Examples of scenarios under the four conditions of the hostile expectancy violation paradigm.
\\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, there are still many areas of controversy surrounding it. We hope this book can contribute to guide the advance of this ancient medical art. In the present work, the reader will find texts written by authors from different parts of the world. The chapters cover strategic areas to collaborate with the consolidation of the knowledge in acupuncture. The book doesn't intend to solve all the questions regarding this issue but the main objective is to share elements to make acupuncture more and better understood at health systems worldwide.",isbn:null,printIsbn:"978-953-307-410-8",pdfIsbn:"978-953-51-6516-3",doi:"10.5772/905",price:119,priceEur:129,priceUsd:155,slug:"acupuncture-concepts-and-physiology",numberOfPages:248,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"a1b327d1a93e8dfd07289ab0a701aa39",bookSignature:"Marcelo Saad",publishedDate:"October 10th 2011",coverURL:"https://cdn.intechopen.com/books/images_new/386.jpg",numberOfDownloads:43869,numberOfWosCitations:8,numberOfCrossrefCitations:1,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:12,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:21,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 22nd 2010",dateEndSecondStepPublish:"December 20th 2010",dateEndThirdStepPublish:"April 26th 2011",dateEndFourthStepPublish:"May 26th 2011",dateEndFifthStepPublish:"July 25th 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"51991",title:"Prof.",name:"Marcelo",middleName:null,surname:"Saad",slug:"marcelo-saad",fullName:"Marcelo Saad",profilePictureURL:"https://mts.intechopen.com/storage/users/51991/images/system/51991.png",biography:"Marcelo Saad, MD, PhD (Brazil), is a physician, board certified in acupuncture. 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Besides traditional stick-built framing, today, mass timber is gaining more acceptance for multi-story building construction. Furthermore, panelized and modular systems are becoming of interest to the economy and the fast construction they offer. The technology of cross-laminated timber is gaining wide acceptance. It has provided the opportunity for timber to be used as the main gravity and lateral load resisting system in multi-story buildings.
\r\n\tThe objective of this book is to provide a state-of-the-art review of the use of timber in building construction from various perspectives, including manufacturing, fabrication, modeling, design, and construction of residential and other types of buildings. Of special interest will be contributions related to new developments in timber technologies, design, construction, testing, sustainability, LCA, building envelope, and the performance of timber buildings in natural and man-made hazard conditions.
Cerebral ischemia is the main disorder of cerebrovascular diseases; currently, according to data from the World Health Organization, it is the second main cause of death worldwide [1] and the third principal cause of disability. In the last 40 years alone, the incidence of this condition has more than doubled in people from low and middle-revenue countries [2].
\nThe increment in the incidence of this condition is due to increased risk factors as diabetes mellitus, hypertension, obesity, hyperlipidemia, and increased longevity of the population [3]. These factors allow the development of atherosclerosis, which is the main cause of ischemia [4]; thereby, it is considered that for the coming years this scenario will be maintained while strategies to reduce these factors are progressing.
\nStroke is distinguished by the brusque reduction of blood flow; therefore, the levels of oxygen and glucose are also reduced significantly, to the point of altering the metabolic activities of the neural tissue [5]. As a consequence of the latter, the low production of ATP and the acidification of the environment induce the depolarization of the membranes causing the intracellular increase of Ca2+ that is added to the one released by the endoplasmic reticulum and mitochondria [6].
\nNeuronal depolarization causes the release of glutamate which, when bound to its ionotropic N-methyl-D-aspartate (NMDA) and -amino-3-hydroxy-5-methyl-4-isoxazolpropionic (AMPA) receptors, achieves greater depolarization and, as a consequence, conditions of excitotoxicity [7]. These conditions are coupled with the production of free radicals [8] and lead to cell death by the activation of molecules that induce necrosis and apoptosis [9].
\nAlong with the lesion caused by the decrease in blood flow, the immune response is added to the events involved in both the detriment of the tissue and its protection.
\nInflammation is usually present before the development of arterial obstruction that gives rise to the ischemic event. The development of atherosclerosis is accompanied by the production of oxygen free radicals (ROS), expression of cell adhesion molecules, and production of proinflammatory cytokines as IL-1β and tumor necrosis factor-α (TNF-α) by endothelial cells [10].
\nShortly after occlusion, endothelial cells express a greater amount of intercellular adhesion molecules (ICAM), deposition of mannose binding lectin molecules that trigger activation of the complement pathway [11], producing higher amounts of ROS. The overproduction of ROS activates the prostaglandin pathway that stimulates the production of matrix metalloproteinases (MMP) that even though degrading constituents of the extracellular matrix, reshape the vascular endothelium seeking to protect of the blood brain barrier (BBB) [12].
\nThe release of chemokines such as CCL2 allows endothelial permeability [13], leading to the translocation of P-selectin from Weibel-Palade bodies, as well as the expression of ICAM-1 and vascular cell adhesion molecule (VCAM)-1 and E-selectin, on the endothelial surface [14]. Theses phenomena, together with the damage of the extracellular matrix facilitate the extravasation of macromolecules and water, which causes the development of vasogenic edema [15]. Peripheral immune cells then enter the injured cerebral parenchyma [16] facilitating the loss of the integrity of the BBB.
\nNeutrophils are the first leukocytes that migrate to the cerebral parenchyma; they have been detected since the first hour after ischemia and reach their maximum peak in 1–3 days [17]. In the clinic, it has been observed that the higher blood neutrophil count is associated with higher infarction volumes in patients with acute stroke [18].
\nThe second cell type that enters the neural tissue are monocytes, these infiltrate within 24 h of the onset of the ischemic event reaching its peak on day 3 [19]; their differentiation process toward macrophages and their activation will be determined by the molecular environment to which they arrive. This process is similar to that experienced by T lymphocytes, which reach the parenchyma 24–96 h post-ischemia [20].
\nAt the same time, the cells of the injured cerebral parenchyma release damage associated molecular patterns (DAMPs) that activate the microglia. Depending on the activation environment, the microglia can acquire a proinflammatory (M1) or anti-inflammatory (M2) phenotype [21]. In the M1 phenotype, the microglia acquires phagocytic capacity, produces NO, free radicals, and proinflammatory cytokines (e.g. TNF-α, IL-12 and IL-6) [22]. Some regions in the ischemic penumbra present an activation of M2 microglia distinguished by the production of anti-inflammatory and repair molecules, such as insulin growth factor 1 (IGF-1), IL-10, and arginase 1 [23].
\nSome researchers suggest that the M2 phenotype is initially activated during the acute phase in the peripheral zone to the infarction [24], since it has been determined that the levels of IL-10, TGF-β, and CD206 increase from the first day after the lesion and reach the maximum point between 4 and 6 days, possibly trying to keep the viability of tissue. In addition, TGF-β induces the anti-inflammatory phenotype of microglia, related with enhanced proliferation and neuroprotection [25, 26].
\nIn contrast, some authors suggest that the first response is proinflammatory [27], due to the loss of regulatory mechanisms; when a stroke occurs there is an important activation of the M1 microglial phenotype [28].
\nAlthough contradictory, both positions could be correct. The fact is that, M1 and M2 phenotypes actively participate in the response observed after ischemic event; however, in normal conditions, there is an important prevalence of the M1 phenotype leading the response to a proinflammatory reaction that, instead of helping, promotes more damage.
\nOn the other hand, perivascular macrophages and monocytes of peripheral origin that arrive at the injured parenchyma induce the synthesis of chemokines like CXCL1 and CXCL2, which are fundamental for recruiting more neutrophils to the injury site [29, 30]. The dendritic cells (DC) present a greater expression of the major histocompatibility complex II (MHCII) and the co-stimulant molecule CD80. This causes an important enhance in the interaction of T cells around and within the damaged areas inducing then a stronger immune response [31].
\nWhen T lymphocytes are activated by antigen-presenting cells (APCs) toward a Th1 phenotype, the secretion of proinflammatory cytokines like as IFN-γ, TNF, and LT-α [lymphotoxin] increases. This cytokine profile, intensify proinflammatory response and thereby, tissue damage. Contrarily, when T cells are activated toward a Th2 phenotype they produce anti-inflammatory cytokines such as IL-4 and IL-10 [32]. These cytokines have been associated with tissue protection mechanisms and even increased neurogenesis. This immune response that exerts protective effects and limits the damage caused by ischemia [19] can be stimulated by immunomodulatory molecules such as copolymer-1.
\nCopolymer-1 [Cop-1], also known as glatiramer acetate (GA) or copaxone [trade name], is a blend of peptides formed by random sequences of four amino acids: glutamic acid, lysine, alanine, and tyrosine; these have a variable length from 45 to 200 amino acid residues and a molecular weight of 4000–9000 Da [33].
\nCop-1 was originally synthesized from mylelin basic protein (MBP) to identify the precise immunogenic sequence and provoke experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS); however, it did not present encephalitogenic characteristics [34]; on the contrary, it has suppressive and protective effects on EAE [35]. In the clinic, copaxone is able to diminish the relapse rate and improve the disability of patients with relapsing-remitting MS [36]. Copaxone obtained its approvement by the Food and Drugs Administration [FDA] of U.S.A. in 1996 and in Europe in 2001 [33].
\nAt this time, the exact mechanism by which Cop-1 exerts its protective effects is not known at all. Studies carried out in EAE suggest that Cop-1 has greater affinity for the MHCII binding site of APC when competing with peptide complexes derived from the MBP, specifically with the epitope 82–100 [37]. This competition may also be present among the complexes for the TCR binding site of the lymphocytes [38] that, when activated, induces a Th2 response [39].
\nThe Cop-1 response is distinguished by increased synthesis of IL-4, IL-5, IL-10, IL-13, and TGF-β [33, 40, 41, 42, 43]. Cop-1 has also been observed to increase the presence of regulatory T lymphocytes [44] and regulatory CD8+ T lymphocytes in patients with multiple sclerosis [45, 46].
\nAnother important effect of copolymer-1 is the production of growth factors, among which stand out; the brain derived neurotrophic factor [BDNF] [47, 48], IGF-1, [49] and neurotrophins NT-3 and NT-4 [47]. It is known that, in addition to inducing neuroprotection and neurorestoration, these growth factors are related to mechanisms such as memory and learning.
\nThe molecular basis by which Cop-1 exerts its neuroprotective effect has been evaluated in several
It has been showed that through the blockade of the nuclear factor kappa B [NF-kB], Cop-1 reduces the expression of the chemokine CCL5 [RANTES], which is upregulated by the presence of IL-1β [50] and TNF-α in human astroglial cells [51]. A similar effect has also been observed on the monocyte chemotactic protein-1 [MPC-1] and adhesion molecules VCAM-1 and selectin E in endothelial cells as well as COX2 and iNOS [52].
\nIt has also been observed that Cop-1 induces differentiation of type II monocytes independently of the binding of Cop-1 to MHCII. Weber et al. demonstrated that this differentiation is due to the fact that Cop-1 reduces the phosphorylation of the transcription factor STAT-1 by stimulating the expression of IL-10 and TGF-β [53].
\nOn the other hand, it has also been observed that Cop-1 has a direct effect on glial cells [microglia and astrocytes] which are activated in conjunction with T cells reducing STAT-1 and STAT-3 phosphorylation through increased expression of cytokine signaling suppressor (SOCS-1) and independently of IFNϒR, accompanied by a reduction of IL-12 by CD4+ T lymphocytes [54].
\nEven though the molecular pathways by which Cop-1 acts are not yet completely established, the microenvironment induced by this compound is capable of allowing neuroprotection since it reduces the deleterious scenario that leads to neural death. Additionally, the new conditions could facilitate tissue restoration through the synthesis of growth factors.
\nThe beneficial effects showed by copaxone in patients with MS, even though the knowledge of its immunomodulatory mechanisms is partial, encouraged the evaluation of its effect in other experimental models.
\nIn the model of optic nerve lesion—which tries to reproduce the characteristics of secondary degeneration—Cop-1 demonstrated an interesting neuroprotective effect. Kipnis et al. [55] evaluated the effect of adoptive anti-Cop-1 T cell transfer and immunization with Cop-1 immediately after causing optic nerve contusion in Lewis rats; their results were very encouraging as they observed reduction in axonal degeneration, accumulation of T lymphocytes in injured areas and obtained a significant increase in IL-10 and BDNF
Parkinson’s disease presents gradual reduction of dopaminergic neurons in the region of the substantia nigra and the striatum in the brain, it is not known the reason that causes the death of these neurons, but the pathology is characterized by a significant increase in oxidative stress, mitochondrial dysfunction, neuroinflammation, and cell death [57]. Patients with PD present an increase in TNF-β, IL-1β, and IL-6 and other inflammatory cytokines resulting from the activation of the macrophages and microglia towards a proinflammatory phenotype capable of releasing NO and superoxide radicals that further damage neural tissue facilitating disease progression [58].
\nIn the traditional model to induce Parkinson’s disease in mice [induction by 1-1-methyl-1,2,3,6-tetrahydropyridine], it was observed that Cop-1 reduces the degeneration of dopaminergic cells. This effect is achieved since Cop-1 induces the up-regulation in the protein expression of tyrosine hydroxylase [59, 60]. Additionally, it has been reported an increase in glial cell-derived neurotrophic factor (GDNF), reduction of activated microglia markers, and restoration of BDNF [61]. Based in these findings, several research groups consider COP-1 as a pharmacological alternative for this pathology which should be deeply studied [62].
\nCopolimer-1 has also been tested in models of Alzheimer’s disease (AD). AD is a pathology that produces deposits of the β-amyloid protein, dystrophic neurites, loss of synapses and neurons, and elevated gliosis [63]. From the early stages of the pathology, it has been observed microgial activation toward a M2 neuroprotective phenotype that is modified as the disease progresses [64]. In advanced stages, a proinflammatory microenvironment characterized by the presence of cytokines such as IL-1β, TNF-α, IL-6 has been reported [65].
\nAfter Cop-1 administration, microglia modulation toward a M2 phenotype is observed, in such a way as to promote neuronal survival and neural tissue repair in AD models [66]. Butovsky and coworkers showed that Cop-1 immunizations lead to enhanced infiltration of monocyte-derived macrophages into neural tissue with an anti-inflammatory profile expressing minor levels of TNF-α and high levels of IL-10, TGF-β1, and IGF1. In this scenario, phagocytosis of preformed fibrillar amyloid-β by bone marrow-derived macrophages increased dramatically after the administration of Cop-1. Also, to demonstrate benefits on the preservation of cognitive function, the investigation showed an important synaptic protection, plaque removal, restriction of astrogliosis, and modulation of the immune molecular environment [67, 68].
\nAnother pathology that evidenced the beneficial effects produced by Cop-1 is amyotrophic lateral sclerosis (ALS). This is a neurodegenerative disease known by the progressive depletion of the upper and lower motor neurons [69]. During pathogenesis, glutamate excitotoxicity, structural and functional anomalies of mitochondria, damaged axonal structure, and oxidative stress conducted by free radicals are strongly observed [70].
\nIn this case, Angelov and colleagues showed—in mouse models—that the administration of Cop-1 promotes the survival of motor neurons [71].
\nThe beneficial effects of Cop-1 on ALS have been assessed in a Phase II trial conducted by Mosley. This investigation evaluated the cytokine response of ALS patients treated with copaxone and showed that copaxone is capable of inducing a temporary change in cytokines from Th1 to Th2 phenotype [72].
\nCopaxone is also tested in other pathologies at clinical settings. For instance, a phase III study on optic neuritis is now being conducted to evaluate the thickness of the layer of nerve fiber of the retina after 6 months of treatment. The results of this study have not been published. Finally, copaxone has been tested in Crohn’s disease and various types of carcinomas, studies where copaxone is in evaluation processes [73].
\nThe ability of Cop-1 to modify the proinflammatory milieu and to stimulate the production of growth factors encourages the idea of testing this compound on other pathologies with characteristics of secondary degeneration caused by inflammation. In line with this, the use of Cop-1 after stroke envisions an optimistic result.
\nAs copolymer-1 has been shown to have beneficial effects in various models where neuroinflammation is a detrimental determinant, our group decided to evaluate its neuroprotective effect on cerebral ischemia. For this purpose, we used the median transient cerebral artery obstruction (tMCAO) model. Sprague-Dawley male rats were used. After being subjected to ischemia for 90 min, the rats were immunized in the interscapular region with a dose of 200 μg of Cop-1.
\nIn the first study, the animals were evaluated for neurological deficit at day 1 and day 7 post-ischemia using the Zea Longa scale [74]. Then, a histological analysis was performed using hematoxylin and eosin staining to determine neuroprotection. The results indicated that Cop-1 is able to avoid up to 85.1% increase in infarct size (4.8 ± 1.5 for Cop-1 vs. 32.2 ± 8 for control group;
Neuroprotective effect of the copolymer-1. (A) Infarction size reduction. (B) Effect of the copolymer-1 on the neurological deficit. n = 8. Each bar represents mean ± SEM. Two-way repeated measure ANOVA. Sidak’s post hoc multiple comparisons test. *
This neuroprotective effect may be due to the reduction of the proinflammatory cytokines TNF-α and IL-1β and the increase of IL-4, as was observed by the Manguin group in a model of ischemia in diabetic mice [75]. Additionally, the production of neurotrophic factors—known to be implicated in the processes of neural survival and proliferation of neuron precursor cells—could also be involved [76].
\nOn the other hand, recovery from neurological deficit can be achieved by diverse mechanisms; for instance, neuroprotection exerted by Cop-1 could be limiting tissue damage caused by inflammation, this could allow the proper functioning of remaining neuronal connections. Functional recovery could also be the result of neurogenesis induced by Cop-1. Neurogenesis is a phenomenon that can replace neurons that died during the ischemic insult by allowing the substitution of neuronal circuits and thus neurorestoration.
\nOur study provided evidences about the neuroprotective effect of Cop-1; however, the fact that Cop-1-induced T cells are able to produce neurotrophic factors, led us to think that, it was imperative to investigate if behind the clinical recovery there was also a possible neurogenesis phenomenon.
\nIn the following study, we evaluated whether Cop-1 induces neurogenesis in the two neurogenic niches of the adult brain: in the subventricular (SVZ) and the subgranular zone of the dentate hippocampus gyrus (SGZ) [77]. To accomplish the evaluation, we performed an immunofluorescence technique using a double marking of 5-bromo-2′-deoxyuridine (BrdU) and doublecortin (Dcx) at 7 and 60 days after ischemia.
\nThe results were very encouraging, the neurological recovery caused by Cop-1 was observed from day 7 post-ischemia as in the first experiment [78] and was improving even in the chronic phase at 60 days (Figure 1B). The number of neuroblasts in the groups treated with Cop-1 was significantly higher in the two neurogenic niches at both 7 and 60 days in the SVZ and SGZ (Figure 2). This neurogenic phenomenon correlated with the clinical recovery of treated rats. Simultaneously, an important increase of NT-3 was observed in the area of the ischemic penumbra [79].
\nEffect of copolymer-1 on neurogenesis at 7, 14, and 60 days. (A) Neurogenesis in SVZ at 7 and 60 days. (B) Neurogenesis in SGZ at 7 and 60 days. (C) Neurogenesis in SVZ and SGZ at 14 days. n = 8 in A and B. n = 5 in C. Each bar represents mean ± SEM. Two-tailed Mann-Whitney
Cop-1-induced neurogenesis has been evaluated in other animal models such as EAE [47], Alzheimer [66], and recently in the model of permanent cerebral ischemia in diabetic male mice C57Bl6 [75]. Regarding the latter, it is important to mention that, in a previous experiment carried out by the same group, they did not observe improvement in the neurological function nor reduction in the volume of the infarction. These findings could be the result of the use of inappropriate evaluation techniques [80] as in their most recent study, they observed a reduction in infarct size of up to 30–40% and an increase in neurogenesis 7 days after permanent ischemia in the SVZ. In addition, they found a reduction of proinflammatory cytokines such as TNF-α, IL-1β, and a significant increase of IL-4 and IL-10 [75].
\nNeurogenesis is a mechanism widely regulated by signals that stimulate the stem cells of neurogenic niches [81]; many of these signals are produced by the choroid plexus (CP), which is a complex structure of cells considered an interface that mediates communication between the immune system and the cerebral parenchyma [82]. Therefore, trying to analyze the mechanism by which Cop-1 induces neurogenesis, we evaluate whether Cop-1 modifies the microenvironment of CP, 14 days after tMCAO.
\nIn the third investigation, we evaluated neurological recovery—which was observed according to our previous experiments [78, 79], neurogenesis and the expression of proinflammatory (IL-1β, TNF-α, INF-ϒ, and IL-17) and anti-inflammatory cytokines (IL-4 and IL-10) as well as the concentration of growth factors (BDNF, NT-3 and IGF-1) at the CP (Figure 3).
\nEffect of the copolymer-1 on the expression of growth factors and IL-10. Gene expression of: (A) BDNF; (B) NT-3; (C) IGF-1; and (D) IL-10. Bars represent mean ± SEM of 5 rats from each group. *
In this experiment, we again proved a significant increase of neurogenesis in the groups treated with Cop-1 in both, the SVZ and SGZ [83]. This data was similar to that previously reported [79]. As for the expression of proinflammatory cytokines, we only found significant differences in the expression of IL-17, which was observed reduced in the groups treated with Cop-1. With respect to anti-inflammatory cytokines, only IL-10 was significantly increased. In this investigation, we also found a significant increase of growth factors (BDNF, NT-3, and IGF-1) in the CP [83].
\nBoth growth factors and IL-10 have been reported to be directly involved in the stimulation of SVZ and SGZ stem cells; specifically, IL-10 has been observed to induce stem cell proliferation but not differentiation in primary cultures [84]. Moreover, IL-10 has immunomodulatory capacity as it inhibits the synthesis and release of proinflammatory cytokines such as TNF-α, IL-6, and IL-1β that are known to affect neurogenesis [85]. Moreover, growth factors such as NT-3 maintain viable stem cells from neurogenic niches facilitating plasticity [86]. BDNF promotes the proliferation and survival of neuroblasts [87] and IGF-1 promotes stem cell differentiation and migration of neuroblasts [88]. Therefore, this investigation allowed to demonstrate that Cop-1 is capable of raising the expression of IL-10 and growth factors, which have beneficial effects on neurogenesis.
\nIn order to know if Cop-1 modulates the number of leukocytes in CP and to know if these intervene in the synthesis and release of growth factors and IL-10, we evaluated the cell types present in the cerebrospinal fluid in animals submitted to tMCAO and Cop-1 therapy. The results showed a significant increment in CD8+ T cells, which positively linked with the increase in growth factors and IL-10 [unpublished data].
\nThe increase in CD8+ T lymphocytes has been observed as an effect of copaxone immunization in patients with MS [46]. In addition, experiments performed in the EAE model have considered these cells indispensable for the development of the beneficial effect of Cop-1 [89]. However, it is necessary to identify the nature of these cells and whether the type of CD8 T lymphocytes is of a regulatory phenotype.
\nFinally, the combination of Cop-1 with other strategies like polyunsaturated fatty acids has shown optimistic results as together, they have a greater capacity to significantly reduce the size of the infarction in the tMCAO model [unpublished data].
\nThe existing evidence of the effect of Cop-1 in the tMCAO model has been very encouraging, as it shows a significant neurological recovery. This beneficial effect could be caused by modulatory mechanisms that allow the increase of IL-4 and the reduction of TNF-α and IL-1β at the lesion site, promoting then neuroprotection. Additionally, neurological recovery could also be reinforced by the changes induced by Cop-1 at the CP as the increase of IL-10 and growth factors in this site stimulate neurogenesis after ischemia. We consider that more investigations are needed in order to analyze in greater detail the mechanism by which Cop-1 acts so that in the medium term, it may be considered as a pharmacological alternative for patients suffering from a cerebrovascular event.
\nPersonality disorders are conditions that can have a destructive impact on an individual’s quality of life and social interactions. Indeed, a person with a personality disorder will experience serious difficulties managing emotions, behaving according to culturally acceptable cognitions, and interacting normally in everyday life [1]. In the United States, 9–15% of people develop a personality disorder and in most cases, this disorder is accompanied by numerous comorbid conditions [2]. The situation is even more worrisome considering that personality disorders are commonly associated with aggression, violence, criminal behavior, and violent recidivism worldwide [3]. According to a systematic review, 65% of incarcerated men and 42% of incarcerated women have a personality disorder [4]. These epidemiological data underline the importance of better understanding and treating personality disorders, particularly those in cluster B. According to the DSM-5, cluster B personality disorders are characterized by relational disorders and impulsive, emotional, and/or unstable behavioral manifestations [1]. They include disorders such as antisocial personality disorder (ASPD) and borderline personality disorder (BPD) and tend to be strongly associated with a variety of maladaptive behaviors, including addictive, suicidal, or aggressive behavior.
BPD is characterized by pervasive instability of affects, self-representations, and interpersonal relationships [1]. It also includes the presence of impulsiveness, paranoia, feelings of emptiness, and/or suicidal gestures. BPD has a lifetime prevalence of approximately 6% among both sexes [5]. In a population of adolescents, BPD traits are associated with high levels of delinquency, antisocial behavior, and all forms of aggression (e.g., sexual harassment, overt aggression, and violence). As such, the diagnosis of borderline personality is, according to some authors, a good predictor of violence and aggression [6]. Moreover, in hospital settings, 65% of patients with BPD report having used physical, verbal, or relational gestures that were aggressive [7]. According to several authors, aggressive behaviors among borderline patients are guided by emotions [8]. In fact, BPD patients are prone to overreact, which leads to irritability, outbursts of anger, and subsequent physical aggression.
The DSM-5 describes ASPD as a pattern of violation of, and disregard for, the rights and interests of others [1]. It is expressed through a lack of social conformity, use of deception for personal gain, lack of remorse, and irresponsible, irritable, or impulsive behavior. In the United States, the prevalence of ASPD is 3.63% in the general population and the prison population, as high as 21–47% [4]. Moreover, in young adults, self-reports of two antisocial characteristics (i.e., sensation-seeking and egocentricity) have been associated with relational aggression [9]. More generally, ASPD diagnosed in clinical populations has been shown to be a strong predictor of violence and aggression [6]. Further, high levels of aggression have been associated with ASPD regardless of gender [3]. Authors suggest that violent behavior by antisocial patients can be explained as being part of an instrumental goal, such as for the purpose of obtaining gratification [8].
Conceptually, aggression refers to intentional and observable action directed toward someone with the goal of physically or mentally harming them [10]. Aggression is said to be reactive when it occurs under provocation, threat, or frustration. It is expressed through outbursts of uncontrolled anger and cognitive scripts involving distinct expectations and hostile perceptions. Aggressive behaviors have disastrous economic, legal, and social consequences [11]. Since the impacts are observable at the individual, family, community, and national levels, many programs have been developed to prevent and reduce aggression. One potential area of intervention could consist of decreasing aggressive cognitions that cause the individual to perceive the world as a dangerous environment and to reconsider the use of aggression when a conflict occurs.
Relatedly, a meta-analysis of studies conducted with people without BPD or ASPD showed a strong relationship between aggression and the hostile attribution bias (HAB) [12]. According to Crick & Dodge’s [13] theory of social information processing, HAB refers to a tendency to attribute hostile intentions to others despite the intention behind their behavior being ambiguous [14]. In more than 100 studies, the positive relationship between reactive aggression and HAB has been demonstrated in clinical and normal samples of individuals of different ages and ethnicities [14, 15, 16].
In an ambiguous and provocative situation, people with BPD tend to interpret events (such as abuse or rejection) as threatening [17]. This leads them to be overly sensitive to rejection, behave impulsively, and feel negative emotions. According to several authors, dysregulation of affect and behavior, which is characteristic of BPD, is associated with various cognitive biases, such as the HAB [18]. In fact, a study by Arntz et al. [19] found that people with BPD showed a readiness to perceive a person as negative, aggressive, malicious, abusive, and rejecting. Thus, it is quite possible that the HAB can explain why people with BPD act aggressively toward others. Smeijers et al. [20] have shown that patients with BPD often produce a lot of hostile interpretation biases.
With regard to ASPD, few studies have tested the HAB as an explanatory variable for reactive aggression [20, 21]. According to Lobbestael et al. [21], ASPD traits and HAB (measured using thumbnails and images) were good predictors of reactive aggression. Further Smeijers et al. [20] found that people with ASPD performed many HABs when looking at facial expressions.
The HAB can be measured using self-reports [22], written vignettes [21], video vignettes [23], and computer tasks [20]. For example, in the study by Lobbestael et al. [21], HAB was measured using eight images from the thematic apperception test and eight text vignettes describing ambiguous and provocative scenes from daily life. Participants were asked to describe the scenes and rate the hostile, positive, negative, and neutral character of each scene on a 4-point scale, ranging from most plausible to least plausible. While all of the previously mentioned HAB measures provide interesting results, they are not without flaws. Indeed, these methods do not allow for the measurement of spontaneous inferences and rapid intention attribution processes that are characteristic of the HAB. The latter occurs in the early stages of social information processing [13]. Before providing their responses, participants have time to consider other, more socially acceptable interpretations.
To capture the first cognitive processes of real-time intention attribution, Gagnon et al. [24] developed an innovative measurement method based on the recording of brain signals. The aim was to present different scenarios on a screen that, in written form, describe a character performing ambiguous behavior toward the reader in a context-specific manner (see Table 1). The context was either hostile or nonhostile and the reader was asked to read the scenarios while imagining the intention of the character. Subsequently, the character’s actual intention was revealed through a final target word and event-related potentials (ERPs) were recorded. The intention could be either hostile or nonhostile. In principle, when the hostile or nonhostile nature of the intention was at odds with the hostile or nonhostile nature of the context, expectations about the intention of the character being portrayed were violated. According to Gagnon et al. [24], the ERP component N400 was observable when hostile expectations were violated. In the literature, N400 is described as a negative deflection occurring around 200–500 ms poststimulus presentation [24, 25]. Its amplitude is maximal in the centro-parietal regions of the brain and is triggered when the word presented is unexpected or inconsistent with the context in the scenario [25]. In a study by Gagnon et al. [26], the N400 directly measured expectation violation, and its amplitude was stronger among aggressive individuals compared to nonaggressive individuals during the hostile expectations violation than during the nonhostile expectations violation.
List | First sentence—context | Second sentence—behavior | Third sentence—intention | Condition |
---|---|---|---|---|
1 | You’re playing soccer against a team that has an aggressive style | On a breakaway, the defender trips you up | The defender wants to | Hma |
2 | You have soccer practice with your team | Hmi | ||
1 | You’re having dinner with friends and Sylvie, who’s obnoxious | She does not mention that your shirt is stained | Sylvie does not want to | NHmi |
2 | You’re having dinner with friends and Sylvie who’s nice | NHma |
Examples of scenarios under the four conditions of the hostile expectancy violation paradigm.
NHma = nonhostile match; NHmi = nonhostile mismatch; Hma = hostile match; Hmi = hostile mismatch. Here, the target word is in bold. Translation in English of a “Le défenseur veut vous
The main goal of this study is to examine the mediating role of the HAB (measured by EEG and self-report) in the relationship between cluster B personality traits and reactive aggression. To achieve this, we present several objectives and hypotheses. (1) First, we want to replicate and validate the HAB measurement method developed by Gagnon et al. [24]. Our first hypothesis is that N400 will be more pronounced in the right posterior brain regions during the hostile expectations violation. (2) Secondly, we aim to evaluate the predictive role of ASPD traits, BPD traits, and HAB (as measured by EEG and self-report) on self-reported reactive aggressive behaviors. (a) We hypothesize that ASPD and BPD traits will positively and significantly predict self-reported reactive aggression. (b) We hypothesize that ASPD and BPD traits will significantly predict self-reported HAB and hostile expectations violation. (c) We expect a neurophysiological and self-reported measure of HAB to significantly predict reactive aggression. (d) Finally, we expect that self-reported and neurophysiological HAB will mediate the relationship between cluster B personality traits and reactive aggression.
Seventy-two French-speaking adults were recruited from university classes in two metropolitan universities, a list of former patients who consulted in a personality disorders clinic, and the general population through posters and announcements on Facebook and Kijiji. Interested individuals were then contacted by email to receive information about the study and to make an appointment for a laboratory visit. All participants were between 18 and 65 years of age, had normal vision with or without correction and had no history of psychosis, neurological disorder, or severe brain damage. Seventeen of them had been taking a central nervous system medication (e.g., anxiolytic, stimulant, SSRI, SNRI, and antidepressant) for at least 2 weeks prior to the day of the experiment. Before the visit, participants were asked not to use other drugs or alcohol for at least 1 week and 24 h prior to the experiment, respectively. Failure to comply with any of these instructions resulted in the postponement of the appointment. All participants received financial compensation of $25 at the end of the appointment. Nine participants were excluded due to attrition, a significant amount of missing data, a mother tongue other than French, or excessive artifacts on the EEG signals caused by eye movements. The final sample consisted of 63 participants (46 females and 17 males) with an average age of 29 (SD = 1.44) and 15 years of education (SD = .40).
The last questionnaire administered assessed age, gender, mother tongue, and education status.
The stimuli constituted 320 scenarios depicting social interactions encountered in everyday life and was developed by Gagnon et al. [24] to test hostile and nonhostile expectancy violations. Each scenario consisted of three sentences (see Table 1). The first sentence described a typically hostile or nonhostile context. The second sentence depicted a character whose intention was ambiguous, thus committing potentially provocative behavior to the reader. The last sentence included a final target word that resolved the ambiguity by clarifying the intention behind the behavior. The scenarios were created under four conditions—hostile match (Hma), hostile mismatch (Hmi), nonhostile match (NHma), and nonhostile mismatch (NHmi). When the conditions were hostile, the target word indicated hostile intent on the part of the character’s behavior. Conversely, when the conditions were nonhostile, the intention was depicted as nonhostile. Conditions were said to be a match when the hostile or nonhostile nature of the intention was consistent with the hostile or nonhostile nature of the context. Similarly, conditions were said to be mismatched when the hostile or nonhostile nature of the intention differed from the hostile and nonhostile nature of the context. Two lists of 160 scenarios (i.e., 2 × 40 scenarios for each of the four conditions) were used to balance the match and the mismatch conditions with the hostile and the nonhostile conditions across participants. For a given scenario, the match and mismatch versions shared the same behaviors and intentions but differed in the hostile or nonhostile nature of the context. The first two sentences were composed of a maximum of 25 words and the last sentence a maximum of eight words. The third sentence was phrased negatively in almost 50% of the scenarios for each condition. The two lists were administered alternately and equally across participants. A list of 20 additional scenarios (i.e., 5 × 4 scenarios for each of the four conditions) was developed for the purpose of practice and comprehension trials.
After completing the online questionnaire and giving their written consent, participants were invited to the laboratory to perform the experimental task. While their brain activity was recorded, they were asked to read the daily life interaction scenarios and visualize them as though they were actually experiencing them. As they read the first two sentences, the reader had to imagine why the characters were behaving in such a way toward them (intention attribution process). Once ready, they could initiate the presentation of the third sentence. For each scenario, a trial consisted of presenting the first two sentences for at least 1500 ms. After pressing the space bar on the keyboard, a delay of 500 ms without stimuli was followed by a fixation cross appearing in the center of the screen for 1000 ms. A third sentence was then displayed, word by word, in the center of the screen and ended with the target word. Each word was presented for 300 ms, with a delay of 200 ms between words. Finally, a fixation cross was displayed in the center of the screen for 2000 ms. The participant had to keep his eyes focused on the center of the screen and refrain from blinking from the appearance of the first cross until the disappearance of the second cross. In total, there were four practice trials followed by 10 blocks of 17 trials (170 trials). Each block consisted of 16 experimental trials (four scenarios for each of the four conditions: Hma, Hmi, NHma, and NHmi) and one trial used as a comprehension test. The comprehension trial was followed by a true or false question. The purpose of this question was to ensure that the participant was reading and understanding the scenarios. The participant could answer by pressing the letter N (true) or M (false). A correct/incorrect answer was followed by feedback (green or red cross, respectively). For our sample, the average rate of correct answers was 91.1%, indicating a high rate of comprehension. The experimental trials were presented in random order and without repetition. The blocks were separated by a break, the duration of which was determined by the participant. The words and fixation crosses were written in white, Helvetica font, size 14, bold, on a 17-inch (43.18 cm) black screen. The distance between the screen and the participant’s eye was 70 cm. Three characters corresponded to approximately 1° of visual angle. The experimental task was created using E-Prime 2.0 software (
The electroencephalography took place in a Faraday cage and under medium brightness. The brain activity of the participants was captured using 64 Ag/AgCI electrodes in an elastic cap. The position of the electrodes was done according to the International 10–10 System [40]. The right and left mastoids were used as references. One electrode was placed below the left eye to capture blinking and vertical eye movements. Two other electrodes were placed at the outer canthi of the eyes to capture horizontal eye movements. The signals were processed and recorded via a Biosemi ActiveTwo amplifier system (Amsterdam, Netherlands) at a sampling frequency of 512 Hz. Online, a 0.16 Hz high-pass filter and a 100 Hz low-pass filter were applied to the EEG signals. On Matlab, a 0.1 Hz high-pass filter and a 30 Hz low-pass filter were applied during offline analyses. The resulting signals were segmented in trials according to a time window of from 200 ms before, to 800 ms after the target word onset. The baseline time window ranged from −200 ms to 0 ms. Trials containing too many artifacts (i.e., eye or muscle movements) were rejected using an independent component analysis [41]. Rejection thresholds were applied for blink (i.e., > 80 mV within a time window of 150 ms) and for eye movement (i.e., > 35 mV within a time window of 300 ms). Electrodes with a noisy EEG signal (i.e., exceeding +/− 100 mV voltage) were interpolated by spherical spline. When more than seven electrodes were noisy in a trial, the trial was rejected. When the number of rejected trials was greater than 20 per condition, the participant was excluded from the sample. In our final sample, the percentage of rejected trials was less than 17.5% in the four conditions (i.e., 0–17.5% for Hma, 0–15% for Hmi, 0–12.5% for NHma, and 0–12.5% for NHmi). The trials were then averaged by condition (Hma, Hmi, NHma, and NHmi) and for each participant. On average, there were 39 trials per condition. The ERP amplitudes captured by the electrodes were averaged over six lateral regions and three midline regions on the scalp. The lateral electrodes were separated as follows: anterior left (AF3, AF7, F1, F3, F5, F7, FT7, FC1, FC3, FC5), central left (TP7, T7, C1, C3, C5, CP1, CP3, CP5), posterior left (P1, P3, P5, P7, PO3, PO7, O1), anterior right (AF4, AF8, F2, F4, F6, F8, FT8, FC2, FC4, FC6), central right (TP8, T8, C2, C4, C6, CP2, CP4, CP6), and posterior right (P2, P4, P6, P8, PO4, PO8, O2). The midline electrodes were analyzed as follows—anterior median (AFZ, FZ, FCZ), central median (CZ, CPZ), and posterior median (PZ, POZ, OZ).
Statistical analyses were performed to evaluate the voltage of the ERP amplitudes (dependent variable) according to the conditions (Hma, Hmi, NHma, and NHmi) and location of sensors on the scalp. Each subject being its own control, two repeated measures ANOVAs with Huynh-Feldt corrections were performed. The first ANOVA was for the lateral electrodes. The independent variables were intention (hostile, nonhostile), Consistency (match, mismatch), Hemisphere (left, right), and Location (anterior, central, posterior). Mean ERP amplitudes observed at midline regions were analyzed in a second ANOVA. The independent variables were Intention, Consistency, and Location. Given that our first objective was to demonstrate the presence of an N400 during expectancy violations (mismatch-match conditions), interaction effects involving the Consistency factor were looked at in the ANOVAs. To assess the role of the N400 in our mediation models, we selected regions showing greater negative amplitude (as shown in [24, 25]). Pearson’s correlations were performed between all variables. Therefore, several multiple linear regressions were conducted to assess whether antisocial characteristics, borderline characteristics, and the HAB (as measured by self-report or EEG) predicted scores on reactive and proactive aggression. A product-of-coefficient test for mediation analyses was performed by using bootstrapping procedures, a nonparametric resampling technique to test for indirect effects [42]. This method has been recommended as bootstrapping was found not to inflate Type I and Type II error rates and to have higher power [43]. In addition, bootstrapping does not assume multivariate normality. The significance of the mediation effect is determined when the 95% bias-corrected confidence intervals (CIs) do not contain zero. In the current study, estimates are based on 5000 bias-corrected bootstrap samples. All analyses were two-tailed, with an α level set at .05.
Figure 1 shows differences in mean ERP amplitudes between mismatch and match conditions for the nine scalp regions. Mean amplitude differences indicate a negative deflection (N400) at around 350–650 ms during hostile expectancy violations (NHmi-NHma conditions). Based on visual inspection, the greatest deflections were at midline and right sites in the central and posterior regions. When nonhostile expectancies were violated (Hmi-Hma conditions), mean perceived amplitudes neared zero in the central and posterior regions. Figure 2 shows the topography of mean amplitude differences observed on the scalp from 350 to 650 ms (post target onset) during hostile and nonhostile expectancy violations. During the hostile expectancy violations, the N400 seems to appear in the central and posterior regions of the right hemisphere and the midline sites.
Difference between the mismatch and match conditions of the grand ERP averages obtained after presentation of the hostile or nonhostile target word for 9 brain regions. LA = anterior left; LC = central left; LP = posterior left; MA = anterior median; MC = central median; MP = posterior median; RA = anterior right; RC = central right; RP = posterior right.
The topographic map of ERP mean differences between mismatch and match conditions from 350 to 650 ms after presentation of hostile or nonhostile target words. On the left, nonhostile expectancy violation (hostile mismatch-match). On the right, hostile expectancy violation (nonhostile mismatch-match).
For the lateral electrodes ANOVA, there was an interaction effect between Intention, Consistency, and Location (F (2.124) = 5.90; p = .01), and between Intention, Consistency, and Hemisphere (F (1,62) = 5.21; p = .03). For these interactions, effect sizes were moderate (partial R2 = .08; partial R2 = .09, respectively). Simple effects for these last two interactions were assessed for Consistency factor by paired comparisons with post hoc Bonferroni adjustment. The levels of the Consistency factor (match and mismatch) differed significantly for the nonhostile intention in the central and posterior regions, with an adjusted alpha of .004. There was no difference between hostile mismatch and hostile match at anterior, central, and posterior sites.
For the midline regions ANOVA, there was an interaction effect between factors of Intention and Consistency (F (1,62) = 16.16; p = .00), between factors of Consistency and Location (F (2,124) = 10.59; p = .00), and between factors of Intention, Consistency, and Location (F (2,124) = 5.60; p = .01). Effect sizes for these interactions were high to moderate (partial R2 = .21; partial R2 = .15; partial R2 = .08). Simple effects for the last interaction were evaluated for the Consistency factor by paired comparisons with post hoc Bonferroni adjustment. The level of Consistency factor differed significantly for nonhostile intention at central and posterior regions on the scalp with an adjusted alpha of .004. There was no difference between mismatch and match for hostile Intention in anterior, central, and posterior regions.
These results confirm the presence of the N400 in central and posterior regions in the nonhostile intention condition (i.e., when hostile expectations were violated). In the hostile Intention condition (i.e., during nonhostile expectancy violations), the N400 was not significantly visible. Since the ERP waveform differences and the topographic map indicated a stronger N400 effect in the central and posterior regions of the right and midline sites, we selected MC, RC, MP, and RP regions for further analysis.
The scores of all self-report scores were normally distributed, except for antisocial behavior that had positive skewed distributions as observed in the general population.
Correlation coefficients of the variables of interest are presented in Table 2. Reactive aggression was significantly correlated with age, depression, antisocial traits, borderline traits, and nonhostile expectancy violations (hostile Intention condition) in the MC (r = −.29, p £ .05 two-tailed), MP (r = −.25, p £ .05 two-tailed), RC (r = −.35, p £ .01 two-tailed), and RP (r = −.32, p £ .01 two-tailed) region. In addition, antisocial traits were significantly correlated with gender, paranoid ideation and borderline traits, and indirect hostile attribution bias (r = .30, p £ .05 two-tailed). Borderline traits were significantly correlated with paranoid ideation, depression, and self-reported HAB. Reactive aggression was not significantly correlated with hostile expectancy violations (nonhostile intention condition). Because the correlation between hostile or nonhostile expectancy violations and aggression scores was more strongly consistent in the RC region than in the MC, MP, and RP regions, regression analyses were performed in the RC region.
Variables | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 |
---|---|---|---|---|---|---|---|---|---|---|---|---|
1. Age | — | |||||||||||
2. Gender | ||||||||||||
3. Education | −.11 | −.12 | — | |||||||||
4. Paranoid idea | .13 | .01 | .09 | |||||||||
5. Depression | .07 | .06 | .08 | — | ||||||||
6. ASPD features | .08 | .04 | .19 | — | ||||||||
7. BPD features | .05 | .03 | .21 | — | ||||||||
8. REAG | .23 | .06 | .24 | — | ||||||||
9. HAB | .13 | .11 | −.11 | .25 | .14 | .16 | — | |||||
10. HN400RC | −.01 | −.08 | .03 | .00 | .10 | −.10 | −.11 | .18 | — | |||
11. NHN400RC | .14 | −.09 | −.13 | −.01 | −.00 | −.21 | .19 | .01 | −.08 | −.03 | — |
Correlation matrix.
p ≤ .05.
p ≤ .01.
REAG: reactive aggression; HAB: hostile attribution bias – SIP-AEQ; HN400RC: N400 effect in RC region for nonhostile expectancy violations; NHN400RC: N400 effect in RC region for hostile expectancy violations.
A first regression was conducted with ASPD features as the independent variable (Figure 3). Hostile expectancy violation (nonhostile intention condition) and self-reported HAB were the mediator variables and age, sex, education, BPD features, paranoid ideation, and depression traits served as covariates. Results showed a nonsignificant indirect effect for the hostile expectancy violation (indirect = −.00,
Mediation of antisocial characteristics—reactive aggression relationship by the hostile attribution bias and the N400 in hostile and the nonhostile conditions.
A third regression was conducted with BPD features as the independent variable, hostile expectancy violation (nonhostile intention condition), and self-reported HAB as mediator variables and age, sex, education, ASPD features, paranoid ideation and depression traits served as covariates (Figure 4). Results showed a nonsignificant indirect effect for the hostile expectancy violation (indirect = −.02,
Mediation of borderline characteristics—reactive aggression relationship by the hostile attribution bias and the N400 in hostile and nonhostile condition.
The first objective of this study was to replicate the measurement method of Gagnon et al. [24] and to validate their results. The aim was to present scenarios describing social interactions while measuring brain activity. In each scenario, characters acted in a provocative and ambiguous manner in both hostile and nonhostile contexts. Participants were asked to read the scenarios on a screen and imagine the intentions behind the behaviors presented. Subsequently, the characters’ hostile or nonhostile intentions were revealed through a final target word. As in the study by Gagnon et al. [24], we were able to observe the N400 ERP component in a time window ranging from 350 to 650 ms post-stimulus onset. Moreover, the amplitude of this deflection was more pronounced during the hostile expectancy violation in the central and posterior cerebral regions at the medial and right electrodes. This implied that participants attributed hostile intent to the characters when the context was hostile. This result has been corroborated by several other studies reporting a maximum amplitude N400 in the centro-parietal regions when expectations are violated [24, 25].
During the nonhostile expectancy violation, ERP amplitudes neared zero at approximately 350–650 ms. Therefore, when a nonhostile context was followed by ambiguous and provocative behavior, participants did not attribute a nonhostile intent to the behavior. Although consistent with findings reported in Gagnon et al. [24], this result appears inconsistent with the established assumption that the N400 would reflect an expectancy violation. Gagnon et al. [24] suggest this phenomenon possibly reflects a cautious interpretation, based on perceived cues, on the part of nonaggressive students. It is indeed possible that, in our study, nonhostile contextual cues conflicted with the ambiguous and provocative nature of the behavior. Therefore, the type of intent attribution depended on the weight the participant gave nonhostile cues versus provocative cues. In the end, in scenarios designed to violate nonhostile expectations, the participant may have had mixed views and not been systematically surprised to see hostile intent appear after a nonhostile context.
The second objective of this study was to demonstrate the predictive role of ASPD traits, BPD traits on self-reported aggressive behaviors. As expected, ASPD traits positively predicted reactive aggression in both models, which is consistent with the scientific literature [9, 21]. BPD traits were highly correlated with reactive aggression. However, when controlling for age, gender, education, depression, paranoid ideation, and ASPD traits, they did significantly predict reactive aggression in one model only. This result was surprising given that several studies have shown BPD to be a good predictor of reactive aggression [6, 7, 9]. In a recent longitudinal study, however, Penson et al. [29] showed that BPD characteristics were not sufficient in significantly predicting aggressive behaviors and rather, that ASPD characteristics were better predictors. Thus, it is likely that, in our regressions, ASPD traits were more effective predictors of reactive aggression than BPD traits. In addition, BPD traits and ASPD traits shared a high percentage of common variance (r2 = .24), possibly explaining the nonsignificant coefficient for BPD traits in the regression.
ASPD traits failed to predict both HAB, as measured by self-report, and hostile or nonhostile expectancy violations. These findings are not consistent with the few studies evaluating HAB in ASPD [20, 21]. However, it is important to mention that the methodology used to measure the HAB could explain the conflicting data. We used the SIP-AEQ questionnaire to measure self-reported HAB and an electrophysiology method developed by Gagnon et al. [24] to measure hostile and nonhostile expectancies violations. As such, it is possible to expect different results across studies. Given that ASPD is characterized by a lack of conformity to societal norms [1], it is also possible that the individuals with ASPD in our study did not relate to the characters or that they experienced difficulty imagining the situations described in our task.
BPD traits also did not predict self-reported HAB and nonhostile expectancy violation. In contrast, they positively predicted the hostile expectancy violation (i.e., BPD traits negatively predicted N400). Thus, the higher the BPD traits, the stronger the hostile expectancy violation. In other words, when the context was hostile, people with high BPD traits made more hostile intent attributions than people with lower BPD traits. This result partially confirmed our expectations and was consistent with findings in Smeijers et al. [18]. In addition, several researchers have provided arguments regarding the meaning of such a prediction [17, 18, 19]. For example, Lobbestael and McNally [17] demonstrated that people with BPD were subject to interpretive biases related to rejection and anger. According to Baer et al. [18], people with BPD have negative beliefs about themselves and their environment. They also interpret and evaluate neutral and ambiguous stimuli negatively. Finally, according to Arntz et al. [19], people with BPD judge other people as negative, aggressive, and malicious.
Self-reported HAB did not predict reactive aggression in all models, which is in contrast with the numerous studies showing that self-reported HAB is positively related to reactive aggression [15, 16, 44]. It is possible that variability in HAB scores was too small in our study to observe correlations. Regarding the hostile and nonhostile expectancies violations as measured by the N400 effect, results showed an opposite relationship with reactive aggression than expected. First, given that HAB and reactive aggression are positively associated as reported in the literature [15, 16, 44], we assumed that N400 effect in the nonhostile intention condition (hostile expectancies violation) would negatively predict reactive aggression (more negative amplitude associated with higher aggression score). However, because of the chronic accessibility to hostile patterns, it is possible that an aggressive person would see aggression in all their social interactions [45]. Since mismatch and match conditions would have a similar effect in this case, their subtraction should have the effect of reducing the N400 (more positive amplitude going up) as aggressive traits increase. Second, we assumed that nonhostile expectancy violation would negatively predict reactive aggression as nonaggressive individuals would be more surprised to see a hostile intention appear after a hostile context. However, given that the N400 effect was nonsignificant when the intention words were hostile, it is difficult to infer the nature of the cognitive processes underlying this relationship. Also, it appears that two other studies have found a negative relationship between HAB and reactive aggression [46, 47] suggesting that the relationship between HAB and reactive aggression could be more complex than we may think and difficult to predict.
Finally, our final hypothesis that self-reported HAB, the hostile expectancy violation, and the nonhostile expectancy violation were mediators of the relationship between cluster B personality traits and reactive aggression, could not be confirmed. These findings were inconsistent with the few studies that have evaluated the mediating role of HAB in the relationship between these personality features and reactive aggression [20, 21]. When it comes to cluster B personality, it is possible that the N400 effect (expectancy violation) may be influenced by other mediators, like sensitivity to rejection, impulsivity, and dysfunctional beliefs [17, 18], which were not included in our study. Further studies are therefore needed to better understand the cognitive and affective processes underlying aggressive behavior in antisocial and borderline personality disorders.
This research project had several methodological limitations, such as sample size and heterogeneity. Future analyses using a larger sample would be warranted to better understand the nature of the observed relationships. In addition, our sample potentially over-represented students in the general population. Out of 63 participants, 49 were from an academic background. It would be interesting and beneficial to evaluate our measures on samples more representative of the clinical population.
In conclusion, our study replicated the measurement of expectation violations by electrophysiology and validated the presence of a strong negative deflection of ERP amplitudes at the time of hostile expectation violations, as demonstrated in the study by Gagnon et al. [24]. Additionally, our results show that antisocial traits and borderline traits were positively associated with self-reported reactive aggressive behaviors. Our mediation models involving intention attribution processes as mediators could not be confirmed and the unexpected results suggested that HAB and reactive aggression sustain a complex relationship. To better understand the meaning of the relationship between hostile and nonhostile expectancy violation and reactive aggression, more studies are in need to verify how N400 effect among aggressive and nonaggressive participants varies according to various parameters of the ERP task. Nonetheless, this study indicates that electrophysiological measurements can be more sensitive than self-report questionnaires when investigating the nature of cognitive processes associated with reactive aggression. Considering the contribution of socio-cognitive treatments that are offered to aggressive individuals (e.g., [48]), we believe that this study can help to open the way to other empirical studies using ERP tasks to understand the cognitions associated with reactive aggression among cluster B personality disorders.
This study was supervised by Dr. Jean Gagnon, PhD, from the Department of Psychology at the University of Montreal. The study was funded by a portion of the supervisor’s research funds. The project was supported by Dr. Monique Bessette, PhD, psychologist and director of the Victoria Institute for participant recruitment. The author would like to thank Dr. Pierre Jolicoeur, PhD, of the Department of Psychology for his support in the analysis of EEG signals. This study was supported by a research grant to JG and PJ from the Social Sciences and Humanities Research Council (SSHRC) (no 435-2018-0963).
There is no conflict of interest. This project was approved by the Research Ethics Board of Education and Psychology of the University of Montreal. All procedures were consistent with the Énoncé de politique des trois conseils (EPTC-2, 2018).
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It binds and interferes with the function of a molecular chaperone, mortalin, leading to mitochondrial swelling and mitophagy that induce apoptosis in cancer cells without harming normal cells. It showed minimal toxicity in preclinical studies and thus is now in Phase-0 clinical trial. This chapter summarizes its evolution, synthesis, structure-activity relationship, mechanism of action, pharmacokinetics, and potential clinical applications in last 12 years. 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However, drug resistance owing to BCR-ABL mutations and overexpression is still an issue. Natural products are chemical compounds or substances produced by living organisms. They are becoming an important research area for cancer drug discovery due to their low toxicity and cost-effectiveness. Several lines of evidence show that many NPs such as alkaloids, flavonoids, terpenoids, polyketides, lignans and saponins inhibit CML cell proliferation and induce apoptosis. NPs not only differentiate CML cells into monocyte/erythroid lineage but also can reverse the multi-drug resistance (MDR) in CML cells. 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He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. 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He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. 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Kasenga",hash:"91cde4582ead884cb0f355a19b67cd56",volumeInSeries:4,fullTitle:"Malaria",editors:[{id:"86725",title:"Dr.",name:"Fyson",middleName:"Hanania",surname:"Kasenga",slug:"fyson-kasenga",fullName:"Fyson Kasenga",profilePictureURL:"https://mts.intechopen.com/storage/users/86725/images/system/86725.jpg",institutionString:"Malawi Adventist University",institution:{name:"Malawi Adventist University",institutionURL:null,country:{name:"Malawi"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7123",title:"Current Topics in Neglected Tropical Diseases",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7123.jpg",slug:"current-topics-in-neglected-tropical-diseases",publishedDate:"December 4th 2019",editedByType:"Edited by",bookSignature:"Alfonso J. Rodriguez-Morales",hash:"61c627da05b2ace83056d11357bdf361",volumeInSeries:3,fullTitle:"Current Topics in Neglected Tropical Diseases",editors:[{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7064",title:"Current Perspectives in Human Papillomavirus",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7064.jpg",slug:"current-perspectives-in-human-papillomavirus",publishedDate:"May 2nd 2019",editedByType:"Edited by",bookSignature:"Shailendra K. Saxena",hash:"d92a4085627bab25ddc7942fbf44cf05",volumeInSeries:2,fullTitle:"Current Perspectives in Human Papillomavirus",editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:303,paginationItems:[{id:"280338",title:"Dr.",name:"Yutaka",middleName:null,surname:"Tsutsumi",slug:"yutaka-tsutsumi",fullName:"Yutaka Tsutsumi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/280338/images/7961_n.jpg",biography:null,institutionString:null,institution:{name:"Fujita Health University",country:{name:"Japan"}}},{id:"116250",title:"Dr.",name:"Nima",middleName:null,surname:"Rezaei",slug:"nima-rezaei",fullName:"Nima Rezaei",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/116250/images/system/116250.jpg",biography:"Professor Nima Rezaei obtained an MD from Tehran University of Medical Sciences, Iran. He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). 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His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. 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