\r\n\tIn this book, the different factors of liquefaction, the field methods and laboratory tests to identify a potentially liquefiable soil aim to be reviewed; in addition with history cases (ground behavior during the occurrence of an earthquake, state of stress, deformation, shear strength, flow, etc.).
\r\n\tA very important aspect of this topic is the presentation of the different constructive techniques used to ground improvement (vibrocompaction, dynamic compaction, jet grouting, chemical injection, replacement, etc.), placing special emphasis on those constructive methods used to solve problems on structures already located in areas of low relative density with liquefaction potential, where the installation of monitoring and control equipment is also required (tiltmeters, piezometers, topographic points, seismographs, pressure cells, etc.).
Acute (≤24 h) and delayed (>24 h) phases of chemotherapy-induced nausea and vomiting cause distressing side-effects which affect the well-being and quality of life of cancer patients receiving chemotherapy, especially cisplatin [1]. Major neurotransmitter mechanisms underlying chemotherapy-induced nausea and vomiting have been subject of considerable research over the past 45 years. As presented in brief in Figure 1, cancer chemotherapeutics such as cisplatin evoke vomiting via local release of a variety of emetic neurotransmitters/mediators (including dopamine, serotonin (5-HT), substance P, prostaglandins and leukotrienes) both from the enterochromaffin cells of the gastrointestinal tract and the brainstem emetic loci in the dorsal vagal complex containing the nucleus tractus solitarius, the dorsal motor nucleus of the vagus and the area postrema [2, 3, 4]. The area postrema and the nucleus tractus solitarius contain large numbers of fenestrated capillaries which lack blood-brain barrier and permit neurons in both areas access to blood-borne circulating factors including emetogens [5]. The chemoreceptor trigger zone, in the area postrema has high concentrations of emetic receptors for serotonin (5-HT3), dopamine (D2/3), neurokinin (NK1), and opioids (μ), among others [2]. Direct stimulation of these receptors in the chemoreceptor trigger zone by emetogens is one important mechanism by which vomiting can occur [6]. The nucleus tractus solitarius receives emesis-related information from the area postrema as well as the gastrointestinal tract conveyed by vagal afferents. The dorsal motor nucleus of the vagus receives axonal projections from nucleus tractus solitarius [7] and sends emetic signals via motor efferent pathways to the gastrointestinal tract and modulates vomiting behaviors [2, 5, 8, 9] (Figure 1). In addition, chemotherapeutic drugs may evoke release of emetic neurotransmitters/mediators from the gastrointestinal tract into the blood to be directly delivered to the area postrema via a blood-borne pathway which then triggers vomiting [2, 10], and/or the released emetic neurotransmitters/mediators stimulate their corresponding receptors present on vagal afferents in the gastrointestinal tract which indirectly activate brainstem emetic loci primarily in the nucleus tractus solitaries to trigger vomiting [6].
\nBrief illustration of the mechanisms underlying vomiting induced by chemotherapeutic agent cisplatin. Mechanisms underlying cisplatin-induced vomiting can be simplified as: (1) cisplatin can increase cytoplasmic Ca2+ level to evoke Ca2+-dependent release of emetic neurotransmitters/mediators at the brainstem emetic loci, the dorsal vagal complex, and subsequently activates diverse receptors and their corresponding signaling pathways. These emetic signals are output to the gastrointestinal tract via efferents to trigger vomiting [2, 4, 5, 6, 7, 8, 9]; (2) cisplatin-induced peripheral release of neurotransmitters/mediators from the gastrointestinal tract into the blood can directly stimulate the dorsal vagal complex, activate receptors signaling pathways and trigger vomiting [2, 10]; and (3) the peripherally-released emetic neurotransmitters/mediators stimulate their corresponding receptors present on vagal afferents in the gastrointestinal tract which indirectly activate brainstem emetic nuclei and trigger vomiting [6].
Ca2+ is not only one of the most universal and versatile signaling molecules, it is also an extremely important factor in both the physiology and pathology of living organisms. At rest, diverse cells have strict and well-regulated mechanisms to maintain low nM cytosolic Ca2+ levels [11]. Cytoplasmic Ca2+ concentration is a dominant factor in determining the amount of transmitter released from nerve terminals [12]. Thus, Ca2+ mobilization can be an important aspect of vomit induction since it is involved in both triggering the quantity of neurotransmitter released coupled with receptor activation, as well as post-receptor excitation-transcription coupling mechanisms [13]. Studies using Ca2+ imaging performed in vitro in the brainstem slice preparation suggest that emetic agents evoke direct excitatory effects on cytosolic Ca2+ signals in vagal afferent terminals in the nucleus tractus solitarius which potentiate local neurotransmitter release [5, 14, 15]. Therefore, chemotherapeutics including cisplatin seem to activate emetic circuits through a number of neurotransmitters released in a Ca2+-dependent manner in specific vomit-associated neuroanatomical structures. In both the periphery and the brainstem, emetic neurotransmitters/mediators—such as acetylcholine, dopamine, 5-HT, substance P, prostaglandins, leukotrienes, and/or histamine—may act independently or in combination to evoke vomiting after cisplatin administration [16] (Figure 1). In this review, we focus on the current evidence supporting the significance of Ca2+ signaling in emesis generation and its relationship to antiemetic efficacy, as well as the corresponding development of potential novel antiemetic medications, as shown in brief in Figure 2.
\nOverview of evidence for suppression of Ca2+ signaling involved in anti-vomiting actions of antiemetic agents. (1) Netupitant and palonosetron are highly selective respective antagonists of NK1Rs and 5-HT3Rs are approved to treat the acute- and delayed- phases of chemotherapy-induced nausea and vomiting (CINV) in cancer patients [79, 80, 81, 82]. Our studies [83, 84, 85, 86] indicate that suppression of Ca2+ signaling is involved in antiemetic efficacy of both palonosetron and netupitant. (2) Cannabinoids such as delta-9-tetrahydrocannabinol exert their antiemetic efficacy via direct activation of CB1 receptors (CB1R) [92, 94, 98, 99, 100]. The ability of CB1R agonists to suppress both extracellular Ca2+ influx [111, 112, 113, 114, 115] and intracellular Ca2+ release from the sarco/endoplasmic reticulum stores [15, 117], result in inhibition of Ca2+-dependent neurotransmitter release [108] and is probably the fundamental mechanisms underlying the antiemetic efficacy of CB1R cannabinoid agonists against CINV [95, 96, 97]. (3) Glucocorticoids such as dexamethasone reduce both acute and delayed CINV [6]. Glucocorticoids’ ability to decrease the abnormal elevation of cytosolic Ca2+ concentration [122], and subsequently control Ca2+-dependent neurotransmitter release [6, 121, 126] and inflammatory responses [6]. Increased release of endocannabinoids and subsequent CB1R activation may also be involved in antiemetic actions of glucocorticoids [123, 124, 125]. (4) The L-type Ca2+ channel (LTCC) antagonist flunarizine can reduce cyclic vomiting in patients [151, 152]. Gabapentin binds to the alpha-2/delta auxiliary subunits of LTCCs, and exerts inhibitory actions on trafficking and activation kinetics of LTCCs [153]. Gabapentin can be used as an anti-nausea and antiemetic agent in postoperative nausea and vomiting [154, 155] and in CINV [156, 157]. (5) LTCC antagonists (nifedipine and amlodipine) are broad-spectrum antiemetics when delivered systemically against diverse specific and nonselective emetogens. (6) Suppression of intracellular Ca2+ release from the sarco/endoplasmic reticulum through the inositol trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs) may be additional targets for the prevention of nausea and vomiting, since functional and physical linkages between Ca2+ channels on cell membrane and IP3Rs/RyRs play a role in Ca2+ signaling [160, 161, 162, 163, 164, 165, 166]. In the least shrew emesis model, the RyRs antagonist dantrolene can potentiate the antiemetic efficacy of amlodipine against 5-HT3R agonist 2-Methyl-5-HT-induced vomiting [25]; and dantrolene together with the IP3R antagonist 2-APB can potentiate the antiemetic efficacy of nifedipine against thapsigargin-induced vomiting [70].
Excitatory receptor activation by corresponding agonists can increase cytosolic Ca2+ levels via both mobilization of intracellular Ca2+ stores (e.g., endoplasmic reticulum = ER) and influx from extracellular fluid [17]. The evoked cytoplasmic Ca2+ increase may result from direct activation of ion channels, or indirectly via signal transduction pathways following G protein-coupled receptor activation. The neurokinin NK1 receptor (NK1R) is a member of the tachykinin family of G-protein-coupled receptors. NK1R stimulation by substance P or corresponding selective agonists such as GR73632, can increase cytosolic Ca2+ concentration. In fact GR73632-induced activation of NK1Rs can evoke intracellular Ca2+ release from the sarco/endoplasmic reticulum stores via Gα/q-mediated phospholipase C pathway, which subsequently evokes extracellular Ca2+ influx through L-type Ca2+ channels (LTCCs) [17, 18, 19]. The serotonergic 5-HT3 receptor (5-HT3R) is a Ca2+-permeable ligand-gated ion channel [20]. Cell lines studies have demonstrated that activation of 5-HT3Rs by 5-HT or its analogs can evoke extracellular Ca2+ influx into cells in a manner sensitive to both 5-HT3R antagonists (tropisetron, MDL7222, metoclopramide) and LTCC blockers (verapamil, nimodipine, nitrendipine) [20, 21, 22, 23, 24]. These studies suggest that both L-type- and 5-HT3-receptor Ca2+-permeable ion channels are involved in extracellular Ca2+ influx evoked by 5-HT3R agonists. Moreover, 5-HT3R activation indirectly causes release of Ca2+ from ryanodine-sensitive intracellular Ca2+ stores subsequent to the evoked extracellular Ca2+ influx which greatly amplifies the cytoplasmic concentration of Ca2+ [23]. In fact, our findings from behavioral studies in the least shrew emesis model [25] further support the notion of Ca2+-induced Ca2+ release following 5-HT3R stimulation, which will be discussed in more detail in Section 3.4. Other emetogens such as agonists of dopamine D2- [26, 27], cholinergic M1- [28, 29], histaminergic H1- [30, 31], and opiate μ- [32, 33] receptors, as well as cisplatin [34], prostaglandins [35, 36], rotavirus NSP4 protein [37, 38] and bacterial toxins [39, 40] also possess the potential to mobilize Ca2+ which involve extracellular Ca2+ influx and/or Ca2+ release from intracellular Ca2+ pools. Much of the discussed evidence has been acquired from isolated cells.
\nThe least shrew is an emesis-competent mammal whose reactions to common emetogens are well-defined and correlate closely with human responses [2]. 2-Methyl-5-HT is a well-known selective emetic agonist targeting the emesis-prone 5-HT3Rs [4]. This vomit-competent species is an excellent animal model for studying the emetic activity of diverse agents [2]. In fact least shrews exhibit dose-dependent full emetic responses to intraperitoneal administration of both the peripherally-acting 5-HT, as well as to its central nervous system-penetrating analog, 2-Methyl-5-HT [4, 41, 42]. In our studies, incubation of least shrew brainstem slices containing the dorsal vagal complex emetic loci with 2-Methyl-5-HT, results in a rapid increase in intracellular Ca2+ concentration as reflected by an increase in fluo-4 AM fluorescence intensity in a palonosetron (a 5-HT3R antagonist)/nifedipine-sensitive manner [22, 25].
\nA variety of Ca2+-permeable ion-channels mediating extracellular Ca2+ influx are present in the plasma membrane. Among them are voltage-gated LTCCs, which can be activated by membrane depolarization, and serve as the principal route of Ca2+ entry in electrically excitable cells such as neurons and muscle [43, 44]. Recently we have acquired direct evidence for the proposal that Ca2+ mobilization is an important facet in the mediation of emesis. In fact we have identified the novel emetogen FPL64176 (Figure 2), a selective agonist of LTCCs, which causes vomiting in the least shrew in a dose-dependent manner [45, 46]. All tested shrews vomited at a 10 mg/kg dose of FPL64176 administered intraperitoneally (i.p.). LTCCs have been shown to be present in enterochromaffin cells of guinea pig and human small intestinal crypts [47]. Furthermore, in these cells FPL64176 not only can enhance cytosolic Ca2+ concentration, but also increases 5-HT release from enterochromaffin cells [47]. The latter findings may have underpinnings for the mechanisms underlying FPL64176-evoked vomiting observed in least shrew model of emesis. FPL64176 (10 mg/kg., i.p.) can cause Ca2+-dependent 5-HT release from shrew intestinal enterochromaffin cells which in turn could increase vagal afferent activity via stimulation of 5-HT3 receptors, thereby indirectly triggering emetic signals in the brainstem [2, 48].
\nOur most recent work has focused on the Ca2+-mobilizing agent thapsigargin (Figure 3), a specific and potent inhibitor of the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump which transports the free cytosolic Ca2+ into the lumen of the sarco/endoplasmic reticulum to counter-balance the cytosolic intracellular Ca2+ release from the sarco/endoplasmic reticulum into the cytoplasm via the inositol trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs) [49, 50, 51]. Thapsigargin also causes intracellular release of stored Ca2+ from the sarco/endoplasmic reticulum into the cytosol which subsequently evokes extracellular Ca2+ influx predominantly through store-operated Ca2+ entry (SOCE) in non-excitable cells [52, 53, 54]. In total, these events lead to a significant rise in the free concentration of cytosolic Ca2+ [55, 56, 57]. In addition, a partial involvement of LTCCs in thapsigargin-evoked contraction has also been demonstrated in rat stomach smooth muscle cells [58], rat gastric smooth muscle [59], and cat gastric smooth muscle [60]. On the other hand, the potential of thapsigargin as a Ca2+-modulating cancer chemotherapeutic agent has been evaluated in both cells and animal models [61]. Thapsigargin-evoked increases in cytosolic Ca2+ concentration can lead to cell apoptosis, which can result in eradication of cancer cells of the breast [62], prostate [63], colon [64] and kidneys [65]. Clinically, a prodrug form of thapsigargin, mipsagargin, is currently under clinical trial as a targeted cancer chemotherapeutic agent with selective toxicity against cancer cells in tumor sites with minimal side-effects to the host [66, 67, 68, 69]. In our studies, intraperitoneal administration of thapsigargin (0.1–10 mg/kg) caused vomiting in least shrews in a dose-dependent, but bell-shaped manner, with maximal efficacy at 0.5 mg/kg. An important consideration for the emetic potential of thapsigargin is that it augments the cytosolic levels of free Ca2+ in emetic loci as a result of SERCA inhibition as indicated in our latest discussed finding [70], which is the first study to reflect emesis as a major side-effect of thapsigargin when delivered systemically.
\nA schematic representation of extracellular Ca2+ influx and intracellular Ca2+ release contributing to thapsigargin-elicited Ca2+ mobilization. Intracellular Ca2+ release from the sarco/endoplasmic reticulum (SER) Ca2+ stores through the inositol triphosphate receptors (IP3Rs) and ryanodine receptors (RyRs) is counter-balanced by continuous Ca2+ uptake from the cytoplasm into SER stores by the SER Ca2+-ATPase pump (SERCA). Thapsigargin is a specific inhibitor of SERCA and thus enhances cytosolic levels of Ca2+, a process involving SER Ca2+ release via IP3Rs and RyRs as well as extracellular Ca2+ entry through Ca2+ channels located in the plasma membrane including store-operated Ca2+ channels (SOCE) and L-type Ca2+ channels (LTCCs) [49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60].
c-Fos induction has been used to evaluate differential neuronal activation [71]. Our lab has applied immunostaining and detected c-Fos induction in the brainstem emetic nuclei to demonstrate central responsiveness to peripheral administration of a variety of emetogens [4, 70, 72, 73]. The participation of the central emetic neurons in FPL64176-induced vomiting is further indicated by evoked c-Fos expression in brainstem emetic nuclei, the nucleus tractus solitarius and the dorsal motor nucleus of the vagus (unpublished data). Thus, the blood-brain barrier permeable agent FPL64176 [74, 75, 76] could excite emetic neurons directly in the nucleus tractus solitarius and the dorsal motor nucleus of the vagus. Thapsigargin (0.5 mg/kg) also causes increases in c-Fos immunoreactivity in the brainstem emetic nuclei including the area postrema, the nucleus tractus solitarius and the dorsal motor nucleus of the vagus [70].
\nThe ultimate aim of prophylactic management of chemotherapy-induced nausea and vomiting is to abolish both the acute- and delayed phases of vomiting which will help to improve the well-being and quality of life of cancer patients receiving chemotherapy. Cisplatin-like chemotherapeutics cause release of multiple emetogenic neurotransmitters in both the central nervous system and the gastrointestinal tract and no available single antiemetic administered alone can provide complete efficacy. Significant initial work had suggested that while activation of 5-HT3Rs by serotonin in the gastrointestinal tract is involved in the mediation of acute phase of chemotherapy-induced nausea and vomiting, the delayed phase is due to stimulation of NK1Rs subsequent to release of substance P in the brainstem [77, 78]. However, our more recent findings suggest that 5-HT and substance P are concomitantly involved in both emetic phases in the gastrointestinal tract as well as in the brainstem [2, 16]. While netupitant is a highly selective and a longer-acting second generation NK1R antagonist, palonosetron is considered as a second generation 5-HT3R antagonist with a unique antiemetic profile in both humans [79, 80] and the least shrew model of emesis [45]. A successful regimen of an oral fixed combined dose of netupitant/palonosetron (NEPA) (Figure 2) has been formulated with over 85% clinical efficacy, good tolerability, and high central nervous system penetrance for the prophylactic treatment of acute and delayed chemotherapy-induced nausea and vomiting in cancer patients receiving chemotherapy [9, 81, 82].
\nRecent evidence accumulated from HEK293 cells stably transfected with 5-HT3Rs suggest that suppression of Ca2+ signaling is involved in antiemetic efficacy of both palonosetron and netupitant. Indeed, Rojas et al. [83, 84] have shown that palonosetron causes a persistent inhibition of 5-HT3R function as reflected by a near complete suppression of 5-HT-evoked extracellular Ca2+ influx. They have further demonstrated that palonosetron can prevent enhancement of substance P-induced intracellular Ca2+ release in response to serotonin in NG108–15 cells expressing both 5-HT3Rs and NK1Rs [85]. Our Ca2+ monitoring studies performed on acutely-prepared least shrew brainstem slices also demonstrate that palonosetron can abolish enhancement of intracellular Ca2+ levels in brainstem slices evoked by the selective 5-HT3R agonist 2-Methyl-5-HT [25]. The latter finding provides more relevant ex-vivo evidence for the Ca2+-modulating antiemetic effect of palonosetron in a vomit-competent species. The role of netupitant in suppression of substance P-evoked enhancement of intracellular Ca2+ levels has also been demonstrated via Ca2+ mobilization assays in vitro in CHO cells expressing the human NK1Rs. Moreover, pronetupitant, an intravenous alternative to the oral netupitant, appears to be more potent than netupitant in both in vitro Ca2+ measurement studies and in vivo animal behavioral evaluations of substance P in rats [86]. In addition, another clinically approved NK1R antagonist antiemetic rolapitant, has been shown to suppress the ability of the selective NK1R agonist GR73632 to evoke intracellular Ca2+ release [9, 87, 88, 89]. The discussed findings clearly suggest that Ca2+ is a major player in the initiation of vomiting evoked by diverse emetogens.
\nBefore the introduction of first generation 5-HT3R antagonists, several phyto- and synthetic cannabinoids including dronabinol (delta-9-tetrahydrocannabinol, Δ9-THC (Figure 2)), levonantradol and nabilone, were evaluated in cancer patients for suppression of chemotherapy-induced nausea and vomiting that were not effectively controlled by other available antiemetics [2, 90]. Cannabinoids are increasingly being tested as antiemetics against cisplatin-induced emesis in animal experiments using house musk shrews [91], ferrets [92], or least shrews [73, 93]; nausea-related behavior in rats [91]; radiation-induced emesis in the least shrew [94]; as well as both phases of chemotherapy-induced nausea and vomiting in the clinic [95, 96, 97]. Cannabinoid agonists exert their antiemetic efficacy via direct activation of CB1 receptors (CB1R) since their antiemetic effects were reversed by CB1R antagonists [92, 94, 98, 99, 100]. Significant evidence for a role for CB2Rs in emesis is currently lacking [101]. The presence of CB1Rs in the brainstem nuclei involved in emesis has been confirmed, with a high density of CB1R immunoreactivity in the dorsal motor nucleus of the vagus and the medial subnucleus of the nucleus tractus solitarius, a moderate density in the commissural subnucleus of the nucleus tractus solitarius, and lower densities in the area postrema and dorsal subnucleus of the nucleus tractus solitarius [73, 92]. CB1R distribution has been also observed in the myenteric plexus of the stomach and duodenum [92]. Furthermore, CB1Rs have been localized in the myenteric plexus of the rat and guinea pig intestine in nearly all cholinergic neuron terminals [102, 103]. These as well as behavioral evidence [42] suggest that the antiemetic action of cannabinoids involve both the central dorsal vagal complex and intestinal emetic loci. In addition, primary cultures of guinea-pig myenteric neurons express CB1Rs and exogenously added cannabinoids suppress their neuronal activity, synaptic transmission and mitochondrial transport along axons [104]. Moreover, the CB1/2R agonist WIN55212-2 can suppress intestinal activity since it can attenuate the electrically-evoked contractions of the myenteric plexus-longitudinal muscle preparation of the guinea-pig small intestine in a Ca2+-dependent and CB1R-specific manner [105]. Thus, CB1R agonists in the in vivo setting can also suppress the gastrointestinal tract motility [104]. Using whole-cell patch-clamp recordings in brainstem slices, Derbenev et al. [106, 107] have shown that activation of presynaptic CB1Rs in the dorsal vagal complex inhibits synaptic transmission to the dorsal motor nucleus of the vagus neurons, which may explain suppression of visceral motor responses caused by cannabinoids.
\nFurthermore, in the central nervous system CB1R stimulation can result in inhibition of Ca2+-dependent neurotransmitter release from presynaptic nerve terminals which consequently leads to inhibition of neurotransmission [108]. In chemotherapy-induced nausea and vomiting, the CB1R-mediated antiemetic action of cannabinoids appears to be directly related to presynaptic inhibition of release of emetic neurotransmitters from nerve terminals. Figure 4 may help to explain the antiemetic action of cannabinoid CB1R agonists from the Ca2+ perspective. Indeed, the adenylyl cyclase/cyclic AMP (cAMP)/protein kinase A (PKA) signal transduction system is a well-established emetic signaling pathway [109]. PKA activation is known to phosphorylate both Ca2+ ion channels on plasma membrane and intracellular endoplasmic IP3Rs, which respectively increase extracellular Ca2+ influx and internal Ca2+ release from the sarco/endoplasmic reticulum stores [110]. CB1Rs are known to be Gi/o-protein coupled receptors which mediates inhibition of adenylate cyclase. This inhibition has been proposed to be the fundamental reason for CB1R agonists attenuating Ca2+-dependent emetic neurotransmitter release which would ultimately reduce postsynaptic neuronal activation in both dorsal vagal complex and gastrointestinal tract [93, 103]. Moreover, dose-dependent inhibitory action of cannabinoid CB1R agonists on extracellular Ca2+ influx via a number of voltage-gated Ca2+ channels residing in the cell membrane including N-type, P/Q type and L-type have been demonstrated in multiple experimental systems [111, 112, 113, 114, 115]. Additionally, cannabinoid CB1R agonists also block 5-HT3Rs in a non-competitive manner and thus prevent extracellular Ca2+ influx [115, 116].
\nA schematic explanation of the antiemetic action of cannabinoid CB1R agonists from the perspective of Ca2+ signaling. Activation of CB1R initiates a Gi/o mechanism leading to the downregulation of extracellular Ca2+ influx through voltage-gated Ca2+ channels (VGCCs) as well as endoplasmic reticulum (ER) Ca2+ release via ryanodine receptors (RyRs) which has the potential to be activated by extracellular Ca2+ entry through VGCCs. The reduction in cytosolic Ca2+ attenuates Ca2+-dependent emetic neurotransmitter release, which further results in a reduction in postsynaptic neuronal activation, and ultimately suppression of the vomiting behavior [93, 103, 117].
Furthermore, CB1R agonists appear to inhibit the intracellular Ca2+ release channels located on the sarco/endoplasmic reticulum membrane, RyRs. Ca2+-induced Ca2+ release is a well-established feature of Ca2+ signal amplification. During neuronal activation, Ca2+-induced Ca2+ release Ca2+ signaling involves increased concentration of cytoplasmic Ca2+ via extracellular Ca2+ influx through voltage-gated Ca2+ channels (e.g., LTCCs) present on the cell membrane, which then causes release of stored intracellular Ca2+ from the sarco/endoplasmic reticulum into the cytosol through RyRs [117]. In fact RyRs have a wide distribution in the central nervous system including the brainstem [118]. RyRs not only can regulate Ca2+ homeostasis, but also other critical brain functions including neurotransmitter release [117]. Increased serum levels of the pro-inflammatory cytokine, tumor necrosis factor alpha (TNF-α), is associated with chemotherapy-evoked vomiting [119]. TNF-α can excite vagal afferent terminals by augmenting Ca2+ release from sarco/endoplasmic reticulum stores via sensitization of RyRs which subsequently amplifies neurotransmission in the brainstem [15]. Cannabinoid CB1R agonists prevent the TNF-α-evoked sensitization of RyRs and therefore attenuate intracellular Ca2+ release from the sarco/endoplasmic reticulum stores [15]. Peripheral RyRs also play a critical role in agonist-evoked Ca2+ oscillations in gut epithelial cells [120]. Therefore, the ability of CB1R agonists in preventing both extracellular Ca2+ influx as well as intracellular Ca2+ release from the sarco/endoplasmic reticulum stores may be the fundamental mechanisms underlying the broad-spectrum antiemetic efficacy of CB1R cannabinoid agonists.
\nGlucocorticoids, used primarily as anti-allergic and anti-inflammatory drugs. They are also effective, either alone or in combination with other antiemetics, for the suppression of nausea and vomiting. Indeed, dexamethasone (Figure 2), one of the clinically used glucocorticoids, is effective in reducing both acute and delayed chemotherapy-induced nausea and vomiting, and when combined with 5-HT3 or neurokinin NK1 antagonists, it is utilized in patients receiving high emetogenic chemotherapy [6]. Glucocorticoids’ antiemetic effect has been related to its inhibitory effects in the following facets: (i) glucocorticoids control the inflammatory response involved in mediating chemotherapy-induced nausea and vomiting by reducing the production of inflammatory mediators such as cytokines, chemokines, inducible nitric oxide synthase, and increasing the gene transcription of anti-inflammatory proteins [6]; (ii) glucocorticoids can inhibit 5-HT and substance P release, both of which can evoke emesis [6, 121], (iii) glucocorticoids can cross the blood-brain barrier and can exert direct central inhibitory effects on the nucleus tractus solitarius [6], which may be due to a decrease in abnormal elevation of cytosolic Ca2+ concentration as well as downstream Ca2+ signals and the maintenance of Ca2+ homeostasis within the cell [122], (iv) inhibitory actions of glucocorticoid could also be due to increased release of endocannabinoids, anandamide and 2-arachidonoylglycerol, evoked by glucocorticoid administration which will then be followed by subsequent CB1R activation as well as glucocorticoid facilitation of synaptic γ-aminobutyric acid (GABA) release and suppression of glutamate release [123, 124]. The endocannabinoid system is composed of CBRs, endocannabinoids and the enzymes involved in their synthesis. Anandamide and 2-arachidonoylglycerol are among the well-studied endocannabinoids and endogenous activators of CBRs [125]. The role of CB1R agonists as antiemetics was discussed in Section 2.2. It has been suggested that dexamethasone may decrease motion sickness through modulation of the endocannabinoid/CB1 receptor system on the terminals of the nucleus tractus solitarius neurons that project to the output neurons of the DMNV as well as by endocannabinoid/CB1 receptor system-mediated inhibition of transmitter release from interneurons of the nucleus tractus solitarius [99, 126]. Selective elevation of 2-arachidonoylglycerol by inhibition of its major metabolic enzyme monoacylglycerol lipase, have been shown to suppress lithium chloride evoked vomiting in the house musk shrew (Suncus murinus) [127]. However, intraperitoneal administration of the endocannabinoid 2-arachidonoylglycerol can evoke vomiting in the least shrew in a dose-dependent manner probably via its rapid metabolism to arachidonic acid which is also a potent emetogen in this species [128]. Moreover, the cancer chemotherapeutic agent cisplatin can increase 2-arachidonoylglycerol but not anandamide levels in the least shrew brain [129].
\nNifedipine along with amlodipine, are among the most studied of Ca2+ channels blockers, and both belong to the dihydropyridine subgroup of LTCC antagonists. Relative to nifedipine, a fast and short-acting LTCC antagonist with a plasma half-life of 1.2 h, amlodipine is slow and longer acting, more extensively bound to plasma protein, with a larger volume of distribution, more gradual elimination, with a half-life of over 30 h [130, 131, 132, 133, 134]. We have evaluated the antiemetic efficacy of both nifedipine and amlodipine (Figure 2) by assessing mean emesis frequency and the percentage of shrews vomiting, and demonstrated that both LTCC blockers [45, 46] behave as broad-spectrum antiemetics when delivered systemically against diverse specific emetogens, including FPL 64176 (10 mg/kg, i.p.), the peripherally-acting and non-selective 5-HT3R agonist 5-HT (5 mg/kg, i.p.), the peripherally/centrally-acting and more selective 5-HT3R agonist 2-Methyl-5-HT (5 mg/kg, i.p.), the dopamine D2R-preferring agonist quinpirole (2 mg/kg, i.p.), the non-selective dopamine D2R agonist apomorphine (2 mg/kg, i.p.), the nonselective cholinergic agonist pilocarpine (2 mg/kg, i.p.), the M1-preferring cholinergic agonist McN-A343 (2 mg/kg, i.p.), and the selective neurokinin NK1R agonist GR73632 (5 mg/kg, i.p.). The vomiting behavior was recorded for 30 min. Our results suggest that both amlodipine and nifedipine act by suppressing the influx of extracellular Ca2+, thereby delay the onset as well as protecting least shrews from vomiting, further supporting our proposed Ca2+ hypothesis of emesis. Nifedipine appears to be more potent than amlodipine against vomiting caused by FPL64176, 5-HT, 2-Methyl-5-HT, GR73632, quinpirole and McN-A343. These potency disparities could be explained in terms of their pharmacokinetic and pharmacodynamic differences [130, 131, 132, 133, 134, 135, 136, 137, 138, 139].
\nUnlike the above tested emetogens which can evoke vomiting within minutes of administration, cisplatin (10 mg, i.p.) requires more exposure time (30–45 min) to begin to induce emesis since only its metabolites are emetogenic. The relative efficacy of amlodipine (5 mg/kg., i.p.) in reducing the frequency of cisplatin-evoked early vomiting by 80% compared with the observed lack of antiemetic action of nifedipine up to 20 mg/kg [45, 46], could be explained in terms of positively charged amlodipine associating more slowly with LTCCs, requiring more exposure time not only to reach its sites of action, but also to compensate for its slower receptor binding kinetics, which can lead to a more gradual onset of antagonism [140]. In addition, intracerebroventricular microinjection of another LTCC antagonist, nitrendipine, has been shown to attenuate nicotine-induced vomiting in the cat [141], which further supports the discussed broad-spectrum antiemetic efficacy of nifedipine and amlodipine as observed in the least shrew model. Cisplatin-based chemotherapeutics induce both immediate and delayed vomiting in humans and in vomit-competent animals [16, 142, 143]. In the least shrew, cisplatin (10 mg/kg, i.p.) causes emesis over 40 h with respective peak early- and delayed-phases occurring at 1–2 and 32–34 h post-injection [144]. Amlodipine, due to its unique pharmacokinetics, may offer practical advantages over other calcium antagonists in cisplatin-evoked delayed emesis.
\nIn 1996 Hargreaves and co-workers [20] demonstrated that members of all three major classes of LTCC antagonists can prevent the ability of the 5-HT3 receptor-selective agonist 1-(m-chlorophenyl)-biguanide to increase intracellular Ca2+ concentration in cell lines that possess either one or both of these two different Ca2+-ion channels. The latter interaction is not competitive since the binding site for the different classes of LTCC antagonists appear not to be the same as the serotonin 5-HT3R binding site itself (i.e., the orthosteric site) but instead, is an allosteric site in the 5-HT3 receptor channel complex. Furthermore, 5-HT release from enterochromaffin cells can be prevented by antagonists of both 5-HT3Rs and LTCCs [145, 146]. These findings provide possible mechanisms via which antagonists of both LTCCs and 5-HT3Rs can mutually prevent the biochemical and behavioral effects of their corresponding selective agonists, including the vomiting behavior induced by their corresponding selective agonists FPL64176 and 2-Methyl-5-HT as we reported previously [45]. We have further demonstrated that when non-effective antiemetic doses of their selective antagonists (nifedipine and palonosetron, respectively) are combined [45], the combination significantly and in an additive manner attenuate both the frequency and the percentage of shrews vomiting in response to either FPL 64176 or 2-Methyl-5-HT. Furthermore, although nifedipine alone up to 20 mg/kg dose failed to protect shrews from acute cisplatin-induced vomiting, its 0.5 mg/kg dose, significantly potentiated the antiemetic efficacy of a non-effective (0.025 mg/kg) as well as a semi-effective (0.5 mg/kg) dose of palonosetron. In another study we also utilized a combination of non-effective doses of amlodipine (0.5 mg/kg or 1 mg/kg) with a non- or semi-effective dose of the 5-HT3R antagonist palonosetron (0.05 or 0.5 mg/kg) [46]. The combined antiemetic doses produced a similar additive efficacy against vomiting induced by either FPL 64176 or cisplatin. In fact relative to each antagonist alone, the combination was at least 4 times more potent in reducing the vomit frequency and provided more protection against FPL 64176-induced vomiting. The observed additive antiemetic efficacy of a combination of 5-HT3- (and/or possibly NK1-) with LTCC-antagonists in the least shrew suggests that such a combination should provide greater emesis protection in cancer patients receiving chemotherapy in a manner similar to that reported between 5-HT3- and NK1-receptor antagonists both in the laboratory [144, 147] and in the clinic [148]. Although in our investigation, the mechanism underlying the additive antiemetic efficacy of combined low doses of LTCC antagonists with 5-HT3R antagonists was not directly studied, the published literature points to their interaction at the signal transduction level involving Ca2+ [20, 149, 150].
\nThere are several published clinical case reports that demonstrate Ca2+ channel blockers may provide protection against several causes of nausea and vomiting. The LTCC antagonist flunarizine (Figure 2) was shown to reduce cyclic vomiting on acute basis in one patient [151] and prophylactically in 8 other patients [152]. Gabapentin is a gamma-aminobutyric acid (GABA) analog and is predominantly used in the clinic for the management of pain [3]. Gabapentin binds to the alpha-2/delta auxiliary subunits of voltage-gated Ca2+ channels (VGCCs) (i.e., LTCCs), and exerts inhibitory actions on trafficking and activation kinetics of VGCCs [153] (Figure 2). Moreover, several other reports indicate that gabapentin can also be used as a well-tolerated, less-expensive and promising anti-nausea and antiemetic agent in diverse conditions including: postoperative nausea and vomiting [154, 155], moderately or highly emetogenic chemotherapy-induced nausea and vomiting, particularly effective against delayed chemotherapy-induced nausea and vomiting [156], and both acute and delayed nausea induced by chemotherapy [157], as well as hyperemesis gravidarum [158]. When combined with dexamethasone, gabapentin can also significantly reduce the 24-h incidence of postoperative nausea and vomiting [159]. Alpha-2/delta subunits of VGCCs control transmitter release and further facilitate excitatory transmission [153]. Gabapentin’s interaction with neuronal alpha-2/delta subunits of VGCCs and subsequent downregulation of neuronal Ca2+ signaling in emesis relevant sites, such as the dorsal vagal complex, is postulated to play a critical role in its anti-nausea and anti-vomiting effects [3].
\nA functional and physical linkage between LTCCs and RyRs appears to exist and plays an important role in intracellular Ca2+ release following voltage-dependent Ca2+ entry through LTCCs during neuronal depolarization to generate a transient increase in cytosolic Ca2+ [160, 161, 162]. Physical attachment of IP3Rs to plasma membrane Ca2+ influx channels through conformational coupling has also been proposed as one of the mechanisms connecting depletion of internal Ca2+ stores with stimulation of extracellular Ca2+ influx [163]. For example, Ca2+ release from IP3Rs was shown to couple with extracellular Ca2+ influx through LTCCs in non-excitable cells such as Jurkat human T lymphocytes [164] and drosophila S2 cells [165], as well as in excitable cells such as submucosal neurons in the rat distal colon [166]. We have found that 5-HT3R-mediated vomiting triggered by 5 mg/kg 2-Methyl-5-HT is insensitive to the intracellular Ca2+ release channel IP3R antagonist 2-APB, but in contrast, was dose-dependently suppressed by the RyR antagonist, dantrolene [25]. Furthermore, a combination of the semi-effective doses of amlodipine and dantrolene was more potent than each antagonist being tested alone [25]. Significant reductions (70–85%) in the frequency of Ca2+ mobilizer thapsigargin-evoked vomiting (see Section 1.2) were observed when shrews were pretreated with antagonists of either IP3Rs (2-APB at 1 and 2.5 mg/kg, i.p.)- or RyRs (dantrolene at 2.5 and 5 mg/kg, i.p.)-ER luminal Ca2+ release channels. Moreover, while a mixture of 2-APB (1 mg/kg) and dantrolene (2.5 mg/kg) did not offer additional protection than what was afforded when each drug administered alone, a combination of the latter doses of 2-APB plus dantrolene with a partially effective dose of nifedipine (2.5 mg/kg), led to a complete elimination of thapsigargin-evoked vomiting [70]. In another set of experiments [167], we found that pretreatment with the IP3R inhibitor 2-APB causes a significant reduction in NK1R agonist GR73632-induced emesis, however the RyR inhibitor dantrolene did not. Thus, RyRs and IP3Rs can be differentially modulated by various emetogens and their antagonists provide further efficacy when combined with LTCC antagonists (Figure 2). Suppression of Ca2+ release from the sarco/endoplasmic reticulum stores through IP3Rs and RyRs may be additional targets for the prevention of nausea and vomiting.
\nIn mammals, cyclic AMP (cAMP) is synthesized by 10 adenylate cyclase isoforms [168]. One of the best-studied second messenger molecules downstream of selected G-protein coupled receptors is cAMP. It is an example of a transient and diffusible second messenger involved in signal propagation by integrating multiple intracellular signaling pathways [169]. cAMP activates protein kinase A (PKA) which results in phosphorylation of downstream intracellular signals. The adenylyl cyclase/cAMP/PKA signaling pathway can phosphorylate Ca2+ ion-channels found on the plasma membrane and intracellular IP3Rs [110]. These Ca2+ channels respectively increase extracellular Ca2+-influx and intracellular Ca2+-release [110]. The emetic role of cAMP has been well established (Figure 5), since microinjection of cAMP analogs (e.g., 8-bromocAMP) or forskolin (to enhance endogenous levels of cAMP) in the brainstem dorsal vagal complex emetic locus area postrema, not only can increase electrical activity of local neurons, but also induces vomiting in dogs [170]. Moreover, administration of 8-chlorocAMP as a potential chemotherapeutic in cancer patients can evoke nausea and vomiting [171]. Furthermore, phosphodiesterase inhibitors (PDEI) such as rolipram prevent cAMP metabolism and consequently increase cAMP tissue levels, which leads to excessive nausea and vomiting in humans [172]. In fact, one major side-effect of older PDEIs is excessive nausea and vomiting which often precludes their use in the clinical setting [173]. In addition, we have demonstrated that increased brain cAMP levels evoke vomiting which can be prevented by SQ22536 (Figure 5), an inhibitor of adenylyl cyclase [109]. Moreover, PKA-phosphorylation is associated with peak vomit frequency during both immediate- and delayed-phases of vomiting caused by either cisplatin or cyclophosphamide in the least shrew [109, 144, 149] (Figure 5).
\nSummarized behavioral and biochemical evidence for intracellular signaling molecules (cAMP, PKA, CaMKII, ERK1/2, PKC) related to emesis based on the least shrew emesis model. First, cyclic AMP (cAMP) is synthesized by adenylate cyclase and cAMP activates protein kinase A (PKA) [110, 168]. The adenylyl cyclase/cAMP/PKA signaling pathway can mediate vomiting. Indeed, increased levels of endogenous cAMP can evoke vomiting in animal models [109, 170] as well as humans [171, 172, 173], which can be prevented by adenylate cyclase inhibitor SQ22536 [109]. Evoked PKA-phosphorylation is associated with peak vomit frequency during both immediate- and delayed-phases of vomiting caused by cancer chemotherapeutics including cisplatin and cyclophosphamide in the least shrew [109, 144, 149]. In addition, Ca2+/calmodulin kinase IIα (CaMKIIα) and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) phosphorylation in the least shrew brainstem were elevated in vomiting evoked by the 5-HT3R agonist 2-Methyl-5-HT [46], thapsigargin [70], or the selective NK1R agonist GR73632 [167]. Phosphorylation of protein kinase Cα/βII (PKCα/βII) and ERK1/2 in least shrew brainstem were also upregulated in the vomiting induced by cisplatin [144, 149].
Vomit-associated Ca2+ mobilization as well as time-dependent Ca2+/calmodulin kinase IIα (CaMKIIα) and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) phosphorylation in the least shrew brainstem occurs: (i) following 5-HT3R-evoked vomiting caused by its selective agonist 2-Methyl-5-HT [46], (ii) thapsigargin-induced emesis in the least shrew [70], as well as (iii) NK1R-mediated vomiting evoked by the selective NK1R agonist GR73632 in the least shrew [167] (Figure 5). Our additional behavioral evidence that inhibitors of CaMKII or ERK1/2 attenuate the evoked emesis provides further credence for involvement of CaMKII and ERK1/2 downstream of the discussed emetic receptors/effectors. Furthermore, other published evidence support phosphorylation of protein kinase Cα/βII (PKCα/βII) and ERK1/2 in least shrew brainstem are associated with cisplatin-induced emesis [144, 149] (Figure 5). In fact significant upregulation of ERK1/2 phosphorylation occurs with peak vomit frequency during both the immediate and delayed phases of emesis caused by cisplatin in the least shrew [144, 149].
\nIt has been suggested that glucocorticoids’ antiemetic efficacy could be due to their anti-inflammatory effects [174] probably via a reduction in the synthesis of prostaglandins and leukotrienes [175], both of which can be increased during chemotherapy [6]. Although not all, but several prostaglandins (e.g., PGE2 and PGF2a) and cysteinyl leukotrienes (e.g., LTC4and LTD4), appear to be potent emetogens [72, 149, 176, 177]. Our findings demonstrate that unlike other leukotrienes (e.g., LTA4, LTB4 and LTF4), the above discussed leukotrienes are effective emetogens with the following potency order: LTC4 = LTD4 > LTE4. Regarding LTC4, the evoked vomiting was shown to be suppressed in a dose-dependent manner in the least shrew by the antiasthmatic drug pranlukast, the corresponding cysteinyl leukotrienes receptor 1 (CysLT1R) antagonist [72]. Although not available in the USA, the cost of other members of this class of drugs (montelukast and Zafirlukast) that are sold in the USA is less than one dollar per pill. Based on pranlukast’s efficacy against LTC4-induced vomiting [72], we envisaged it may have potential utility against cisplatin-evoked emesis. Our most recent publication [178] shows the potential of pranlukast (currently used for the treatment of various respiratory disorders including asthma), as a new class of antiemetic for the suppression of the acute- and delayed- phases of cisplatin-evoked vomiting in the least shrew. An intraperitoneal (i.p.) dose of 10 mg/kg pranlukast by itself significantly reduced the mean frequency of vomits by 70% and fully protected 46% of least shrews during the delayed-phase of cisplatin (10 mg/kg, i.p.)-evoked vomiting. Although pranlukast tended to substantially reduce both the mean frequency of vomits and the number of shrews vomiting during the early-phase, these reductions failed to attain significance. When pranlukast was combined with a first (tropisetron)- or a second (palonosetron)-generation 5-HT3R antagonist, it potentiated their antiemetic efficacy during both acute- and delayed-phases of cisplatin-evoked vomiting. Moreover, pranlukast potentiated the antiemetic efficacy of serotonin 5-HT3 receptor antagonists, tropisetron and palonosetron, against chemotherapy-induced nausea and vomiting. In fact per hour efficacy antiemetic profile of pranlukast combined with palonosetron or tropisetron during both phases of chemotherapy-induced nausea and vomiting in the least shrew resembles those of: (i) the NK1 receptor antagonist netupitant (5 mg/kg) plus palonosetron (0.1 mg/kg) in the same species [144]; (ii) netupitant plus ondansetron in ferrets [179]; and (iii) ondansetron plus aprepitant in combination with dexamethasone in ferrets [179]; and (iv) palonosetron plus netupitant in combination with dexamethasone in ferrets [179]. If analogs of pranlukast such as montelukast and zafirlukast can also provide similar antiemetic potential, then clinical trials should be initiated since this class of drugs are relatively inexpensive than available effective antiemetic regimens against chemotherapy-induced nausea and vomiting. Our related biochemical data indicates the mechanisms of antiemetic action of pranlukast are linked to suppression of cisplatin-elicited PKCα/βII, ERK1/2 and PKA activation (phosphorylation) in the least shrew brainstem [178]. Moreover, suppression of these signaling molecules may be shared in the anti-inflammatory signaling pathway of pranlukast.
\nWhen antiemetic mechanism of action of pranlukast against LTC4-induced vomiting or cisplatin-induced responses is discussed, Ca2+ is also an essential element. Montelukast and pranlukast were found to inhibit nucleotide-induced Ca2+ mobilization in a human monocyte-macrophage-like cell line, DMSO-differentiated U937 [180]. CysLT1 receptors belonging to the rhodopsin family of the G protein-coupled receptor genes respond to LTD4 with a strong increase in cytosolic Ca2+ concentration partially sensitive to pertussis toxin, and with the activation of the Ras-MAPK cascade totally dependent upon Gi/o [144]. These signaling effects were totally inhibited by various specific CysLT1-receptor antagonists, and CysLT1 antagonists inhibit both the P2Y agonist-induced activation of phospholipase C and intracellular Ca2+ mobilization [144].
\nChemotherapy-induced nausea and vomiting is a particularly distressing side-effect of chemotherapeutics for oncology patients both physically and psychologically. The use of 5-HT3R antagonists combined with NK1R antagonists, has enhanced physician’s ability to further suppress nausea, the rates of acute- and delayed-vomiting in cancer patients receiving chemotherapy. In addition to the commonly reported adverse effects of these agents (including headache, diarrhea, constipation, hiccups, and fatigue), many patients still experience nausea and delayed vomiting [181, 182, 183]. Furthermore, the use of second generation 5-HT3R and NK1R antagonists for the prevention of chemotherapy-induced nausea and vomiting is currently cost-prohibitive for most patients in the world. Mechanisms that cause nausea are only partially understood and probably in part overlap with those of vomiting. There are still unmet needs for newer and less expensive therapeutic options to improve the treatment across the entire spectrum of chemotherapy-induced nausea and vomiting. Additional studies should involve combinations of agents that inhibit other neurotransmitter systems involved in nausea and vomiting.
\nAs concluded in Figure 2, this systematic review shows clear evidence that Ca2+ modulation is an important contributor to antiemetic and probably anti-nausea signaling pathways. LTCC blockers, antagonists of intracellular IP3Rs and RyRs Ca2+ release channels as well as CysLT1R antagonists have the potential to provide less expensive (e.g., nifedipine, amlodipine, dantrolene, and pranlukast) broad-spectrum antiemetic agents for the clinic against diverse causes of nausea and vomiting. The discussed findings from the least shrew should help to open new avenues of research in other established animal models of emesis as well as in patients, targeting not only the already discussed Ca2+ channels, but also other Ca2+ channels that exist on both the plasma membrane and the membranes of intracellular organs such as the sarco/endoplasmic reticulum and mitochondria.
\nThis work was supported by NIH/NCI grant (RO1CA207287) and Western University of Health Science startup fund to NAD.
\nAn implementation of smart healthcare solutions can improve the quality of patient care to enhanced patient treatments. These kinds of solutions enable healthcare professionals to deliver the needed and adjusted medical treatment in a smarter and faster way [1]. With the increasing world population, the well-known conventional patient-doctor relationship has lost its effectiveness [2]. Hence, smart healthcare becomes very important and can be implemented at all levels in an organization or society starting from tracking vital signs in the elderly to temperature monitoring for babies. In other terms, smart healthcare technologies are not an end in itself [3]. With the implementation of healthcare technologies, organizations can create efficient workflows to ensure a high-quality in-patient treatment. This ambition is only achieved when technologies are put into use and fully utilized. The focus should therefore be in ensuring efficient use of both existing and new technologies [4, 5].
\nHealthcare technology is an interdisciplinary discipline that links technology and medical/clinical with a focus on developing new diagnostic and treatment methods [6]. Healthcare technology covers a number of technologies, such as medical technology, pharmacology, and biotechnology [7].
\nThe World Health Organization (WHO) has defined and described healthcare technology as the use of medicine, vaccines, procedures and systems—with the associated knowledge and skills—to address a health problem or improve quality of life [8]. Healthcare technology can be defined as technologies used to improve human health [9, 10]. The definition of health technology can be based on the WHO’s definition of health: “Health is not just freedom of disease, but maximum physical, mental and social well-being”
At the same time, one can apply a holistic approach to technology that covers technology, organization, knowledge, and product [12]. A user-oriented technology solution helps to maintain or even develop welfare services [13].
\nSmart healthcare feeds friendly hospital that enables patients and preferred partner in using hospital services with the best and newest health technology [14]. This means that hospitals must focus on developing services that motivate the use of healthcare technologies and focus on optimizing the workflows at clinics [15]. A better basis is needed, because without a better basis there cannot be a continuous focus on optimizing the internal processes and the ongoing support and maintenance of health technology and infrastructure [16]. Almost every hospital has the ambition to have effective use of health technology at the highest international level. The ambition to ensure efficient use of healthcare technology is all about how hospitals contribute locally and regionally to increase the quality of patient treatment and realize efficiency enhancements through health technology [17]. Therefore, healthcare technology plays a central role in supporting hospitals. Investing in healthcare technology has huge benefits. Realizing the need gains benefits through increased technology support and utilizing the experience gained at the individual hospitals. This means consistently developing and optimizing the task solution and patient treatment with health technology [18]. Services must be relevant and based on the needs of hospitals. The implementation should be based on deep knowledge, task solving, and priorities [19]. For effective and efficient use of health technology, it requires the greatest possible use of existing technology before developing new technologies with the necessary support for the users’ daily lives through qualified and efficient support. The journey toward becoming more efficient and therefore not to forget requires a common center and not a local branch. This means a constant balance for local needs, the overall gains for the region, and the ongoing standardization and follow-up [19].
\nResearch in new technology is developing rapidly in the health field. Six of the potential technologies to change the way we understand and safeguard human health is listed as follows [20].
\nIn term the telemedicine covers a broad concept [21]. This includes treatment and monitoring in patients’ own home, for example, through apps, video consultations, and automatic measuring equipment. Most municipalities over the world and regions are investing heavily in these technologies at the moment [22].
\nPhysiotherapists over video can do multi-patient exercises at once, and patients with severe wounds can consult remotely [23]. And people with heart problems can automatically get monitored blood pressure and distance activity. Even though the technology is in use there is still a long way to go [23].
\nHowever, telemedicine solutions do not work as intended [24]. In a small case study, a research team has shown a markedly increased mortality among patients treated via telemedicine [25].
\nNowadays, robots are used for surgeries when doing operation as gastric bypass, uterus, kidney, bladder, prostate, and colon. The advantage is that the robot surgery can be performed without opening the stomach up and the patient can leave the hospital earlier than with open surgery [26]. At the same time, the robot can see the body in 3-D; it is more flexible and has more precision. The result is less blood loss, fewer infections, less scars, shorter hospitalization, and fewer pains [27].
\nAmong young people, but it also spread quickly in the country’s nursing home, where the elderly also had the pleasure and benefit of the machine, because it was both entertaining and good training—a concept called exergaming, exercise and gaming [28, 29].
\nSince then, gaming technology has really gained momentum in healthcare. Today, games are used, among other things, for rehabilitation after cerebral hemorrhage and for the care of dementia, which through reversal play with old family pictures can get cognitive training and become calmer [30, 31].
\nImagine a home where it is being registered online every time you open the refrigerator door. The floor is pressure sensitive and can follow your walk around the house. In the potted plants, there are small sensors that measure every time you water the plant, and when you turn on the light, it is logged [32].
\nFor some, it sounds like a dystopic surveillance society. But for others, there are great opportunities to prevent hospital admissions among the elderly. The technology has huge potential. For example, pneumonia and urinary tract infections in the elderly can be traced in their everyday rhythms. If one can measure as soon as a breach of the patient ordinary routine occurs, treatment can put in much faster [33].
\nThese days, the body and technology are becoming closer and closer together. The so-called wearables—small pieces of electronics that you carry on the body, for example, in the form of clocks, glasses, or even electronic skin—can become the major revolution in the health world [34].
\nToday wearables are used to collect all sorts of data about your body: sleep rhythm, pulse, location, and, among other things, how much you exercise [35]. In the future, it will be even more comprehensive: reading insulin levels, anticipating ovulation, or monitoring how much sun you get.
\nHealth technology needs to be adapted to the users. Two basic elements of telescopic health must be present before it works: firstly, the technology must work, and secondly, the technology must be available to the many patient groups that need it. It is not the technology itself that is interesting, but what technology can be used for.
\nThere is one basic element of telecommunications health. The technology must be applicable to all the many patient groups, disease groups, and populations that need it, and where it can contribute valuable to health, safety, cohesion, learning, and quality of life [36].
\nThe patient, or the user, is thus the focal point. There is nothing new in that and it has been a good custom in healthcare and health technology for many years. But the demographic development of the Western world requires even more action than before to put action behind the words. Hence, a lot is needed to achieve a well-functioning telecommunications health when technology is ready.
\nOne of the pieces in this great puzzle is about “usability.” It must be easy, safe, useful and motivating for users to use the technology. The technology user interface must be intuitive and tailored to the specific user group, and when needed, the right effort must be organized to equip users to apply the technology properly. Human factors are an important part of health technology [37].
\n“Human factors” are becoming an increasingly important part as more and more patients with psychiatric disorders are being treated through technology [38]. Three aspects in particular are important in designing telecommunications health solutions, namely:
setting precise goals;
following and monitoring; and
giving feedback and promoting motivation [39].
Algorithms are already being researched, which can detect stress on the basis of voting, and early warning score (EWS) and mobile applications are being tested which, by means of individually adapted questions, can help schizophrenic patients maintain reality and achieve greater security [40].
\nThe technology itself is not interesting? Yes and no. It is only because of the many impressive technological achievements that it is even possible to create new value for patients, citizens, and communities. But the technologies only get value when they are realized for effective and usable health solutions. This includes competent involvement of human factors when developing, designing, and implementing telescopic health solutions [41].
\nHealth technology is rapidly evolving and embracing many areas and aspects where both public and private actors are at stake [42]. New terminologies and the development of new technology are constantly demanding health education programs [43, 44]. But there should also be a focus on the meeting between the health professional, the citizen, and the health technology. Furthermore, new technology requires a new set of skills, namely health and eHealth literacy. The concept of eHealth literacy is introduced and defined as the ability to seek, find, understand, and appraise health information from electronic sources and apply the knowledge gained to addressing or solving a health problem [45]. Health literacy refers to accessing, understanding, and using information to make health decisions [10].
\nIn Denmark, telecommunication is a commonly used technology. For example, the purpose of Patient@home is to develop welfare technology for the benefit of patients, the health sector, and society as a whole. Patient@home supports a general development toward more outpatient treatments and expansions to own home followed by home-monitored treatment, care, and/or rehabilitation. The goal of this is fewer and shorter hospital admissions as well as the development of new welfare technology, which in the long term can create jobs, exports, and growth in society. Patient empowerment is a central focus of Patient@home [46]. It is intended that a user-driven development of technologies is in progress so that the patient is supported in taking responsibility for their own health and treatment and at the same time makes it possible to be a patient in their own home [47].
\nFinland is one of the world’s leading countries in terms of health and welfare technology, and it needs to benefit the world [48, 49].
\nFinland is at the top of the world in terms of IT skills. This is reflected in a well-developed healthcare sector, where virtual reality, cloud-based data platforms, medicine robots, sensor systems, and more, which belongs to everyday life. Today, Finland ranks as the world’s third strongest country in health technology, and health technology is the country’s largest tech export product [49].
\nThe world faces convincing health challenges in an increased demand and fewer resources. Personal health technology enables a personalized, engaging, preventive, predictive effort in the field of prevention, diagnosis and monitoring, treatment, and assistive technology [50].
\nImplementation of welfare technology stands high on all municipalities’ agenda. Society is challenged by increasing life expectancy, fewer “warm hands,” and greater demands for charitable services [51].
\nWhen a patient is affected by illness or mister functioning, there is a need for rapid and effective efforts to resume an independent life, and, therefore, welfare technology is an optimal tool that can both contribute to training, support, and compensation and thereby help to promote the rehabilitation process. We already have the technologies.
\nThe challenge is to put them in play in everyday life for the benefit of both patient’s and healthcare professionals.
\nThere must not be health technology for the sake of health technology. The technology must be a need to and not nice to have the because it is something that gives value, either for healthcare professionals or patients- and very much for both healthcare professionals and patients. The staff’s knowledge and motivation are crucial for a good implementation.
\nDoes the healthcare professional not have the necessary knowledge of how a technology works, loses the face, seems unprofessional, and the technology is not being used? Instead, the staff should be thoroughly dressed so that they can safely operate and, not least, facilitate the citizens to use the technology [52].
\nPatients can seek their knowledge in the future and have less need to get the healthcare professionals’ expert knowledge. What they need is to be facilitated in how they use their knowledge and move on. Health professionals will change from being some who have the expertise to be someone who facilitates patients in using health technology [53].
\nHealthcare professionals’ motivation and engagement are also important to focus on in the implementation phase if they need to be adaptable and open to learning. Learn to take the new technologies, learn how to use them, and learn the new working methods that come with you.
\n\n
Experience of doubtful necessity
Implementation of welfare technology requires change in the organization. One of the most for achieving this change is that healthcare professionals experience the changes as compelling necessary. Does that mean that there must be an order from management that now they will use the technologies? No, the experience must come from the healthcare professionals themselves. Healthcare professionals must be able to see the benefits of using the technologies; for example, they can avoid heavy lifting with lifts and thus prevent many colleagues from being sick due to back problems [54].
If we can go to point out such things in collaboration with the healthcare professionals, so they can see that there is actually a scam here, they get an experience of imperative necessity. At the same time, it is important that we avoid self-satisfaction and “as we always have done.” If we fall into it, then there is no change.
Compose a working group
Next step is to put together a working group of motivated healthcare professionals who have an experience of imperative necessity and who wants changes. The workgroup should preferably consist of healthcare professionals, but there must also be a management level that can go in and take the organization and allocate the necessary resources, as well as being a technologist, with an overview of what technologies does the organization have and what they can used for. The working group must be present, where things happen.
Vision and strategy
The task of the working group is now to set the road. They must formulate the visions and strategies for where they are heading and how they will achieve the goal: to implement welfare technology. A strategy that ensures that staff feel safe using technology and taking it into service must be formulated.
It requires a clear vision and a clear strategy which are to be communicated internally within the working group and which are then communicated easily and clearly to the entire organization. These are not only for the healthcare professionals but also for the patients who come in as they may be able to use it when they get home [55].
Short-term goals against the goal
It is important that during the process that the workgroup can set some short-term goals that lead the organization toward the long-term goal: implementing welfare technology. The staff wants to experience and momentum and not get the whole change at once. There may be small instructional videos that present the solutions along the way or walked in living labs where staff can do things, so they are not used to using a new technology for the first time on a citizen, thus appearing insecure and unprofessional in working situation [56].
Give the healthcare professionals some resources and opportunities to practice, for example, in a living lab in a living room, safely and without being hurt because you do not know which button to press.
Consolidation via success stories
Finally, the technology must be consolidated by emphasizing all the small success stories that have been underway in the implementation phase. The healthcare professionals and patients must be able and encouraged to share and experience each other’s successor so that everyone can see that the technology can be used and that it works [57].
Healthcare technology is facing major challenges in relation to both human and financial resources. Therefore, there is a need for innovation. In the area of health and care, it is all about finding solutions where the technology makes us better able to service the patients remotely to free up resources, so that the patients achieve a much greater freedom and independence when the technology allows them to carry out several tasks from home via the technology themselves.
\nYou have been successfully unsubscribed.
",metaTitle:"Unsubscribe Successful",metaDescription:"You have been successfully unsubscribed.",metaKeywords:null,canonicalURL:"/page/unsubscribe-successful",contentRaw:'[{"type":"htmlEditorComponent","content":""}]'},components:[{type:"htmlEditorComponent",content:""}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. His current research interests include the areas of mobile communication systems and channel modeling in addition to atmospheric optical communications, adaptive optics and statistics",institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5775},{group:"region",caption:"Middle and South America",value:2,count:5238},{group:"region",caption:"Africa",value:3,count:1721},{group:"region",caption:"Asia",value:4,count:10409},{group:"region",caption:"Australia and Oceania",value:5,count:897},{group:"region",caption:"Europe",value:6,count:15805}],offset:12,limit:12,total:118374},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{hasNoEditors:"0",sort:"ebgfFaeGuveeFgfcChcyvfu"},books:[],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:18},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:5},{group:"topic",caption:"Business, Management and Economics",value:7,count:2},{group:"topic",caption:"Chemistry",value:8,count:8},{group:"topic",caption:"Computer and Information Science",value:9,count:6},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:7},{group:"topic",caption:"Engineering",value:11,count:20},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:4},{group:"topic",caption:"Materials Science",value:14,count:5},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:26},{group:"topic",caption:"Neuroscience",value:18,count:2},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:3},{group:"topic",caption:"Physics",value:20,count:3},{group:"topic",caption:"Psychology",value:21,count:4},{group:"topic",caption:"Robotics",value:22,count:1},{group:"topic",caption:"Social Sciences",value:23,count:3},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:1}],offset:0,limit:12,total:null},popularBooks:{featuredBooks:[{type:"book",id:"9521",title:"Antimicrobial Resistance",subtitle:"A One Health Perspective",isOpenForSubmission:!1,hash:"30949e78832e1afba5606634b52056ab",slug:"antimicrobial-resistance-a-one-health-perspective",bookSignature:"Mihai Mareș, Swee Hua Erin Lim, Kok-Song Lai and Romeo-Teodor Cristina",coverURL:"https://cdn.intechopen.com/books/images_new/9521.jpg",editors:[{id:"88785",title:"Prof.",name:"Mihai",middleName:null,surname:"Mares",slug:"mihai-mares",fullName:"Mihai Mares"}],equalEditorOne:{id:"190224",title:"Dr.",name:"Swee Hua Erin",middleName:null,surname:"Lim",slug:"swee-hua-erin-lim",fullName:"Swee Hua Erin Lim",profilePictureURL:"https://mts.intechopen.com/storage/users/190224/images/system/190224.png",biography:"Dr. Erin Lim is presently working as an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates and is affiliated as an Associate Professor to Perdana University-Royal College of Surgeons in Ireland, Selangor, Malaysia. She obtained her Ph.D. from Universiti Putra Malaysia in 2010 with a National Science Fellowship awarded from the Ministry of Science, Technology and Innovation Malaysia and has been actively involved in research ever since. Her main research interests include analysis of carriage and transmission of multidrug resistant bacteria in non-conventional settings, besides an interest in natural products for antimicrobial testing. She is heavily involved in the elucidation of mechanisms of reversal of resistance in bacteria in addition to investigating the immunological analyses of diseases, development of vaccination and treatment models in animals. She hopes her work will support the discovery of therapeutics in the clinical setting and assist in the combat against the burden of antibiotic resistance.",institutionString:"Abu Dhabi Women’s College",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Perdana University",institutionURL:null,country:{name:"Malaysia"}}},equalEditorTwo:{id:"221544",title:"Dr.",name:"Kok-Song",middleName:null,surname:"Lai",slug:"kok-song-lai",fullName:"Kok-Song Lai",profilePictureURL:"https://mts.intechopen.com/storage/users/221544/images/system/221544.jpeg",biography:"Dr. Lai Kok Song is an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates. He obtained his Ph.D. in Biological Sciences from Nara Institute of Science and Technology, Japan in 2012. Prior to his academic appointment, Dr. Lai worked as a Senior Scientist at the Ministry of Science, Technology and Innovation, Malaysia. His current research areas include antimicrobial resistance and plant-pathogen interaction. His particular interest lies in the study of the antimicrobial mechanism via membrane disruption of essential oils against multi-drug resistance bacteria through various biochemical, molecular and proteomic approaches. Ultimately, he hopes to uncover and determine novel biomarkers related to antibiotic resistance that can be developed into new therapeutic strategies.",institutionString:"Higher Colleges of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Higher Colleges of Technology",institutionURL:null,country:{name:"United Arab Emirates"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10020",title:"Operations Management",subtitle:"Emerging Trend in the Digital Era",isOpenForSubmission:!1,hash:"526f0dbdc7e4d85b82ce8383ab894b4c",slug:"operations-management-emerging-trend-in-the-digital-era",bookSignature:"Antonella Petrillo, Fabio De Felice, Germano Lambert-Torres and Erik Bonaldi",coverURL:"https://cdn.intechopen.com/books/images_new/10020.jpg",editors:[{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9560",title:"Creativity",subtitle:"A Force to Innovation",isOpenForSubmission:!1,hash:"58f740bc17807d5d88d647c525857b11",slug:"creativity-a-force-to-innovation",bookSignature:"Pooja Jain",coverURL:"https://cdn.intechopen.com/books/images_new/9560.jpg",editors:[{id:"316765",title:"Dr.",name:"Pooja",middleName:null,surname:"Jain",slug:"pooja-jain",fullName:"Pooja Jain"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10192",title:"Background and Management of Muscular Atrophy",subtitle:null,isOpenForSubmission:!1,hash:"eca24028d89912b5efea56e179dff089",slug:"background-and-management-of-muscular-atrophy",bookSignature:"Julianna Cseri",coverURL:"https://cdn.intechopen.com/books/images_new/10192.jpg",editors:[{id:"135579",title:"Dr.",name:"Julianna",middleName:null,surname:"Cseri",slug:"julianna-cseri",fullName:"Julianna Cseri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9243",title:"Coastal Environments",subtitle:null,isOpenForSubmission:!1,hash:"8e05e5f631e935eef366980f2e28295d",slug:"coastal-environments",bookSignature:"Yuanzhi Zhang and X. San Liang",coverURL:"https://cdn.intechopen.com/books/images_new/9243.jpg",editors:[{id:"77597",title:"Prof.",name:"Yuanzhi",middleName:null,surname:"Zhang",slug:"yuanzhi-zhang",fullName:"Yuanzhi Zhang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9644",title:"Glaciers and the Polar Environment",subtitle:null,isOpenForSubmission:!1,hash:"e8cfdc161794e3753ced54e6ff30873b",slug:"glaciers-and-the-polar-environment",bookSignature:"Masaki Kanao, Danilo Godone and Niccolò Dematteis",coverURL:"https://cdn.intechopen.com/books/images_new/9644.jpg",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9550",title:"Entrepreneurship",subtitle:"Contemporary Issues",isOpenForSubmission:!1,hash:"9b4ac1ee5b743abf6f88495452b1e5e7",slug:"entrepreneurship-contemporary-issues",bookSignature:"Mladen Turuk",coverURL:"https://cdn.intechopen.com/books/images_new/9550.jpg",editors:[{id:"319755",title:"Prof.",name:"Mladen",middleName:null,surname:"Turuk",slug:"mladen-turuk",fullName:"Mladen Turuk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9027",title:"Human Blood Group Systems and Haemoglobinopathies",subtitle:null,isOpenForSubmission:!1,hash:"d00d8e40b11cfb2547d1122866531c7e",slug:"human-blood-group-systems-and-haemoglobinopathies",bookSignature:"Osaro Erhabor and Anjana Munshi",coverURL:"https://cdn.intechopen.com/books/images_new/9027.jpg",editors:[{id:"35140",title:null,name:"Osaro",middleName:null,surname:"Erhabor",slug:"osaro-erhabor",fullName:"Osaro Erhabor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8558",title:"Aerodynamics",subtitle:null,isOpenForSubmission:!1,hash:"db7263fc198dfb539073ba0260a7f1aa",slug:"aerodynamics",bookSignature:"Mofid Gorji-Bandpy and Aly-Mousaad Aly",coverURL:"https://cdn.intechopen.com/books/images_new/8558.jpg",editors:[{id:"35542",title:"Prof.",name:"Mofid",middleName:null,surname:"Gorji-Bandpy",slug:"mofid-gorji-bandpy",fullName:"Mofid Gorji-Bandpy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5247},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9521",title:"Antimicrobial Resistance",subtitle:"A One Health Perspective",isOpenForSubmission:!1,hash:"30949e78832e1afba5606634b52056ab",slug:"antimicrobial-resistance-a-one-health-perspective",bookSignature:"Mihai Mareș, Swee Hua Erin Lim, Kok-Song Lai and Romeo-Teodor Cristina",coverURL:"https://cdn.intechopen.com/books/images_new/9521.jpg",editors:[{id:"88785",title:"Prof.",name:"Mihai",middleName:null,surname:"Mares",slug:"mihai-mares",fullName:"Mihai Mares"}],equalEditorOne:{id:"190224",title:"Dr.",name:"Swee Hua Erin",middleName:null,surname:"Lim",slug:"swee-hua-erin-lim",fullName:"Swee Hua Erin Lim",profilePictureURL:"https://mts.intechopen.com/storage/users/190224/images/system/190224.png",biography:"Dr. Erin Lim is presently working as an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates and is affiliated as an Associate Professor to Perdana University-Royal College of Surgeons in Ireland, Selangor, Malaysia. She obtained her Ph.D. from Universiti Putra Malaysia in 2010 with a National Science Fellowship awarded from the Ministry of Science, Technology and Innovation Malaysia and has been actively involved in research ever since. Her main research interests include analysis of carriage and transmission of multidrug resistant bacteria in non-conventional settings, besides an interest in natural products for antimicrobial testing. She is heavily involved in the elucidation of mechanisms of reversal of resistance in bacteria in addition to investigating the immunological analyses of diseases, development of vaccination and treatment models in animals. She hopes her work will support the discovery of therapeutics in the clinical setting and assist in the combat against the burden of antibiotic resistance.",institutionString:"Abu Dhabi Women’s College",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Perdana University",institutionURL:null,country:{name:"Malaysia"}}},equalEditorTwo:{id:"221544",title:"Dr.",name:"Kok-Song",middleName:null,surname:"Lai",slug:"kok-song-lai",fullName:"Kok-Song Lai",profilePictureURL:"https://mts.intechopen.com/storage/users/221544/images/system/221544.jpeg",biography:"Dr. Lai Kok Song is an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates. He obtained his Ph.D. in Biological Sciences from Nara Institute of Science and Technology, Japan in 2012. Prior to his academic appointment, Dr. Lai worked as a Senior Scientist at the Ministry of Science, Technology and Innovation, Malaysia. His current research areas include antimicrobial resistance and plant-pathogen interaction. His particular interest lies in the study of the antimicrobial mechanism via membrane disruption of essential oils against multi-drug resistance bacteria through various biochemical, molecular and proteomic approaches. Ultimately, he hopes to uncover and determine novel biomarkers related to antibiotic resistance that can be developed into new therapeutic strategies.",institutionString:"Higher Colleges of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Higher Colleges of Technology",institutionURL:null,country:{name:"United Arab Emirates"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10020",title:"Operations Management",subtitle:"Emerging Trend in the Digital Era",isOpenForSubmission:!1,hash:"526f0dbdc7e4d85b82ce8383ab894b4c",slug:"operations-management-emerging-trend-in-the-digital-era",bookSignature:"Antonella Petrillo, Fabio De Felice, Germano Lambert-Torres and Erik Bonaldi",coverURL:"https://cdn.intechopen.com/books/images_new/10020.jpg",editors:[{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9560",title:"Creativity",subtitle:"A Force to Innovation",isOpenForSubmission:!1,hash:"58f740bc17807d5d88d647c525857b11",slug:"creativity-a-force-to-innovation",bookSignature:"Pooja Jain",coverURL:"https://cdn.intechopen.com/books/images_new/9560.jpg",editors:[{id:"316765",title:"Dr.",name:"Pooja",middleName:null,surname:"Jain",slug:"pooja-jain",fullName:"Pooja Jain"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10192",title:"Background and Management of Muscular Atrophy",subtitle:null,isOpenForSubmission:!1,hash:"eca24028d89912b5efea56e179dff089",slug:"background-and-management-of-muscular-atrophy",bookSignature:"Julianna Cseri",coverURL:"https://cdn.intechopen.com/books/images_new/10192.jpg",editors:[{id:"135579",title:"Dr.",name:"Julianna",middleName:null,surname:"Cseri",slug:"julianna-cseri",fullName:"Julianna Cseri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9243",title:"Coastal Environments",subtitle:null,isOpenForSubmission:!1,hash:"8e05e5f631e935eef366980f2e28295d",slug:"coastal-environments",bookSignature:"Yuanzhi Zhang and X. San Liang",coverURL:"https://cdn.intechopen.com/books/images_new/9243.jpg",editors:[{id:"77597",title:"Prof.",name:"Yuanzhi",middleName:null,surname:"Zhang",slug:"yuanzhi-zhang",fullName:"Yuanzhi Zhang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9644",title:"Glaciers and the Polar Environment",subtitle:null,isOpenForSubmission:!1,hash:"e8cfdc161794e3753ced54e6ff30873b",slug:"glaciers-and-the-polar-environment",bookSignature:"Masaki Kanao, Danilo Godone and Niccolò Dematteis",coverURL:"https://cdn.intechopen.com/books/images_new/9644.jpg",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9550",title:"Entrepreneurship",subtitle:"Contemporary Issues",isOpenForSubmission:!1,hash:"9b4ac1ee5b743abf6f88495452b1e5e7",slug:"entrepreneurship-contemporary-issues",bookSignature:"Mladen Turuk",coverURL:"https://cdn.intechopen.com/books/images_new/9550.jpg",editors:[{id:"319755",title:"Prof.",name:"Mladen",middleName:null,surname:"Turuk",slug:"mladen-turuk",fullName:"Mladen Turuk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"9243",title:"Coastal Environments",subtitle:null,isOpenForSubmission:!1,hash:"8e05e5f631e935eef366980f2e28295d",slug:"coastal-environments",bookSignature:"Yuanzhi Zhang and X. San Liang",coverURL:"https://cdn.intechopen.com/books/images_new/9243.jpg",editedByType:"Edited by",editors:[{id:"77597",title:"Prof.",name:"Yuanzhi",middleName:null,surname:"Zhang",slug:"yuanzhi-zhang",fullName:"Yuanzhi Zhang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10020",title:"Operations Management",subtitle:"Emerging Trend in the Digital Era",isOpenForSubmission:!1,hash:"526f0dbdc7e4d85b82ce8383ab894b4c",slug:"operations-management-emerging-trend-in-the-digital-era",bookSignature:"Antonella Petrillo, Fabio De Felice, Germano Lambert-Torres and Erik Bonaldi",coverURL:"https://cdn.intechopen.com/books/images_new/10020.jpg",editedByType:"Edited by",editors:[{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9521",title:"Antimicrobial Resistance",subtitle:"A One Health Perspective",isOpenForSubmission:!1,hash:"30949e78832e1afba5606634b52056ab",slug:"antimicrobial-resistance-a-one-health-perspective",bookSignature:"Mihai Mareș, Swee Hua Erin Lim, Kok-Song Lai and Romeo-Teodor Cristina",coverURL:"https://cdn.intechopen.com/books/images_new/9521.jpg",editedByType:"Edited by",editors:[{id:"88785",title:"Prof.",name:"Mihai",middleName:null,surname:"Mares",slug:"mihai-mares",fullName:"Mihai Mares"}],equalEditorOne:{id:"190224",title:"Dr.",name:"Swee Hua Erin",middleName:null,surname:"Lim",slug:"swee-hua-erin-lim",fullName:"Swee Hua Erin Lim",profilePictureURL:"https://mts.intechopen.com/storage/users/190224/images/system/190224.png",biography:"Dr. Erin Lim is presently working as an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates and is affiliated as an Associate Professor to Perdana University-Royal College of Surgeons in Ireland, Selangor, Malaysia. She obtained her Ph.D. from Universiti Putra Malaysia in 2010 with a National Science Fellowship awarded from the Ministry of Science, Technology and Innovation Malaysia and has been actively involved in research ever since. Her main research interests include analysis of carriage and transmission of multidrug resistant bacteria in non-conventional settings, besides an interest in natural products for antimicrobial testing. She is heavily involved in the elucidation of mechanisms of reversal of resistance in bacteria in addition to investigating the immunological analyses of diseases, development of vaccination and treatment models in animals. She hopes her work will support the discovery of therapeutics in the clinical setting and assist in the combat against the burden of antibiotic resistance.",institutionString:"Abu Dhabi Women’s College",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Perdana University",institutionURL:null,country:{name:"Malaysia"}}},equalEditorTwo:{id:"221544",title:"Dr.",name:"Kok-Song",middleName:null,surname:"Lai",slug:"kok-song-lai",fullName:"Kok-Song Lai",profilePictureURL:"https://mts.intechopen.com/storage/users/221544/images/system/221544.jpeg",biography:"Dr. Lai Kok Song is an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates. He obtained his Ph.D. in Biological Sciences from Nara Institute of Science and Technology, Japan in 2012. Prior to his academic appointment, Dr. Lai worked as a Senior Scientist at the Ministry of Science, Technology and Innovation, Malaysia. His current research areas include antimicrobial resistance and plant-pathogen interaction. His particular interest lies in the study of the antimicrobial mechanism via membrane disruption of essential oils against multi-drug resistance bacteria through various biochemical, molecular and proteomic approaches. Ultimately, he hopes to uncover and determine novel biomarkers related to antibiotic resistance that can be developed into new therapeutic strategies.",institutionString:"Higher Colleges of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Higher Colleges of Technology",institutionURL:null,country:{name:"United Arab Emirates"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9560",title:"Creativity",subtitle:"A Force to Innovation",isOpenForSubmission:!1,hash:"58f740bc17807d5d88d647c525857b11",slug:"creativity-a-force-to-innovation",bookSignature:"Pooja Jain",coverURL:"https://cdn.intechopen.com/books/images_new/9560.jpg",editedByType:"Edited by",editors:[{id:"316765",title:"Dr.",name:"Pooja",middleName:null,surname:"Jain",slug:"pooja-jain",fullName:"Pooja Jain"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9669",title:"Recent Advances in Rice Research",subtitle:null,isOpenForSubmission:!1,hash:"12b06cc73e89af1e104399321cc16a75",slug:"recent-advances-in-rice-research",bookSignature:"Mahmood-ur- Rahman Ansari",coverURL:"https://cdn.intechopen.com/books/images_new/9669.jpg",editedByType:"Edited by",editors:[{id:"185476",title:"Dr.",name:"Mahmood-Ur-",middleName:null,surname:"Rahman Ansari",slug:"mahmood-ur-rahman-ansari",fullName:"Mahmood-Ur- Rahman Ansari"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10192",title:"Background and Management of Muscular Atrophy",subtitle:null,isOpenForSubmission:!1,hash:"eca24028d89912b5efea56e179dff089",slug:"background-and-management-of-muscular-atrophy",bookSignature:"Julianna Cseri",coverURL:"https://cdn.intechopen.com/books/images_new/10192.jpg",editedByType:"Edited by",editors:[{id:"135579",title:"Dr.",name:"Julianna",middleName:null,surname:"Cseri",slug:"julianna-cseri",fullName:"Julianna Cseri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9550",title:"Entrepreneurship",subtitle:"Contemporary Issues",isOpenForSubmission:!1,hash:"9b4ac1ee5b743abf6f88495452b1e5e7",slug:"entrepreneurship-contemporary-issues",bookSignature:"Mladen Turuk",coverURL:"https://cdn.intechopen.com/books/images_new/9550.jpg",editedByType:"Edited by",editors:[{id:"319755",title:"Prof.",name:"Mladen",middleName:null,surname:"Turuk",slug:"mladen-turuk",fullName:"Mladen Turuk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editedByType:"Edited by",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9313",title:"Clay Science and Technology",subtitle:null,isOpenForSubmission:!1,hash:"6fa7e70396ff10620e032bb6cfa6fb72",slug:"clay-science-and-technology",bookSignature:"Gustavo Morari Do Nascimento",coverURL:"https://cdn.intechopen.com/books/images_new/9313.jpg",editedByType:"Edited by",editors:[{id:"7153",title:"Prof.",name:"Gustavo",middleName:null,surname:"Morari Do Nascimento",slug:"gustavo-morari-do-nascimento",fullName:"Gustavo Morari Do Nascimento"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9888",title:"Nuclear Power Plants",subtitle:"The Processes from the Cradle to the Grave",isOpenForSubmission:!1,hash:"c2c8773e586f62155ab8221ebb72a849",slug:"nuclear-power-plants-the-processes-from-the-cradle-to-the-grave",bookSignature:"Nasser Awwad",coverURL:"https://cdn.intechopen.com/books/images_new/9888.jpg",editedByType:"Edited by",editors:[{id:"145209",title:"Prof.",name:"Nasser",middleName:"S",surname:"Awwad",slug:"nasser-awwad",fullName:"Nasser Awwad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"1152",title:"Reconstructive Surgery",slug:"reconstructive-surgery",parent:{title:"Surgery",slug:"surgery"},numberOfBooks:7,numberOfAuthorsAndEditors:219,numberOfWosCitations:79,numberOfCrossrefCitations:47,numberOfDimensionsCitations:113,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"reconstructive-surgery",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"8853",title:"Breast Cancer and Breast Reconstruction",subtitle:null,isOpenForSubmission:!1,hash:"5947d4ba7ac1e9c39c9083e89201275c",slug:"breast-cancer-and-breast-reconstruction",bookSignature:"Luis Tejedor, Susana Gómez Modet, Lachezar Manchev and Arli Aditya Parikesit",coverURL:"https://cdn.intechopen.com/books/images_new/8853.jpg",editedByType:"Edited by",editors:[{id:"81170",title:"Dr.",name:"Luis",middleName:null,surname:"Tejedor",slug:"luis-tejedor",fullName:"Luis Tejedor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5428",title:"Designing Strategies for Cleft Lip and Palate Care",subtitle:null,isOpenForSubmission:!1,hash:"20bcf2aa877c04447d31d6e0db2e437e",slug:"designing-strategies-for-cleft-lip-and-palate-care",bookSignature:"Mazen Ahmad Almasri",coverURL:"https://cdn.intechopen.com/books/images_new/5428.jpg",editedByType:"Edited by",editors:[{id:"150413",title:"Dr.",name:"Mazen Ahmad",middleName:null,surname:"Almasri",slug:"mazen-ahmad-almasri",fullName:"Mazen Ahmad Almasri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3283",title:"Skin Grafts",subtitle:null,isOpenForSubmission:!1,hash:"51201608d5c5d7ff6f47e5afd2abdb9f",slug:"skin-grafts",bookSignature:"Madhuri Gore",coverURL:"https://cdn.intechopen.com/books/images_new/3283.jpg",editedByType:"Edited by",editors:[{id:"157243",title:"Dr.",name:"Madhuri",middleName:null,surname:"Gore",slug:"madhuri-gore",fullName:"Madhuri Gore"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"984",title:"Current Concepts in Plastic Surgery",subtitle:null,isOpenForSubmission:!1,hash:"46fb663adfdfb9ceeb2df2013b08038f",slug:"current-concepts-in-plastic-surgery",bookSignature:"Francisco J. Agullo",coverURL:"https://cdn.intechopen.com/books/images_new/984.jpg",editedByType:"Edited by",editors:[{id:"49319",title:"Dr.",name:"Frank",middleName:null,surname:"Agullo",slug:"frank-agullo",fullName:"Frank Agullo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"943",title:"Bone Grafting",subtitle:null,isOpenForSubmission:!1,hash:"9afab8beeb4879b2751907783a3de842",slug:"bone-grafting",bookSignature:"Alessandro Zorzi and Joao Batista de Miranda",coverURL:"https://cdn.intechopen.com/books/images_new/943.jpg",editedByType:"Edited by",editors:[{id:"80871",title:"M.D.",name:"Alessandro Rozim",middleName:null,surname:"Zorzi",slug:"alessandro-rozim-zorzi",fullName:"Alessandro Rozim Zorzi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1007",title:"Xenotransplantation",subtitle:null,isOpenForSubmission:!1,hash:"45fde91777f91583197a5b5dfecb207a",slug:"xenotransplantation",bookSignature:"Shuji Miyagawa",coverURL:"https://cdn.intechopen.com/books/images_new/1007.jpg",editedByType:"Edited by",editors:[{id:"73965",title:"Prof.",name:"Shuji",middleName:null,surname:"Miyagawa",slug:"shuji-miyagawa",fullName:"Shuji Miyagawa"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1305",title:"Advances in Endoscopic Surgery",subtitle:null,isOpenForSubmission:!1,hash:"84236c28c671a83f6cd1cd8bb84d873f",slug:"advances-in-endoscopic-surgery",bookSignature:"Cornel Iancu",coverURL:"https://cdn.intechopen.com/books/images_new/1305.jpg",editedByType:"Edited by",editors:[{id:"33183",title:"Prof.",name:"Cornel",middleName:null,surname:"Iancu",slug:"cornel-iancu",fullName:"Cornel Iancu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:7,mostCitedChapters:[{id:"33456",doi:"10.5772/30442",title:"Basic Knowledge of Bone Grafting",slug:"basic-knowledge-of-bone-grafting",totalDownloads:27429,totalCrossrefCites:6,totalDimensionsCites:9,book:{slug:"bone-grafting",title:"Bone Grafting",fullTitle:"Bone Grafting"},signatures:"Nguyen Ngoc Hung",authors:[{id:"82591",title:"Prof.",name:"Nguyen",middleName:null,surname:"Ngoc Hung",slug:"nguyen-ngoc-hung",fullName:"Nguyen Ngoc Hung"}]},{id:"33460",doi:"10.5772/31149",title:"Congenital Pseudarthrosis of the Tibia: Combined Pharmacologic and Surgical Treatment Using Biphosphonate Intravenous Infusion and Bone Morphogenic Protein with Periosteal and Cancellous Autogenous Bone Grafting, Tibio-Fibular Cross Union, Intramedullary",slug:"treatment-of-congenital-pseudarthrosis-with-periosteal-and-cancellous-bone-grafting-",totalDownloads:3003,totalCrossrefCites:4,totalDimensionsCites:9,book:{slug:"bone-grafting",title:"Bone Grafting",fullTitle:"Bone Grafting"},signatures:"Dror Paley",authors:[{id:"85789",title:"Dr.",name:"Dror",middleName:null,surname:"Paley",slug:"dror-paley",fullName:"Dror Paley"}]},{id:"39014",doi:"10.5772/51852",title:"Treatment of Leg Chronic Wounds with Dermal Substitutes and Thin Skin Grafts",slug:"treatment-of-leg-chronic-wounds-with-dermal-substitutes-and-thin-skin-grafts",totalDownloads:3144,totalCrossrefCites:0,totalDimensionsCites:6,book:{slug:"skin-grafts",title:"Skin Grafts",fullTitle:"Skin Grafts"},signatures:"Silvestro Canonico, Ferdinando Campitiello, Angela Della Corte, Vincenzo Padovano and Gianluca Pellino",authors:[{id:"68551",title:"Dr.",name:"Gianluca",middleName:null,surname:"Pellino",slug:"gianluca-pellino",fullName:"Gianluca Pellino"},{id:"157129",title:"Prof.",name:"Silvestro",middleName:null,surname:"Canonico",slug:"silvestro-canonico",fullName:"Silvestro Canonico"},{id:"157133",title:"Dr.",name:"Ferdinando",middleName:null,surname:"Campitiello",slug:"ferdinando-campitiello",fullName:"Ferdinando Campitiello"},{id:"165428",title:"Dr.",name:"Angela",middleName:null,surname:"Della Corte",slug:"angela-della-corte",fullName:"Angela Della Corte"},{id:"165429",title:"Dr.",name:"Vincenzo",middleName:null,surname:"Padovano",slug:"vincenzo-padovano",fullName:"Vincenzo Padovano"}]}],mostDownloadedChaptersLast30Days:[{id:"53788",title:"Surgical Techniques for Treatment of Unilateral Cleft Lip",slug:"surgical-techniques-for-treatment-of-unilateral-cleft-lip",totalDownloads:3042,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"designing-strategies-for-cleft-lip-and-palate-care",title:"Designing Strategies for Cleft Lip and Palate Care",fullTitle:"Designing Strategies for Cleft Lip and Palate Care"},signatures:"Mustafa Chopan, Lohrasb Sayadi and Donald R. Laub",authors:[{id:"67264",title:"Dr.",name:"Donald",middleName:"R",surname:"Laub Jr.",slug:"donald-laub-jr.",fullName:"Donald Laub Jr."},{id:"189368",title:"Mr.",name:"Mustafa",middleName:null,surname:"Chopan",slug:"mustafa-chopan",fullName:"Mustafa Chopan"},{id:"189370",title:"Mr.",name:"Lorasb",middleName:null,surname:"Sayadi",slug:"lorasb-sayadi",fullName:"Lorasb Sayadi"}]},{id:"53858",title:"Surgical Strategy of Cleft Palate Repair and Nasometric Results",slug:"surgical-strategy-of-cleft-palate-repair-and-nasometric-results",totalDownloads:1249,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"designing-strategies-for-cleft-lip-and-palate-care",title:"Designing Strategies for Cleft Lip and Palate Care",fullTitle:"Designing Strategies for Cleft Lip and Palate Care"},signatures:"Norifumi Nakamura and Masahiro Tezuka",authors:[{id:"72560",title:"Prof.",name:"Norifumi",middleName:null,surname:"Nakamura",slug:"norifumi-nakamura",fullName:"Norifumi Nakamura"},{id:"189479",title:"Dr.",name:"Masahiro",middleName:null,surname:"Tezuka",slug:"masahiro-tezuka",fullName:"Masahiro Tezuka"}]},{id:"67059",title:"Oncoplastic Surgery in Breast Cancer",slug:"oncoplastic-surgery-in-breast-cancer",totalDownloads:392,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"breast-cancer-and-breast-reconstruction",title:"Breast Cancer and Breast Reconstruction",fullTitle:"Breast Cancer and Breast Reconstruction"},signatures:"Atallah David, Moubarak Malak and Abdallah Abdallah",authors:[{id:"219535",title:"Associate Prof.",name:"David",middleName:null,surname:"Atallah",slug:"david-atallah",fullName:"David Atallah"},{id:"221488",title:"Dr.",name:"Malak",middleName:null,surname:"Moubarak",slug:"malak-moubarak",fullName:"Malak Moubarak"},{id:"299454",title:"Dr.",name:"Abdallah",middleName:null,surname:"Abdallah",slug:"abdallah-abdallah",fullName:"Abdallah Abdallah"}]},{id:"54055",title:"Cleft Lip and Palate Patients: Diagnosis and Treatment",slug:"cleft-lip-and-palate-patients-diagnosis-and-treatment",totalDownloads:1864,totalCrossrefCites:2,totalDimensionsCites:2,book:{slug:"designing-strategies-for-cleft-lip-and-palate-care",title:"Designing Strategies for Cleft Lip and Palate Care",fullTitle:"Designing Strategies for Cleft Lip and Palate Care"},signatures:"Letizia Perillo, Fabrizia d’Apuzzo, Sara Eslami and Abdolreza\nJamilian",authors:[{id:"171777",title:"Prof.",name:"Abdolreza",middleName:null,surname:"Jamilian",slug:"abdolreza-jamilian",fullName:"Abdolreza Jamilian"},{id:"173044",title:"Prof.",name:"Letizia",middleName:null,surname:"Perillo",slug:"letizia-perillo",fullName:"Letizia Perillo"},{id:"197679",title:"Dr.",name:"Sara",middleName:null,surname:"Eslami",slug:"sara-eslami",fullName:"Sara Eslami"},{id:"198961",title:"MSc.",name:"Fabrizia",middleName:null,surname:"D'Apuzzo",slug:"fabrizia-d'apuzzo",fullName:"Fabrizia D'Apuzzo"}]},{id:"33481",title:"Tuberous Breast: Clinical Evaluation and Surgical Treatment",slug:"tuberous-breast-clinical-evaluation-and-surgical-treatment",totalDownloads:13769,totalCrossrefCites:2,totalDimensionsCites:3,book:{slug:"current-concepts-in-plastic-surgery",title:"Current Concepts in Plastic Surgery",fullTitle:"Current Concepts in Plastic Surgery"},signatures:"Giovanni Zoccali and Maurizio Giuliani",authors:[{id:"75465",title:"Prof.",name:"Maurizio",middleName:null,surname:"Giuliani",slug:"maurizio-giuliani",fullName:"Maurizio Giuliani"},{id:"76973",title:"Dr.",name:"Giovanni",middleName:null,surname:"Zoccali",slug:"giovanni-zoccali",fullName:"Giovanni Zoccali"}]},{id:"33456",title:"Basic Knowledge of Bone Grafting",slug:"basic-knowledge-of-bone-grafting",totalDownloads:27425,totalCrossrefCites:6,totalDimensionsCites:9,book:{slug:"bone-grafting",title:"Bone Grafting",fullTitle:"Bone Grafting"},signatures:"Nguyen Ngoc Hung",authors:[{id:"82591",title:"Prof.",name:"Nguyen",middleName:null,surname:"Ngoc Hung",slug:"nguyen-ngoc-hung",fullName:"Nguyen Ngoc Hung"}]},{id:"33455",title:"Introduction",slug:"introduction1",totalDownloads:1630,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"bone-grafting",title:"Bone Grafting",fullTitle:"Bone Grafting"},signatures:"Alessandro Rozim Zorzi and João Batista de Miranda",authors:[{id:"80871",title:"M.D.",name:"Alessandro Rozim",middleName:null,surname:"Zorzi",slug:"alessandro-rozim-zorzi",fullName:"Alessandro Rozim Zorzi"},{id:"84386",title:"Prof.",name:"João",middleName:null,surname:"Batista de Miranda",slug:"joao-batista-de-miranda",fullName:"João Batista de Miranda"}]},{id:"53715",title:"Cleft Lip and Palate in the Dog: Medical and Genetic Aspects",slug:"cleft-lip-and-palate-in-the-dog-medical-and-genetic-aspects",totalDownloads:6438,totalCrossrefCites:1,totalDimensionsCites:4,book:{slug:"designing-strategies-for-cleft-lip-and-palate-care",title:"Designing Strategies for Cleft Lip and Palate Care",fullTitle:"Designing Strategies for Cleft Lip and Palate Care"},signatures:"Enio Moura and Cláudia Turra Pimpão",authors:[{id:"91097",title:"Prof.",name:"Enio",middleName:null,surname:"Moura",slug:"enio-moura",fullName:"Enio Moura"},{id:"194711",title:"Dr.",name:"Cláudia",middleName:null,surname:"Pimpão",slug:"claudia-pimpao",fullName:"Cláudia Pimpão"}]},{id:"42570",title:"Polyethylene Surgical Drape Dressing for Split Thickness Skin Graft Donor Areas",slug:"polyethylene-surgical-drape-dressing-for-split-thickness-skin-graft-donor-areas",totalDownloads:1564,totalCrossrefCites:0,totalDimensionsCites:2,book:{slug:"skin-grafts",title:"Skin Grafts",fullTitle:"Skin Grafts"},signatures:"Madhuri A. Gore, Kabeer Umakumar and Sandhya P. Iyer",authors:[{id:"157243",title:"Dr.",name:"Madhuri",middleName:null,surname:"Gore",slug:"madhuri-gore",fullName:"Madhuri Gore"}]},{id:"53918",title:"Epidemiology of Cleft Lip and Palate",slug:"epidemiology-of-cleft-lip-and-palate",totalDownloads:2032,totalCrossrefCites:3,totalDimensionsCites:3,book:{slug:"designing-strategies-for-cleft-lip-and-palate-care",title:"Designing Strategies for Cleft Lip and Palate Care",fullTitle:"Designing Strategies for Cleft Lip and Palate Care"},signatures:"Mairaj K. Ahmed, Anthony H. Bui and Emanuela Taioli",authors:[{id:"188212",title:"Dr.",name:"Mairaj K.",middleName:null,surname:"Ahmed",slug:"mairaj-k.-ahmed",fullName:"Mairaj K. Ahmed"},{id:"194367",title:"Dr.",name:"Emanuela",middleName:null,surname:"Taioli",slug:"emanuela-taioli",fullName:"Emanuela Taioli"},{id:"203416",title:"Dr.",name:"Anthony",middleName:null,surname:"Bui",slug:"anthony-bui",fullName:"Anthony Bui"}]}],onlineFirstChaptersFilter:{topicSlug:"reconstructive-surgery",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"10176",title:"Microgrids and Local Energy Systems",subtitle:null,isOpenForSubmission:!0,hash:"c32b4a5351a88f263074b0d0ca813a9c",slug:null,bookSignature:"Prof. Nick Jenkins",coverURL:"https://cdn.intechopen.com/books/images_new/10176.jpg",editedByType:null,editors:[{id:"55219",title:"Prof.",name:"Nick",middleName:null,surname:"Jenkins",slug:"nick-jenkins",fullName:"Nick Jenkins"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:1},route:{name:"profile.detail",path:"/profiles/120501/gudeta-sileshi",hash:"",query:{},params:{id:"120501",slug:"gudeta-sileshi"},fullPath:"/profiles/120501/gudeta-sileshi",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()