Phenothiazine class of antipsychotic drugs oppose several SARS-CoV-2 actions.
\r\n\tThe book will cover six broad topics namely: Soft tissue and bony anatomy in Rhinoplasty, Patient assessment in rhinoplasty, Crooked or twisted nose in rhinoplasty, Concepts of functional reconstructive nasal surgery, and Addressing the nasal valve in rhinoplasty, and Revision rhinoplasty. There is increasing demand for facial plastic surgery with more awareness and advancements in surgical procedures and their outcomes. Many patients who seek surgery for their nasal aesthetics also have complaints of nasal obstruction and sometimes snoring. Severe gross septal deviations present surgical challenges for the operating surgeon. In functional rhinoplasty, the role of a spreader graft, columellar extension graft, shield graft, only conchal graft, nasal valve suture suspension, and flaring sutures has been advocated by numerous authors. General ENT surgeons, rhinologists, plastic surgeons, maxillofacial surgeons, postgraduates, researchers, trainees, and general practitioners with a special interest in rhinoplasty will find this book useful and interesting.
",isbn:null,printIsbn:null,pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"e85f3e4534abe1e73bf65c055610a55f",bookSignature:" Balwant Singh Gendeh",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11689.jpg",keywords:"Anatomy, Soft Tissue, Bony, Rhinoplasty, Nasal Endoscopy, Crooked Nose, Twisted Nose, Reconstructive Nasal Surgery, Nasal Valve, Septum, Columella, Revision Rhinoplasty",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 3rd 2022",dateEndSecondStepPublish:"May 31st 2022",dateEndThirdStepPublish:"July 30th 2022",dateEndFourthStepPublish:"October 18th 2022",dateEndFifthStepPublish:"December 17th 2022",remainingDaysToSecondStep:"9 days",secondStepPassed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"Due to his vast contribution to the academia in research and clinical publication, he was elected as a Diploma of Fellowship Academy of Medicine Malaysia (FAMM)2000, International Fellow of the Academy of Otolaryngology-Head and Neck Surgery 2004, Fellow of the Academy of Sciences Malaysia (FASc) 2016 and Fellow of Malaysian Scientific Association (FMSA) 2017. He has written 96 scientific papers with more than 550 citations and is editor/co-editor of 8 books and 37 book chapters with an H index of 15.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"67669",title:null,name:"Balwant Singh",middleName:null,surname:"Gendeh",slug:"balwant-singh-gendeh",fullName:"Balwant Singh Gendeh",profilePictureURL:"https://mts.intechopen.com/storage/users/67669/images/system/67669.png",biography:"Dr. Balwant Singh Gendeh is a senior consultant ENT surgeon with a sub-specialty interest in rhinology (allergy, sino-nasal diseases, endoscopic sinus, anterior and ventral skull base surgery, and functional and cosmetic nasal surgery). He was an ENT registrar at the Royal Infirmary, Middlesbrough, UK, in 1993, and a JW Fulbright scholar, University of Pittsburgh, USA, in 1997. During his Fulbright experience, he also worked at the Hospital of the University of Pennsylvania (HUP), Philadelphia, USA, and St. Joseph’s Hospital, Chicago, USA, with a sub-specialty interest in rhinology and aesthetic nasal surgery. Dr. Gendeh retired after thirty-eight years of government service as a consultant ENT surgeon at the National University of Malaysia Medical Centre (UKMMC) in 2014. Currently, he is a visiting professor at the Department of Otorhinolaryngology-Head and Neck Surgery, UKMMC, and a resident ENT consultant at Pantai Hospital Kuala Lumpur. He is an executive member of numerous national and international bodies including board chairman of the Malaysian American Commission on Educational Exchange (MACEE). He was elected as a diploma of the Fellowship Academy of Medicine Malaysia (FAMM) in 2000, an international fellow of the Academy of Otolaryngology Head and Neck Surgery in 2004, a fellow of the Academy of Sciences Malaysia (FASc) in 2016, and a fellow of Malaysian Scientific Association (FMSA) in 2017. 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But, even after more than 100 years of research, they remain some of the most mysterious and costliest mental disorders [2] that can only be detected and treated once the symptoms are manifest. More recently, psychosis research has increasingly shifted its focus to the non-clinical part of the general population.
Delusions and hallucinations are the core features of psychosis. They are also referred to as “positive symptoms,” as it appears that they have been added to the experience of affected individuals. While they are the hallmark feature of different psychotic disorders, it is their combination with other psychological difficulties as well as their relative expression that defines a specific diagnostic categorization of an affected individual [3, 4]. Research on the symptoms of schizophrenic patients has suggested the presence of two additional basic symptom clusters associated with psychosis, namely disorganized and negative symptoms [5]. Disorganized speech and disorganized behavior refer to loose associations in speech and physical actions that do not appear to be goal-directed (e.g., catatonia, which is maintaining peculiar and often uncomfortable postures) [6]. As opposed to positive and disorganized symptoms, the term “negative” symptoms refers to the impression that something has been taken away from the patient’s behavior and experience. Negative symptoms manifest in flat or blunted affect (a reduced range of expression of emotions, reduced amount or fluency of speech) and avolition (the loss of will to do things). According to a more recently suggested model, psychosis exists as a transdiagnostic phenotype including affective symptoms as additional factors, i.e. depression and mania [7, 8]. The notion of transdiagnostic associations between psychotic and affective symptoms has recently been adopted in the fifth and latest edition of the standard diagnostic manual in the United States (DSM5, see [4]) in that bipolar disorders were separated from depressive disorders and relocated between depressive disorders and schizophrenia spectrum disorders [9]. Hence, if affective difficulties are not the predominant symptoms, but positive, disorganized, and negative symptoms are prominent, an affected individual might be diagnosed with schizophrenia (or “non-affective psychosis”) [7]. In contrast, individuals with fewer negative symptoms but with a high prevalence of affective symptoms (manic and depressive symptoms) might be diagnosed with psychotic depression or bipolar disorder. Lastly, if affective and psychotic symptoms are similarly present, an individual might be diagnosed with schizoaffective disorder.
In contrast to the categorical, “Kraepelinian” approach, the Swiss psychiatrist Eugen Bleuler thought already 100 years ago that psychosis was just an extreme expression of thoughts and behaviors that could be found in varying degrees throughout the general population [10]. This was seminal for different models considering psychosis as a series of symptoms that are aligned along a continuum between clinical and non-clinical populations, such as schizotypy, psychosis proneness, subclinical psychosis, or at-risk mental states [11, 12, 13, 14]. More recently, it has been suggested that psychosis exists as an extended
Importantly, it has been shown that PLE and psychotic disorders share etiological risk factors, cognitive correlates, demographic characteristics, and diminished well-being, which supports a continuum of psychotic symptoms and associated factors across the general population [20, 21, 22]. However, while it is generally agreed upon that a psychosis continuum exists, there is no consensus even on the most basic dimensions of the psychosis phenotype and involved constructs lack clear definitions [23, 24, 25]. While PLE are generally seen as indicators of psychosis proneness, studies suggest that they are frequently reported in the general population and are not necessarily associated with distress, help-seeking, or the onset of psychotic disorders [20, 26, 27]. More specifically, there is some evidence indicating they might be differentially implicated in mental health and the formation of mental disorders [28, 29, 30, 31, 32]. However, as psychosis research has tended not to differentiate between different PLE and to categorize them homogeneously, only little is known about their individual psychopathological significance and their role in the formation of different psychosis spectrum disorders [32, 33]. Similarly, only little attention has been given to comparing the phenotypical similarity of psychotic experiences between healthy and clinical individuals [19, 34]. Therefore, new instruments have been called for in order to allow accurate mapping out of the psychosis continuum [35]. Further complicating the study of PLE, a variety of terms and self-report instruments with different conceptualizations of psychosis and PLE are being used, which may entail inconsistent results and blur the sources of these inconsistencies [24, 34, 36]. However, these limitations are rarely addressed or regarded in the study of PLE although they might ultimately impede progress in all areas of psychosis research.
Importantly, attaining a clearer picture of PLE and associated factors might contribute to elucidating psychosis formation, improving risk screening, as well as facilitating new therapeutic approaches. Understanding the specific meaning of different subtypes of PLE for mental health might have become even more important since recent approaches aim at studying the subclinical interplay of symptoms leading to mental illness or the retention of mental health [37, 38]. In this context, an empirically established and generally agreed upon categorization of PLE regarding their psychopathological significance may be of fundamental importance. Although similar categorizations have been proposed [30, 39], it has not yet been clarified to which categories certain PLE should be assigned.
This chapter presents empirical findings that necessitate a more differentiated investigation of PLE and points out limitations in their current assessment. Further, it advocates a more differentiated view on PLE and clearer use of the associated terminology, concepts, and instruments. Aiming to stimulate further research in this area, a tentative categorization of PLE is provided, and possible future research directions are indicated.
Research into subclinical psychosis is marked by a rather general view on psychotic-like experiences (PLE) and the interchangeable use of various instruments and terms with different underlying conceptualizations of psychosis [24, 25, 32, 34]. This section presents evidence necessitating a more differentiated view on PLE and points to pitfalls in their assessment that need to be considered when researching subclinical psychosis.
Some of the earliest evidence raising the question if different PLE might be variably associated with disadvantage and mental health comes from research using the Wisconsin Schizotypy Scales [40, 41, 42]. It was found across several studies that PLE relating to magical thinking (MT) (and perceptual aberrations) were negatively correlated with physical anhedonia, but not other scales measuring negative-like symptoms [28, 41, 43, 44]. Notably, the negative associations were detected in samples of college students and healthy adults while the correlation was close to zero in outpatient clinic clients and schizophrenics [40, 43]. However, analyses indicated a true incompatibility of magical ideation and physical anhedonia rather than sampling effects as a cause for this pattern [43]. It was suggested that people scoring high on both magical ideation and physical anhedonia are more likely to become hospitalized, which might cancel out the otherwise negative correlation in these populations. Whereas these findings still remain to be explained, it has been speculated that magical ideation might reduce physical anhedonia by conveying meaning to (sensory) experiences or that both are linked through a third factor, e.g., extraversion and emotional stability [28, 45]. However, room for interpretation is limited, as most of the aforementioned scales for PLE may contain several different constructs rather than one. For example, the Magical Ideation Scale (MIS), (see [41]) includes paranormal beliefs, superstitious beliefs, ideas of reference, and suspicious-paranoid thoughts [46]. Hence, it is not clear which of the contained constructs are ultimately responsible for the observed associations. Nonetheless, the results indicated that it might be important to differentiate between subtypes of PLE, as they might be variably associated with other psychological (risk) factors.
Less ambiguous evidence for differences in the psychopathological significance of PLE comes from more recent research using the Community Assessment of Psychic Experiences Questionnaire (CAPE), (see [47]). The CAPE was constructed to investigate the extended psychosis phenotype [15] and has become one of the most frequently used self-report instruments for PLE [34]. A few studies have investigated which categories underlie PLE in the CAPE and how they are related to factors indicating risk for transition to psychotic disorder, i.e. distress, depression, and impairment [48]. Using exploratory factor analyses, one study identified bizarre experiences (BE), persecutory ideas (PI), and magical thinking (MT) to underlie the CAPE positive dimension in a sample of non-psychotic help-seekers [31]. Interestingly, only BE and PI were found to be associated with distress, depression, and poor functioning while MT was not. Notably, reminiscent of the aforementioned studies implementing the MIS, the researchers also found that MT was not correlated with anhedonic depression, unless accompanied by distress. Further, MT even turned out to be a negative predictor of anhedonic depression when adjusted for BE and PI. The apparent lack of associations of MT with any maladaptive feature such as depression and poor functioning lead the researchers to suggest that MT might be benign. Similarly, in a community sample of high school students, four types of PLE were found, namely BE, perceptual abnormalities (PA), PI, and MT [30]. Again, only BE, PI, and PA but not MT were strongly associated with distress, depression, and poor functioning. It was thought that the lacking association of MT with indicators of disadvantage could be explained with the finding that two items referring to paranormal beliefs were more closely associated with age and cultural background than psychopathology [30, 31]. Therefore, two corresponding items were dropped from the analyses in a subsequent study [29]. This time, PLE clustered into four classes, i.e. BE, PI, PA, and grandiosity while all subtypes were associated with one or more indicators of disadvantage. The authors speculated that PI and BE might lead to more evident symptoms than PA and GR, as they are more invasive experiences and more disruptive of the self-structure. Importantly, the studies showed that all forms of PLE were associated with disadvantage, once items specifically related to paranormal beliefs (but not grandiosity) were removed. At the same time, however, they indicated that PLE might be maladaptive in different ways and it was speculated that they may confer varying levels of risk for psychosis and other mental disorders [29].
The latter studies inspired a more extensive investigation of the specific relationships between different subtypes of PLE and “co-morbid” subclinical symptoms in healthy adults [28]. The study aimed at gaining first information about possible symptom-level mechanisms implicated in the emergence of mental disorders featuring psychotic symptoms and a meaningful categorization of PLE. Importantly, the researchers not only included experiences that are relevant regarding the specific extended psychosis phenotype (i.e., including positive-, negative-, and disorganized-like symptoms) but also those that are associated with the more recent notion of a transdiagnostic extended psychosis phenotype (i.e., also including affective symptoms). PLE were operationalized using the positive scales of the Schizotypal Personality Questionnaire (SPQ), (see [49]). Further extending the description of PLE, a novel questionnaire was included whose items were not derived from clinical symptom presentations (the revised Questionnaire for Assessing the Phenomenology of Exceptional Experiences (PAGE-R), see [50]) and that had just recently been introduced into psychosis research [44]. Whereas most subclinical symptoms were correlated, the researchers found unique associations between certain PLE and subclinical symptoms that were consistent across the numerous applied scales when co-occurring PLE were controlled for: paranoia-like experiences (suspiciousness) were uniquely associated with various scales measuring negative-like experiences. In contrast, different hallucination-like experiences (including dissociation) exclusively predicted different anxiety-related experiences while ideas of reference appeared to be specifically implicated with affective symptoms (anxiety and depression). Importantly, numerous negative associations between PLE and other subclinical difficulties were detected, namely between ideas of reference and physical anhedonia, magical thinking and constricted affect, PAGE-R odd beliefs (e.g., seeing meaning in coincidences) and depression, emotional instability, as well as unspecific symptoms (e.g., difficulties falling asleep). Notably, unlike suspiciousness and ideas of reference, magical thinking and PAGE-R odd beliefs did not positively predict any subclinical symptoms. While these results pointed to possible symptom-level interactions implicated in the development of psychosis spectrum disorders [37, 38], they also contributed to an empirically founded and much-needed categorization of PLE [30, 39]. Furthermore, the findings suggested that negative associations between PLE and other subclinical symptoms might be more extensive than previously thought and indicated that some delusion-like PLE
Odd beliefs as measured by the PAGE-R were prominently represented in the detected negative associations. Importantly, odd beliefs refer not to beliefs in a strict sense, but to experiences characterized by “seeing” patterns in noise (e.g., meaningful linking of separate events, correctly anticipating future events). Importantly, this sets odd beliefs apart from scales assessing e.g., magical thinking that often contain paranormal beliefs rather than experiences, which might be less relevant for the study of subclinical psychosis [54]. Further, in contrast to most studied forms of delusion-like experiences (e.g., suspiciousness), odd beliefs in healthy individuals were particularly enriching and positively-valenced experiences. Nonetheless, odd beliefs are conceptually similar to other delusion-like experiences and may be associated with indicators of psychosis proneness, such as biases in probabilistic reasoning and a tendency to jump to conclusions [55, 56], alterations in attributional styles [57, 58], differences in theory of mind [59], and magical ideation [60]. Importantly, experiences similar to odd beliefs have been suggested to reduce distress in perceptually ambiguous or stressful situations [61, 62] and to facilitate (perceived) control as well as to confer confidence and agency under lack of control [63]. Before this background, it was speculated that odd beliefs in healthy individuals might represent a psychologically stabilizing cognitive response to burdensome experiences [28]. Hence, despite their delusion-like quality, odd beliefs might paradoxically exert a positive effect on psychological well-being. Intriguingly, a new study investigating specificities between PLE and forms of childhood trauma found for the first time that odd beliefs in healthy adults were associated with stronger self-concept of own competences (SC), when adverse childhood experiences were held constant [64]. In contrast, paranoid-like experiences remained negatively associated with SC once adjusted for childhood adversities. SC is the fourth dimension of locus of control according to Rotter’s social learning theory [65, 66] and refers to the self-perceived capability to act in new, difficult or ambiguous situations [67]. Notably, addressing SC might also strengthen self-esteem, which has been identified by individuals with schizophrenia to be the most important treatment target [68]. Moreover, strengthening SC in therapy might help to alleviate psychotic symptoms SC [66]. Due to their positive association with SC the question was raised if odd beliefs might contribute to resilience toward mental illness, despite conferring an inaccurate perception of the world [64]. Further, as an individual’s inability to give meaning to an adverse experience is important in determining its long-term effect [69], the tendency to have positive delusion-like experiences might perhaps be exploited for therapeutic purposes.
The presented findings suggest that despite their tendency to co-occur, PLE may be variously implicated in mental illness and mental health. These results are in line with earlier suggestions that a co-occurrence of characteristics seen in pathological and non-pathological conditions must not necessarily mean that they are indicators of psychopathology [70]. More specifically, some characteristics could simply be by-products of the psychosis dimension but not be clinically relevant
Self-report instruments for psychotic-like experiences (PLE) are a central source of information in epidemiological research on subclinical psychosis. However, it is mostly not regarded that these instruments are tied to certain conceptualizations of (subclinical) psychosis and originally served a specific purpose [24, 25, 34]. Notably, many instruments used to assess PLE stem from schizotypy research and are fundamentally influenced by the underlying schizotypy model and the assumed link between schizotypal personality features and schizophrenia. For example, one of the earliest and most frequently used schizotypy scales is the Magical Ideation Scale (MIS, see [41]) [34]. It bases on Meehl’s [11] quasi-dimensional schizotypy model and as a screening tool for psychosis proneness (and vulnerability to schizophrenia in particular) its scope is restricted to illness and schizophrenia risk [25]. Accordingly, the MIS conceptualizes “psychotic-like symptoms” as attenuated or milder forms of Schneiderian first-rank symptoms of schizophrenia that manifest in the acceptance of unconventional forms of causality. Hence, the items in the MIS might have a distinct bias toward schizophrenia-related PLE. Furthermore, the selection of items might not be reflective of different forms of PLE in the general population, as items with extremely high and low difficulties were chosen to attain normality of the scale score. In comparison, the popular Schizotypal Personality Questionnaire (SPQ, see [49]) was constructed to screen for schizotypal personality
In addition to the mostly non-transparent choice of instruments [34] and their heterogeneous designs, unclear content validity of scales may additionally entail mixed results across studies and contribute to a blurred picture of psychosis [25]. Studies investigating symptom-level associations have applied multiple regression modeling to account for overlapping variance between different PLE scales in order to gain insight into their specific psychopathological significance [29, 30]. Whereas these results are meaningfully interpretable, the reliability of the interpretations ultimately depends on the choice of instruments and the (content) validity of the applied scales. Notably, scales measuring certain PLE may often conflate different constructs impeding a reliable interpretation of results, as exemplified by the MIS [24, 46]. Additionally, the emergence of ever-new concepts and terms as well as the interchangeable use of different terms for PLE with overlapping but not necessarily identical meanings has resulted in a “near Babylonian speech confusion” that hinders clarity in the nomenclature, blurs sources of inconsistencies between findings and constricts their interpretation [24, 32, 36]. Hence, to successfully elucidate the complex structure of psychosis, researchers should have detailed knowledge of existing constructs and be familiar with the limitations of their operationalizations.
A generally agreed upon and empirically substantiated categorization of PLE would be a helpful tool for clinicians as well as researchers. For example, it might help to provide more accurate screening procedures, predict risk for certain disorders featuring psychotic symptoms, facilitate more adequate treatment, and counteract stigmatization [29]. Further, it might also help to integrate findings across studies implementing different psychometric instruments and conceptualizations of PLE.
More recently, similar categorizations of three basic types of PLE have been proposed, suggesting that: (1) some indicate a specific vulnerability toward psychosis while (2) others might be non-specific and also be implicated in the development of affective disorders, and (3) some might not be associated with any clinical disorder at all [30, 39]. It has been speculated that some PLE such as paranormal beliefs are benign and might explain why they are mostly not associated with mental illness [32]. In contrast, it has been suggested that PLE specifically associated with distress and poor functioning might be more likely to indicate vulnerability to psychotic disorders [30]. However, it yet remains to be clarified to which category certain PLE should be assigned [32].
Recently, to shed light onto possible categorizations of PLE, a study investigated unique associations of certain PLE with subclinical symptoms relevant for psychosis spectrum disorders [76], i.e. negative-like symptoms, affective symptoms (anxiety, depression), and other psychological difficulties in a sample of healthy adults [28]. Referring to the model introduced above, following categorizations are suggested: Paranoid-like experiences in healthy individuals might specifically indicate vulnerability to psychosis (category 1), as they were the only significant predictor of schizophrenia-like negative symptoms (physical anhedonia, no close friends, and constricted affect) but were not associated with any type of affective symptoms. In contrast, hallucination-like experiences were uniquely associated with experiences from the anxiety spectrum (e.g., phobic anxiety, obsessive-compulsive symptoms) but not with negative-like symptoms. Further, ideas of reference were a positive predictor of anxiety symptoms and depressive symptoms. Therefore, the latter PLE might belong to the category of non-specific PLE, hence, predisposing toward affective and psychosis spectrum disorders (category 2). Lastly, paranormal beliefs and PAGE-R odd beliefs did not positively predict any of the subclinical difficulties, which might reflect that they are not associated with any clinical disorder at all (category 3). The latter categorization was underlined by the observation that paranormal beliefs and odd beliefs were negatively associated with various psychological difficulties. Notably, these findings raise the question if more categories for PLE might be needed that account for associations of PLE with well-being and stronger resilience [51, 64] and lower load of negative-like symptoms. However, it remains to be determined if these findings can be accommodated within a framework encompassing three classes of PLE.
The tentative categorization of PLE presented above requires more data and replications in samples representative of the healthy general population. Ultimately, longitudinal studies are needed to determine if specific PLE predict certain psychosis spectrum disorders more likely than other diagnoses and how they are implicated in the maintenance of mental health. Notably, other symptom factors that are relevant for determining the psychopathological significance of PLE were not regarded. Amongst other factors, these include intrusiveness, distress, and frequency of experiences as well as the associated development of functional impairment [47]. Furthermore, similar analyses are needed including other subclinical difficulties that might be part of the psychosis phenotype [16], such as disorganized symptoms and mania [51].
A comprehensive and phenomenological differentiated description of psychotic-like experiences (PLE) might be the prerequisite for attaining reliable classifications of PLE and new insights regarding their individual roles in the exacerbation of subclinical symptoms and the maintenance of mental health [34, 35].
The clinical perception that psychosis presents itself as “cases” in need of treatment has profoundly shaped the way the psychosis phenotype is conceptualized in the current classification systems [15]. Consequently, this has also influenced the way PLE are operationalized across various psychometric instruments (e.g., be it as psychotic “symptoms” or their attenuated equivalents) [25]. However, there is evidence indicating that the phenomenological quality of psychotic experiences may differ between healthy and clinical individuals [28, 77]. Further, it might be argued that there are experiences belonging to the PLE spectrum that may not have been sufficiently regarded in research. In this context, the novel PAGE-R questionnaire assessing “exceptional experiences” is worth mentioning, as its items are not derived from clinical symptoms but are based on reports from individuals from the general population seeking advice due to their experiences [50]. Indeed, a recent study suggested that EE in healthy individuals can be meaningfully integrated into positive-like symptomatology while potentially expanding the existing description of PLE [44]. Importantly, the PAGE-R might capture more subtle PLE that are often not considered in psychosis research, such as sleep-related perceptions [4, 20] or enriching delusion-like experiences [45, 78]. At the same time, it focuses on experiences and does not include beliefs in the paranormal that might be less relevant for the study of subclinical psychosis [31, 54]. Interestingly, factor analyses suggested the presence of three types of experiences that paralleled the basic structure of the CAPE positive dimension [48], encompassing odd beliefs (
However, the PAGE-R was originally not created to study PLE, but a construct referred to as “exceptional experiences” (EE, see [50]). More specifically, its representativeness for PLE in healthy states might be questioned, as individuals reporting EE are characterized by diverse psychological problems [79] and the selection and design of items are substantially influenced by the underlying concept of EE. However, the PAGE-R is currently under further development (Fach, pers. comm.). Nonetheless, its use in psychosis research might be a first step in the right direction regarding a more comprehensive assessment of PLE, as the PAGE-R is not restricted to experiences derived from clinical symptoms and inquires comfort that the experiences may confer and the context in which they occurred (e.g., during meditation). Both might be important but mostly neglected factors for evaluating the clinical relevance of certain PLE. However, pursuing this “non-clinical” approach, psychosis research might tap into supposed indicators of subclinical psychopathology that might as well measure healthy and socially desired abilities. For example, the PAGE-R item referring to perceiving thoughts and feelings of others might not only capture an attenuated version of a Schneiderian first-rank symptom of schizophrenia (thought transmission) but just as well an individual’s ability to empathize with others.
Psychosis research has tended not to differentiate between subtypes of psychotic-like experiences (PLE) and to hold a predominantly deficit-oriented perspective on them. However, studies indicate that PLE might fundamentally differ regarding their individual psychopathological significance and risk for psychosis spectrum disorders. These results require further (longitudinal) investigations aiming at the creation of an empirically founded and accurate categorization of PLE. Importantly, new instruments featuring PLE not derived from clinical symptoms including positive valence ratings might contribute to a more accurate and comprehensive description of subclinical psychosis. Ultimately, these steps might help to advance psychosis research in explaining why some individuals with PLE become ill while others do not and could contribute to more precise risk screenings and more effective therapeutic strategies in the long run.
This chapter was funded by Prof. Gerd Folkers, ETH Zurich.
None.
The author thanks Prof. Gerd Folkers for his kind support and for providing the funding of this open-access book chapter. Further thanks go to Dr. Thomas Wyss, Dr. Diana Wotruba, Dr. Helene Haker, and Prof. Wulf Rössler for their collaboration in the research project “Exceptional Experiences, Salience and Dopaminergic Neurotransmission.”
The COVID-19 pandemic has altered many aspects of daily life, contributing to the higher incidence of psychiatric conditions, including depression, anxiety, posttraumatic stress disorder (PTSD) and substance use [1, 2, 3, 4, 5, 6, 7, 8]. In addition, as SARS-CoV-2 is a neurotropic virus, delirium, cognitive impairment and psychosis were demonstrated in up to 40% of infected patients [9, 10, 11]. Moreover, like the previous pandemics, COVID-19 may be followed by delayed or even next-generation neuropsychiatric sequelae [12, 13, 14]. For example, the offspring of women pregnant during the 1918 influenza pandemic achieved lower education, socioeconomic status, and income as adults, indicating hidden and long-lasting effects [15] (Figure 1).
The two-hit paradigm: Excessive angiotensin II (ANG II) and loss of angiotensin (1–7) (ANG 1–7) generate oxidative stress both directly and indirectly (via ANG II-AT-1R and ANG II-NMDAR axes). COVID-19 critical illness is triggered when a preexistent redox dysfunction (second hit) is present.
Several psychotropic drugs have been associated with antiviral and antitumor properties, suggesting that they may lower the severity of COVID-19 critical illness [16]. For example, imipramine, clomipramine and the phenothiazine class of drugs have demonstrated efficacy against other viruses, including Ebola, Dengue and West Nile [17, 18, 19, 20]. In addition, thioridazine, another phenothiazine, was found to slow the progression of lung cancers, probably by enhancing antitumor immunity [21]. Other antipsychotics evidenced some beneficial effects in patients with glioblastoma and pancreatic cancer, suggesting immuno-oncological properties [22].
The recently published SARS-CoV-2/host protein–protein interaction and phosphorylation studies demonstrated viral interference with several pathways previously implicated in psychiatric disorders and targeted by psychotropic drugs [23, 24]. For example, upon binding to ACE-2, the SARS-CoV-2 virus ingresses host cells via the endocytic pathway (EP), a vesicular system inhibited by chlorpromazine (CPZ) and linked to schizophrenia and neurodegenerative disorders [25, 26]. Indeed, several antipsychotic drugs were found to interact with both the EP and extracellular vesicles (EVs), demonstrating previously unknown mechanisms of action [27, 28]. Other pathways involved in both the SARS-CoV-2 infection and psychiatric illness include autophagy, redox and calmodulin systems, connecting the virus to neuropathology [23, 29, 30, 31].
Several studies have associated NMDARs with sigma-1 nonopioid receptor, a protein hijacked by the SARS-CoV-2 to enable viral entry and replication [24, 32]. Indeed, sigma-1 agonists, such as fluvoxamine, sertraline and the antipsychotic drug, haloperidol inhibit exploitation of sigma-1, dampening viral ingress [33, 34, 35]. In addition, fluvoxamine was found to decrease ANG II-induced cardiac hypertrophy, indicating protective effects against both the SARS-CoV-2 infection and its complication [36]. Moreover, ifenprodil, an NMDAR antagonist (and sigma-1 receptor agonist), is currently in phase III clinical trials for COVID-19, linking oxidative stress to the severity of SARS-CoV-2 infection [37] (NCT04382924).
In the immune compartment, both COVID-19 and schizophrenia were associated with dysregulated inflammatory processes and lower levels of regulatory T cells (Tregs), suggesting possible autoimmune pathology [38, 39, 40]. In contrast, antipsychotic drugs were found to upregulate Tregs, lowering autoimmune inflammation [39]. Indeed, NMDARs are abundantly expressed not only in the central nervous system (CNS) but also in the immune compartment where they regulate T-cell proliferation in response to antigens. Along these lines, NMDAR antagonists, including antipsychotic drugs upregulate Tregs, enhancing immunological tolerance that in return decreases neuroinflammation [41].
In the following sections, we take a closer look at the SARS-CoV-2 interactome, looking for pathways altered by viral infection, psychiatric disorders and the action mechanism of psychotropic drugs. In other words, learning from the virus to design better psychiatric treatments (Table 1).
SARS-CoV-2 | Phenothiazines | References |
---|---|---|
Internalization via EP endocytosis | Inhibit EP endocytosis | [42] |
Lowers autophagy | Augment autophagy | [43] |
Augments calmodulin | Lower calmodulin | [44] |
Augments sigma-1 receptor signaling | Lower sigma-1 receptor signaling | [45] |
Lower regulatory T cells (Tregs) number | Upregulate the number of regulatory T cells (Tregs) | [39] |
Phenothiazine class of antipsychotic drugs oppose several SARS-CoV-2 actions.
SARS-CoV-2 is an enveloped, positive-sense, single-stranded, RNA virus with a genome of 30 kb, encoding for 29 viral proteins. These proteins target about 332 human molecules, some of which are also involved in psychiatric disorders and the action mechanism of psychotropic drugs [24]. The virus accesses host cells via its spike (S) glycoprotein that attaches to the cell surface receptor ACE-2 [46]. Viral binding is mediated by TMPRSS2, a human protease, that cleaves S antigen into the S1 subunit, the receptor binding site, and S2, the mediator of viral fusion with host cell membranes [47]. Upon fusion the virus is internalized through the EP pits that join the early and late endosomes, reaching the lysosomes. The later, link the EP to autophagy via autolysosomes (autophagosomes fused with lysosomes) (Figure 2).
Upon receptor binding and fusion, SARS-CoV-2/ACE-2 complexes enter human cells through the endocytic pathway (EP) pits early and late endosomes that subsequently join the lysosomes. Lysosomes link the EP to autophagy as authophagosomes (that can also carry the virus) fuse with the lysosomes, engendering the autolysosomes. Viruses are released from the endoplasmic reticulum - Golgi intermediate compartment (ERGIC)(not shown) to the cell surface, either individually or packed in extracellular vesicles (EVs). Viruses connected to ACE-2 receptors that are not endocytosed are shed by ADAM17. Both endocytosis and shedding contribute to ACE-2 downregulation, a marker of COVID-19 critical illness.
The SARS-CoV-2 protein–protein interaction studies have reported that 40% of viral proteins interact with human EP, indicating that vesicular trafficking plays a crucial role in COVID-19 pathogenesis [24]. In addition, several viral proteins usurp mitochondria and autophagy, cellular systems associated with host antiviral defenses [48]. Indeed, the SARS-CoV-2 interactome revealed that the virus hijacks both the mammalian target of rapamycin complex 1 (mTORC1), the master regulator of autophagy, and the E3 ubiquitin ligases in the outer mitochondrial membrane [24].
Upon release from EP into the cytosol, the SARS-CoV-2 virus replicates and assembles in the endoplasmic reticulum - Golgi intermediate compartment (ERGIC) from which the viral progeny is released at the cell surface [49].
Novel studies have reported that the S antigen of SARS-CoV-2 virus attaches with high affinity to ACE-2 receptors, promoting oxidative stress by several mechanisms, including ANG 1–7 downregulation, ANG II accumulation and NMDRs or AT-1Rs overstimulation (Figure 1) [49, 50, 51, 52, 53, 54].
Aside from the S antigen, several other SARS-CoV-2 proteins interact directly with the human molecules, disrupting numerous pathways, including EP, epigenome, mitochondria and autophagy (Table 2).
SARS-CoV-2 proteins | Human proteins | References psychiatric pathology |
---|---|---|
NSP4, NSP8, ORF9C | Mitochondrial dysfunction/oxidative stress | [55] |
NSP2, NSP6, NSP7, NSP10, NSP13, NSP15, ORF3A, E, M, ORF8 | Endocytic pathway (EP) | [56] |
NSP6, ORF9C | Sigma receptors, Autophagy | [57] |
NSP5, NSP8, NSP13, E | Epigenome | [58, 59] |
The SARS-CoV-2 non-S antigen interactions with human proteins.
Both the S antigen and non-S-induced molecular changes affect molecular pathways previously associated with schizophrenia and autism. For example, excessive NMDAR activation and externalization of phosphatidylserine (PS) on the outer leaflet of plasma membrane was documented in both COVID-19 critical illness and schizophrenia [60]. This is relevant because PS exposure has been linked to dysregulated immunosuppression and the activation of coagulation cascade, changes associated with severe COVID-19 and some psychiatric disorders [61, 62]. With the same token, NMDAR/PS exposure facilitates SARS-CoV-2 endocytosis via the EP [63, 64, 65]. Interestingly, PS externalization was associated with schizophrenia as it inhibits monoamine oxidase B (MAO-B), a dopamine (DA) metabolizing enzyme [66]. Loss of MAO-B with subsequent DA upregulation is believed to trigger psychosis, linking PS exposure to severe psychiatric conditions. Furthermore, other studies have associated normal aging with EP upregulation, likely explaining the increased risk of COVID-19 complications in elderly [67].
The SARS-CoV-2 fusion with host cellular membrane occurs at the level of EP pits, structures comprised of the clathrin heavy chains and adaptor protein 2 (AP2), molecules altered by both schizophrenia and the psychotropic drugs [25, 68, 69, 70] (Figure 2).
The SARS-CoV-2/ACE-2 complexes that are not endocytosed, are shed by ADAM17, contributing to ACE-2 downregulation and increased COVID-19 severity. The exacerbation of SARS-CoV-2 infection is likely the result of virus/ACE-2 complexes dissemination throughout the body via the circulatory system, increasing infectivity (Figure 3) [71].
Activation of ANG II-NMDAR axis results in intracellular calcium influx and calmodulin upregulation. Calmodulin-activated ADAM17 orchestrates the shedding of ACE-2/SARS-CoV-2 complexes, leading to ACE-2 downregulation and high infectivity by ACE-2/SARS-CoV-2 circulatory dissemination.
Novel studies have shown that oxidative stress can directly activate ADAM17, triggering ACE-2 downregulation [72, 73]. This takes place as NMDARs interacts with dopamine 1 receptors (D1Rs) activating ADAM17 to excessively cleave ACE-2 from the cell membranes [74, 75, 76]. Moreover, ADAM17 can be activated directly by viral proteins NSP6 and ORF9C interaction with sigma-1 receptors [24, 77] (Table 2). Furthermore, PS exposure at the cell surface facilitates ACE-2 downregulation, suggesting that the virus may utilize multiple mechanisms to lower this protein and enable infectivity [78].
Another novel study found that ACE-2 contains a calmodulin-binding site, implicating calcium in ADAM17 activation and COVID-19 critical illness [79, 80]. Indeed, it was established that intracellular calcium influx via NMDARs upregulates calmodulin, activating ADAM17 (Figure 3) [81, 82]. On the other hand, calmodulin antagonists, including psychotropic drugs amitriptyline, phenothiazines and melatonin, inhibit ACE-2 downregulation and the odds of COVID-19 complications [83]. In addition, recent studies found that SARS-CoV-2 could activate calcium/calmodulin-dependent protein kinase II (CAMK II), linking the virus further to excitotoxicity (excessive intracellular calcium) [23].
Taken together, ADAM17 promotes ACE-2 downregulation via oxidative stress mediated by NMDARs-upregulated intracellular calcium, mechanisms involved in schizophrenia, drug addictions and COVID-19 critical illness [83, 84, 85, 86].
The connection between viruses, and psychiatric disorders has been around for many centuries. In the ancient world, Thucydides reported “total and immediate loss of memory” in the survivors of “plague of Athens”, a disease suggestive of viral encephalitis [87, 88]. In our time, MRI studies have associated herpes simplex encephalitis, a condition marked by amnesia, with specific neuroimaging markers, linking viruses to cognition [89]. In addition, novel genetic studies have demonstrated that the HK2 retrovirus, frequently detected in the genome of drug addicts, was an ancestral pathogen incorporated into human DNA [90]. Over the past century, numerous studies linked in utero or early postnatal viral infections with the development of schizophrenia and autism later in life [91]. For example, women pregnant during the 1964 rubella epidemic in the United States gave birth to offspring that frequently developed autism or schizophrenia, suggesting that other viruses, probably including COVID-19, may have similar outcomes [92, 93]. In addition, obsessive–compulsive disorder (OCD), schizophrenia, attention deficit hyperactivity disorder (ADHD) and Tourette syndrome were traced to prenatal viral infections [94]. Neurodegenerative disorders, especially Parkinson’s disease (PD), were documented to surge after prior pandemics, including the 1918 influenza, suggesting that COVID-19 may promote neurodegeneration [95]. On the positive side, the SARS-CoV-2 virus may prompt the development of novel PD therapies, including angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEi) that have demonstrated efficacy in animal models [96].
Aside from linking prenatal viral exposure to severe psychiatric illness, several new studies reported that dormant CNS viruses could also engender this pathology [97]. For example, a recent report found that compared to controls, patients with schizophrenia demonstrated higher titers of Borna disease virus (BDV) immune complexes [98]. Others have connected influenza A, varicella-zoster, herpes simplex, hepatitis C and human immunodeficiency virus with the development of serious psychiatric disorders [99].
Autoantibodies against NMDARs, demonstrated in some schizophrenia patients, were recently found to be the result of molecular mimicry between the M2 protein of influenza A virus and NMDARs [100, 101]. Indeed, several large epidemiological studies found increased prevalence of autoimmune diseases in patients with schizophrenia, indicating that autoantibodies may be the result of either molecular mimicry or virus-induced modifications in human proteins [102]. For example, the molecular resemblance between an H1N1 influenza antigen and human hypocretin molecule triggers narcolepsy as virus-induced hypocretin modification may elicit autoantibodies [103]. Along these lines, the NMDAR partial antagonist, memantine, utilized in Alzheimer’s disease (AD), was found to possess immunosuppressant properties [39, 103, 104]. Indeed, prior studies have demonstrated memantine efficacy against Trypanosoma cruzi, a disease with established autoimmune pathogenesis [105].
Untreated patients with schizophrenia were reported to be at high risk of COVID-19 complications, probably due to SARS-CoV-2-associated neuroinflammation, an established risk factor of many psychiatric disorders. On the other hand, psychotropic drugs with anti-inflammatory properties may lower the SARS-CoV-2-mediated neuroinflammation, explaining the protective effects of these agents [24, 106].
According to the two-hit paradigm presented here, the COVID-19 prognosis is likely determined by the status of premorbid redox reserves, especially those comprised of the antioxidant enzymes G6PD and GPX. These proteins maintain homeostasis by neutralizing ANG II-activated NADPH oxidase (NOX) [107]. NOX upregulation was documented in patients with neurodegenerative disorders, schizophrenia, and suicidal behaviors, linking CNS pathology to redox system failure [108, 109, 110].
G6PD is a potent antioxidant enzyme that lowers NOX by upregulating the synthesis of NADPH and glutathione (GSH) [111]. Conversely, G6PD deficiency was associated with hemolysis and endothelial dysfunction caused by lower GSH and increased oxidative stress [111].
We surmise that the SARS-CoV-2 virus engenders acquired deficits of G6PD and GPX via ANG II-aldosterone upregulated NOX [112] (Figure 4). When COVID-19-induced deficiency of antioxidant enzymes occurs on the background of a hereditary G6PD deficit (observed in some populations with ancestral exposure to malaria), the resultant redox failure trigger COVID-19 critical illness [113] (Figure 4).
The SARS-CoV-2 virus causes oxidative stress by inhibiting both GPX (directly) and G6PD (indirectly via ANG II and aldosterone-upregulated NOX). Individuals with hereditary G6PD deficiency are at higher risk for developing COVID-19 critical illness as the loss of antioxidant enzymes is more profound and oxidative stress higher.
Several recent studies have supported this model as they established that G6PD deficient individuals, including many African Americans, are more likely to develop COVID-19 critical illness [6, 7, 114, 115, 116]. Moreover, G6PD deficiency was associated with cardiovascular disease, hypertension, liver fibrosis and iron dyshomeostasis, indicating the importance of redox balance in this pathology [117, 118, 119, 120, 121].
Malaria is an old enemy of mankind that throughout the past centuries exacted a heavy toll on the population of Africa and the surrounding regions. Residents of these areas have gradually developed phenotypes of plasmodium-resistant erythrocytes, including G6PD deficiency, thalassemia, and hemoglobin C, to protect against malaria [122]. Although these modified red blood cells may block plasmodial ingress, individuals with these changes are more susceptible to hemolysis and iron-mediated oxidative stress that in turn promote infections, hypertension, cancer and neuropsychiatric disorders [123, 124, 125, 126]. Indeed, both
Neuropsychiatric manifestations of malaria have been known since the ancient era however, they were more thoroughly studied only in World War I when French Army physicians encountered malaria during the campaign in Northern Greece [127, 128, 129]. More recent studies demonstrated that ROS play a major role in the pathogenesis of malaria and the CNS manifestations of this infection. For example, excessive ROS were shown to directly activate nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing-3 (NLRP3) inflammasomes, molecular structures involved in numerous pathological processes, including t psychiatric disorders [130, 131]. Interestingly, some antipsychotic drugs, including clozapine, function as NLRP3 inhibitors, indicating anti-neuroinflammatory properties [132]. The SARS-CoV-2 interactome established that viral protein OPR3a can activate NLRP3 directly, suggesting a pathway for virus-induced neuroinflammation [133, 134].
Several studies reported that
Population groups throughout the world with exposure to malaria during the previous centuries were found to be at higher risk of hereditary G6PD deficiency and antioxidant failure. This background increases the odds not only of viral infections but also of other redox disorders, including hypertension, cancer and cardiac disease. For example, 12.2% of African American males and 4.1% of females are G6PD deficient, indicating a potentially higher risk of COVID-19 complications [141]. Indeed, novel studies found a 2.4 percent higher COVID-19 mortality in African Americans compared to Whites, Asians or Latinos [142].
Moreover, the lower GSH and nitric oxide (NO) levels in African Americans compared to other groups, places this population at higher risk of both hypertension and prostate cancer, suggesting that the SARS-CoV-2 infection may precipitate these complications [143, 144, 145, 146, 147, 148, 149]. In this regard, African Americans with COVID-19 should be routinely assessed for G6PD deficiency and supplemented with the widely available antioxidant, N-acetylcysteine [150].
Oxidative stress was demonstrated to directly trigger hypertension by resetting the CNS baroreflex, therefore the G6PD-deficient individuals could be more prone to COVID-19-related cardiovascular complications [151]. On the other hand, ARBs and ACEi lower ANG II-mediated ROS, likely averting these complications [152, 153, 154, 155, 156, 157]. Indeed, the lower utilization of ARBs and ACEi in the treatment of hypertensive African Americans may place this population at higher risk of COVID-19 critical illness [158]. Although numerous clinical trials supported the efficacy of ARBs and ACEi in African Americans, these drugs are rarely utilized in this population as an initial therapeutic options [158, 159]. This is significant as both ARBs and ACEi appear to lower COVID-19 mortality rate, probably by dampening oxidative stress-ACE-2 downregulation. For example, a novel study found that COVID-19 patients treated with ACEi or ARBs at the time of initial infection had fewer unfavorable outcomes and lower mortality rate compared to individuals unexposed to these drugs [160].
Taken together, the SARS-CoV-2-upregulated ANG II, triggers hypertension and cardiovascular disease by augmenting oxidative stress and altering the baroreceptor setting. Individuals with G6PD deficiency are at increased risk of both hypertension and COVID-19 critical illness, indicating alignment with the two-hit paradigm presented here.
The COVID-19 pandemic has exacerbated the disease course in many psychiatric patients as mandatory social isolation and decreased frequency of therapeutic meetings promoted fear and uncertainty in this fragile population. The restrictive measures associated with the pandemic have often led to decreased medication adherence, increased depression, anxiety and substance use disorders, often contributing to unfavorable outcomes.
On a positive note, the SARS-CoV-2 virus may be a catalyst for a better understanding of the role of viruses in the pathogenesis of psychiatric illness. As SARS-CoV-2 (and probably other viruses) utilize the molecular machinery involved in severe psychiatric disorders, the clarification of these mechanisms may help with the development of better therapies. Indeed, the EP and antioxidant enzymes may become the new psychiatric paradigms, expanding the current dopamine and serotonin models to include viruses and microbes in psychopathology.
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It uncovers the capability of quantum computers that can impact our lives in various viewpoints like cyber security, traffic optimization, medicines, artificial intelligence and many more. At last, we concluded all the importance, advantages and disadvantages of quantum computers. Small-scale quantum computers are being developed recently. This development is heading towards a great future due to their high potential capabilities and advancements in ongoing research. Before focusing on the significances of a general-purpose quantum computer and exploring the power of the new arising technology, it is better to review the origin, potentials, and limitations of the existing traditional computing. This information helps us in understanding the possible challenges in developing exotic and competitive technology. 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Quantum mechanics is established on the basis of the phenomenology and the lack of ontology builds the wall which blocks the causality. It is very difficult to reconcile the probability and the causality in such a platform. A higher dimension consideration may leverage this dilemma by expanding the vision. Information may seem to be discontinuous or even so weird if only be viewed from a part of the degree of freedoms. Based on this premise, we reexamined the microscopic world within a complex space. Significantly, some knowledge beyond the empirical findings is revealed and paves the way for a more detailed exploration of the quantum world. The random quantum motion is essential for atomic particle and exhibits a wave-related property with a bulk of trajectories. It seems we can break down the wall which forbids the causality entering the quantum kingdom and connect quantum mechanics with classical mechanics. The causality returns to the quantum world without any assumption in terms of the quantum random motion under the optimal guidance law in complex space. 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The study of nano-particles significantly challenges our current perception of the universe and the fabric of reality itself. Quantum particles have both wave-like and particle-like characteristics. The fundamental equation that predicts the physical behaviour of a quantum system is the Schrödinger equation and the Poisson equation using Monte Carlo simulations. This gives rise to the wavefunction, electron and hole densities, energy levels and band structure of the system which contains all the measurable information about the particle such as time and position, where position is represented using probabilities. This is because particles do not have one definite position during the time before measurement. In fact, they exist as a fuzzy distribution of all possible states where the likelihood of finding the particle in some states is more probable than others. This is known as being in a superposition of all states. When the quantum system is observed, however, its wavefunction collapses so it consequently falls into one specific position. Moreover, in this chapter we present the simulation results of conduction band profile, electron density (classical and quantum mechanical), eigenstate and eigenfunctions for Si, SOI and III-V MOSFET structures at bias voltage 1.0 V using 1D Poisson-Schrödinger solver.",book:{id:"10076",slug:"quantum-mechanics",title:"Quantum Mechanics",fullTitle:"Quantum Mechanics"},signatures:"Aynul Islam and Anika Tasnim Aynul",authors:[{id:"316001",title:"Dr.",name:"Islam",middleName:null,surname:"Aynul",slug:"islam-aynul",fullName:"Islam Aynul"},{id:"325161",title:"BSc.",name:"Anika Tasnim",middleName:null,surname:"Aynul",slug:"anika-tasnim-aynul",fullName:"Anika Tasnim Aynul"}]},{id:"71547",title:"Dipolar Interactions: Hyperfine Structure Interaction and Fine Structure Interactions",slug:"dipolar-interactions-hyperfine-structure-interaction-and-fine-structure-interactions",totalDownloads:613,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The interaction between the nuclear spin and the electron spin creates a hyperfine structure. Hyperfine structure interaction occurs in paramagnetic structures with unpaired electrons. Therefore, hyperfine structure interaction is the most important of the fundamental parameters investigated by electron paramagnetic resonance (EPR) spectroscopy. For EPR spectroscopy the two effective Hamiltonian terms are the hyperfine structure interaction and the electronic Zeeman interaction. The hyperfine structure interaction has two types as isotropic and anisotropic hyperfine structure interactions. The zero-field splitting term (electronic quadrupole fine structure), the nuclear Zeeman term, and the nuclear quadrupole interaction term are among the Hamiltonian terms used in EPR. However, their effects are not as much as the term of the hyperfine structure interaction. The zero-field splitting term and the nuclear quadrupole interaction term are the fine structure terms. The interaction of two electron spins create a zero-field splitting, the interaction between the two nucleus spins form the nuclear quadrupole interaction. Hyperfine structure interaction, zero-field interaction, and nuclear quadrupole interaction are subclasses of dipolar interaction. Interaction tensors are available for all three interactions.",book:{id:"10076",slug:"quantum-mechanics",title:"Quantum Mechanics",fullTitle:"Quantum Mechanics"},signatures:"Betül Çalişkan and Ali Cengiz Çalişkan",authors:[{id:"199110",title:"Dr.",name:"Betül",middleName:null,surname:"Çalişkan",slug:"betul-caliskan",fullName:"Betül Çalişkan"},{id:"208732",title:"Dr.",name:"Ali Cengiz",middleName:null,surname:"Çalişkan",slug:"ali-cengiz-caliskan",fullName:"Ali Cengiz Çalişkan"}]},{id:"73016",title:"Exactly Solvable Problems in Quantum Mechanics",slug:"exactly-solvable-problems-in-quantum-mechanics",totalDownloads:679,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Some of the problems in quantum mechanics can be exactly solved without any approximation. Some of the exactly solvable problems are discussed in this chapter. Broadly there are two main approaches to solve such problems. They are (i) based on the solution of the Schrödinger equation and (ii) based on operators. The normalized eigen function, eigen values, and the physical significance of some of the selected problems are discussed.",book:{id:"10076",slug:"quantum-mechanics",title:"Quantum Mechanics",fullTitle:"Quantum Mechanics"},signatures:"Lourdhu Bruno Chandrasekar, Kanagasabapathi Gnanasekar and Marimuthu Karunakaran",authors:[{id:"239576",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Karunakaran",slug:"marimuthu-karunakaran",fullName:"Marimuthu Karunakaran"},{id:"252354",title:"Dr.",name:"Bruno Chandrasekar",middleName:null,surname:"L",slug:"bruno-chandrasekar-l",fullName:"Bruno Chandrasekar L"},{id:"325784",title:"Dr.",name:"K",middleName:null,surname:"Gnanasekar",slug:"k-gnanasekar",fullName:"K Gnanasekar"}]}],onlineFirstChaptersFilter:{topicId:"230",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. These advances have helped foster better support for animal health, more humane animal production, and a better understanding of the physiology of endangered species to improve the assisted reproductive technologies or the pathogenesis of certain diseases, where animals can be used as models for human diseases (like cancer, degenerative diseases or fertility), and even as a guarantee of public health. Bridging Human, Animal, and Environmental health, the holistic and integrative “One Health” concept intimately associates the developments within those fields, projecting its advancements into practice. This book series aims to tackle various animal-related medicine and sciences fields, providing thematic volumes consisting of high-quality significant research directed to researchers and postgraduates. It aims to give us a glimpse into the new accomplishments in the Veterinary Medicine and Science field. By addressing hot topics in veterinary sciences, we aim to gather authoritative texts within each issue of this series, providing in-depth overviews and analysis for graduates, academics, and practitioners and foreseeing a deeper understanding of the subject. Forthcoming texts, written and edited by experienced researchers from both industry and academia, will also discuss scientific challenges faced today in Veterinary Medicine and Science. In brief, we hope that books in this series will provide accessible references for those interested or working in this field and encourage learning in a range of different topics.",coverUrl:"https://cdn.intechopen.com/series/covers/13.jpg",latestPublicationDate:"May 18th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:10,editor:{id:"38652",title:"Dr.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"19",title:"Animal Science",coverUrl:"https://cdn.intechopen.com/series_topics/covers/19.jpg",isOpenForSubmission:!0,editor:{id:"259298",title:"Dr.",name:"Edward",middleName:null,surname:"Narayan",slug:"edward-narayan",fullName:"Edward Narayan",profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",biography:"Dr. Edward Narayan graduated with Ph.D. degree in Biology from the University of the South Pacific and pioneered non-invasive reproductive and stress endocrinology tools for amphibians - the novel development and validation of non-invasive enzyme immunoassays for the evaluation of reproductive hormonal cycle and stress hormone responses to environmental stressors. \nDr. Narayan leads the Stress Lab (Comparative Physiology and Endocrinology) at the University of Queensland. A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null},{id:"20",title:"Animal Nutrition",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",isOpenForSubmission:!0,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"28",title:"Animal Reproductive Biology and Technology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/28.jpg",isOpenForSubmission:!0,editor:{id:"177225",title:"Prof.",name:"Rosa Maria Lino Neto",middleName:null,surname:"Pereira",slug:"rosa-maria-lino-neto-pereira",fullName:"Rosa Maria Lino Neto Pereira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9wkQAC/Profile_Picture_1624519982291",biography:"Rosa Maria Lino Neto Pereira (DVM, MsC, PhD and) is currently a researcher at the Genetic Resources and Biotechnology Unit of the National Institute of Agrarian and Veterinarian Research (INIAV, Portugal). She is the head of the Reproduction and Embryology Laboratories and was lecturer of Reproduction and Reproductive Biotechnologies at Veterinary Medicine Faculty. She has over 25 years of experience working in reproductive biology and biotechnology areas with a special emphasis on embryo and gamete cryopreservation, for research and animal genetic resources conservation, leading research projects with several peer-reviewed papers. Rosa Pereira is member of the ERFP-FAO Ex situ Working Group and of the Management Commission of the Portuguese Animal Germplasm Bank.",institutionString:"The National Institute for Agricultural and Veterinary Research. Portugal",institution:null},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:19,paginationItems:[{id:"81793",title:"Canine parvovirus-2: An Emerging Threat to Young Pets",doi:"10.5772/intechopen.104846",signatures:"Mithilesh Singh, Rajendran Manikandan, Ujjwal Kumar De, Vishal Chander, Babul Rudra Paul, Saravanan Ramakrishnan and Darshini Maramreddy",slug:"canine-parvovirus-2-an-emerging-threat-to-young-pets",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"81271",title:"The Diversity of Parvovirus Telomeres",doi:"10.5772/intechopen.102684",signatures:"Marianne Laugel, Emilie Lecomte, Eduard Ayuso, Oumeya Adjali, Mathieu Mével and Magalie Penaud-Budloo",slug:"the-diversity-of-parvovirus-telomeres",totalDownloads:23,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"79909",title:"Cryopreservation Methods and Frontiers in the Art of Freezing Life in Animal Models",doi:"10.5772/intechopen.101750",signatures:"Feda S. Aljaser",slug:"cryopreservation-methods-and-frontiers-in-the-art-of-freezing-life-in-animal-models",totalDownloads:167,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Animal Reproduction",coverURL:"https://cdn.intechopen.com/books/images_new/10664.jpg",subseries:{id:"28",title:"Animal Reproductive Biology and Technology"}}},{id:"79782",title:"Avian Reproduction",doi:"10.5772/intechopen.101185",signatures:"Kingsley Omogiade Idahor",slug:"avian-reproduction",totalDownloads:151,totalCrossrefCites:0,totalDimensionsCites:0,authors:[{name:"Kingsley O.",surname:"Idahor"}],book:{title:"Animal Reproduction",coverURL:"https://cdn.intechopen.com/books/images_new/10664.jpg",subseries:{id:"28",title:"Animal Reproductive Biology and Technology"}}}]},overviewPagePublishedBooks:{paginationCount:10,paginationItems:[{type:"book",id:"7233",title:"New Insights into Theriogenology",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7233.jpg",slug:"new-insights-into-theriogenology",publishedDate:"December 5th 2018",editedByType:"Edited by",bookSignature:"Rita Payan-Carreira",hash:"74f4147e3fb214dd050e5edd3aaf53bc",volumeInSeries:1,fullTitle:"New Insights into Theriogenology",editors:[{id:"38652",title:"Dr.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}}]},{type:"book",id:"7144",title:"Veterinary Anatomy and Physiology",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7144.jpg",slug:"veterinary-anatomy-and-physiology",publishedDate:"March 13th 2019",editedByType:"Edited by",bookSignature:"Catrin Sian Rutland and Valentina Kubale",hash:"75cdacb570e0e6d15a5f6e69640d87c9",volumeInSeries:2,fullTitle:"Veterinary Anatomy and Physiology",editors:[{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",institutionURL:null,country:{name:"United Kingdom"}}}]},{type:"book",id:"8524",title:"Lactation in Farm Animals",subtitle:"Biology, Physiological Basis, Nutritional Requirements, and Modelization",coverURL:"https://cdn.intechopen.com/books/images_new/8524.jpg",slug:"lactation-in-farm-animals-biology-physiological-basis-nutritional-requirements-and-modelization",publishedDate:"January 22nd 2020",editedByType:"Edited by",bookSignature:"Naceur M'Hamdi",hash:"2aa2a9a0ec13040bbf0455e34625504e",volumeInSeries:3,fullTitle:"Lactation in Farm Animals - Biology, Physiological Basis, Nutritional Requirements, and Modelization",editors:[{id:"73376",title:"Dr.",name:"Naceur",middleName:null,surname:"M'Hamdi",slug:"naceur-m'hamdi",fullName:"Naceur M'Hamdi",profilePictureURL:"https://mts.intechopen.com/storage/users/73376/images/system/73376.jpg",biography:"Naceur M’HAMDI is Associate Professor at the National Agronomic Institute of Tunisia, University of Carthage. He is also Member of the Laboratory of genetic, animal and feed resource and member of Animal science Department of INAT. He graduated from Higher School of Agriculture of Mateur, University of Carthage, in 2002 and completed his masters in 2006. Dr. M’HAMDI completed his PhD thesis in Genetic welfare indicators of dairy cattle at Higher Institute of Agronomy of Chott-Meriem, University of Sousse, in 2011. 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