\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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However, it was unusual for such a pointed disease state to occur in someone so young. Over the next four and half years, Deter became increasingly demented, until her death at the age of 55. Upon examination of Deter’s brain, Dr. Alzheimer found microscopic strands of protein which he described as “tangled bundles of fibrils” (neurofibrillary tangles) in addition to “miliary foci” (amyloid plaques). In 1906, at the 37th Conference of South-West German Psychiatrists in Tübingen, Alois Alzheimer presented Deter’s case as, “a peculiar disease of the cerebral cortex.”
To this day both the cause of and treatment for AD remain a mystery. AD is a multifaceted disease of great complexity, however, over 100 years of research has provided clues to its mechanisms. Of particular recent interest is the emerging realization that another rapidly growing disease, type 2 diabetes mellitus (T2DM), is linked to development of AD [1].
This chapter examines the current state of knowledge regarding the association of T2DM to vascular changes in the brain and the implications these changes have in AD development. Other factors that contribute to AD such as insulin resistance and accumulation of the neurotoxic peptide amyloid beta (Aβ) are also examined. It’s likely that no central cause of AD exists but rather, the disease represents a breakdown of several critical components involved in the general health and function of the brain.
T2DM is a known risk factor for AD [1] suggesting that insulin signaling abnormalities play a central role in AD pathology. Moreover, AD brains show decreased insulin levels, decreased activity of insulin receptors and signs of compensatory mechanisms such as increased insulin receptor density [3] indicating AD as “type 3 diabetes” [4, 5].
Loss of insulin signaling in diabetes can occur by either type 1 or type 2 processes. Type 1 diabetes mellitus (T1DM) is characterized as an autoimmune disease that results in the destruction of insulin producing β cells found in the pancreas. In contrast, T2DM is a state of insulin resistance in which insulin levels are normal or elevated but tissues are unresponsive to its effects. While both T1DM and T2DM can lead to cognitive deficits, T2DM poses a greater risk for AD development [6, 7] and as a result the parallels between T2DM and AD are studied more vigorously than T1DM associations. Therefore, the majority of information presented here pertains to type 2 diabetic pathologies.
In addition to insulin resistance, T2DM is associated with the development of vascular dysfunction in the brain [8, 9]. T2DM is a risk factor for microvascular complications as well as macrovascular defects [10] such as stroke [11]. Vascular abnormalities are strongly associated with AD [12-16] implying further involvement of T2DM in disease onset.
The vascular complications associated with diabetes can be divided into two classes based on the vascular etiology of their pathology: macrovascular (hypertension, coronary artery disease, atherosclerosis, stroke) and microvascular (neuropathy, retinopathy, nephropathy). Macrovascular complications are those that affect the larger (non-capillary) blood vessels. Statistics show that diabetes increases the risk of stroke and atherosclerosis [31]. Atherosclerosis accounts for 70% of morbidity associated with T2DM [32], while other studies have shown an association between the degree of hyperglycemia and increased risk of myocardial infarction and stroke [33-36]. While macrovascular complications themselves represent important pathological consequences of T2DM, they have also been shown to provide the etiological link between T2DM and the development of Alzheimer’s disease.
Ischemic CVD caused by T2DM is positively associated with AD through shared pathological mechanisms such as hyperinsulinemia, impaired insulin signaling, oxidative stress, inflammatory mechanisms and advanced glycation end-products (AGEs) [40]. Defective insulin signaling is associated with decreased cognitive ability and development of dementa, including AD [41], rendering signaling neurons more vulnerable to metabolic stress and accelerating neuronal dysfunction [42]. In vitro insulin-stimulated Akt phosphorylation is decreased in hyperinsulinemic conditions in cortical neurons [43]. Finally, all forms of amyloid beta (Aβ) (monomers, oligomers and Aβ-derived diffusible ligands (ADDLs)) can inhibit insulin signaling by directly binding to the insulin receptor and inhibit insulin signaling [44].
In the insulin resistant state, there is a specific impairment in the vasodilatory PI3K pathway, whereas the Ras/MAPK-dependent pathway is unaffected [46, 47]. This results in decreased production of NO and an increased secretion of ET-1 in humans [48] leading to increased vasoconstriction. The decrease in NO production is significant in that NO protects blood vessels from endogenous injury by mediating molecular signals that prevent platelet and leukocyte interaction with the vascular wall and inhibit vascular smooth muscle cell proliferation and migration [49, 50]. Decreased production of NO allows for increased expression of proinflammatory transcription factor NF-κB, and subsequent expression of leukocyte adhesion molecules and production of chemokines and cytokines [51]. Activation of these proteins promote monocyte and vascular smooth muscle cell migration into the intima and formation of macrophage foam cells, initiating the morphological changes associated with the onset of atherosclerosis [52, 53].
Pathways leading to macrovascular complications of type 2 diabetes mellitus (T2DM). In non-diabetic individuals (
High levels of FFAs are found in insulin-resistant individuals. FFAs generated by increased activity of hormone-sensitive lipase that contribute to and result in insulin resistance [54-56]. In vitro vascular endothelial cell culture treated with FFA resulted in decreased insulin-stimulated eNOS activity and NO production [57]. It is believed that FFA increases cellular levels of diacylglycerols, ceramide, and long-chain fatty acyl coenzyme A (CoA), all of which have been shown to activate protein kinase C (PKCβ1). Activation of PKCβ1 results in increased phosphorylation of IRS-1 that leads to reduced Akt and eNOS resulting in decreased vasodilatory capacity [58, 59]. Increase in FFAs result in an increase in reactive oxygen species (ROS) from NADPH and the mitochondrial electron transport chain [60]. The increase in ROS results in increased PKC which activates the hexosamine biosynthetic pathway leading to increased AGEs and subsequent decrease in endothelial-derived NO [60]. Hyperglycemia has been found to decrease activation of Akt and eNOS via O-GlcNAC of eNOS at the Akt phosphorylation sites [61, 62]. Hyperglycemia increases activation of PKCα, PKCβ, PKCδ resulting in decreased eNOS and concomitant increase in endothelial ET-1 [60]. T2DM is associated with vascular dysfunction as a result of increased atherosclerosis and decreased cerebral blood flow. The combination of both processes is decreased glucose and oxygen supply to vital organs such as the brain. The biochemical events leading to the macrovascular impairment has particular significance to brain health as the risk of stroke is a major complication of T2DM.
Pre-existing CVD has been identified as a significant risk factor for AD. The vascular hypothesis of AD posits that vascular dysfunction, such as stroke, is a pre-requisite for the development of this disorder. It has been reported that the risk of AD is three times greater after the occurrence of stroke [72]. Stroke may result in neurodegeneration [73, 74], resulting in the rapid cognitive decline observed in AD patients [75]. It has even been proposed that stroke may be the underlying cause of 50% of AD cases [74]. Conversely, individuals presenting with severe cognitive impairments, and possibly AD, may be at a greater risk for the development of stroke or CVD [76, 77].
The amyloid hypothesis of AD was long held as the prevailing theory explaining the etiology of AD. However, emerging evidence compiled from the last 20 years has suggested that the pathology associated with AD is vascular in origin. The vascular hypothesis of AD states that pre-existing cardiovascular dysfunction such as stroke, hypertension and atherosclerosis results in chronic cerebral hypoperfusion that could encourage the onset of AD. Several lines of evidence have been provided in support of this hypothesis. For example, it has been shown that cerebrovascular dysfunction precedes cognitive decline and the onset of neurodegenerative changes in AD and AD animal models [12, 13]. In rhesus monkeys, dystrophic axons labeled with amyloidogenic enzyme, BACE1, were found in close proximity or in direct contact with cortical blood vessels [78], asserting a tight association with AD pathology and vascular dysfunction. Clinical and epidemiological evidence provides further support of the vascular hypothesis.
AD patients show a greater degree of vascular narrowing of carotid arteries [65] and cerebral arteries of the Circle of Willis [79, 80]. In addition, large artery CVD was positively correlated to the frequency of neuritic plaques [81]. Several vascular risk factors such stroke (silent infarcts, transient ischemic attacks), atherosclerosis, hypertension, heart disease (coronary artery disease, atrial fibrillation) and diabetes mellitus have been associated with an increased risk AD-type dementia [82]. Between 60 to 90% of AD patients exhibit various cerebrovascular pathologies including White matter lesions, cerebral amyloid angiopathy (CAA), microinfarcts, small infarcts, hemorrhages and microvascular degeneration [12-16]. It believed that cardiovascular dysfunctions act as a nidus for accelerated Aβ deposition resulting in the onset of AD [83].
Aberrant blood brain barrier (BBB) function exposes neurons to neurotoxic substances. Chronic cerebral hypoperfusion is believed to render the brain more vulnerable to various insults, resulting in AD and associated cognitive loss [84]. Clinical observations in AD patients have revealed extensive degeneration of endothelium [85] and features indicative of BBB breakdown [86]. At the cellular level, AD is known to cause abnormal structural changes to arterioles and capillaries, swelling and increased number of pinocytotic vesciles in endothelial cells, decreased mitochondrial content, increased deposition of proteins of the basement membrane, reduced microvascular density and occasional swelling of astrocyte endfeet [87-92]. Aβ trafficking across the BBB deposition is also dependent on mechanisms of influx and efflux. Increased expression of receptor for advanced glycation endproducts (RAGE) may be responsible for Aβ influx from the blood to the brain has been reported in addition to a decrease in LRP1 receptors that are responsible for clearing Aβ from the brain to the blood [12, 93].
A functional consequence associated with BBB dysfunction is the resultant impairment in cerebral hemodynamics. AD impairs autoregulation, the mechanism that is responsible for the stabilization of blood flow to the brain in response to changes in cerebral perfusion pressure [94]. In an APP x PS1 mouse model neurovascular coupling, the process in which activation of a brain region evokes a local increase in blood flow, was impaired [95]. Finally, AD has shown to adversely affect vasomotor/vascular reactivity, the process that mediates vasodilatory or vasoconstrictor responses of cerebral blood vessels to hypercapnic or hypocapnic stimuli (ie. global or regional brain blood flow response to systemic changes in arterial CO2) [96-98]. Cumulatively, the impairment of these processes adversely affects cerebral blood regulation that, in turn, would negatively affect nutrient availability to neurons. This would result in cerebral hypoperfusion, a process that is widely believed to initiate the onset of AD pathology.
There are a number of known direct links between biochemical pathways central to AD and hypoxia/ischemia. A rat model for vascular cognitive impairment has been developed referred to as the two-vessel occlusion model of cerebral ischemia. Studies found decreased cerebral blood flow up to 4 weeks, cognitive deficits, APP proteolysis to form Aβ-sized fragments [99-101]. Other studies have observed an overexpression of Aβ persisting for up to 3 months after surgery [102] and cognitive impairment [103], strongly suggesting that decreased CBF is a key mediator in the pathophysiology of AD. Several studies have been able to identify some of the molecular mechanisms as to how hypoxia/ischemia exerts its effects on AD-related genes.
APP expression increases following chronic cerebral hypoperfusion and ischemia [104, 105], and a greater proportion of APP is proteolytically cleaved by increased activity of amyloidogenic enzyme, BACE1, which is concurrently increased in AD following ischemic events [106]. Hypoxia inducible factor-1α (HIF-1α) plays an essential role in cellular and systemic responses to low oxygen and has been found to increase BACE1 mRNA expression [107]. Furthermore, BACE1 stabilization is enhanced in AD in addition to a decrease in its trafficking [108, 109]. Increased BACE results in greater γ-secretase-mediated production of Aβ [110]. In an APP overexpressing mouse model, chronic cerebral hypoperfusion as the result of cerebral amyloid angiopathy (pathological deposition of Aβ1-40 in brain blood vessels) was followed by an increased rate of leptomeningeal Aβ precipitating the risk of microinfarcts [111]. Hypoxia/ischemia not only causes increased amyloidogenic cleavage of APP and greater Aβ production, but also impairs Aβ degradation and trafficking [12, 112].
Decreased Aβ-degrading enzymes in response to hypoxic conditions increase the likelihood of developing pathological levels of Aβ in the brain [113-115]. Aβ serves not only as the end result of a pathological cascade, but Aβ itself has been found to contribute to dysfunction in components of the neurovascular unit. In endothelial cells Aβ was observed to decrease endothelial cell proliferation and accelerate senescence of endothelial cells in vivo and in vitro, inhibit VEGF-induced activation of Akt and eNOS in endothelial cells [116, 117]. Aβ has been found to decrease eNOS (via PKC-dependent pathway) resulting in decreased vascular tonus and decreased substance P-induced vasodilation of the basilar artery[118, 119]. In vascular smooth muscle cells (VSMCs), Aβ affects cellular morphological changes [120] and increases expression of transcription factors, serum response factor and myocardin, resulting in decreased Aβ clearance by downregulating LRP expression [12]. Finally, Aβ has been shown to cause retraction and swelling of astrocyte endfeet in an AD mouse model with CAA [121] as well as increase cholinergic denervation of cortical microvessels which, taken together, results in impaired functional hyperemia [122].
Differing clinical manifestations separate VaD from AD dementia. For example, VaD progression appears more varied than AD in relation to symptoms, its rate of progression and the disease outcome [131]. Increased damage to the ganglia-thalamo-cortical circuits specific to VaD results in problems with attention and the planning and speed of mental processing whereas the primary impairments characteristic of AD are memory and language-related [132]. It has been suggested that differences in the clinical observations in AD and VaD patients may be due to the type, severity and location of vascular damage [133-135]. Furthermore, perturbations in vascular hemodynamics have been observed in VaD and AD [136, 137], however, AD patients had comparatively less impairment in cerebral perfusion than those with VaD [138] suggesting that hemodynamic disturbances may underlie different types of dementia [138]. While the precise mechanism that vascular risk factors initiate cognitive decline remains elusive [139], T2DM have been identified as an important contributing factor to the development of VaD.
The source of brain insulin remains controversial. While preproinsulin mRNA has been reported in the neurons [153-155], very little insulin is synthesized in the brain [156]. Additionally, glial cells have been found not to be involved in insulin production [157], therefore, it is recognized that the majority of insulin in the brain is produced by pancreatic β cells [158-161]. In contrast, IGF-1 is produced locally in the brain and does not depend on growth hormone influence as is the case of liver and other tissues [148].
Neuronal insulin receptors are different than those found in the periphery [162]. Insulin receptors are present in one of two isoforms; the IR-A isoform that lacks exon 11 that the other isoform, IR-B, expresses [163, 164]. A major functional difference between the two isoforms is that IR-A has a higher affinity for the neurotrophic factor Insulin-like Growth Factor – 2 (IGF-II) [165] and a slightly higher affinity for insulin [166] and has also been shown to associate/dissociate with insulin quicker than IR-B [149]. Brain specific insulin receptors are mainly the IR-A isoform and as result of differential glycosylation have a lower molecular weight than their peripheral counterparts [162].
Structurally, the insulin receptor is a homodimer composed 2α chains and 2β chains held together with disulphide bonds [167-169]. Insulin receptor binding of insulin/IGF-1 results in a conformational change that activates the catalytic tyrosine kinase activity of the β subunits [170]. This activation of the insulin receptor results in autophosphorylation at multiple tyrosine residues [171, 172] including tyrosine 960 in the juxtamembrane region of the β subunit [173, 174]. Phosphorylation at this site is a vital component of the insulin signaling cascade because it provides a binding motif for the phospho-tyrosine binding (PTB) domain of IRS [173, 174]. Once docked to the insulin receptor, IRS is phosphorylated on tyrosine residues [170].
Tyrosine phosphorylation of IRS proteins creates binding sites for Src homology 2 (SH2) domain containing proteins such as PI3K [175]. PI3K catalyzes the production of 3’phosphoinositide secondary messengers which are critical to the insulin signaling cascade. PI3K is composed of a catalytic p110 subunit and a regulatory p85 subunit that contains SH2 domains that interact with activated IRS [176]. Formation of the IRS/PI3K complex increases the catalytic activity of the p110 subunit [177].
3’phosphoinositides produced by PI3K are important signal conductors that bind to PH (pleckstrin homology) domains on proteins such as IRS [177] and Akt [178]. This interaction is needed to bring IRS and AKT proteins towards the inner layer of the plasma membrane near the juxtamembrane region of the insulin receptor [179] and in close proximity to activating kinases, respectively [180-185]. Furthermore, binding of 3’phosphoinositides is required for Akt to be competent for phosphorylation [184, 186-188].
Akt has two phosphorylation sites, Thr 308 and Ser 473, capable of inducing catalytic activity [189]. PDK1, which also depends on 3’phosphoinosites for its function, phosphorylates Akt at Thr 308 [189, 190].While overexpression of PDK1 has been shown to activate Akt [186], optimal activation of Akt requires additional phosphorylation at Ser 473 by mTORC2 [191] which stabilizes the conformation state of Akt [192].
Akt mediates the neurotrophic effects of insulin/IGF-1, in part, by inhibiting pro-apoptotic machinery [193] and concomitantly activating anti-apoptotic proteins [194-198]. Akt’s role in neurotrophic support also involves the regulation of survival transcription factors such as NF-κB [199] and CREB [198] as well as those involved in pro-death gene expression such as the FoxO family [200-202]. Moreover, Akt is involved in production of the neurotrophin BDNF [198], activation of proteins involved in neurite outgrowth (for review see: [203]) and regulation of the metabolic protein GSK-3β [204].
Mitochondrial stress incurred by ROS can lead to elevated Ca2+ levels in the mitochondrial matrix [211, 212] resulting in increased mitochondrial membrane permeability and release of pro-apoptotic factors such as Cytochrome c, and AIF (apoptosis inducing factor) [213]. Bcl-xL is an anti-apoptotic Bcl-2 family member that prevents Ca2+ induced mitochondrial permeability [214]. In the absence of insulin/IGF-1 stimulation, the survival effects of Bcl-xL are blocked as Bcl-xL is complexed with the pro-death Bcl-2 family member Bad [215-217]. Akt liberates Bcl-xL by phosphorylating Bad [195-197, 218] allowing for mitochondrial stabilization.
Mitochondrial permeability marks a critical event in the cell death cascade. Akt promotes cell survival prior to Cytochrome c release through Bcl-xL activity but has also been found to act post apoptotic factor release. When Cytochrome c is released from the mitochondria, it will associate with Apaf-1, dATP and Caspase-9 forming a structure known as the apoptosome (For review see [219]). Formation of the apoptosome activates the proteolytic activity of caspase-9 which cleaves and activates other caspases critical to the apoptotic process [220, 221]. Akt blocks apoptosome formation by phosphorylating Caspase 9 [193].
Bcl-2 is another anti-apoptotic protein under the control of Akt [222]. Bcl-2’s role in cell survival is similar to that of Bcl-xL in that in maintains mitochondrial membrane integrity [223]. Mitochondrial permeability has been linked to an oxidized shift in the mitochondria [224] while Bcl-2 has been shown to promote a more reduced state [225]. Up-regulation of Bcl-2 may lead to higher cell reductive capacity [224] which is supported by the observation that Bcl-2 overexpressing cells show increased amounts of NADPH and are resistant to ROS generation [226].
The Bcl-2 promoter contains a cAMP response element site (CRE) that can enhance Bcl-2 expression by binding the transcription factor CREB. Akt is known to phosphorylate CREB which results in increased CREB binding to CBP and increased transcriptional activity [198]. Therefore, the ability of Akt to promote cell survival is mediated, in part, by influence over gene expression such as the up-regulation of Bcl-2 [227-230] and through direct protein interactions such as Bad phosphorylation resulting in Bcl-xL liberation [194-197].
The transcription factor NF-κB is also under Akt control [199]. Like CREB, NF-κB plays critical roles in neuron survival [201, 243, 244] and is also involved in neurite outgrowth, myelin formation and axonal regeneration [245]. Genes for antioxidant proteins such as MnSOD [246] and Cu/ZnSOD [247] and anti-apoptotic proteins Bcl-2 and Bcl-xL are targets of NF-κB [248].
In its inactive form, NF-κB is bound to IκB proteins that sequester it to the cytosol (for review see [249, 250]). NF-κB is activated when IκB proteins are phosphorylated by IκB Kinase (IKK) complexes and targeted for degradation which allows NF-κB to translocate to the nucleus where it binds to regulatory DNA sequences [251]. The IKK complex consists of catalytic IKKα and IKKβ subunits and a regulatory IKKγ subunit [251]. Akt facilitates NF-κB activation by phosphorylating IKKα at a critical regulatory site that promotes IKK activation [252] and subsequent IκB degradation.
Akt influence is not limited to only survival transcription factors but extends to pro-death modulators as well [253, 254].The forkhead box class O (FoxO) family of transcription factors contribute to apoptosis through the induction of pro-death genes such as Fas L [201, 255, 256] and the Bcl-2 member BIM-1 [257]. Fas L facilitates apoptosis by activation of caspases [258] while BIM-1 activates the pro-apoptotic Bcl-2 family memeber BAX [259]. In the absence of Akt, FoxO transcription factors are transcriptionally active in the nucleus [200-202]. Akt phosphorylates FoxO family members at a conserved c-terminal sequence [253] which leads to nuclear exclusion and inhibition of transcriptional activity.
p53,another pro-death transcription factor known to be inactivated by Akt, [260] induces the expression of the pro-apoptotic Bcl-2 family member BAX. BAX proteins form oligomers that insert into the outer mitochondrial membrane which provide a passageway for Cytochrome c and other pro-apoptotic proteins to escape through [261]. Increased p53 activity leading to BAX expression has been linked to neuronal deprivation of neurotrophic factors [262].
Insulin receptor binding of insulin triggers a complex signaling cascade (in blue) leading to activation of the serine/threonine kinase Akt. Upon binding of insulin, insulin receptors are autophophorylated and subsequently bind IRS proteins. IRS proteins are then phsophorylated by activated insulin receptors and complex with PI3K resulting in PI3K activation. Activated PI3K produces phospholipid secondary messengers by catalyzing the conversion of phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 messengers activate PDK1 which phosphorylates Akt at Threonine 308. Akt is further activated by phosphorylation at Ser 473 by mammalian target of rapamyicin 2 (mTORC2). Targets of activated Akt include pro-apoptotic mediators (in red) as well as pro-survival machinery (in green). Loss of insulin signaling (at sites labeled with numbers 1-6 in purple) allows FoxO and p53 transcription factors to remain active and (1) transcribe genes for pro-apoptotic proteins such as BIM, BAX and FasL. Akt inhibits the activity of GSK-3β that, when active, (2) causes increased amyloidogenic processing and hyperphosphorylation of tau. Other pro-apoptotic proteins inhibited by Akt include (3) caspase-9, which forms an apoptotic structure known as the apoptosome, and (6) Bad, which blocks activity of the ant-apoptotic protein Bcl-xL. Pro-survival modulators regulated by Akt include CREB and NF-κB. Reduction of CREB transcriptional activity as a result of a loss of insulin signaling leads to (4) decreased BDNF and Bcl-2 expression while inhibition of NF-κB leads to (5) reduced expression of anti-oxidants such as MnSOD and CuSOD as well as anti-apoptotic Bcl-2 family members.
The mitochondrial permeability transition mediates apoptosis through the release of pro apoptotic factors. Insulin signaling maintains mitochondrial membrane integrity by increasing levels and activity of anti-apoptotic Bcl-2 family members [194-197, 227-230]. In the absence of insulin signaling, the balance of Bcl-2 proteins tips in favor of pro-apoptotic members resulting in cell death. Post mitochondrial collapse, normal insulin signaling can still prevent apoptosis by blocking formation of apoptotic complexes [193, 229] while a state of insulin resistance allows this process to continue unimpeded.
Even under normal circumstances, ROS are produced in respiratory chain reactions in the mitochondria [289]. However, if not properly managed, ROS can cause oxidative damage to proteins, lipids, and nucleic acids. Insulin supplies cells with antioxidant proteins capable of diffusing the oxidative effects of ROS by activating protective transcription factors such as NF-κB [246, 247, 263]. Insulin resistance not only results in reduced antioxidants but also leaves cells susceptible to ROS mediated mitochondrial collapse because of the before mentioned lack of anti-apoptotic Bcl-2 members.
The FoxO family of transcription factors is known to play a role in the cell’s response to oxidative stress, however, their prolonged activation results in apoptosis [290]. Insulin signaling inactivates FoxO transcription factors through phosphorylation by Akt. Absence of insulin signaling allows FoxO members to remain in the nucleus and sustain transcription of pro-death genes [201, 255-257].
Insulin resistance is linked to structural changes in AD by overactive GSK-3β. Neurofibrillary tangles are a pathological hallmark of AD [283] and produced by hyperphosphorylation of tau by GSK-3β. Under normal insulin signaling, GSK-3β is inactivated by Akt. Neurofibrillary tangles are one of two significant pathological characteristics of AD the other being accumulation of Aβ [291]. Aβ toxicity and aggregation into plaques has devastating consequences in the brain such as synaptic disruption [292] and inhibition of LTP [293], interference of detoxifying enzymes [294], increased ROS and oxidative stress [295], increased vulnerability to calcium overload [296] and the before mentioned effects on brain vasculature. Aβ also depresses insulin signaling [297] which results in further loss of neurotrophic support. Insulin signaling, on the other, hand is involved in Aβ clearance [298] introducing a convoluted relationship between insulin and Aβ.
While the physiological role of APP remains unknown, it has been suggested that APP plays a part in neurite outgrowth, synaptogenesis, neuronal trafficking along the axon, transmembrane signal transduction, cell adhesion and calcium metabolism, all of which still require in vivo evidence (for review see [303]). APP concentrations are elevated in the brain during the prenatal period in mice which implies a role of APP in brain development [304]. In the adult brain, APP is expressed in regions of synaptic modification [304] and has been shown to increase hippocampal neuronal response to glutamate [305].
APP belongs to a family of transmembrane proteins that includes APP-like protein 1 and 2 (APPLP1/APPLP2). All APP family members are processed in a similar fashion by α, β, and γ secretases [306-308], however the Aβ domain is unique to APP. Three isoforms of APP have been identified consisting of 695, 751, or 770 amino acids which arise from alternative splicing of the same gene located on chromosome 21 [309]. APP 751 and APP 770 are expressed in most tissues and contain a 56 amino acid Kunitz Protease inhibitor (KPI) domain not found in the neuron specific 695 isoform [310, 311]. mRNA levels of the 2 KPI containing isoforms are elevated in AD brains and are associated with Aβ deposition [312].
Synthesis of APP occurs in the endoplasmic reticulum where it is then transported through the golgi apparatus to the trans golgi network where the highest concentrations of APP are found in neurons [313-315]. From there, APP can be transported in secretory vesicles to the cell surface where α-secretases are located, however, Aβ production occurs within the trans golgi network where γ-secretase complexes are thought to reside [315-318].
APP cleavage by BACE1 results in two fragments: sAPPβ and Beta Carboxyl Terminal Fragment (βCTF) [301, 325]. sAPPβ has been identified as a ligand for Death Receptor 6 which mediates axonal pruning and neuronal death [326]. The remaining βCTF can be cleaved by γ secretase to produce Aβ [301]. γ-secretase is a complex composed of at least 4 components: PS1 or PS2, nicastrin, anterior pharynx defective-1 (APH-1) and presenilin enhancer-2 (PEN-2) [327, 328]. βCTF cleavage by γ secretase produces either Aβ40 or Aβ42 peptides [301]. Aβ42 is the more hydrophic and amyloidogenic of the 2 species and makes up about 10% of Aβ produced [329]. An increased Aβ42/Aβ40 ratio has consistently been shown in fAD patients suggesting that Aβ42 is critical to AD pathogensis [330, 331].
Development of insulin resistance provides neurons with a dangerous dilemma as neurons rely on insulin signaling for Aβ clearance and inhibition of amyloidogenic processing. Insulin increases Aβ trafficking from the trans golgi-network leading to secretion [333]. Secretion of Aβ may be important in preventing neurodegeneration as intraneural Aβ accumulations have been found in brain regions prone to early AD in patients with mild cognitive impairment [334] and studies done with transgenic mice indicate that intracellular Aβ accumulation is an early event of the neuropathological phenotype [335-337]. Insulin signalling protects against Aβ toxicity [298] and inhibits GSK-3β activity [204] which, in addition to hyperphosphorylating tau, promotes amyloidogenic APP cleavage [160, 338].
Insulin signaling pathways in the brain are complex and depend on a delicate balance of cell activity to function properly. Accumulation of Aβ perturbs this balance resulting in insulin resistance and formation of a vicious cycle as insulin signaling is no longer able to clear and regulate Aβ. As Aβ oligomers increase, insulin resistance worsens. This cycle is perpetuated by competition between insulin and Aβ as substrates for IDE.
In summary, Aβ contributes to insulin resistance [297, 332] by occupying binding sites on insulin receptors [297] and is associated with decreased insulin receptor numbers in neurons [332]. Decreases in insulin signaling result in increased Aβ processing as well as activation of GSK-3β which promotes Aβ processing [160, 338]. Insulin signaling impairment also leads to decreased IDE, which is needed to degrade Aβ [339-341, 343]. IDE deficiencies are exacerbated in hyperinsulinemic conditions as IDE binding sites are overloaded with excess insulin and made unavailable for Aβ [115]. Lack of insulin signaling and IDE availability allows for continued accumulation of Aβ, further depression of insulin signaling systems, increased neuronal vulnerability and further neurodegeneration.
T2DM can lead to the induction of insulin resistance in the brain. (2) Reduction of insulin signaling in the brain increases the activities of GSK-3β and β secretases which (3) increase levels of toxic Aβ oligomers. Furthermore, (4) insulin resistance lowers the expression of Aβ-degrading IDE. (5) Reduced IDE then leads to increased Aβ and (6) accumulation of Aβ oligomers. T2DM also causes (7) hyperinsulinemia which exacerbates IDE deficiencies because (8) excess insulin occupies IDE binding sites rendering them unavailable for Aβ. The increased amyloidogenic processing that occurs in insulin resistance combined with decreased Aβ clearance by IDE results in a deleterious positive-feedback cycle as (9) Aβ oligomers contribute to insulin resistance in the brain. As Aβ levels continue to rise, insulin resistance worsens leading to further production of the toxic peptide.
By 2050 it’s estimated that over 100 million people worldwide will have AD [344] causing a substantial financial burden for health care systems. In that same time span, the annual cost of treating AD is predicated to exceed $1 trillion in the United States alone [345]. These crippling social and economical effects place increased priority for advancement of AD research.
Vascular hypothesis of AD. The vascular complications have been casually linked to the progression of AD. Vascular dysfunction resulting from type 2 diabetes results in a state of cerebral hypoperfusion, leading to significant energy depletion in the brain. Neurodegeneration results in cognitive impairments and ultimately AD.
While AD remains a disease of more questions than answers, a wide array of evidence suggests a close relationship between AD and T2DM. T2DM has been characterized as having both macrovascular and microvascular complications that result in CVD. It is the vasculature that provides the tangible pathological link between T2DM and AD. Significant data has been collected in favor of the vascular hypothesis of AD, which is founded on the idea that pre-existing CVD sets into motion pathological cascades that ultimately result in AD.
AD and T2DM also share commonality in the form of insulin resistance. Lack of insulin neurotrophic support in the brain leaves neurons defenseless against oxidative stress, Aβ toxicity and apoptosis. Aβ is especially dangerous to neurons because it further depresses insulin signaling and can alter levels of protective enzymes involved in its degradation such as IDE. AD is a disease that not only causes death in weakened cells but also further depresses protective mechanisms making recovery unattainable.
Because AD affects multiple structures and pathways, it is likely that successful treatment will involve a comprehensive battery of therapeutics rather than a single therapy. T2DM plays a major role in vascular abnormalities and insulin resistance which parallel AD pathologies. As a result, further exploration of the relationship between T2DM and AD may be a promising direction of future research. Moreover, preventative measures against T2DM such as proper diet and dedication to an active lifestyle may take center stage as a means of curbing the AD epidemic.
The genus
Phialid showing production of conidia in highly branched conidiophore (photo credit: Dr. Pranab Dutta & Lipa deb, CPGSAS, CAU (Imphal), Umiam, Meghalaya.
Pure culture of Trichoderma harzianum in PDA plate (photo credit: Dr. Pranab Dutta, CPGSAS, CAU (Imphal), Umiam, Meghalaya.
The mass production of
It is a common method for mass production of
The formulation depends on the type of application, its combination of active ingredients, such as fungal spores with the inert material as diluents of the desirable form. The formulation developed through standard air dried mats and mixed with the carrier contain 108–109 propagules per gram [80].
The common methods are seed treatment, seed bio-priming, seedling root dip, and soil application and wound dressing.
Seed coating with dry powder of
Treated seeds with
It is suitable for transplanting rice and vegetable crops. The seedlings can be treated with the spore suspension by mixing 10 g of
Trichoderma is capable of colonizing on farmyard manure (FYM) and then applied to the soil is the most effective method for the management of soil-borne disease
One of the critical problems in the commercialization of bio-agents is the loss of viability of the propagules over time. The shelf life of the bio-control product is dependent on the storage temperature and carriers as used in the formulation of bio control agents. The shelf life of bio- control agent plays a significant role in successful marketing.
Bio-control agents are playing an important role in controlling of plant pathogens, especially soil borne fungal pathogens. Biological control agents reduce the disease of the target crop usually by one or more of the modes of action manly antibiosis, competition, mycoparasitism, cell wall degrading enzymes and induced resistance. The indirect interaction with pathogens is competition for nutrients and space and directly with the pathogen by hyperparasitism or antibiosis [108]. Bio-control agents might directly interact with the pathogens by hyperparasitism [109], and antibiosis [110]. Bio-agents induce resistance enhanced in plants against pathogens, competitions for nutrients and spaces [111]. Various chemical compounds such as lectins during the initial contact, recognition and cell wall-degrading enzymes such as β-1,3-glucanases, chitinases, proteinases, and lipases, during the penetration [112]. In hyper-parasitism growth of bio control agent towards the target organism, coiling, final attack and dissolution of target pathogens cell wall by the activity of enzymes [86].
Mycoparasitism is one of the most important direct antagonism mechanisms that attack one fungus on another [113]. and causes complete death of fungal propagules or destruction and lysis [114]. Mycoparasitism is a complex process which involves chemotrophic growth, recognition and coiling, the interaction of hyphae and secretion of specific lytic enzymes [113].
Antibiosisis is the condition of antagonistic to the suppression of pathogenic microorganisms due to toxic compounds (antibiotics). Antibiotic is a secondary metabolite with a low molecular weight that is harmful to the other microorganisms at a low concentration [124]. The antibiotic is produced by bio-control agents and is the main contributing mechanism under soil conditions [125]. Soil-borne microorganisms have different strains of
Competition is the
Induce resistance is indirect mechanism in host physio-biochemical pathways that trigger defense cascades inside the plants and lead to suppression of disease development. Induced defense mechanisms involve the production of reactive oxygen species, phytoalexins, phenolic compounds, pathogenesis-related proteins, physical barriers [134]. The role of
“The authors declare no conflict of interest.”
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2022",editors:[{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"235",title:"Gerontology",slug:"gerontology",parent:{id:"21",title:"Psychology",slug:"psychology"},numberOfBooks:4,numberOfSeries:0,numberOfAuthorsAndEditors:72,numberOfWosCitations:29,numberOfCrossrefCitations:42,numberOfDimensionsCitations:80,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"235",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"7904",title:"Aging",subtitle:"Life Span and Life Expectancy",isOpenForSubmission:!1,hash:"4507619de679dfa85bc6e073d163f3c8",slug:"aging-life-span-and-life-expectancy",bookSignature:"Robert J. Reynolds and Steven M. Day",coverURL:"https://cdn.intechopen.com/books/images_new/7904.jpg",editedByType:"Edited by",editors:[{id:"220737",title:"Dr.",name:"Robert",middleName:null,surname:"J. Reynolds",slug:"robert-j.-reynolds",fullName:"Robert J. Reynolds"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6704",title:"Geriatrics Health",subtitle:null,isOpenForSubmission:!1,hash:"7cac7767e0b34391318cd4a680ca0d68",slug:"geriatrics-health",bookSignature:"Hülya Çakmur",coverURL:"https://cdn.intechopen.com/books/images_new/6704.jpg",editedByType:"Edited by",editors:[{id:"190636",title:"Associate Prof.",name:"Hülya",middleName:null,surname:"Çakmur",slug:"hulya-cakmur",fullName:"Hülya Çakmur"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6381",title:"Gerontology",subtitle:null,isOpenForSubmission:!1,hash:"bf232563c8fe15ef0848ed6ffb8f832d",slug:"gerontology",bookSignature:"Grazia D’Onofrio, Antonio Greco and Daniele Sancarlo",coverURL:"https://cdn.intechopen.com/books/images_new/6381.jpg",editedByType:"Edited by",editors:[{id:"272628",title:"Dr.",name:"Grazia",middleName:null,surname:"D'Onofrio",slug:"grazia-d'onofrio",fullName:"Grazia D'Onofrio"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5925",title:"Perception of Beauty",subtitle:null,isOpenForSubmission:!1,hash:"11f483d631557ad26d48b577e23a724f",slug:"perception-of-beauty",bookSignature:"Martha Peaslee Levine",coverURL:"https://cdn.intechopen.com/books/images_new/5925.jpg",editedByType:"Edited by",editors:[{id:"186919",title:"Dr.",name:"Martha",middleName:null,surname:"Peaslee Levine",slug:"martha-peaslee-levine",fullName:"Martha Peaslee Levine"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:4,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"60564",doi:"10.5772/intechopen.76249",title:"Ageing Process and Physiological Changes",slug:"ageing-process-and-physiological-changes",totalDownloads:6978,totalCrossrefCites:18,totalDimensionsCites:33,abstract:"Ageing is a natural process. Everyone must undergo this phase of life at his or her own time and pace. In the broader sense, ageing reflects all the changes taking place over the course of life. These changes start from birth—one grows, develops and attains maturity. To the young, ageing is exciting. Middle age is the time when people notice the age-related changes like greying of hair, wrinkled skin and a fair amount of physical decline. Even the healthiest, aesthetically fit cannot escape these changes. Slow and steady physical impairment and functional disability are noticed resulting in increased dependency in the period of old age. According to World Health Organization, ageing is a course of biological reality which starts at conception and ends with death. It has its own dynamics, much beyond human control. However, this process of ageing is also subject to the constructions by which each society makes sense of old age. In most of the developed countries, the age of 60 is considered equivalent to retirement age and it is said to be the beginning of old age. In this chapter, you understand the details of ageing processes and associated physiological changes.",book:{id:"6381",slug:"gerontology",title:"Gerontology",fullTitle:"Gerontology"},signatures:"Shilpa Amarya, Kalyani Singh and Manisha Sabharwal",authors:[{id:"226573",title:"Ph.D.",name:"Shilpa",middleName:null,surname:"Amarya",slug:"shilpa-amarya",fullName:"Shilpa Amarya"},{id:"226593",title:"Dr.",name:"Kalyani",middleName:null,surname:"Singh",slug:"kalyani-singh",fullName:"Kalyani Singh"},{id:"243264",title:"Dr.",name:"Manisha",middleName:null,surname:"Sabharwal",slug:"manisha-sabharwal",fullName:"Manisha Sabharwal"}]},{id:"55388",doi:"10.5772/intechopen.68944",title:"Beauty, Body Image, and the Media",slug:"beauty-body-image-and-the-media",totalDownloads:7750,totalCrossrefCites:5,totalDimensionsCites:12,abstract:"This chapter analyses the role of the mass media in people’s perceptions of beauty. We summarize the research literature on the mass media, both traditional media and online social media, and how they appear to interact with psychological factors to impact appearance concerns and body image disturbances. There is a strong support for the idea that traditional forms of media (e.g. magazines and music videos) affect perceptions of beauty and appearance concerns by leading women to internalize a very slender body type as ideal or beautiful. Rather than simply being passive recipients of unrealistic beauty ideals communicated to them via the media, a great number of individuals actually seek out idealized images in the media. Finally, we review what is known about the role of social media in impacting society’s perception of beauty and notions of idealized physical forms. Social media are more interactive than traditional media and the effects of self‐presentation strategies on perceptions of beauty have just begun to be studied. This is an emerging area of research that is of high relevance to researchers and clinicians interested in body image and appearance concerns.",book:{id:"5925",slug:"perception-of-beauty",title:"Perception of Beauty",fullTitle:"Perception of Beauty"},signatures:"Jennifer S. Mills, Amy Shannon and Jacqueline Hogue",authors:[{id:"202110",title:"Dr.",name:"Jennifer S.",middleName:null,surname:"Mills",slug:"jennifer-s.-mills",fullName:"Jennifer S. Mills"}]},{id:"59227",doi:"10.5772/intechopen.73385",title:"Differentiating Normal Cognitive Aging from Cognitive Impairment No Dementia: A Focus on Constructive and Visuospatial Abilities",slug:"differentiating-normal-cognitive-aging-from-cognitive-impairment-no-dementia-a-focus-on-constructive",totalDownloads:1347,totalCrossrefCites:3,totalDimensionsCites:6,abstract:"Constructive and visuospatial abilities in normal and in pathological aging (cognitive impairment, no dementia, CIND) are investigated. The sample includes 188 participants over 60 years of age, divided in 2 groups: healthy subjects (MMSE ≥28), without cognitive complaints, and individuals with CIND (MMSE between 24 and 27 and subjective cognitive complains). Drawing of cube and drawing of house, Benton Visual Retention Test (BVRT), and Block design are used to test the hypothesis that short visuoconstructive and visuospatial tests can distinguish normal from pathological cognitive aging in its very early stages. Results proved the discriminative sensitivity of BVRT general assessment criteria and of omissions and distortions in CIND. The diagnostic sensitivity of a modification of Moore and Wike [1984] scoring system for house and cube drawing tasks was confirmed as well. Drawing of cube and house could be used for quick screening of CIND in subjects over 60. Principal component analysis with oblimin rotation was performed to explore the different dimensions in the visuospatial and visuoconstructive abilities in old age. A four-factor structure was established, all four factors explaining 71% of the variance.",book:{id:"6381",slug:"gerontology",title:"Gerontology",fullTitle:"Gerontology"},signatures:"Radka Ivanova Massaldjieva",authors:[{id:"75907",title:"Associate Prof.",name:"Radka Ivanova",middleName:null,surname:"Massaldjieva",slug:"radka-ivanova-massaldjieva",fullName:"Radka Ivanova Massaldjieva"}]},{id:"59658",doi:"10.5772/intechopen.74748",title:"Ageing Better in the Netherlands",slug:"ageing-better-in-the-netherlands",totalDownloads:1189,totalCrossrefCites:1,totalDimensionsCites:4,abstract:"The Dutch National Care for the Elderly Programme was an initiative organized by the Netherlands Organisation for Health Research and Development (ZonMw) between 2008 and 2016. The aim of the programme was to collect knowledge about frail elderly, to assess their needs and to provide person-centred and integrated care better suited to their needs. The budget of EUR 88 million was provided by the Dutch Ministry of Health, Welfare and Sports. Putting the needs of elderly people at the heart of the programme and ensuring their active participation were key to the programme’s success. The programme outcomes included the establishment of eight geriatric networks around the medical universities with 650 organisations and the completion of 218 projects. These projects, involving 43,000 elderly people and 8500 central caregivers, resulted in the completion of 45 PhD theses and the publication of more than 400 articles and the development of 300 practice toolkits, one database and a website, www.beteroud.nl. The Dutch National Care for the Elderly Programme has since developed into a movement and continues under the consortium Ageing Better, made up of eight organisations. Through the use of ambassadors, Ageing Better promotes the message that ageing is not a disease but a new phase of life.",book:{id:"6381",slug:"gerontology",title:"Gerontology",fullTitle:"Gerontology"},signatures:"Betty Meyboom-de Jong, Klaske Wynia and Anjo Geluk-Bleumink",authors:[{id:"224997",title:"Emeritus Prof.",name:"Betty",middleName:null,surname:"Meyboom-De Jong",slug:"betty-meyboom-de-jong",fullName:"Betty Meyboom-De Jong"},{id:"232900",title:"Dr.",name:"Klaske",middleName:null,surname:"Wynia",slug:"klaske-wynia",fullName:"Klaske Wynia"},{id:"232901",title:"Mrs.",name:"Anjo",middleName:null,surname:"Geluk-Bleumink",slug:"anjo-geluk-bleumink",fullName:"Anjo Geluk-Bleumink"}]},{id:"57952",doi:"10.5772/intechopen.71904",title:"Neurocognitive Implications of Tangential Speech in Patients with Focal Brain Damage",slug:"neurocognitive-implications-of-tangential-speech-in-patients-with-focal-brain-damage",totalDownloads:1594,totalCrossrefCites:0,totalDimensionsCites:3,abstract:"There are no studies on the neurocognitive implications of tangential speech (TS). This research aims to take a step forward in the study of narrative processing, by evaluating TS in a sample that helps to detect this deficit when it is neurogenic and recently manifested. The relationship between TS, secondary to focal brain injury, and neuropsychological and neuroanatomical variables was explored. A comprehensive neuropsychological battery was administered to 175 volunteers: 95 alert inpatients, without aphasia, without psychiatric history and without TS history, and 80 healthy participants, without TS. Results: TS (prevalence 16%) was independent of type or site of injury. An adverse effect of TS on global neuropsychological performance was observed. This effect was significantly related to attentional errors along with prolonged processing times but not to correct responses. Reliability and validity indices for the present TS screening scale were provided. Conclusion: Present results support the hypothesis that this neurogenic inability to spontaneously find, organize and communicate verbal information, beyond single words, depends on extended brain networks involving processes such as sustained attention, complex-syntax comprehension, the (implicit) interpretation and spontaneous recall of a narrative, and emotional and behavioral alterations. Early TS detection is advisable for prevention and treatment at any age.",book:{id:"6381",slug:"gerontology",title:"Gerontology",fullTitle:"Gerontology"},signatures:"Nora Silvana Vigliecca",authors:[{id:"202008",title:"Dr.",name:"Nora",middleName:"Silvana",surname:"Vigliecca",slug:"nora-vigliecca",fullName:"Nora Vigliecca"}]}],mostDownloadedChaptersLast30Days:[{id:"60564",title:"Ageing Process and Physiological Changes",slug:"ageing-process-and-physiological-changes",totalDownloads:6996,totalCrossrefCites:19,totalDimensionsCites:34,abstract:"Ageing is a natural process. Everyone must undergo this phase of life at his or her own time and pace. In the broader sense, ageing reflects all the changes taking place over the course of life. These changes start from birth—one grows, develops and attains maturity. To the young, ageing is exciting. Middle age is the time when people notice the age-related changes like greying of hair, wrinkled skin and a fair amount of physical decline. Even the healthiest, aesthetically fit cannot escape these changes. Slow and steady physical impairment and functional disability are noticed resulting in increased dependency in the period of old age. According to World Health Organization, ageing is a course of biological reality which starts at conception and ends with death. It has its own dynamics, much beyond human control. However, this process of ageing is also subject to the constructions by which each society makes sense of old age. In most of the developed countries, the age of 60 is considered equivalent to retirement age and it is said to be the beginning of old age. In this chapter, you understand the details of ageing processes and associated physiological changes.",book:{id:"6381",slug:"gerontology",title:"Gerontology",fullTitle:"Gerontology"},signatures:"Shilpa Amarya, Kalyani Singh and Manisha Sabharwal",authors:[{id:"226573",title:"Ph.D.",name:"Shilpa",middleName:null,surname:"Amarya",slug:"shilpa-amarya",fullName:"Shilpa Amarya"},{id:"226593",title:"Dr.",name:"Kalyani",middleName:null,surname:"Singh",slug:"kalyani-singh",fullName:"Kalyani Singh"},{id:"243264",title:"Dr.",name:"Manisha",middleName:null,surname:"Sabharwal",slug:"manisha-sabharwal",fullName:"Manisha Sabharwal"}]},{id:"55388",title:"Beauty, Body Image, and the Media",slug:"beauty-body-image-and-the-media",totalDownloads:7764,totalCrossrefCites:5,totalDimensionsCites:12,abstract:"This chapter analyses the role of the mass media in people’s perceptions of beauty. We summarize the research literature on the mass media, both traditional media and online social media, and how they appear to interact with psychological factors to impact appearance concerns and body image disturbances. There is a strong support for the idea that traditional forms of media (e.g. magazines and music videos) affect perceptions of beauty and appearance concerns by leading women to internalize a very slender body type as ideal or beautiful. Rather than simply being passive recipients of unrealistic beauty ideals communicated to them via the media, a great number of individuals actually seek out idealized images in the media. Finally, we review what is known about the role of social media in impacting society’s perception of beauty and notions of idealized physical forms. Social media are more interactive than traditional media and the effects of self‐presentation strategies on perceptions of beauty have just begun to be studied. This is an emerging area of research that is of high relevance to researchers and clinicians interested in body image and appearance concerns.",book:{id:"5925",slug:"perception-of-beauty",title:"Perception of Beauty",fullTitle:"Perception of Beauty"},signatures:"Jennifer S. Mills, Amy Shannon and Jacqueline Hogue",authors:[{id:"202110",title:"Dr.",name:"Jennifer S.",middleName:null,surname:"Mills",slug:"jennifer-s.-mills",fullName:"Jennifer S. Mills"}]},{id:"56505",title:"Aesthetics of the Naked Human Body: From Pornography (Sexualised Lust Object) to Iconography (Aesthetics of Human Nobility and Wisdom) in an Anthropology of Physical Beauty",slug:"aesthetics-of-the-naked-human-body-from-pornography-sexualised-lust-object-to-iconography-aesthetics",totalDownloads:2100,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"In many religious circles and philosophies of life, the human body is excluded from the realm of spirituality and meaning. Due to a dualistic approach, nudity is viewed as merely a physical and corporeal category. In social media, there is the real danger that the naked human body is exploited for commercial gain. Advertisements often leave the impression that the body, very specifically the genitals, is designed merely for physical desire and corporeal chemistry. They become easily objects for lust, excluded from the beauty of graceful existence and noble courage. It is argued that the naked human body is not designed for pornographic exploitation and promiscuous sensuality but for compassionate intimacy and nurturing care in order to instil a humane dimension in human and sexual encounters. In this regard, antiquity and the Michelangelesque perspective can contribute to a paradigm shift from abusive exploitation to the beauty of vulnerable sensitivity. In order to foster an integrative approach to theory formation in anthropology, the methodology of stereometric thinking is proposed.",book:{id:"5925",slug:"perception-of-beauty",title:"Perception of Beauty",fullTitle:"Perception of Beauty"},signatures:"Daniel J Louw",authors:[{id:"200645",title:"Prof.",name:"Daniel",middleName:"Johannes",surname:"Louw",slug:"daniel-louw",fullName:"Daniel Louw"}]},{id:"56059",title:"A Plastic Surgeon’s Perspective on Stereotyping and the Perception of Beauty",slug:"a-plastic-surgeon-s-perspective-on-stereotyping-and-the-perception-of-beauty",totalDownloads:1918,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"In the world of plastic surgery, misconceptions may lead to irrational requests or outcomes not appreciated by patients. Those who manage aesthetics should always listen and recognize the variability of cultural identities, desires, attitudes, anxieties and uncertainties of the patient. Emerging from a diversity of cultures and its transforming trends, the scope of cosmetic surgery and its practice reflect not only the individual’s personality, but also the culture as a whole. When counseling an individual, one has to recognize that even in groups of seemingly identical social or cultural standards; there are subtle differences in expectations. To illustrate the potential for inaccuracy of ethnic profiling in the field of plastic surgery authors quote their own work on Asian subjects and facial beauty and resort to experience of others. To reaffirm their opinion and to exemplify how sometimes “fine” differences in the perception of beauty exist, an original study that evaluates the preferences among selected groups of Latina women in respect to buttock aesthetics has been included. This dissertation will focus on how cultural factors influence beauty perception; strengthen the fact that beauty is in the eye of the beholder and how variable differences exist even between small subgroups.",book:{id:"5925",slug:"perception-of-beauty",title:"Perception of Beauty",fullTitle:"Perception of Beauty"},signatures:"Johanna D’Agostino and Marek Dobke",authors:[{id:"17590",title:"Dr.",name:"Marek K.",middleName:null,surname:"Dobke",slug:"marek-k.-dobke",fullName:"Marek K. Dobke"},{id:"201244",title:"Dr.",name:"Johanna",middleName:null,surname:"D'Agostino",slug:"johanna-d'agostino",fullName:"Johanna D'Agostino"}]},{id:"80326",title:"Anti-Senescence Therapy",slug:"anti-senescence-therapy",totalDownloads:110,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The development of therapeutic strategies aimed at the aging process of cells has attracted increasing attention in recent decades due to the involvement of this process in the development of many chronic and age-related diseases. Interestingly, preclinical studies have shown the success of a number of anti-aging approaches in the treatment of a range of chronic diseases. These approaches are directed against aging processes such as oxidative stress, telomerase shortening, inflammation, and deficient autophagy. Many strategies has been shown to be effective in delaying aging, including antiaging strategies based on establishing healthy lifestyle habits and pharmacological interventions aimed at disrupting senescent cells and senescent-associated secretory phenotype. Caloric restriction and intermittent fasting were reported to activate autophagy and reduce inflammation. In turn, immune-based strategies, senolytic agents, and senomorphics mediate their effects either by eliminating senescent cells through inducing apoptosis or by disrupting pathways by which senescent cells mediate their detrimental effects. In addition, given the association of the decline in the regenerative potential of stem cells with aging, many experimental and clinical studies indicate the effectiveness of stem cell transplantation in preventing or slowing the progress of age-related diseases by enhancing the repairing mechanisms and the secretion of many growth factors and cytokines.",book:{id:"10935",slug:null,title:"Mechanisms and Management of Senescence",fullTitle:"Mechanisms and Management of Senescence"},signatures:"Raghad Alshadidi",authors:null}],onlineFirstChaptersFilter:{topicId:"235",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82112",title:"Comparative Senescence and Lifespan",slug:"comparative-senescence-and-lifespan",totalDownloads:17,totalDimensionsCites:0,doi:"10.5772/intechopen.105137",abstract:"The word senescence is derived from the Latin word “senex” (meaning old). In biology, senescence is a process by which a cell ages and permanently stops dividing. Senescence is a natural universal phenomenon affecting all living organisms (e.g., humans, animals, and plants). It is the process of growing old (aging). The underlying mechanisms of senescence and aging at the cellular level are not fully understood. Senescence is a multifactorial process that can be induced by several stimuli including cellular stress, DNA damage, telomere shortening, and oncogene activation. The most popular theory to explain aging is the free radical theory. Senescence plays a role in the development of several age-related chronic diseases in humans (e.g., ischemic heart disease, osteoporosis, and cancer). Lifespan is a biological characteristic of every species. The lifespan of living organisms ranges from few hours (with mayfly) to potential eternity (with jellyfish and hydra). The maximum theoretical lifespan in humans is around 120 years. The lifespan in humans is influenced by multiple factors including genetic, epigenetic, lifestyle, environmental, metabolic, and endocrine factors. There are several ways to potentially extend the lifespan of humans and eventually surpass the maximum theoretical lifespan of 120 years. The tools that can be proposed include lifestyle, reduction of several life-threatening diseases and disabilities, hormonal replacement, antioxidants, autophagy inducers, senolytic drugs, stem cell therapy, and gene therapy.",book:{id:"10935",title:"Mechanisms and Management of Senescence",coverURL:"https://cdn.intechopen.com/books/images_new/10935.jpg"},signatures:"Hassan M. Heshmati"},{id:"81638",title:"Aging and Neuropsychiatric Disease: A General Overview of Prevalence and Trends",slug:"aging-and-neuropsychiatric-disease-a-general-overview-of-prevalence-and-trends",totalDownloads:30,totalDimensionsCites:0,doi:"10.5772/intechopen.103102",abstract:"The increasing trend of life-expectancy is becoming a significant demographic, societal and economic challenge. Currently, global number of people above sixty years of age is 900 million, while United Nations expect this number to rise to over 1.4 billion in 2030 and over 2.5 billion by 2050. Concordant to this trend, numerous physiological changes are associated with aging and brain-related ones are associated with neuropsychiatric diseases. The main goal of this chapter is to identify the most important neuropsychiatric diseases to assess in older patients to help to promote health and prevent diseases and complications associated with chronic illness, as these changes are progressive and require important psychological and setting-related social adjustments. Findings identify several health-aspects highly present in elderly: stroke, white matter lesions, dementia rise with age, changes in levels of neurotransmitters and hormones, depression as well as the bereavement following loss of the loved one, and the most common neurodegenerative disease—Alzheimer’s disease and Parkinson’s. In conclusion, studying the aging process should include all developmental, circumstantial, and individual aspects of aging. This offers opportunities to improve the health of elderly by using a wide range of skills and knowledge. Thus, further studies are necessary to elucidate what can be done do to improve the aging process and health of elderly in the future.",book:{id:"10935",title:"Mechanisms and Management of Senescence",coverURL:"https://cdn.intechopen.com/books/images_new/10935.jpg"},signatures:"Jelena Milić"},{id:"80326",title:"Anti-Senescence Therapy",slug:"anti-senescence-therapy",totalDownloads:110,totalDimensionsCites:0,doi:"10.5772/intechopen.101585",abstract:"The development of therapeutic strategies aimed at the aging process of cells has attracted increasing attention in recent decades due to the involvement of this process in the development of many chronic and age-related diseases. Interestingly, preclinical studies have shown the success of a number of anti-aging approaches in the treatment of a range of chronic diseases. These approaches are directed against aging processes such as oxidative stress, telomerase shortening, inflammation, and deficient autophagy. Many strategies has been shown to be effective in delaying aging, including antiaging strategies based on establishing healthy lifestyle habits and pharmacological interventions aimed at disrupting senescent cells and senescent-associated secretory phenotype. Caloric restriction and intermittent fasting were reported to activate autophagy and reduce inflammation. In turn, immune-based strategies, senolytic agents, and senomorphics mediate their effects either by eliminating senescent cells through inducing apoptosis or by disrupting pathways by which senescent cells mediate their detrimental effects. In addition, given the association of the decline in the regenerative potential of stem cells with aging, many experimental and clinical studies indicate the effectiveness of stem cell transplantation in preventing or slowing the progress of age-related diseases by enhancing the repairing mechanisms and the secretion of many growth factors and cytokines.",book:{id:"10935",title:"Mechanisms and Management of Senescence",coverURL:"https://cdn.intechopen.com/books/images_new/10935.jpg"},signatures:"Raghad Alshadidi"},{id:"79828",title:"Cellular Senescence in Bone",slug:"cellular-senescence-in-bone",totalDownloads:119,totalDimensionsCites:0,doi:"10.5772/intechopen.101803",abstract:"Senescence is an irreversible cell-cycle arrest process induced by environmental, genetic, and epigenetic factors. An accumulation of senescent cells in bone results in age-related disorders, and one of the common problems is osteoporosis. Deciphering the basic mechanisms contributing to the chronic ailments of aging may uncover new avenues for targeted treatment. This review focuses on the mechanisms and the most relevant research advancements in skeletal cellular senescence. To identify new options for the treatment or prevention of age-related chronic diseases, researchers have targeted hallmarks of aging, including telomere attrition, genomic instability, cellular senescence, and epigenetic alterations. First, this chapter provides an overview of the fundamentals of bone tissue, the causes of skeletal involution, and the role of cellular senescence in bone and bone diseases such as osteoporosis. Next, this review will discuss the utilization of pharmacological interventions in aging tissues and, more specifically, highlight the role of senescent cells to identify the most effective and safe strategies.",book:{id:"10935",title:"Mechanisms and Management of Senescence",coverURL:"https://cdn.intechopen.com/books/images_new/10935.jpg"},signatures:"Danielle Wang and Haitao Wang"},{id:"79668",title:"Identification of RNA Species That Bind to the hnRNP A1 in Normal and Senescent Human Fibroblasts",slug:"identification-of-rna-species-that-bind-to-the-hnrnp-a1-in-normal-and-senescent-human-fibroblasts",totalDownloads:81,totalDimensionsCites:0,doi:"10.5772/intechopen.101525",abstract:"hnRNP A1 is a member of the hnRNPs (heterogeneous nuclear ribonucleoproteins) family of proteins that play a central role in regulating genes responsible for cell proliferation, DNA repair, apoptosis, and telomere biogenesis. Previous studies have shown that hnRNPA1 had reduced protein levels and increased cytoplasmic accumulation in senescent human diploid fibroblasts. The consequence of reduced protein expression and altered cellular localization may account for the alterations in gene expression observed during senescence. There is limited information for gene targets of hnRNP A1 as well as its in vivo function. In these studies, we performed RNA co-immunoprecipitation experiments using hnRNP A1 as the target protein to identify potential mRNA species in ribonucleoprotein (RNP) complexes. Using this approach, we identified the human double minute 2 (HDM2) mRNA as a binding target for hnRNP A1 in young and senescent human diploid fibroblasts cells. It was also observed that alterations of hnRNP A1 expression modulate HDM2 mRNA levels in young IMR-90 cells. We also demonstrated that the levels of HDM2 mRNA increased with the downregulation of hnRNP A1 and decrease with the overexpression of hnRNP A1. Although we did not observe a significant decrease in HDM2 protein level, a concomitant increase in p53 protein level was detected with the overexpression of hnRNP A1. Our studies also show that hnRNP A1 directly interacts with HDM2 mRNA at a region corresponding to its 3′ UTR (untranslated region of a gene). The results from this study demonstrate that hnRNP A1 has a novel role in participating in the regulation of HDM2 gene expression.",book:{id:"10935",title:"Mechanisms and Management of Senescence",coverURL:"https://cdn.intechopen.com/books/images_new/10935.jpg"},signatures:"Heriberto Moran, Shanaz A. Ghandhi, Naoko Shimada and Karen Hubbard"},{id:"79295",title:"Genetic and Epigenetic Influences on Cutaneous Cellular Senescence",slug:"genetic-and-epigenetic-influences-on-cutaneous-cellular-senescence",totalDownloads:133,totalDimensionsCites:0,doi:"10.5772/intechopen.101152",abstract:"Skin is the largest human organ system, and its protective function is critical to survival. The epithelial, dermal, and subcutaneous compartments are heterogeneous mixtures of cell types, yet they all display age-related skin dysfunction through the accumulation of an altered phenotypic cellular state called senescence. Cellular senescence is triggered by complex and dynamic genetic and epigenetic processes. A senescence steady state is achieved in different cell types under various and overlapping conditions of chronological age, toxic injury, oxidative stress, replicative exhaustion, DNA damage, metabolic dysfunction, and chromosomal structural changes. These inputs lead to outputs of cell-cycle withdrawal and the appearance of a senescence-associated secretory phenotype, both of which accumulate as tissue pathology observed clinically in aged skin. 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Singh",profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"8018",title:"Extracellular Matrix",subtitle:"Developments and Therapeutics",coverURL:"https://cdn.intechopen.com/books/images_new/8018.jpg",slug:"extracellular-matrix-developments-and-therapeutics",publishedDate:"October 27th 2021",editedByType:"Edited by",bookSignature:"Rama Sashank Madhurapantula, Joseph Orgel P.R.O. and Zvi Loewy",hash:"c85e82851e80b40282ff9be99ddf2046",volumeInSeries:23,fullTitle:"Extracellular Matrix - Developments and Therapeutics",editors:[{id:"212416",title:"Dr.",name:"Rama Sashank",middleName:null,surname:"Madhurapantula",slug:"rama-sashank-madhurapantula",fullName:"Rama Sashank Madhurapantula",profilePictureURL:"https://mts.intechopen.com/storage/users/212416/images/system/212416.jpg",institutionString:"Illinois Institute of Technology",institution:{name:"Illinois Institute of Technology",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Proteomics",value:18,count:4},{group:"subseries",caption:"Metabolism",value:17,count:6},{group:"subseries",caption:"Cell and Molecular Biology",value:14,count:9},{group:"subseries",caption:"Chemical Biology",value:15,count:14}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:9},{group:"publicationYear",caption:"2021",value:2021,count:7},{group:"publicationYear",caption:"2020",value:2020,count:12},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:2}],authors:{paginationCount:250,paginationItems:[{id:"274452",title:"Dr.",name:"Yousif",middleName:"Mohamed",surname:"Abdallah",slug:"yousif-abdallah",fullName:"Yousif Abdallah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274452/images/8324_n.jpg",biography:"I certainly enjoyed my experience in Radiotherapy and Nuclear Medicine, particularly it has been in different institutions and hospitals with different Medical Cultures and allocated resources. Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"243698",title:"Dr.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:null,institution:null},{id:"7227",title:"Dr.",name:"Hiroaki",middleName:null,surname:"Matsui",slug:"hiroaki-matsui",fullName:"Hiroaki Matsui",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Tokyo",country:{name:"Japan"}}},{id:"312999",title:"Dr.",name:"Bernard O.",middleName:null,surname:"Asimeng",slug:"bernard-o.-asimeng",fullName:"Bernard O. 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Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}},editorTwo:null,editorThree:null,series:{id:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188"},editorialBoard:[{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",institutionString:null,institution:{name:"Grenoble Alpes University",institutionURL:null,country:{name:"France"}}},{id:"188219",title:"Prof.",name:"Imran",middleName:null,surname:"Shahid",slug:"imran-shahid",fullName:"Imran Shahid",profilePictureURL:"https://mts.intechopen.com/storage/users/188219/images/system/188219.jpeg",institutionString:null,institution:{name:"Umm al-Qura University",institutionURL:null,country:{name:"Saudi Arabia"}}},{id:"214235",title:"Dr.",name:"Lynn",middleName:"S.",surname:"Zijenah",slug:"lynn-zijenah",fullName:"Lynn Zijenah",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSEJGQA4/Profile_Picture_1636699126852",institutionString:null,institution:{name:"University of Zimbabwe",institutionURL:null,country:{name:"Zimbabwe"}}},{id:"178641",title:"Dr.",name:"Samuel Ikwaras",middleName:null,surname:"Okware",slug:"samuel-ikwaras-okware",fullName:"Samuel Ikwaras Okware",profilePictureURL:"https://mts.intechopen.com/storage/users/178641/images/system/178641.jpg",institutionString:null,institution:{name:"Uganda Christian University",institutionURL:null,country:{name:"Uganda"}}}]},onlineFirstChapters:{paginationCount:20,paginationItems:[{id:"82800",title:"Repurposing Drugs as Potential Therapeutics for the SARS-Cov-2 Viral Infection: Automatizing a Blind Molecular Docking High-throughput Pipeline",doi:"10.5772/intechopen.105792",signatures:"Aldo Herrera-Rodulfo, Mariana Andrade-Medina and Mauricio Carrillo-Tripp",slug:"repurposing-drugs-as-potential-therapeutics-for-the-sars-cov-2-viral-infection-automatizing-a-blind-",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Molecular Docking - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11451.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"82582",title:"Protecting Bioelectric Signals from Electromagnetic Interference in a Wireless World",doi:"10.5772/intechopen.105951",signatures:"David Marcarian",slug:"protecting-bioelectric-signals-from-electromagnetic-interference-in-a-wireless-world",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Biosignal Processing",coverURL:"https://cdn.intechopen.com/books/images_new/11153.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"82586",title:"Fundamentals of Molecular Docking and Comparative Analysis of Protein–Small-Molecule Docking Approaches",doi:"10.5772/intechopen.105815",signatures:"Maden Sefika Feyza, Sezer Selin and Acuner Saliha Ece",slug:"fundamentals-of-molecular-docking-and-comparative-analysis-of-protein-small-molecule-docking-approac",totalDownloads:26,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Molecular Docking - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11451.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"82184",title:"Biological Sensing Using Infrared SPR Devices Based on ZnO",doi:"10.5772/intechopen.104562",signatures:"Hiroaki Matsui",slug:"biological-sensing-using-infrared-spr-devices-based-on-zno",totalDownloads:10,totalCrossrefCites:0,totalDimensionsCites:0,authors:[{name:"Hiroaki",surname:"Matsui"}],book:{title:"Biosignal Processing",coverURL:"https://cdn.intechopen.com/books/images_new/11153.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"82122",title:"Recent Advances in Biosensing in Tissue Engineering and Regenerative Medicine",doi:"10.5772/intechopen.104922",signatures:"Alma T. 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