synthesis of vitamin K [ 38]. Lithium, magnesium and copper had used to convert 2-bromomenadiol to its corresponding metallo derivative. As an electrophilic partner authors chosen initially aldehydes, but aldehydes are unsuccessful as the resultant alcohol functionality removal afforded either vinyl alkenes or α-isoprene double bond isomerization. Later, the prenyl halides are found to be the appropriate substrates of electrophiles for these transformations. Primarily, reactions were performed to evaluate the stereoretention of the α-isoprene double bond in each of the 2-metallo derivatives. As per their expectation, all these metallo derivatives could not affect the configuration of the isoprene component of the vitamins. It was found that, organo magnesium reagents are more efficient than organocuprates and that in turn efficient than organo lithium reagents. Among the prenyl halides, prenyl bromides are generated excellent yields of menaquinone analogs (Figure 11). The coupling of 2-magnesio or 2-cupro-3-methyl-l,4-dimethoxynaphthalene with geranyl bromide produced in >90% yield. In this method, MK-9 was obtained in 73% yield by treating solanesyl bromide with menadiol.
Efficient transmetallation reaction to menaquinones.
In the various synthetic strategies to the vitamin K in the literature, Friedel-Crafts alkylation protocol of menadiols is the most popular across the literature. Hirschmann group developed a method wherein the applicability of various Lewis and Bronsted-Lowry acids were being used for the synthesis of vitamin K1 [48]. Monoacetate of menadiol substrate was treated with phytol in presence of various acids. Among, the acids, BF3.Et2O afforded appreciable yields (67%) rather others being tested KHSO4, oxalic acid and Duolite C-60. After Friedel-Crafts alkylation, finally, the acetate group was removed by the treatment with Ag2O (Figure 12).
Application of Friedel-crafts alkylation to the synthesis of vitamin K1.
Later, in 1990 Schmid and group enriched the yield of the reaction by treating the reaction of menadiol monoacetate with phytyl chloride in presence of a base potassium carbonate, wherein O-phytylated derivative had obtained. This was further undergoing Claisen rearrangement under acidic treatment with catalytic amount of BF3.Et2O to C-phytylated product in 76–80% yield and the ratio of the configurations of E and Z isomers was found to be 97:3. The deacetylation was carried out in basic medium (Figure 13). Vitamin K1 obtained in this procedure is to be 96.5% and with E-configuration, Z -configuration compound was with very low yield (3%) [49].
BF3.Et2O catalyzed Claisen rearrangement to vitamin K1.
Apart from the electrophilic side chain attachment to the menadiones, radicals also found to do the same work to make the synthesis of vitamin K. Jacobson and coworkers in 1972, developed a method to the alkylation of quinones by the use of radicals and that were produced by metal/persulphate catalyzed decorboxylation of the corresponding carboxylic acid. 4-Methyl-3-pentenoic acid produced the 3,3-dimethylallyl radical while in presence of AgNO3, (NH4)2S2O8. Initially Ag+ is reacted with S2O8−2 to form Ag+2 and which abstract an electron from carboxylic acid to produce allyl radical by the ejection of CO2. This allyl radical resonates and unexpectedly less stable isoform γ,γ-dimethylallylquinone was given the product instead to α,α-dimethylallylquinone (Figure 14). By this procedure MK-1 obtained in 70% yield as a γ,γ-dimethylallylquinone as to hold a stable alkene [50].
Ag+/S2O8−2 mediated radical directed synthesis to MK-1.
Later, Yamago et al., found the applicability of organotellurium compounds to the radical coupling reactions with a variety of quinone substrates [51]. This method could offer the general protocol to the synthesis of polyprenyl menadiones with complete retention of stereochemistry. Organotellurides were prepared by SmI2 mediated coupling reaction of its corresponding bromides with ditollyl ditelluride (Tol)2Te2. This telluride later produced prenyl radical under photo/thermal energy source and that interact with menadione to produce respective MK-n related to the length of the prenyl side chain. While geranyl tolyl telluride (73:23 mixture of the trans and cis isomers) react with 2-methyl-1,4-naphthoquinone to produce MK-2 in moderate yield. The stereochemistry of the product (7:3) informed that the reaction gave the retention of stereo chemistry of organic telluride in to the product (Figure 15).
Organo telluride mediated radical coupling synthesis to vitamin K.
Diels-Alder reactions were useful to construct napthoquinine structural unit, as Rüttimann and group being used this concept to develop protocol for the synthesis of vitamin K1. The reaction of dihydroisobenzofurane was performed with activated alkyne dienophile (96:4 E/Z) at 80°C overnight to form the trimethyl sillyl ether of Diels-Alder adduct and its reaction further carried out with methanol and then methyl group at C2 position is achieved through the reduction of ester with bis(2-methoxyethoxy)aluminum hydride followed by air oxidation produces vitamin K in moderate yield (Figure 16a, 50%) [52]. During the reaction the isoprene double bond configuration was not altered. Later, he developed the reaction by taking an auxiliary to support the reaction. Rüttimann along with Büchi had taken cyclopentadiene as a substrate auxiliary and its reaction was carried out with menadione to generate Diels-Alder adduct (Figure 16b). Prenylation/ alkylation at C3 position of Diels-Alder adduct was performed under strong base (KO
a) Diels-Alder reaction mediated synthesis to vitamin K1; b) Cyclopentadiene auxiliary driven synthesis to vitamin K1.
Inspired by menadione auxiliary applicability in the synthesis of vitamin K1, Battula, S., and group, thought to introduce the polyprenyl side chain on to the menadione to synthesis MK-n variants. This menadione surrogate was utilized to the synthesis of MK-9 in one pot protocol. The reaction of 1-Chloro-
One-pot synthesis to MK-9.
In the view of the requirement of MK-7 owing to its high lipophilicity and good bioavailability in small intestines and about 3 days half-life than compare to other menaquinones and ubiquinone, Aneta et al. in 2016 developed a practical synthetic strategy for vitamin K2 (MK-7) [54]. The synthesis of MK-7 was achieved in all the
Convergent synthesis of MK-7.
Among the two coupling components, hexaprenyl fragment was obtained from commercially available
As this method was convenient in the availability of starting substrates and perfect stereochemistry of the product, Battula, S., and group developed the similar convergent synthetic strategy to MK-6 as well (vitamin K2 variant) in all the trans forms of side chain through “1+5 convergent synthetic approach” of pentaprenyl chloride with monoprenyl menadione derivative [53]. During this survey, authors found that bromo based polyprenyl substrate was produced S
Convergent synthesis of MK-6.
Lipshutz and group developed a method to introduce a one carbon handle at the C-3 position of menadione molecules and it offered a good synthetic protocol to a wide range of MK-derivatives through a highly probable
Synthesis of MK-3 & vitamin K1 through using phytyl and prenyl organoalane compounds.
In the early of 1900s, Saa and group successfully established a protocol by which aldehydes were being used as electrophiles to launch the prenyl side chains in to menadione molecules in the production of MK-2 and MK-4 [57]. During this protocol, bismethyl ether of 2-bromomenadiol undergoes reaction with
Synthesis of MK-2 & MK-4 by using birch hydrolysis conditions.
Biologically these molecules are very important and have been reported for several biomedical purposes. Owing to their severe liphophilicity/ hydrophobicity due to containing multiple isoprene units in the side chain, they are with less solubility and thus causes to difficulties to assess in-vitro studies as these are performed in aqueous solutions. These napthoquinones have been displayed promising biological activities against tubercular [60, 61], cancer [62, 63, 64], cardiovascular [65, 66] and diabetes [67, 68].
In mycobacteria, MenJ (
MenJ reductase reduction transformation of MK-9.
As a known fact that vitamin K is an essential nutrient that displays potential anticancer properties on a variety of tumor cells [71, 72]. Quinones are the important natural and synthetic molecules as they have considerable biological potential. These compounds are display antitumor activity through several mechanism of action. Generally, these molecules have problems with respect to solubility, stability and toxicity. Owing to this reason, these molecules are using as drugs through alternative procedures like controlled-release system of these quinones, and it could be a strategy for improving the pharmacological profile of this class of compounds. Vitamin K mediated mechanisms proceeds to prevent the cell proliferation and growth although unclear, but mostly through oxidative effect and direct arylation of thiols may deplete glutathione and cell cycle arrest. The quinone structure in vitamin k is responsible for the modulation of redox-balance and induction of oxidative stress in cancer cells. The anticancer properties of vitamin K1 and vitamin K2 mostly mediated by non-oxidative mechanisms, probably through transcription factors, but vitamin K3 does by reducing oxidative stress and arylation at higher concentrations. It’s been evidenced that, bulk doses of vitamin K2 (2.5 grams given per day) could be safe and not caused to enhancing toxicity levels [73]. Vitamin K2 also prevents hepatocarcinogenesis in patients with hepatic cirrhosis [74]. Quinones generally undergo one-electron and two-electron reductions, leads to produce semiquinone radicals, as well as hydroquinone’s respectively. These factors reduce oxidative stress through the consumption of superoxide radicals and cause to cancer cell homeostasis.
Vitamin K known to reduce complications and improve clinical issues of pre-diabetes and diabetes. Type-2 diabetes mellitus (T2DM) demonstrates when pancreatic
Vitamin K2 also useful to the bone and cardiovascular related problems. As we know, lower intake of calcium can decrease the bone mineral density, and thus can increase the risk of bone fractures. Although supplemental calcium helps to enhance bone mineral density and strength (prevent osteoporosis), recent evidences informed that higher consumption of calcium supplements may lead to the risk for heart diseases and also can cause to accelerated deposit of calcium in blood-vessel walls and soft tissues. While the vitamin K2 is related with the inhibition of arterial calcification and arterial stiffening, which means that increased vitamin K2 intake could be lower the risk of vascular damage as it activates matrix GLA protein (MGP), and that inhibits the deposits of calcium on the walls, and thus reducing the health risks that are associated with calcium levels [77, 78]. The essential component to the synthesis of Gla-protein family is vitamin K and that is very important to the hemostasis as its deficiency causes to acute and dangerous condition due to excessive bleeding.
This chapter summarized various synthetic approaches of different variants of vitamin K and their biological application. Although several methods are available, but menadione and its substrate auxiliaries (for example, Diels-Alder adducts, organometallic compounds and others) are the choices to the synthesis of vitamin K’s. Their synthesis proceeds through several reactions like, Friedel-Craft alkylation’s, condensation reactions, Claisen rearrangement, Diels-Alder reactions and others and by the involvement of nucleophilic and free radical reactions. It also included the information regarding their natural sources. As the huge importance of vitamin K to the mankind, it is being used as food supplementation because it’s not produced by mankind. The major dietary source of vitamin K is phylloquinone, which is synthesized by plants and algae. Vitamin K2 (various forms of menaquinone; MK-4 to MK14), produces from bacteria in the human gut and plays a lesser role in the provision of vitamin K, since it is taken up by the body to only a limited extent. In infants the development of vitamin K is very low, due to its deficiency they are offering vitamin K immediately after the birth and the initial days life. Also incorporated the utility of vitamin K, as its great role in the blood coagulation, in the maintenance of bone health and healthy nervous system, prevention of cardio vascular disease and diabetes.
Menadione, a synthetic product and being used as a pharmaceutical interested molecule. Menaquinone-4 mainly resides in the brain tissues and generates from a tissue-specific transformation of vitamin K. The metabolism of vitamin K is an essential factor to study further vitamin K biology. Further knowledge in this context of vitamin K proved to be beneficial in many areas of science for example like medicine [79].
Uka Tarsadia University, Bardoli, Gujarat, India.
The authors declare no conflict of interest.
.
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They are a natural extension of network science since almost all real-world networks evolve over time, either by adding or by removing nodes or links over time: elementary actor-level network measures like network centrality change as a function of time, popularity and influence of individuals grow or fade depending on processes, and events occur in networks during time intervals. Other problems such as network-level statistics computation, link prediction, community detection, and visualization gain additional research importance when applied to dynamic online social networks (OSNs). Due to their temporal dimension, rapid growth of users, velocity of changes in networks, and amount of data that these OSNs generate, effective and efficient methods and techniques for small static networks are now required to scale and deal with the temporal dimension in case of streaming settings. This chapter reviews the state of the art in selected aspects of evolving social networks presenting open research challenges related to OSNs. The challenges suggest that significant further research is required in evolving social networks, i.e., existent methods, techniques, and algorithms must be rethought and designed toward incremental and dynamic versions that allow the efficient analysis of evolving networks.",book:{id:"6822",slug:"social-media-and-journalism-trends-connections-implications",title:"Social Media and Journalism",fullTitle:"Social Media and Journalism - Trends, Connections, Implications"},signatures:"Mário Cordeiro, Rui P. 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The lines between professional journalists and amateurs have been blurred; consequently, the structure of news media has substantially changed affecting the core traits of the profession and its ethics. This phenomenon has challenged the already disputed concepts of journalism as profession and journalists as professionals. While this challenge is tremendous, research on its implications to journalism identity and ethics is scant. The existing literature focuses on new or digital media usage, newsgathering, production, dissemination, and consumption, with little emphasis on journalism ethics or the profession itself. 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Our research line is based, on the one hand, on the esthetic processes of contemporary art by Cervantes of persuasive graphic and visual communication. On the other hand, it is based on Mindfulness as a sophisticated method that allows us to find a way to calm and rescue the potential and maximize the value and effects of communicative and artistic compositions. Innovative analytical method of the communicative process of visual artistic communication establishes, and raises, in our chapter, a connection with sophisticated concepts of Mindfulness applied to visual and graphic composition, efficient, and its application to contemporary art in the theme of Cervantes.",book:{id:"5736",slug:"the-evolution-of-media-communication",title:"The Evolution of Media Communication",fullTitle:"The Evolution of Media Communication"},signatures:"José Jesús Vargas Delgado",authors:[{id:"204406",title:"Dr.",name:"José Jesús",middleName:null,surname:"Vargas Delgado",slug:"jose-jesus-vargas-delgado",fullName:"José Jesús Vargas Delgado"}]}],mostDownloadedChaptersLast30Days:[{id:"64442",title:"Scholarly Communication and the Academic Library: Perceptions and Recent Developments",slug:"scholarly-communication-and-the-academic-library-perceptions-and-recent-developments",totalDownloads:1465,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"This chapter focuses on the role that academic libraries play in the process of scholarly communication and presents a mixed-methods study to investigate (a) how faculty members perceive the involvement of academic librarians in scholarly communication and (b) how academic librarians perceive their own abilities to be involved in this process. The research population included faculty members from the faculties of humanities and social sciences in three Israeli academic institutions and academic librarians working in the libraries affiliated with these faculties. Interviews regarding the role of academic librarians in scholarly communication indicated wide gaps between faculty members and academic librarians and between individual members of each group, while questionnaires showed that a similar percentage of librarians and faculty members believe that academic librarians are potentially capable of being involved in this process. However, when asked whether the academic librarians should be involved in scholarly communication, only 36% of the librarians answered positively, as compared with 55% of the faculty members. These gaps highlight the need for change in academic libraries, as librarians should possess adequate technological skills, broad general knowledge, and an understanding of how to reorganize the library work so as to accommodate collaborations with faculty members.",book:{id:"8119",slug:"a-complex-systems-perspective-of-communication-from-cells-to-societies",title:"A Complex Systems Perspective of Communication from Cells to Societies",fullTitle:"A Complex Systems Perspective of Communication from Cells to Societies"},signatures:"Liat Klain-Gabbay and Snunith Shoham",authors:null},{id:"61780",title:"Journalism and Social Media Frame Social Movements: The Transition to Media Matrix",slug:"journalism-and-social-media-frame-social-movements-the-transition-to-media-matrix",totalDownloads:1863,totalCrossrefCites:0,totalDimensionsCites:2,abstract:"Audiences all over the globe are experiencing an unprecedented communication challenge. The intensity of the transnational media platforms and the rapid media distribution information implies a huge adaptation and interaction to diverse media technologies. These have created a transition in the culture of citizens’ acts, creating the era of “Media Matrix.” The printed press and the television still today cover the social movements’ demonstrations playing an important role in which these are revealed to the public. The importance of the news framing and Internet, as well as social media, depends upon one other crucial component for the social movements’ visibility. The present study aims to offer a theoretical reflection on this issue describing a three-stage analyses, which the media coverage underwent. The study describes the different stages in the coverage and “news-making” of social movements, which brings us to today’s matrix era. Furthermore, it also deliberates the impact this phenomenon has had in the civil society.",book:{id:"6822",slug:"social-media-and-journalism-trends-connections-implications",title:"Social Media and Journalism",fullTitle:"Social Media and Journalism - Trends, Connections, Implications"},signatures:"Alonit Berenson",authors:[{id:"243980",title:"Ph.D.",name:"Alonit",middleName:null,surname:"Berenson",slug:"alonit-berenson",fullName:"Alonit Berenson"}]},{id:"54896",title:"Online Journalism: Current Trends and Challenges",slug:"online-journalism-current-trends-and-challenges",totalDownloads:4190,totalCrossrefCites:5,totalDimensionsCites:6,abstract:"In the past 25 years, the journalistic sphere has gone through radical changes and transformations, progressively adapting to the contemporary global trends in news‐making. Traditional understanding of journalism as a profession has changed significantly, mostly due to the fact that digital media environment has brought new opportunities but also challenges related to the journalistic practice. The text aims to offer a theoretical reflection on the issue of online journalism. At the same time, the chapter discusses specific forms of Internet‐delivered journalistic production and professional requirements placed on journalists who specialise in online news‐making, taking into consideration the current development tendencies of digital communication forms. The authors work with a basic assumption that many aspects related to form and content of online news need to be discussed in the light of much needed terminological and paradigmatic revisions related to both the general theory of journalism and our practical understanding of journalism as a continual, creative and highly professional, publicly performed activity.",book:{id:"5736",slug:"the-evolution-of-media-communication",title:"The Evolution of Media Communication",fullTitle:"The Evolution of Media Communication"},signatures:"Ján Višňovský and Jana Radošinská",authors:[{id:"196996",title:"Associate Prof.",name:"Ján",middleName:null,surname:"Višňovský",slug:"jan-visnovsky",fullName:"Ján Višňovský"},{id:"197484",title:"Dr.",name:"Jana",middleName:null,surname:"Radošinská",slug:"jana-radosinska",fullName:"Jana Radošinská"}]},{id:"63049",title:"Social Media: A Turning Point into Global Journalism Identity and Ethics",slug:"social-media-a-turning-point-into-global-journalism-identity-and-ethics",totalDownloads:1991,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"Social media are growing drastically representing a further step in the ongoing deterioration of journalism profession and ethics. The lines between professional journalists and amateurs have been blurred; consequently, the structure of news media has substantially changed affecting the core traits of the profession and its ethics. This phenomenon has challenged the already disputed concepts of journalism as profession and journalists as professionals. While this challenge is tremendous, research on its implications to journalism identity and ethics is scant. The existing literature focuses on new or digital media usage, newsgathering, production, dissemination, and consumption, with little emphasis on journalism ethics or the profession itself. This chapter seeks to examine how social media contribute to the ethical dilemmas off and online journalism encounter and how this transformation puts the profession at risk.",book:{id:"6822",slug:"social-media-and-journalism-trends-connections-implications",title:"Social Media and Journalism",fullTitle:"Social Media and Journalism - Trends, Connections, Implications"},signatures:"Basyouni Ibrahim Hamada",authors:[{id:"245157",title:"Prof.",name:"Basyouni",middleName:null,surname:"Hamada",slug:"basyouni-hamada",fullName:"Basyouni Hamada"}]},{id:"55225",title:"Internet and Social Media in Malaysia: Development, Challenges and Potentials",slug:"internet-and-social-media-in-malaysia-development-challenges-and-potentials",totalDownloads:4766,totalCrossrefCites:8,totalDimensionsCites:13,abstract:"The penetration of the Internet and social media has helped Malaysia abreast with the other developed countries. Nonetheless, being a multicultural country, Malaysia has to ensure her multiracial population lives in harmony and peace. This happens with the integrated help of media control and regulations exercise in Malaysia: the Printing Presses and Publications Act (PPPA), Film Censorship Act, Broadcasting Act, Communication and Multimedia Act (CMA), and media ownership control. Many researches have been conducted pertaining to the Internet and social media that have been published locally in line with the development of the Internet and social media in Malaysia. Similarly, new media is also subjected to being controlled through methods such as controlling the Internet, blocking and filtering, and content removal. The chapter also looks into the impact of the Internet and social media on civil society, thus creating a momentum to promote toward giving suggestions for future research involving not only theories but also models using more sophisticated analyses. More research can be done and the future of research is bright. 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Military Reserve Officer serving with the 100 Support Command, 100 Troop Command, 40 Infantry Division, CA National Guard.",institutionString:null,institution:{name:"Loma Linda University",institutionURL:null,country:{name:"United States of America"}}}]},{type:"book",id:"6925",title:"Endoplasmic Reticulum",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6925.jpg",slug:"endoplasmic-reticulum",publishedDate:"April 17th 2019",editedByType:"Edited by",bookSignature:"Angel Català",hash:"a9e90d2dbdbc46128dfe7dac9f87c6b4",volumeInSeries:2,fullTitle:"Endoplasmic Reticulum",editors:[{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. 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His research interest focuses on computational chemistry and molecular modeling of diverse systems of pharmacological, food, and alternative energy interests by resorting to DFT and Conceptual DFT. He has authored a coauthored more than 255 peer-reviewed papers, 32 book chapters, and 2 edited books. He has delivered speeches at many international and domestic conferences. He serves as a reviewer for more than eighty international journals, books, and research proposals as well as an editor for special issues of renowned scientific journals.",institutionString:"Centro de Investigación en Materiales Avanzados",institution:{name:"Centro de Investigación en Materiales Avanzados",country:{name:"Mexico"}}},{id:"76477",title:"Prof.",name:"Mirza",middleName:null,surname:"Hasanuzzaman",slug:"mirza-hasanuzzaman",fullName:"Mirza Hasanuzzaman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/76477/images/system/76477.png",biography:"Dr. Mirza Hasanuzzaman is a Professor of Agronomy at Sher-e-Bangla Agricultural University, Bangladesh. He received his Ph.D. in Plant Stress Physiology and Antioxidant Metabolism from Ehime University, Japan, with a scholarship from the Japanese Government (MEXT). Later, he completed his postdoctoral research at the Center of Molecular Biosciences, University of the Ryukyus, Japan, as a recipient of the Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship. He was also the recipient of the Australian Government Endeavour Research Fellowship for postdoctoral research as an adjunct senior researcher at the University of Tasmania, Australia. Dr. Hasanuzzaman’s current work is focused on the physiological and molecular mechanisms of environmental stress tolerance. Dr. Hasanuzzaman has published more than 150 articles in peer-reviewed journals. He has edited ten books and written more than forty book chapters on important aspects of plant physiology, plant stress tolerance, and crop production. According to Scopus, Dr. Hasanuzzaman’s publications have received more than 10,500 citations with an h-index of 53. He has been named a Highly Cited Researcher by Clarivate. He is an editor and reviewer for more than fifty peer-reviewed international journals and was a recipient of the “Publons Peer Review Award” in 2017, 2018, and 2019. He has been honored by different authorities for his outstanding performance in various fields like research and education, and he has received the World Academy of Science Young Scientist Award (2014) and the University Grants Commission (UGC) Award 2018. He is a fellow of the Bangladesh Academy of Sciences (BAS) and the Royal Society of Biology.",institutionString:"Sher-e-Bangla Agricultural University",institution:{name:"Sher-e-Bangla Agricultural University",country:{name:"Bangladesh"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",biography:"Kusal K. Das is a Distinguished Chair Professor of Physiology, Shri B. M. Patil Medical College and Director, Centre for Advanced Medical Research (CAMR), BLDE (Deemed to be University), Vijayapur, Karnataka, India. Dr. Das did his M.S. and Ph.D. in Human Physiology from the University of Calcutta, Kolkata. His area of research is focused on understanding of molecular mechanisms of heavy metal activated low oxygen sensing pathways in vascular pathophysiology. He has invented a new method of estimation of serum vitamin E. His expertise in critical experimental protocols on vascular functions in experimental animals was well documented by his quality of publications. He was a Visiting Professor of Medicine at University of Leeds, United Kingdom (2014-2016) and Tulane University, New Orleans, USA (2017). For his immense contribution in medical research Ministry of Science and Technology, Government of India conferred him 'G.P. Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. degree in chemistry in 2000 and Ph.D. degree in physical chemistry in 2007 from the University of Khartoum, Sudan. He moved to School of Chemistry, Faculty of Science, University of Sydney, Australia in 2009 and joined Dr. Ron Clarke as a postdoctoral fellow where he worked on the interaction of ATP with the phosphoenzyme of the Na+/K+-ATPase and dual mechanisms of allosteric acceleration of the Na+/K+-ATPase by ATP; then he went back to Department of Chemistry, University of Khartoum as an assistant professor, and in 2014 he was promoted as an associate professor. In 2011, he joined the staff of Department of Chemistry at Taif University, Saudi Arabia, where he is currently an assistant professor. His research interests include the following: P-Type ATPase enzyme kinetics and mechanisms, kinetics and mechanisms of redox reactions, autocatalytic reactions, computational enzyme kinetics, allosteric acceleration of P-type ATPases by ATP, exploring of allosteric sites of ATPases, and interaction of ATP with ATPases located in cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. His Works are realted to the Green chemistry field, biolubricants, biodiesel, transesterification reactions for biodiesel production and the manipulation of oils for therapeutic purposes.",institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",country:{name:"Argentina"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",biography:"Francisco Javier Martín-Romero (Javier) is a Professor of Biochemistry and Molecular Biology at the University of Extremadura, Spain. He is also a group leader at the Biomarkers Institute of Molecular Pathology. Javier received his Ph.D. in 1998 in Biochemistry and Biophysics. At the National Cancer Institute (National Institute of Health, Bethesda, MD) he worked as a research associate on the molecular biology of selenium and its role in health and disease. After postdoctoral collaborations with Carlos Gutierrez-Merino (University of Extremadura, Spain) and Dario Alessi (University of Dundee, UK), he established his own laboratory in 2008. The interest of Javier's lab is the study of cell signaling with a special focus on Ca2+ signaling, and how Ca2+ transport modulates the cytoskeleton, migration, differentiation, cell death, etc. He is especially interested in the study of Ca2+ channels, and the role of STIM1 in the initiation of pathological events.",institutionString:null,institution:{name:"University of Extremadura",country:{name:"Spain"}}},{id:"217323",title:"Prof.",name:"Guang-Jer",middleName:null,surname:"Wu",slug:"guang-jer-wu",fullName:"Guang-Jer Wu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217323/images/8027_n.jpg",biography:null,institutionString:null,institution:null},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/148546/images/4640_n.jpg",biography:null,institutionString:null,institution:null},{id:"272889",title:"Dr.",name:"Narendra",middleName:null,surname:"Maddu",slug:"narendra-maddu",fullName:"Narendra Maddu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272889/images/10758_n.jpg",biography:null,institutionString:null,institution:null},{id:"242491",title:"Prof.",name:"Angelica",middleName:null,surname:"Rueda",slug:"angelica-rueda",fullName:"Angelica Rueda",position:"Investigador Cinvestav 3B",profilePictureURL:"https://mts.intechopen.com/storage/users/242491/images/6765_n.jpg",biography:null,institutionString:null,institution:null},{id:"88631",title:"Dr.",name:"Ivan",middleName:null,surname:"Petyaev",slug:"ivan-petyaev",fullName:"Ivan Petyaev",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Lycotec (United Kingdom)",country:{name:"United Kingdom"}}},{id:"423869",title:"Ms.",name:"Smita",middleName:null,surname:"Rai",slug:"smita-rai",fullName:"Smita Rai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424024",title:"Prof.",name:"Swati",middleName:null,surname:"Sharma",slug:"swati-sharma",fullName:"Swati Sharma",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"439112",title:"MSc.",name:"Touseef",middleName:null,surname:"Fatima",slug:"touseef-fatima",fullName:"Touseef Fatima",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424836",title:"Dr.",name:"Orsolya",middleName:null,surname:"Borsai",slug:"orsolya-borsai",fullName:"Orsolya Borsai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",country:{name:"Romania"}}},{id:"422262",title:"Ph.D.",name:"Paola Andrea",middleName:null,surname:"Palmeros-Suárez",slug:"paola-andrea-palmeros-suarez",fullName:"Paola Andrea Palmeros-Suárez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Guadalajara",country:{name:"Mexico"}}}]}},subseries:{item:{id:"8",type:"subseries",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",hasOnlineFirst:!1,hasPublishedBooks:!0,annualVolume:11404,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. His research interests include Biomedical Signal Processing and Modelling, Assistive Technology, Rehabilitation Engineering, Neuroengineering and Parkinson's Disease.",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,series:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343"},editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",slug:"hitoshi-tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",slug:"marcus-vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",slug:"ramana-vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},onlineFirstChapters:{paginationCount:0,paginationItems:[]},publishedBooks:{paginationCount:6,paginationItems:[{type:"book",id:"9008",title:"Vitamin K",subtitle:"Recent Topics on the Biology and Chemistry",coverURL:"https://cdn.intechopen.com/books/images_new/9008.jpg",slug:"vitamin-k-recent-topics-on-the-biology-and-chemistry",publishedDate:"March 23rd 2022",editedByType:"Edited by",bookSignature:"Hiroyuki Kagechika and Hitoshi Shirakawa",hash:"8b43add5389ba85743e0a9491e4b9943",volumeInSeries:27,fullTitle:"Vitamin K - Recent Topics on the Biology and Chemistry",editors:[{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",institutionURL:null,country:{name:"Japan"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9759",title:"Vitamin E in Health and Disease",subtitle:"Interactions, Diseases and Health Aspects",coverURL:"https://cdn.intechopen.com/books/images_new/9759.jpg",slug:"vitamin-e-in-health-and-disease-interactions-diseases-and-health-aspects",publishedDate:"October 6th 2021",editedByType:"Edited by",bookSignature:"Pınar Erkekoglu and Júlia Scherer Santos",hash:"6c3ddcc13626110de289b57f2516ac8f",volumeInSeries:22,fullTitle:"Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects",editors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoğlu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoğlu",profilePictureURL:"https://mts.intechopen.com/storage/users/109978/images/system/109978.jpg",institutionString:"Hacettepe University",institution:{name:"Hacettepe University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7004",title:"Metabolomics",subtitle:"New Insights into Biology and Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/7004.jpg",slug:"metabolomics-new-insights-into-biology-and-medicine",publishedDate:"July 1st 2020",editedByType:"Edited by",bookSignature:"Wael N. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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