\r\n\tThis book will intend to look at different migrant patterns, voluntary and involuntary migration, over the last three centuries. What influenced people to leave their home countries, family, and friends and settle somewhere else? The book may include histories of the 19th century, consider tragedies and movements activated by political events in the 20th century, and/or look at recent events of the 21st century. Push and pull factors are important points. While most of us may be influenced in a negative way by the current happenings in Eastern Europe, the Russian invasion and resulting tragedies also demonstrate some very positive human traits – the preparedness of Ukraine’s surrounding countries to help those in need and to provide a safe place for the present.
\r\n\tWhether one looks at voluntary or involuntary migration into any country, after a period of adjustment, migrants do play a positive role. The research found that migrants contribute to the economy (food, shelter, employment, tax) and enrich a country’s cultural norms. Prerequisites for successful settlements are that the host society adopts a tolerant approach and that the migrants recognize the law and the language of the host country. Nothing is ever easy or without controversy, but I am a migrant (German Australian), and life in Australia has been relatively harmonious. Issues that could be considered in the book are multicultural societies (do monocultural societies still exist?) and theories of acculturation versus integration (settlement processes).
\r\n\tTwo further issues are very important in relation to human migration. There is climate change, global warming, and the environment, which clearly affect people’s movement. Small island populations are very concerned about rising sea levels. 2021 has also seen floods costing human lives: Turkey (August 2021), Brazil (December 2021), Chile (January 2021), and South India (November 2021), to name but a few. In Australia (March 2022), farms and whole townships in New South Wales and Queensland have been flooded for the second time in five years, and plans to resettle these towns are considered. Official and social media provide ample coverage of the events, which leads me to the next issue. There is today’s very important role of the media, of the official and social media. We are constantly bombarded with images of human war tragedies and flood victims. People in industrialized, western countries must be the best-informed populace. How far do the images and up-to-date TV news influence us, make us change our behavior, and perhaps even consider us more generous than we have been?
\r\n\tClimate change and the media are relatively new to the human migration debate, but both issues play important parts, and some interesting discussions are appreciated.
\r\n\t
The term nanoparticle (NP) refers to particles with at least one dimension less than 100 nanometers [1]. NPs are an essential part of earth’s biogeochemical system, produced by many physical and chemical processes including different natural and human activities. They are commonly classified as naturally occurring and synthetic or anthropogenic NPs, depending on their origin. Synthetic or anthropogenic NPs can be further categorized into two types: incidental and engineered nanoparticles [2]. Naturally occurring nanoparticles can be formed by chemical, photochemical, mechanical, thermal, and biological processes occurring in all spheres of the Earth. NPs such as alumina, iron oxide, gold, sulfur manganese oxide, and so on derived from natural sources can be found in volcanic ash, fine sand, ocean spray, and even some biological matter [1]. Incidental nanoparticles are unintentionally produced as a byproduct of human day-to-day activities involving combustion process such as running diesel engines, large-scale mining, and even starting a fire. On the other hand, the engineered or manufactured NPs such as silver, gold, zinc, metal oxides like manganese dioxide (MnO2), aluminum oxide Al2O3, titanium oxide (TiO2) of controlled shape, sizes, and compositions are specifically designed and deliberately synthesized by human beings [3]. Engineered NP include nonmetals like carbon nanotubes and quantum dots, polymers like chitosan, alginate, lipids like stearic acid, and metal sulfide like CuS, AgS, ZnS and so on [4]. Another classification of NP is their grouping into organic nanoparticles and inorganic nanoparticles. Organic nanoparticles include liposomes, dendrimers, micelles and so on. Examples of some of inorganic NP include metallic NP like gold, iron, silver, aluminum, titanium oxide (TiO2), and zinc oxide (ZnO). Nanomaterials can also be classified based on their size for example zero-dimension, one dimension, two dimension, and three dimensions [5]. Silver, gold, copper, and platinum are some of the most commonly used metals NP. Metal-based NPs can be easily conjugated with various functional groups, like polylysine, polyethylene glycol (PEG) or bovine serum albumin [6, 7].
The technological advancements of human society as well as progress in the field of nanotechnology have shown a sharp rise in consumer products that deliberately include synthetic nanoparticles [8]. This has resulted in high levels of exposure to many types of synthetic NPs, and it is likely that this trend will continue in future. The easiest place to find these nano-enabled products in our own homes is in health care products, cosmetics, and food additives. In the past decade, many companies have used ZnO and TiO2 NPs as sun block materials because these materials are very effective at absorbing UV radiation [9]. Some commonly used nanomaterials as food additives include silver, silicon dioxide (SiO2), titanium TiO2, and iron oxide (Fe2O3) [10]. Silver NPs are also commonly used as antibacterial and antiviral agents, while gold NPs are used for drug delivery, photothermal therapy and diagnostic applications, and polymeric NPs are used for controlled and targeted drug delivery [11].
Extensive use of engineered NP poses risk to human health. The health hazards are cause of concern in pregnant women and their unborn children. Therefore, it is important to study the toxic effect of NP on developing fetuses. In this chapter, we summarize the developmental toxicity of NP on the nervous system.
The embryonic toxicity of nanoparticles depends on their bioaccumulation, which in turn depends on the following [12]:
Chemical composition, particle size, shape, surface modification, and degree of agglomeration. Smaller NPs have been shown to induce more pronounced blood brain barrier (BBB) breakdown, brain edema and neuronal injuries, glial fibrillary acidic protein upregulation, and myelin vesiculation in young animals [13]. Similarly, different shapes of the same NP have been shown to induce different cellular responses by nonspecific uptake into cells [14]. In vivo animal studies have demonstrated that administration of higher doses of smaller particles NP caused their increased accumulation in placental and embryonic/fetal tissues [15].
Type of coating, concentration of particles, surface charge of the particles, zeta potential, and crystal form. Unmodified fullerene NPs can generate reactive oxygen species (ROS) to damage cells, whereas surface-modified fullerene NPs have been demonstrated to enter cerebral microvessel endothelial cells and protect these cells by attenuating ROS-induced cellular damage, such as F-actin depolymerization [16].
Other factors include the pH of the solution, salt concentration and the temperature [17], “protein corona,” chemical characteristics, metal impurities, and degradation properties [18].
Particle dissolution also alters the particle presence [15].
Routes of exposure in in vivo studies. Inhalation is the main route of exposure in occupational and environmental settings. Experimental studies commonly use intravenous and intra peritoneal routes [15].
The anatomical and functional state of the placenta [19, 20] and the critical period of exposure during gestation [15].
Zeta potential of the NP. The charges on the NP determine their interactions with the biological system. Also, the zeta potential determines the stability of the NP in colloidal systems [21].
The exogenous entry of engineered NP is mainly from hand-to-mouth contact in the workplaces. Nanoparticles enter the body through food, drinking water, drugs, or exposure during medical procedures. Inhalation of airborne nanoparticles is also an important point of entry into the body [22]. Larger particles are trapped in the nasopharyngeal region (5–30 μm), while the smaller particles (1–5 μm) get deposited in the tracheobronchial region. These particles can be removed by mucociliary clearance. Finally, the remaining submicron particles (< 1 μm) and nanoparticles (< 100 nm) with the smallest size distribution penetrate deeply into the alveolar region, where removal mechanisms may be insufficient. Nanosized particles can reach the alveolar region of the lungs where they get in contact with the alveolar epithelium. From the alveolar epithelium these particles can cross the blood-air-tissue barrier and enter the bloodstream to reach various organs [22]. Inhaled ultrafine particles may get deposited in the olfactory mucosa from where they can translocate in the central nervous system (CNS), which in turn might cause neurotoxicity. Studies have shown that the CNS may be a crucial target for nanoparticle inhalation or intranasal installation exposure [23, 24]. The third route of entry of NP into the body is through dermal penetration [22, 25].
The NPs enter the CNS through three main routes: (1) Transport through the lymphatic and circulatory system; (2) Activity of the mucocilliary escalator followed by oral exposure; and (3) Transport through the olfactory and trigeminal nerves [18, 26]. This pathway involves the passage of nanoparticles through the olfactory epithelium and the neurons associated with it to the brain [18]. Carbonaceous nanomaterials have been reported to show increased access to the brain via the facilitation of olfactory mucosa and olfactory nerve [23]. After uptake, NPs can permeate into other parts of the brain by simple diffusion and then travel along the direction of the convection of the interstitial fluid and the cerebrospinal fluid flow [27].
The blood-brain barrier (BBB) is a term used to describe the unique properties of the microvasculature of the central nervous system (CNS). CNS is made of continuous and non-fenestrated vessels. These blood vessels function to regulate the movement of molecules, ions, and cells between the blood and the CNS [28, 29]. The central nervous system of vertebrates is isolated from the rest of the body by BBB. Normal functioning of BBB is essential for homeostasis. The BBB is made of two main types of cells, that is, endothelial cells (EC) and mural cells. ECs function to regulate the movement of ions, molecules, and cells between the blood and the brain. ECs are held together by tight junctions (TJs), which greatly restrict the paracellular movement of solutes [30]. The tight junctions hold CNS ECs in place forming a paracellular barrier to molecules and ions [30].
Mural cells are the cells surrounding the large vessels and pericytes, which are present on the abluminal surface of the endothelium [31]. Pericytes and astrocytes are considered the key cell types involved in BBB regulation through their interactions with brain endothelial cells. Astrocytes interact with brain endothelium and are thought to be involved in the maintenance of BBB endothelial cell properties [32] and regulate BBB permeability [33]. The BBB restricts the movement of molecules by forming a physical barrier, which is represented by tight junctions between the endothelial cells. The endothelial cells express two main types of transporters: the efflux transporters, which transport lipophilic substances toward the blood [34] and nutrient transporters, which transport nutrients into the CNS and remove waste products from the CNS to the blood [35]. The EC cells of the CNS are characterized by a higher number of mitochondria [36]. These mitochondria supply the BBB with Adenosine triphosphate to carry out their transport processes.
Other cell types of the BBB are astrocytes and immune cells, mainly macrophages and microglial cells [30]. Pericytes, astrocyte end-feet, and a discontinuous basal membrane support the functions of the BBB. The highly selective functionality of the BBB is due to endothelial tight junctions that are assisted by astrocytes and pericytes. The tight influx control is complemented by the efflux transport system, which rapidly eliminates classic xenobiotics and NMs buildup in the brain [37]. However, nanomaterials have been reported to cross the BBB via a transcytosis-mediated route [38].
A second barrier observed in the nervous system is the metabolic barrier. The metabolic barrier is composed of enzymes and transport systems [39]. The metabolism of endothelial cells plays an important role in the function of BBB. L-Dihydroxyphenylalanine is the precursor of dopamine which enters the brain through the neutral amino acid-transport system. However, its entry is restricted due to L-Dihydroxyphenylalanine decarboxylase and monoamine oxidase inside the endothelial cells of the brain capillaries. This “enzymatic blood-brain barrier” limits the passage of L-Dihydroxyphenylalanine into the brain (https://nba.uth.tmc.edu/neuroscience/m/s4/chapter11.html). The brain capillaries contain enzymes that metabolize neurotransmitters. These enzymes include endopeptidases, cholinesterases, aminopeptidases, and Gamma-Aminobutyric acidtransaminases. The brain capillaries also contain drug and toxin-metabolizing enzymes found in the liver [40].
The endothelium of the BBB lacks pinocytic vesicles. This limits pinocytosis by the cells of BBB. The cells of BBB express many enzymes on the intra and extracellular surfaces, which restrict the movement of substances through the BBB. P-glycoproteins, and similar substances present on the endothelial cells also help to eliminate various endogenous and exogenous toxins [18]. P-glycoproteins cause multi-drug-resistant cancer cells to pump out the drugs. The endothelial cells have P-proteins, which help to pump some hydrophobic substances like cyclosporin A, domperidone, digoxin and so on into the blood.
A third barrier represented by the blood-Cerebrospinal fluid barrier also serves to prevent indiscriminate entry of substances in the CNS [41]. This barrier is made up of choroid plexus epithelial cells. The blood-Cerebrospinal fluid barrier is made up of choroid plexus epithelial cells, which have smaller tight junctions than the BBB endothelia. The blood-Cerebrospinal fluid barrier prevents the entry of macromolecules into the Cerebrospinal fluid. The active transport systems of the BBB actively remove therapeutic organic acids from the Cerebrospinal fluid [42].
Some of the ways by which NP can circumvent the blood brain barrier include the following (Figure 1):
Transcellular diffusion—Low molecular weight solid lipid nanoparticles [43].
Paracellular diffusion—this route is taken by silica and reduced graphene oxide NP [44, 45].
Receptor-mediated transcytosis—Engineered nanomaterials with ligands such as transferrin, insulin, ApoE can avoid the BBB by this route [46].
Adsorptive-mediated transcytosis—Cationic albumin-conjugated pegylated NPs enter the brain by adsorptive-mediated transcytosis [47].
Cell mediated transcytosis—Macrophages take up engineered nanomaterials and release them into the CNS [48].
Possible pathways through which nanoparticles cross the blood-brain barrier (BBB) and damage the neurons. Engineered nanomaterials with specific physicochemical properties can cross the BBB through various transport pathways such as (A) transcellular diffusion; (B) paracellular diffusion; (C) receptor-mediated transcytosis; (D) adsorptive-mediated transcytosis; and (E) cell mediated transcytosis. Nanoparticles interact directly with neuronal cells and cause neurotoxicity.
Exposure of pregnant mice to different NPs has been reported to induce pregnancy complications or damage to the fetus. Placenta is the maternal-fetal interface, which is formed of both maternal and fetal tissues that protects the embryo from harmful substances in the maternal blood. Placenta functions to exchange oxygen, nutrients, metabolic waste, and other molecules between the maternal and fetal bloodstream [49]. Factors that control the transfer of substances between maternal and fetal circulation include membrane surface area and thickness, blood flow, hydrostatic pressure in the intervillous chamber and the difference between fetal and maternal osmotic pressure [50]. Beside the placenta, amnion, chorion and parietal decidua also surround the fetus. These membranes are impervious to most of the xenobiotics in the maternal blood [51].
The brains from the fetuses of rats and mice have shown the presence of NP when the pregnant mothers were exposed to NP [52, 53]. Nano-silica and nano-TiO2 have been reported to accumulate in the placenta, fetal liver, and fetal brain when injected to pregnant mice [54]. The extent of transfer of nanoparticle across the placenta depends on the characteristics and functionalization of the particles [55, 56]. NPs with diameters 1–100 nm have been shown to transverse the placental barrier and were detected in the brain of the offspring [57, 58]. Gestational age is an important factor affecting the toxicity of NP on the fetus [50]. Fennell et al. [59] have demonstrated that AgNP administered through oral and IV route on gestational day 18 resulted in placental accumulation after 48 h. Campagnolo et al. [60] demonstrated that inhalation of Ag NP during the first gestational day until the fifteenth gestational day in female rats caused fetal resorption. This was accompanied with an increased expression of pregnancy-relevant inflammatory cytokines in the placentas. Zhang et al. [19] have shown that maternal exposure of mice to TiO2 NP decreased in angiogenesis in placental tissue and activated apoptotic pathways through caspase-3 in placental tissue.
Studies have demonstrated that various NPs can cross the BBB and placental barrier [61, 62]. Titanium dioxide nanomaterials (nTiO2) have been reported to cross the placental barrier in pregnant mice and cause neurotoxicity in their offspring. Toxicity to the brain cells was reported to be caused due to necrosis (Figure 2) [63].
Maternal exposure of nanoparticles (NPs) results in neural fetotoxicity and developmental abnormalities. Direct translocation of NPs from maternal circulation across the placental barrier into growing fetus has been recognized as the major factor involved in NP-induced fetotoxicity. Accumulation of NPs in the fetus can cause structural and functional abnormalities in various fetal tissues, including the central nervous system (CNS) which is the main target of metallic NPs. Oxidative stress, induction of inflammatory responses, alterations in gene expression, DNA damage, necrosis, and apoptosis are the mechanisms associated with NP-induced neural fetotoxicity.
Rodents, primarily mice and rats have been commonly used for gestational translocation of NPs [15]. Mice have been commonly used for mammalian embryo toxicity studies [64, 65, 66]. Although rabbits have been used in fewer studies, rabbit placentae bear closer resemblance to human placentae than that of other rodents. Therefore, rabbits should be the preferable animal model to study gestational particle exposure [15]. Other nonmammalian species like drosophila and zebrafish have also been used in
The developing brain is highly vulnerable to nanomaterials [18] due to the incomplete development of BBB in the fetus [68]. The CNS shows considerable plasticity in the early stages of development and therefore highly susceptible to the toxic effects of NP [69]. The placenta is a multifunctional organ forming a barrier between maternal and fetal tissues. In utero exposure to NPs is one of main routes of exposure during the development of the nervous system [70]. Neurodevelopmental studies have shown that both male and female offspring show differential phenotypes after prenatal insults by NPs [18].
Among various NPs, many studies have been reported on the neurotoxicity of TiO2 NP. Injection of TiO2 NP into pregnant mice resulted in altered expression of genes associated with brain development and function of the central nervous system in embryos [71]. The effects of TiO2 seem to continue on the developing brain even during lactation [72]. The effects of titanium dioxide nanomaterials in pregnant mice include reduced size of the placenta and disrupted anatomical structure of the fetal brain and liver. Toxicity to the brain cells was reported to be caused due to necrosis [63]. One study showed that TiO2 NPs administered subcutaneously to pregnant mice resulted in an increased number of apoptotic cells in the olfactory bulb of the brain and damage to cranial nerves [58]. A subsequent study showed that the mice fetuses that were exposed to TiO2 NPs prenatally exhibited an increased level of dopamine and its metabolites in the prefrontal cortex and neostriatum. This demonstrates that prenatal exposure to TiO2 NPs might affect the development of the central dopaminergic system in mouse offspring [73]. In utero exposure of mice to TiO2, NP has been shown to cause changes in the genes associated with the brain development and functions of central nervous system in the embryo [71]. Accumulation of TiO2 NP in the placenta may interfere with the development of nervous system of the fetus by impairing the transport of nutrients to the fetus [74].
Injection of silica (Si) NPs to pregnant mice resulted in their accumulation in the brain of the embryo [54]. Other studies have reported that ZnO and TiO2 NPs causes neurotoxic effects in fetus after passing through the placenta [71, 75]. Injection of cobalt-chrome (CoCr) NPs into pregnant mice has been reported to cause neurodevelopmental abnormalities, like reactive astrogliosis and increased DNA damage in the fetal hippocampus [76].
Here, we briefly enumerate some of the effects of NPs in offspring associated with prenatal exposure. The effects of prenatal exposure to nanoparticles include neurobehavioral alterations in the offspring [77]. Other effects of prenatal exposure include accumulation of NP in the hippocampus [58, 78, 79]. These NPs in the fetal brain cause disturbances in the CNS homeostasis. The accumulated NP has been reported to cause psychiatric disorders such as autism, schizophrenia, and depression in offspring [80]. Exposure of pregnant mice to aluminum NP has been shown to induce neurodevelopmental changes which persisted during adulthood. This was accompanied by an anxiety-like behavior and impairment of cognitive function in offspring exposed to aluminum nanoparticles during in utero life [20]. Prenatal exposure to TiO2 NPs has been shown to impair the antioxidant status, cause oxidative damage to nucleic acids and lipids in the brain of newborn pups and enhanced the depressive-like behaviors during adulthood. Prenatal exposure to TiO2 NP has been associated with depressive behavior in adults [81]. In the case of ZnO NP, the depressive behavior has been attributed to their neurotoxic effects on neural development [82].
Pups from mice exposed to Al2O3 before and during pregnancy have been shown to have higher levels of Al accumulation in the hippocampus [20]. Similarly, in the case of Sprague Dawley rats the pups of dams exposed to silver NP showed the accumulation of silver in the brain, lung, liver, and kidneys [78]. Subcutaneous injection of TiO2 NP to CD-1 pregnant mice caused the accumulation of TiO2 NPs in the brain and testis of offspring [58]. However, exposure of Sprague Dawley rats to Zn NPs before mating and during lactation caused no accumulation of these NPs in the brain of offspring [83]. Prenatal exposure of mice to TiO2 NPs causes anatomical alterations in cerebral cortex, olfactory bulb and regions associated with the dopamine systems in the offspring [84].
Studies of Mohammadipour et al. [85] and Gao et al. [72] showed that in pregnant rats treated with TiO2 NPs significantly decreased hippocampal cell proliferation, impaired learning, and memory, and affected synaptic plasticity in the hippocampal dentate gyrus area in newborn rats. Similarly, the study of Zhou and his collogues [86] showed that maternal exposure to TiO2 NP results in inhibition of hippocampal and dysfunction of the rho/NMDAR signaling pathway in offspring. Maternal CB-NP exposure induced the long-term activation of astrocytes resulting in reactive astrogliosis in the brains of young mice [87]. TiO2 NP injection to pregnant mice has been reported to cause symptoms akin to autism spectrum disorder (ASD) and neurodevelopment disorders in neonates, without the detectable presence of NP in the placenta [88]. Another study indicated that nano-TiO2 can cross the blood-fetal barrier and placental barrier, thereby delaying the development of fetal mice and inducing skeletal malformation [89].
Various hypothesizes have been proposed from time to time regarding the toxicity of NP. Nanoparticles can directly cross the placenta and cause damage to the fetus because of their high surface reactivity. Because of their small size, NPs can easily reach the brain and are taken up by the brain cells, such as neurons and glia. Mechanisms of NP uptake by cells include pinocytosis, endocytosis dependent on caveolae and lipid raft composition, clathrin-dependent endocytosis, and phagocytosis [90]. Due to their high surface reactivity, the nanoparticles can cause the generation of reactive oxygen species [91] and inflammation [92]. The metal ions of the NP have been proposed to contribute to their toxicity [93, 94]. The neurotoxic effects can either result in the direct alteration of the structure or activity of the neural system or lead to subsequent effects due to glial activations and glial-neuronal interactions [95]. The nanoparticles may also exert their toxic effects due to their limited elimination/excretion from the brain.
Oxidative stress has been implicated as one of the major mechanisms of NP toxicity. Consequences of oxidative stress include mitochondrial membrane damage and dysfunction, which in turn leads to cell death [96]. Inflammation caused by the production of cytokines appear to be a second mechanism by which the NP exerts their cytotoxic effects [97]. ZnO NPs have been shown to induce the production of pro-inflammatory cytokines in the brain of mice, accompanied by an impairment of cAMP/CREB signaling pathway. The degree of inflammation correlated with the age of the mice [56]. NPs interact with enzymes, potential apoptotic, or necrotic factors and induces inflammatory processes [12]. NP show properties similar to that of viruses and cause damage to DNA affecting cell proliferation [90]. NP can reduce mitochondrial function [98] and generate cellular morphological abnormalities [99] Cui et al. [81] postulated that prenatal exposure to NP resulted in an impairment of antioxidant capabilities in the brain of newborn pups.
Accumulation of NPs along the endosomal pathway may affect the morphology and functioning of the BBB. The interaction of the NP with biological macromolecules like DNA, lipids, and proteins may lead to the generation of oxidative stress, conformational changes in the macromolecules, mutations, alterations in membrane permeability, activation of various signaling pathways, alterations in the functions of enzymes, and exposure of new protein epitopes [100]. Genotoxic effects of NP include chromosomal aberrations, DNA strand breaks, oxidative DNA damage, DNA adducts, and micronucleus formation [101, 102]. Interactions of NP with microglia and astrocyte may activate NF-κB signaling and result in the release of mediators of inflammation and apoptosis [103]. On the other hand, oxidative stress induced mitochondrial DNA damage results in Nod-like receptor protein 3 (NLRP3) inflammasome activation, which subsequently regulates inflammatory responses by activating caspase-1 and interleukin-1β (IL-1β) release [104].
Most of the resulting damage of the nervous tissue is usually irreversible [18]. NPs have been reported to disrupt the cytoskeleton of cells of the CNS and thus cause cell death. NPs been shown to regulate the expression of neuronal channels and other proteins involved in excitability and neurotransmission [105]. Microglia, account for ~20% of the glial cells in the brain. They are a type of glial cells, which are the resident innate immune cells in the brain and regulate neuroinflammation [106]. Choi et al. [107] demonstrated that low levels of SiNPs can alter microglial function by changing the expression of proinflammatory genes and cytokine release. Excessively activated or uncontrollable microglia can cause nerve toxicity by inducing proinflammatory factors, such as interleukin-1β, tumor necrosis factor (TNF)-α, prostaglandin E2, and interferon-γ (Figure 3) [18].
Mechanism of nanoparticles (NPs)-induced neurotoxicity. Supraphysiological levels of reactive oxygen species (ROS) induce oxidative damage to the cellular macromolecules such as lipids, protein, and both mitochondrial and nuclear DNA. ROS-induced protein peroxidation may result in loss of catalytic activity of many enzymes including the antioxidant enzymes. NPs-mediated genotoxic stress in turn, can drive apoptosis mainly through the intrinsic mitochondrial apoptotic cell death pathway in neuronal cells. Mitochondrial dysfunction activates inflammasomes, which triggers the release of proinflammatory cytokines IL-1β and IL-18 via caspase-1 activation. Moreover, ROS-induced activation of nuclear factor kappa B (NF-κB) pathway may trigger proinflammatory responses, which is one of the key factors associated with NPs-induced neurological inflammation.
Autophagy (autophagic flux) is a highly regulated cellular process which by eliminating long-lived proteins and damaged organelle components through the lysosomal mechanism maintains cellular homeostasis [18]. NPs have been demonstrated to be autophagic inducers [108]. Autophagy has been found to be correlated with increased DNA strand breaks and other defensive mechanisms [109]. NPs have been reported to induce autophagy through the generation of ROS and lysosomal-dependent mechanism [18]. Autophagy induced by NPs can have protective or detrimental effect on cells. During intracellular oxidative stress, imbalance and excessive ROS generation decline in autophagy-lysosome degradation function results in autophagic flux impairment, which leads to significant accumulation of the substrate of autophagy within the cell and may even trigger cell death through mitochondrial pathway [110].
The brain has a limited capacity to excrete NPs [111]. Therefore, NPs that bypass the blood brain barrier and reach the fetal brain during embryonic development result in neurodevelopmental toxicity in growing fetus and psychiatric disorders in offspring. Compelling evidence from animal studies on nanotoxicity during pregnancy shows that cautions must be taken by pregnant women when using NP-based products or medicine. Deeper understanding of interaction of NPS with the biological system and the underlying mechanism on neurotoxicity will help in the development of safety guidelines on the use of engineered NPs in medicine and commercial products without health hazard. However, there is a need to study the effects of long-term exposure to NP with realistic routes and levels of exposure to identify the chronic effects of NP to fetal nervous system.
“The authors thank the Deanship of Scientific Research and RSSU at King Saud University for their technical support.”
IntechOpen publishes different types of publications
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\n\nEdited Volumes can be comprised of different types of chapters:
\n\nRESEARCH CHAPTER – A research chapter reports the results of original research thus contributing to the body of knowledge in a particular area of study.
\n\nREVIEW CHAPTER – A review chapter analyzes or examines research previously published by other scientists, rather than reporting new findings thus summarizing the current state of understanding on a topic.
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\n\nPERSPECTIVE CHAPTER – A perspective chapter offers a new point of view on existing problems, fundamental concepts, or common opinions on a specific topic. Perspective chapters can propose or support new hypotheses, or discuss the significance of newly achieved innovations. Perspective chapters can focus on current advances and future directions on a topic and include both original data and personal opinion.
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\n\nSingle or multiple author manuscript
\n\nCompacts provide a mid-length publishing format that bridges the gap between journal articles, book chapters, and monographs, and cover content across all scientific disciplines.
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Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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