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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"7111",leadTitle:null,fullTitle:"Poisoning in the Modern World - New Tricks for an Old Dog?",title:"Poisoning in the Modern World",subtitle:"New Tricks for an Old Dog?",reviewType:"peer-reviewed",abstract:'Over 400 years ago, Swiss alchemist and physician Paracelsus (1493-1541) cited: "All substances are poisons; there is none that is not a poison. The right dose differentiates a poison from a remedy." This is often condensed to: "The dose makes the poison." So, why are we overtly anxious about intoxications?In fact, poisons became a global problem with the industrial revolution. Pesticides, asbestos, occupational chemicals, air pollution, and heavy metal toxicity maintain high priority worldwide, especially in developing countries. Children between 0 and 5 years old are the most vulnerable to both acute and chronic poisonings, while older adults suffer from the chronic effects of chemicals. This book aims to raise awareness about the challenges of poisons, to help clinicians understand current issues in toxicology.',isbn:"978-1-83880-786-3",printIsbn:"978-1-83880-785-6",pdfIsbn:"978-1-83880-787-0",doi:"10.5772/intechopen.73906",price:119,priceEur:129,priceUsd:155,slug:"poisoning-in-the-modern-world-new-tricks-for-an-old-dog-",numberOfPages:128,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"08164f9300bc6bf4900c9166d960278b",bookSignature:"Ozgur Karcioglu and Banu Arslan",publishedDate:"June 19th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/7111.jpg",numberOfDownloads:18297,numberOfWosCitations:0,numberOfCrossrefCitations:111,numberOfCrossrefCitationsByBook:2,numberOfDimensionsCitations:256,numberOfDimensionsCitationsByBook:3,hasAltmetrics:1,numberOfTotalCitations:367,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"July 11th 2018",dateEndSecondStepPublish:"August 29th 2018",dateEndThirdStepPublish:"October 28th 2018",dateEndFourthStepPublish:"January 16th 2019",dateEndFifthStepPublish:"March 17th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"221195",title:"Prof.",name:"Ozgur",middleName:null,surname:"Karcioglu",slug:"ozgur-karcioglu",fullName:"Ozgur Karcioglu",profilePictureURL:"https://mts.intechopen.com/storage/users/221195/images/system/221195.jpeg",biography:"In 1994, I started residency in Dokuz Eylul University Medical School, Department of Emergency Medicine. I completed Fellowship Program in International EM in Pennsylvania State University (2005). I have served as the chairman of the department in DEU (2005-2007). I have been in charge of the ED of Bakirkoy Research and Training Hospital (2007-2009), and then faculty member in Acıbadem University (2009-15).\nI have served as a founder and a board member of The Emergency Medical Association of Turkey (2007-2009). 159 articles of mine were published in international journals. I have contributed in six books as editor, and authored 40 chapters. I’m serving as a member of The Editorial Board or as a section editor in a number of indexed journals. I’m also an instructor of the AHA-based Basic and Advanced Cardiac Life Support Course.",institutionString:"University of Health Sciences",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"4",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"232986",title:"Dr.",name:"Banu",middleName:null,surname:"Arslan",slug:"banu-arslan",fullName:"Banu Arslan",profilePictureURL:"https://mts.intechopen.com/storage/users/232986/images/system/232986.JPG",biography:null,institutionString:"Marmara University, Pendik Education and Research Hospital",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Marmara University",institutionURL:null,country:{name:"Turkey"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1208",title:"Medical Toxicology",slug:"medical-toxicology"}],chapters:[{id:"66310",title:"General Approach to Poisoned Patient",doi:"10.5772/intechopen.84681",slug:"general-approach-to-poisoned-patient",totalDownloads:1966,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Poisoning is a serious worldwide public health problem. Based on the World Health Organization data in 2012, almost 190,000 people died worldwide and the number of deaths due to poisoning in 2008 exceeded the number of deaths due to motor vehicular crashes; also, poisoning death rate nearly tripled worldwide. The number of patients presenting to the emergency departments with overdose had been increased both intentionally and accidentally. All the previous facts make toxicology an important field in emergency medicine. According to the American Association of Poison Control Centers (AAPCC) in the United States, over 2.1 million human exposure calls are reported in 2016. Management of intoxicated patients has a unique approach because of the challenge in diagnosis and treatment of overdose cases. This chapter focuses on general approaches for intoxicated patients and initial management and on how the history and physical examinations could help physicians to have a clue about the drugs that have been abused. Patients are most commonly poisoned via oral ingestion, but other routes could also cause intoxication including inhalation, insufflation, cutaneous and mucous membrane exposure, and injection.",signatures:"Ehab Said Aki and Jalal Alessai",downloadPdfUrl:"/chapter/pdf-download/66310",previewPdfUrl:"/chapter/pdf-preview/66310",authors:[{id:"230047",title:"Dr.",name:"Ehab",surname:"Aki",slug:"ehab-aki",fullName:"Ehab Aki"}],corrections:null},{id:"65525",title:"Poisoning in the Pediatric Intensive Care Unit",doi:"10.5772/intechopen.83573",slug:"poisoning-in-the-pediatric-intensive-care-unit",totalDownloads:1175,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Poisonings during childhood (both accidental and voluntary) are a common cause of presentation in the emergency departments (EDs) and the pediatric intensive care unit (PICU). The admission to PICU is warranted both for treatment and for continuous monitoring, as sometimes the evolution of a poisoning could be unpredictable. Sometimes, complications arise that may prolong the patients’ hospitalization and may contribute to lowering the survival rate. The staff in these departments must be well trained to ensure patient monitoring, early detection of complications, and rapid intervention. Supporting vital functions is the main objective of the management of a poisoned patient admitted in PICU. In recent years, staff competence and advanced medical technology have helped to improve the prognosis of the patients admitted to these departments, including of the poisoned patients.",signatures:"Nicolai Nistor, Otilia Frăsinariu, Aniela Rugină, Irina Mihaela Ciomaga and Violeta Ștreangă",downloadPdfUrl:"/chapter/pdf-download/65525",previewPdfUrl:"/chapter/pdf-preview/65525",authors:[{id:"219606",title:"Dr.",name:"Nicolai",surname:"Nistor",slug:"nicolai-nistor",fullName:"Nicolai Nistor"},{id:"219884",title:"Dr.",name:"Otilia",surname:"Frasinariu",slug:"otilia-frasinariu",fullName:"Otilia Frasinariu"},{id:"219885",title:"Dr.",name:"Violeta",surname:"Streanga",slug:"violeta-streanga",fullName:"Violeta Streanga"},{id:"271778",title:"Dr.",name:"Irina",surname:"Ciomaga",slug:"irina-ciomaga",fullName:"Irina Ciomaga"},{id:"271779",title:"Dr.",name:"Aniela",surname:"Rugina",slug:"aniela-rugina",fullName:"Aniela Rugina"}],corrections:null},{id:"65005",title:"Forensic Toxicology",doi:"10.5772/intechopen.82869",slug:"forensic-toxicology",totalDownloads:1362,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Forensic toxicology is a broad science that integrates principles and practices about toxicology and legal aspects, which occur in conjunction with medicolegal instances as with homicide, suicide, road traffic and other types of accident and/or disasters. Nowadays, the practitioners of forensic toxicology science have to deal with three chief sections, namely: postmortem, drug testing, and human performance forensic toxicology. Postmortem forensic toxicology is dealing mostly with investigation of abnormal deaths, or when drug intoxication incidence is assumed as a cause of death and no abnormal findings were detected during autopsy.",signatures:"Sahar Y. Issa",downloadPdfUrl:"/chapter/pdf-download/65005",previewPdfUrl:"/chapter/pdf-preview/65005",authors:[{id:"268527",title:"Dr.",name:"Sahar",surname:"Issa",slug:"sahar-issa",fullName:"Sahar Issa"}],corrections:null},{id:"65686",title:"Review of Health Hazards and Toxicological Effects of Constituents of Cosmetics",doi:"10.5772/intechopen.84590",slug:"review-of-health-hazards-and-toxicological-effects-of-constituents-of-cosmetics",totalDownloads:1687,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Cosmetic products are designed for use on human body for beautifying and promoting attractiveness and appearance; for these reasons, cosmetics are in high demand especially among women of all ages in every country. Despite many vulnerabilities associated with cosmetic usage, the cosmetic and ‘makeup’ continues to enjoy wide acceptability irrespective of age and sex. This is made possible by massive advertising employed by producers and marketers of cosmetics. Advertising is the link between manufactured products and would-be consumers; it plays a crucial role in determining the product that is mostly patronised and vice versa. Therefore, ethical advertising that promotes utilitarian benefits of cosmetics should be encouraged over and above emotional advertisement that lowers self-esteem of consumers and offers such products as solution to their low self-esteem. Despite the ban in many countries of poisonous substances in cosmetic products, inexhaustive list of substances, such as lead, chromium, nickel, mercury, arsenic, cadmium, hydroquinone, steroids, nitrosamine, etc. are still present in many cosmetic products. In most cases, above regulatory values, cancers, renal disorders, thinning and easy brushing of the skin, dermatophyte infection with lesions, macular hyper pigmentation, pityriasis vesicular, diabetes mellitus, micropapular eruption, hypertension, etc. are possible toxicological and health hazards that may be associated with continuous cosmetic application.",signatures:"John Kanayochukwu Nduka, Henrietta Ijeoma Kelle and Isaac Omoche Odiba",downloadPdfUrl:"/chapter/pdf-download/65686",previewPdfUrl:"/chapter/pdf-preview/65686",authors:[{id:"107866",title:"Dr.",name:"John Kanayochukwu",surname:"Nduka",slug:"john-kanayochukwu-nduka",fullName:"John Kanayochukwu Nduka"}],corrections:null},{id:"64762",title:"Mechanism and Health Effects of Heavy Metal Toxicity in Humans",doi:"10.5772/intechopen.82511",slug:"mechanism-and-health-effects-of-heavy-metal-toxicity-in-humans",totalDownloads:10469,totalCrossrefCites:107,totalDimensionsCites:247,hasAltmetrics:1,abstract:"Several heavy metals are found naturally in the earth crust and are exploited for various industrial and economic purposes. Among these heavy metals, a few have direct or indirect impact on the human body. Some of these heavy metals such as copper, cobalt, iron, nickel, magnesium, molybdenum, chromium, selenium, manganese and zinc have functional roles which are essential for various diverse physiological and biochemical activities in the body. However, some of these heavy metals in high doses can be harmful to the body while others such as cadmium, mercury, lead, chromium, silver, and arsenic in minute quantities have delirious effects in the body causing acute and chronic toxicities in humans. The focus of this chapter is to describe the various mechanism of intoxication of some selected heavy metals in humans along with their health effects. Therefore it aims to highlight on biochemical mechanisms of heavy metal intoxication which involves binding to proteins and enzymes, altering their activity and causing damage. More so, the mechanism by which heavy metals cause neurotoxicity, generate free radical which promotes oxidative stress damaging lipids, proteins and DNA molecules and how these free radicals propagate carcinogenesis are discussed. Alongside these mechanisms, the noxious health effects of these heavy metals are discussed.",signatures:"Godwill Azeh Engwa, Paschaline Udoka Ferdinand, Friday Nweke Nwalo and Marian N. Unachukwu",downloadPdfUrl:"/chapter/pdf-download/64762",previewPdfUrl:"/chapter/pdf-preview/64762",authors:[{id:"241837",title:"Mr.",name:"Godwill Azeh",surname:"Engwa",slug:"godwill-azeh-engwa",fullName:"Godwill Azeh Engwa"},{id:"274194",title:"BSc.",name:"Paschaline Ferdinand",surname:"Okeke",slug:"paschaline-ferdinand-okeke",fullName:"Paschaline Ferdinand Okeke"},{id:"286975",title:"Dr.",name:"Friday",surname:"Nweke Nwalo",slug:"friday-nweke-nwalo",fullName:"Friday Nweke Nwalo"},{id:"286976",title:"Dr.",name:"Marian",surname:"Unachukwu",slug:"marian-unachukwu",fullName:"Marian Unachukwu"}],corrections:null},{id:"65306",title:"Nephrotoxic Effects of Drugs",doi:"10.5772/intechopen.83644",slug:"nephrotoxic-effects-of-drugs",totalDownloads:1654,totalCrossrefCites:4,totalDimensionsCites:7,hasAltmetrics:0,abstract:"Drug-induced nephrotoxicity is a renal dysfunction that occurs as a result of exposure to nephrotoxic drugs. It is a common problem in certain clinical situations such as underlying renal dysfunction, cardiovascular disease, diabetes, and sepsis. Drugs can cause mild to moderate nephrotoxic problems such as intrarenal obstruction, interstitial nephritis, nephrotic syndrome, acid-base and fluid-electrolyte disturbances, alteration in intraglomerular hemodynamics, inflammatory changes in renal tubular cells, tubulointerstitial disease, and renal scarring leading to acute or chronic kidney injury. Therefore, early detection of adverse effects of drugs as well as the clinical history of the patient, basic renal functions, drug-related risk factors, and nephrotoxic drug combinations must be well known in order to prevent drug-induced nephrotoxicity and progression to end-stage renal disease.",signatures:"Azade Sari",downloadPdfUrl:"/chapter/pdf-download/65306",previewPdfUrl:"/chapter/pdf-preview/65306",authors:[{id:"271267",title:"Dr.",name:"Azade",surname:"Sari",slug:"azade-sari",fullName:"Azade Sari"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"6662",title:"Trauma Surgery",subtitle:null,isOpenForSubmission:!1,hash:"9721b9ac98bf237058cafd0a0303bdbc",slug:"trauma-surgery",bookSignature:"Ozgur Karcioglu and Hakan Topacoglu",coverURL:"https://cdn.intechopen.com/books/images_new/6662.jpg",editedByType:"Edited 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He was appointed (2017) as a Minister of Innovative Development of Uzbekistan.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"213344",title:"Prof.",name:"Ibrokhim Y.",middleName:null,surname:"Abdurakhmonov",slug:"ibrokhim-y.-abdurakhmonov",fullName:"Ibrokhim Y. Abdurakhmonov",profilePictureURL:"https://mts.intechopen.com/storage/users/213344/images/system/213344.jpg",biography:'Ibrokhim Y. Abdurakhmonov received a BS in Biotechnology from the National University, California, in 1997, an MS in Plant Breeding from Texas A&M University in 2001, and a Ph.D. in Molecular Genetics, DSc in Genetics, and a full professorship in Molecular Genetics and Molecular Biotechnology from the Academy of Sciences of Uzbekistan in 2002, 2009, and 2011, respectively. He founded the Center of Genomics and Bioinformatics of Uzbekistan in 2012. 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Nowadays, organizations are facing a lot of challenges when competing in various sectors of the global market such as economics, technology, and labor. One of the crucial strategies for an organization to gain competitive advantage is exploitation of training. In particular, training is an important function for an organization to cultivate employees’ explicit and implicit knowledge, skills, and abilities and transfer employees into the valuable resources of an organization. This function is not only linked to improvement of business performance but also an effective determinant in shaping employee attitudes, which are critical variables to influence job performance [1]. According to the literature, job satisfaction is defined as “a pleasurable emotional state resulting from the appraisal of one’s job or job experiences” ([2], p. 94). It is one of the major job attitudes to affect employees’ behaviors and shows a strong relationship with other affective outcomes such as learning motivation, turnover rate, and firm performance [3].
\nSince training and job satisfaction are two important variables which individually produces impacts on firm performance, this chapter aims to elaborate training in organization toward job satisfaction. This chapter is organized in four sections. The first section describes how to plan and carry out an effective training program. It begins by discussing the definition of training and the meaning of learning. Next, a training effectiveness model is constructed to present a whole picture about the factors which influence the training outcomes. Elucidation will be provided for each part of the model which includes individual characteristics, organizational characteristics, and task characteristics, followed by needs assessment, training design, and training evaluation. The second section focuses on job satisfaction in which the fundamental concepts are introduced. This is followed by discussion of the impacts of job satisfaction on job performance. The third section describes job training satisfaction and how it contributes to job satisfaction, job performance, and other work-related attitudes. The final section is Conclusions.
\nWhat is training? Training refers to “a planned effort by a company to facilitate employees’ learning of job-related competencies” ([4], p. 5). It is also defined as “a planned and systematic effort to modify or develop knowledge, skills and attitudes through learning experiences to achieve effective performance in an activity or a range of activities” ([5], p. 41). Training is the major means to be used by organizations to cultivate employee competence to reach the appropriate required levels. It is also an important business strategy for organizations to cope with a variety of forces affecting the workplace [6, 7]. It is stated that training is organized and used by an organization as a business strategy to help employees develop and acquire competence, which includes knowledge, skills, behaviors, and attitudes that are critical for successful job performance. Typically, training can be distinguished by two basic types of locations where it is conducted, i.e., off-the-job and on-the-job. Off-the-job training provides learning opportunities on a variety of topics at a site other than where the work is actually done, whereas on-the-job training (OJT) occurs in the work setting itself [6]. With the assistance of modern technology, online training can be realized as well [8]. No matter which sites or ways the training is conducted, the key to effective training is to activate learning to occur.
\nIn most of the textbooks, learning is defined as an effect of experience on behavior [9]. It is related to a process of change in behavior that is due to experience. Actually, all learning involves two processes: one is an external interaction process between the learner and his or her social, cultural, and material environment, and the other is an internal psychological process of elaboration and acquisition in which new impulses are connected with the results of prior learning [10]. However, if the outputs of learning process (either through external or internal) only produce change in people’s behavior, such a definition cannot be satisfied by many researchers [9]. Therefore, learning has also been defined as “a relatively permanent change in human capabilities that is not a result of growth processes” ([4], p. 140). Based on this definition, learning can bring out three different outcomes. The first one is the content dimension, which refers to knowledge, understanding, skills, abilities, and attitudes. The second one is the incentive dimension which includes emotion, feelings, motivation, and volition. The final one is the social dimension, which involves interaction, communication, and cooperation [10]. Learning, thus, can be further referred to as a process that is “seen” through changes in knowledge, skills, attitudes, behaviors, emotion managing ability, communication style, and more during training and generalization to the transfer context.
\nTraditionally, in the workplace, learning occurs through formal training and development. All formal learning activities are designed with specific learning objectives to cultivate employees in lifelong processes for ongoing development and acquisition of competencies to meet the challenges that the organization faces from its internal and external environment [8]. Typically, such learning is activated through direct instruction, which engage learners in lectures, discussions, simulations, role-plays, and other structured activities [11]. With technological advancement and intense competition, training scholars have claimed that employees must extend their learning outside the formal classroom or work settings to ensure competencies are maximized [12]. Thus, informal learning becomes important because it represents the most part of learning occurring in organizations. Watkins and Marsick characterized informal learning as a process “based on learning from experience, embedded in the organizational context, oriented to a focus on action; governed by non-routine conditions; concerned with tacit dimensions that must be made explicit; delimited by the nature of the task, the way in which the problems are framed, and the work capacity of the individual underlying the task; and enhanced by proactivity, critical reflectivity, and creativity” ([13], p. 287). It is unstructured and occurs outside a learning institution [11].
\n\nFigure 1 shows the relationships between training and learning. Training, either off-the-job, on-the-job, or online, involves transferring expertise and knowledge from experts who have it to novices who need it [14]. Both training and learning activities consist of a process of knowledge sharing, which is an element of reciprocity and is a giving-taking exchange process of information or assistance to others [15]. Knowledge sharing between employees and across teams allows an organization to exploit existing knowledge-based resources and has been identified as a positive force in creating innovative organizations [15–17].
\nThe relationships between training and learning.
In a competitive environment, while employee training and learning have become an increasingly important strategic issue for organizations [8], the core concern is how to help the company and trainees receive benefits from the training activities? The related questions include “what kind of factors that may affect the success and effectiveness of training” and “what/how trainers can do to make training program effective?” Training effectiveness, according to Noe ([4], p. 216), refers to “the benefits that the company and trainees receive from training.” It focuses on understanding the whole learning system to determine why learners learn or do not. It also explains why the learning results happen and assists training designers to make troubleshooting to improve training [18]. Thus, theoretically, training effectiveness is the study of the individual, training, and organizational characteristics that influence the training process before, during, and after training [18]. Training effectiveness differs from the training evaluation. Training effectiveness is a theoretical approach to understand learning outcomes, whereas training evaluation is a methodological approach to measure these learning outcomes [18]. A summarized model of training effectiveness is presented in Figure 2 [19]. Figure 2 shows the factors that impact the training outcomes and job performance and the relationships between them. Three major topics will be discussed, that is, needs assessment before training (shaded with gray color), program design and delivery during training (shaded with orange color), and training evaluation after training (shaded with pink color).
\nThe comprehensive model of training effectiveness.
Effective training practices involving the use of a training design process begin with a needs assessment [4, 8, 18]. A need is a measureable gap between two conditions—what currently is and what should be [20]. In order to define the gap of need in training, a complete assessment process should be conducted to figure out problem areas, issues, or difficulties that should be resolved [20]. Thus, a training needs assessment refers to the process used to determine whether training is necessary and why specific training activities are required [4, 8]. In most contexts, a needs assessment focuses on gaps rather than solutions [20]. Theoretically, it involves three levels of analysis: organizational analysis, person analysis, and task analysis. Organizational characteristics, individual characteristics, and task characteristics are factors to be considered for three levels of analysis in the beginning of training design. The purpose of these levels of analysis is to realize the gaps in current training programs and further to collect information for program design and problem-solving [4, 8].
\nIn Figure 2, the first factor is organizational characteristics. Organizational characteristics include organizational structure, business strategies, support of managers for training activities, training resources, organizational procedures, reward systems, culture, and climate [4, 8, 18, 21]. Each variable plays a very critical role to impact training effectiveness. For example, Facteau et al. [22] found that intrinsic and compliance incentives, organizational commitment, and social support for training are able to predict trainees’ pretraining motivation. Motivation is the key determinant of the choices individuals make to engage in, attend to, and persist in learning activities, which will affect learning performance [3]. Because organizational analysis is concerned with identifying whether (1) training fits the company’s strategic objectives; (2) training supports the company’s culture, climate, and policies; and (3) the company has the budget, time, and expertise to carry out training, this analysis is usually conducted in the first place [4]. Several major questions will be assessed in this analysis: “How does the training relate to business objectives?” “How does training support business strategy?” “What are the threats to the talent base?” “How does the training impact day-to-day workplace dynamics?” “What are the costs and expected benefits of the training?” [4, 8].
\nAnother factor, individual characteristics, includes cognitive ability, attitudes, locus of control, personality, anxiety, age, self-efficacy, expectations, job involvement, pretraining motivation, need for achievement, independence, and more [18, 19, 23]. A large number of studies have been demonstrating how individual differences influence transfer of learning and learning performance, which further impacts on training effectiveness [7, 24]. For example, Noe showed that individuals with an internal locus of control had more positive attitudes toward training since they viewed training as a means to help them receive tangible benefits [25]. Mathieu et al. proposed that trainees with high achievement motivation were more motivated to learn and perform well in the training program [26]. Klein et al. found that the learners with high learning goal orientation (LGO) would be significantly related to the factor of motivation to learn [27]. Macey and Schneider claimed that four individual characteristics like positive affectivity, proactive personality, conscientiousness, and autotelic personality were more likely to have greater psychological availability to learn and also perceived learning activities being more meaningful such that they are likely to participate actively in the training activities [28]. In addition, many researches have suggested that learning is negatively related to aging [24]. Also, three of the big five factors—conscientiousness, neuroticism (emotional stability), and openness to experience—significantly impact learning, training, and transfer outcomes [29]. Since employees’ individual characteristics make huge impacts on learning performance, personal analysis helps to identify employees’ characteristics and readiness for training and recognize who needs training and who will perform well in the training program.
\nThe third factor, task characteristics, consists of the knowledge, skills, and abilities required to complete the tasks, the equipment, and environment that the employee works in, time constraints for a task, safety considerations, or performance standards [4]. Thus, for task-level assessment, it involves checking specific duties and responsibilities assigned to various jobs and the types of skills and knowledge needed to perform each task [8]. In other words, the major purpose of task analysis is to collect job-related information to identify the task and the training that employees will require in terms knowledge, skills, and abilities. This analysis should be conducted only after the organizational analysis because it is a time-consuming process to gather and summarize data from persons in different layers of the company [4]. Several questions will be addressed in this analysis. For example, what kinds of responsibilities are to be assigned to the job? What are the skills or knowledge needed for successful performance? What are the implications of mistakes? What tasks should employees be trained [4, 8]?
\nAfter identifying the gaps and training objectives through the needs assessment, the next step is the design and delivery of the training itself [8]. Program design is rooted in learning theories and refers to “the organization and coordination of the training program” ([4], p. 172). More specifically, “it is a process for helping to create effective training in an efficient manner. It is a system that helps designers ask the right questions, make the right decision, and produce a useful and useable product as the situation requires and allows” [30]. Thus, the purpose of a program design is to make learning occur and training effective. Research has indicated that each element of training design process is related to the quality of training. Researchers such as Baldwin et al. and Klein et al. presented that training design with organizational characteristics and individual characteristics together influences trainees’ motivation to learn and, motivation to transfer, and real training transfer [27, 31]. Latif presented a model of training effectiveness which points out that training satisfaction comes from trainees’ feeling of satisfaction with training session, training content, trainers, and learning transfer [1]. Noe et al. also showed that technology-based and face-to-face learning methods and contextual factors such as organizational climate, interpersonal dynamics, and individual differences are able to promote psychological engagement in learning, which is a crucial factor to enhance the effectiveness of training, development, and related learning activities [7].
\nTraining methodology was also found to be an important factor in the equation of job training satisfaction [32]. Compared to other training methods, on-the-job training is one of the oldest, most widely used training methods in the workplace. It can be useful for training newly hired employees, orienting promoted or transferred employees to the new job positions, upgrading employees’ competencies when new technology is used, and delivering cross-culture training to employees who are assigned to work overseas [4]. Since OJT occurs at or near the workplace using actual equipment and tools, most of the time, trainees are highly motivated to learn and can be customized to the experiences and abilities [4]. Although there are many advantages, OJT is informal or unstructured in nature and has received serious criticism such as incomplete and unpredictable [33]. Thus, structured on-the-job training (S-OJT) was proposed by Jacobs and McGiffin [34]. In contrast to informal and unstructured OJT, structured OJT adopts a planned approach to train and develop employees’ competencies [33]. Many research results indicated that S-OJT is superior to unstructured on-the-job training in terms of having lower training cost, enhancing skills acquisition, and removing learning anxieties [6].
\nIn the past, a large portion of the research in program design has paid great attention to traditional instructional design (ISD) model, which includes conducting a needs assessment, setting the objectives of training, identifying evaluation criteria, selecting appropriate trainers and training methods, making meaningful materials, and properly coordinating and arranging training delivery. In addition, it involves ensuring training transfer, offering a good training site, and providing opportunities for practice and feedback [4, 7]. Although the traditional instructional design brings a lot of benefits to enhance training effectiveness, it is more instructor-oriented where lecture proceeds with adding sophisticated elements and feedback loop with interaction and communication [35]. Some scholars have recently claimed that instructor-oriented design is deemed to be disadvantageous for effective learning. They argued that the learners in instructor-centered program may be passive in learning activities and seldom grasp the significance or realize the intricacies of the model from the instructors during the training [16, 35]. Thus, it has been claimed that the instructional design model needs to be modified or adapted to better fit the learner-centered learning, particularly technology-based learning [16, 36].
\nWhat is learner-centered learning? Learner-centered learning involves the balance between instructor and learner shifting the roles, so that the learners take on the responsibility to learn and the instructor becomes more of a facilitator [37, 38]. In this learning paradigm, instead of transferring factual knowledge to the learners, the instructor focuses more on creating a learning environment and providing learning opportunities that empower learners to construct knowledge for themselves [39]. Attention, in this paradigm, is given not only to what the learners learn but also to how they learn and whether they are able to retain and apply the knowledge or not [36]. More specifically, the instructor with the role of facilitator utilizes multiple teaching methods beyond traditional lecturing to help the learners actively participate in learning [35].
\nThus, several tips for delivering the training with the learner-centered approach are described as follows [36]. First, at the beginning of the training, the trainer involves learners into decision-making process for choosing the course textbook. Second, after choosing the textbooks, the trainer invites learners to pick up the topics which they are interested in and also fit personal needs. In this way, the learners would take responsibility for learning by themselves. Third, the class will be run like a discussion session. The trainer gives training materials before the class and asks them to read in advance. Following the Shor’s suggestion that the trainer controls his/her “authoritative academic voice” [40], the trainer says as little as necessary and focuses on determining what they are interested in, what they have troubles with and what they want to talk about. The trainer offers questions, comments, structures, and academic knowledge while patiently listening to trainees’ thoughts and ideas. The trainer and the learners learn from each other through interaction. Fourth, Weimer suggested that the careful design of assignments which help students effectively use the power they are given is the key component of sharing power to the learners [41]. Thus, the trainer needs to structure the assignments well and allows the trainees to make choices about the ways to complete the projects, for example, by conducting interview or submitting a real lesson activity.
\nThree critical issues must be considered in the designing and delivering stage [8]. The first one is interference. Interference occurs “when prior training, learning, or established habits act as block or obstacle in the learning process” ([8], p. 391). That is, someone who has more experience in behaving in a certain way will have more difficulties in changing the way he/she responds when encountering a situation. Therefore, when designing the training, the trainers need to be aware of this issue. The second one is transfer design [8]. Transfer refers to whether the trainee or learner can actually perform the new skills or use the new knowledge on the job [4]. Transfer design, thus, is defined as the ability to transfer learning to the job and to which the training instruction matches the job requirements [42]. In order to ensure that the organizations are able to receive benefit from training, Lim and Johnson suggested that training design, content, and instructional strategies must be related to the objective of transfer, whether near or far transfer [43]. In other words, transfer mechanisms such as climate for transfer, management and peer support, opportunity to perform, training awareness, and using self-management strategies need to be included in the design of a training program for maximizing transfer [4, 21, 44]. The third one is the needs of adult learners. It is said that the ways of children’s learning are different from those of adults. Several assumptions were proposed by Malcolm Knowles [45]: (1) adults have the need to know why they learn, (2) adults have the need to be self-managed, (3) adults bring more work-related experiences into the learning context than children or teenagers, (4) adults learn with a problem-centered approach, and (5) adults are motivated to learn by getting both extrinsic and intrinsic motivators. Since most of the job-related training is targeted for employees whose age is over 18, the training program must meet the needs of these adult learners in order to enhance training effectiveness.
\nEvaluation is an integral part and the final stage of most instructional design (ID) models [46]. Theoretically, it is a systematic process of collecting data in an effort to measure and determine success or failure of a training program with regard to content and design [18, 47]. Two questions intend to be answered in the evaluation process, that is, whether (1) training objectives are achieved in the learning process and (2) accomplishment of those objectives results in enhanced job performance [48]. Thus, evaluation can be divided into two categories, formative evaluation and summative evaluation [46, 49, 50]. Formative evaluation is an evaluation with the purpose to improve design and development to enhance learning, whereas summative evaluation is intended to determine whether the training program is worthy or effective [51, 52]. Besides, Campbell stressed that the most important and fundamental thing is whether trainees have learned the materials covered in training or not [53].
\nTraditionally, Kirkpatrick’s model was one of the first efforts to create a framework for training evaluation. It is also the simplest method to understand training effectiveness [18, 54]. According to Kirkpatrick, training can be evaluated at four levels. Level 1 is the “reactions” criteria, which evaluates trainees’ affective and attitudinal perceptions to a training program, including facilities, trainers, and content. For the “reactions” criteria, evaluation is performed via a questionnaire completed by trainees or self-reported regarding perceived learning gains [55]. Level 2 is the “learning” criteria, which evaluates the extent to which trainees have learned the training materials covered in training and acquired knowledge, skills, attitudes, and behavior from a training program. Learning outcomes are typically measured by using various forms of knowledge tests such as pencil-and-paper test or by immediate post-training measures of performance and skill demonstration in the training context [56]. Level 3 is the “behavior” criteria. It refers to as transfer criteria and evaluates the extent to which trainees have applied the learned competencies on the job. For behavioral criteria, evaluation is assessed by self-ratings, supervisor ratings, or objective performance indicators [56–58]. Level 4 is the “results” criteria, which evaluates the extent to which the training program has improved business outcomes and to increase organizational-level profits [47]. Although this kind of assessment is the most difficult to be obtained, it is highly desirable for the organizations. Most of the time, “results” are operationalized by productivity gains, reduced costs related to employee turnover, increased customer satisfaction, enhancing employee commitment, or increase in profitability [57, 58].
\nAlthough Kirkpatrick’s framework is the most accepted approach for training evaluation, it has been criticized by many scholars. One of the criticisms is that the criteria used for evaluation in Kirkpatrick’s framework do not relate to the training needs, the learning objectives, and strategic goals of the organizations [4]. The second one is the lack of relationship between reaction, learning, behavior, and results’ criteria [55]. As a result, both training practitioners and academic researchers have developed a more comprehensive model for training criteria. For example, Kraiger et al. attempted to expand the original Kirkpatrick model by linking the learning outcomes with training evaluation [48]. Based on Kraiger et al.’s proposition, three categories of learning outcomes, that is, cognitive, skill-based, and affective outcomes, should be included in evaluation [48, 59]. Specifically, cognitive outcomes are used to determine the degree to which trainees are familiar with principles, facts, techniques, procedures, or processes emphasized in the training program. It includes verbal knowledge, knowledge organization, and cognitive strategies. Skill-based outcomes, including skill learning and skill transfer, are used to assess the level of technical or motor skills and behaviors. Affective outcomes include both attitudinal and motivational change, which also involves disposition, motivation to learn, self-efficacy, tolerance for diversity, safety attitudes, customer service orientation, and goal setting [4, 48].
\nAmong three categories of learning outcomes, affective outcomes have attracted a lot of attentions in different research areas such as education, psychology, and organizational behavior. The scholars are particularly interested in the issue regarding whether self-efficacy or motivation to learn can be changed through training and how different training methods impact self-efficacy and motivation to learn. For example, Gist found that a training method comprising cognitive modeling with practice and reinforcement generated significantly higher participant self-efficacy than a method involving only lecture and practice [60]. Torkzadeh and Dyke suggested that training significantly improved Internet self-efficacy for trainees, both males and females [61]. Combs and Luthans stated that the diversity training enhanced trainees’ diversity self-efficacy [62]. Huang and Jacobs claimed that structured on-the-job training could generate higher self-efficacy to achieve training outcomes than classroom training with lecture only, especially for trainees with lower general self-efficacy (GSE) [63]. Huang and Jao reported that structured on-the-job training could generate higher trainees’ motivation to learn than classroom training [64].
\nAmong thousands of attitudes, job satisfaction is one of important work-related attitudes in the work environment [3]. Specifically, job satisfaction refers to the degree to which the feeling of satisfaction is derived from the employees’ perceptions toward different facets of their tasks or jobs [65, 66]. In other words, job satisfaction is a pleasurable or positive emotional state emerging as the result of appraising one’s job or job experiences and as the fulfillment or gratification of certain needs that are associated with one’s work [3, 67, 68]. Simply put, job satisfaction is the combination of feelings, beliefs, and behavioral intentions that workers hold a relation to their current jobs [3, 69]. The employees’ job satisfaction is measurable and can be changed [3]. A popular way to explain job satisfaction has been the person-environment fit paradigm, which suggests that the more a person’s work environment is fulfilling one’s needs, personality, values, or personal characteristics, the greater the degree of job satisfaction is [70].
\nWhile tackling the issue of job satisfaction, some typical questions were raised by researchers. For example, why are some employees more satisfied than others? What kinds of work tasks are especially satisfying? How to design a task to make employees feel satisfied? Colquitt et al. claimed that values play a key role in explaining job satisfaction [2]. What is value? Values are “the things that people consciously or unconsciously want to seek or attain” ([2], p. 94). Thus, value-percept theory argues that “job satisfaction depends on whether the employee perceives that his or her job supplies the things that he or she values” ([2], p. 94). Based on the value-percept theory, the dissatisfaction of employees can be expressed as follows:
\nwhere Vwant refers to how much of a value an employee wants, Vhave is the value the job supplies, and Vimportance reflects the importance of the value to the employee. It can be seen that, although the difference between Vwant and Vhave causes the dissatisfaction, it is the importance of the value that will either magnify or minimize the dissatisfaction [2]. In the value-percept theory, five specific facets of satisfaction, i.e., pay satisfaction, promotion satisfaction, supervision satisfaction, coworker satisfaction, and satisfaction with the work itself, must be met in order to achieve overall job satisfaction.
\nWhile explaining job satisfaction from the perspective of value-percept theory, personal characteristics make the issue of “the things that each employee
Besides personal characteristics, situational characteristics also influence job satisfaction, which can explain what kinds of work tasks are especially satisfying. The situational factors include pay, opportunities for promotion, administration style, coworker, and working conditions [73]. For employees, a job is not “just a job.” Instead, it is a collection of tasks, relationships, and rewards. Any job-related conditions happened in the workplace may influence their emotion, which further impacts how they judge and perceive toward their job [3]. Therefore, in order for employees to have job satisfaction, the situational factors need to be carefully considered. For example, is the pay commensurate with the job duties? Is the pay secure? Are the promotions frequent, fair, and based on ability? Is the supervisor competent, polite, and a good communicator? Are the coworkers responsible, helpful, and interesting? Is the work challenging, interesting, respected? If it is yes to all the above questions, then it is highly possible that employees would be satisfied with their job [2].
\nThe needs of employees toward the work itself can be further realized through job characteristic theory. In other words, this theory helps to answer the question of how to design a task to make employees feel satisfied. Job characteristic theory suggested that job dimensions such as task identify, task significance, skill variety, autonomy, and feedback impact employees’ satisfaction with the work itself [3, 74]. Among these dimensions, skill variety, task identities, and task significance together produce a sense of meaningfulness of work, which reflects the extent the work tasks fit in the employees’ value and beliefs. The dimension of autonomy allows employees to experience the responsibility for outcomes of the work. Responsibility for outcomes refers to the extent the employees feel that they are responsible for the quality of the work. Providing either positive or negative feedback to employees make them have the opportunities to know the actual results of the work activities. Knowledge of results means that employees know how well or poorly they are doing. Thus, research suggests that the higher the three psychological states, the higher the working motivation, which leads to higher job satisfaction. An employee who has a high level of job satisfaction holds positive feelings toward his or her job, while he/she may hold negative feelings if he/she has a low level of job satisfaction [3].
\nThe next question to be answered is “does job satisfaction really matter?” This question can be answered through elaborating the relationship between job satisfaction and job performance, job commitment, organizational citizenship behavior (OCB), absenteeism, and turnover.
\nFirst, a number of researchers have been curious about the relationships between job satisfaction and job performance. For this question, many people may intuitively believe that job satisfaction is an important factor to impact job performance. Their presumption is that happy workers are more likely to be productive workers. However, at the early stage, the results indicated that job satisfaction was not meaningfully associated with job performance [75]. Till recently, studies showed that job satisfaction was moderately correlated with task performance. In other words, job satisfaction did predict job performance [2]. The satisfied employees who held positive feelings toward their work did a better job to fulfill the duties [76], to increase creativity in job [77], to enhance decision-making and problem-solving ability [78], and furthermore, to strengthen the memory and recall ability [79].
\nSecond, job satisfaction is interrelated to job commitment. Commitment is defined as that an employee identifies with a particular organization and its goals and wishes to remain as a member [3]. Commitment can be divided into three types, i.e., affective commitment, continuance commitment, and normative commitment, which are emotional-based, cost-based, and obligation-based, respectively [2]. Research found that job satisfaction was strongly correlated with affective and normative commitment but not correlated with continuance commitment [80]. Thus, the employees who have positively affective reaction to their jobs will be committed to their job and feel an obligation to remain in the organization [80–84].
\nThird, job satisfaction is moderately positive related to organizational citizenship behavior [2, 85]. OCB has been defined as “individual behavior that is discretionary, not directly or explicitly recognized by the formal reward system, and that in the aggregate promotes the effective functioning of the organization” ([86, 87], p. 4). Williams and Anderson found that the cognitive component of job satisfaction predicted the emergence of OCB [88], which was also supported by Moorman’s study [89]. Therefore, the satisfied employees would like to engage in more work-related behaviors to offer help to coworkers and increase desire to interact with others. OCB is extremely important for the employees to contact with the customers since it leads to improved customer evaluation of service quality [90].
\nFinally, job satisfaction reduces job turnover and absenteeism [91, 92]. Turnover refers to “…the voluntary and involuntary permanent withdrawal from an organization” ([93], p. 72). Since actual turnover behavior is difficult to measure, Lingard suggested using turnover intention as a predictor of actual turnover behavior [94]. Karatepe et al. found that job satisfaction was a negative association with turnover intention [95]. As to absenteeism, it refers to “unscheduled employee absences from the workplace” ([96], p. 144). Vroom found that low levels of job satisfaction contributed to higher absenteeism rates [97], and such a finding was confirmed by Clegg [98]. In addition, Drago and Wooden conducted a survey of 601 workers from Australia, New Zealand, Canada, and the USA and found that absenteeism was lower while employees’ job satisfaction was high [99]. The relationship between job satisfaction and turnover was stronger than between satisfaction and absenteeism [3].
\nThe concept of job training satisfaction was proposed by Schmidt [32]. He combined the definitions of job training and job satisfaction into one of the affective outcomes, called job training satisfaction (JTS). As mentioned above, training involves employees acquiring knowledge and learning skills that they will be able to apply on the job immediately [8]. Job satisfaction involves how an employee feels and what he/she thinks about the job [2]. Job training satisfaction, thus, is defined as “…how people feel about aspects of the job training they receive. Job training satisfaction is the extent to which people like or dislike the set of planned activities or dislike the set of planned activities organized to develop the knowledge, skills, and attitudes required to effectively a given tasks or job” ([32], p. 483). According to Schmidt, the definition of job training satisfaction has several key components [100]. First, the focus of evaluation is on-the-job training as a whole, rather than on a single part of training activities such as a training course, trainers, facilities, or training content. Second, it refers to a pleasurable or positive emotional state resulting from each element and the whole process before and after the job training, such as fulfillment of needs, enhancing motivation to learn, or satisfied with the transferring the learned competencies to the job. Third, the subjects of evaluation target on the trainees where formal or planned training activities are offered by the organization rather than the informal learning effort endeavors by the employees themselves. When measuring job training satisfaction, not only the employees’ feelings about the job training are measured but also the training activities offered by the organization are examined [32, 101].
\nIn the past, the impact of training on job satisfaction was not emphasized until it was found that job satisfaction tended to be higher where workplace training was held in organizations [102]. In order to explore the relationships between these two variables, Schmidt conducted a survey of job training and satisfaction for employees in customer and technical service department in nine major organizations in the USA and Canada to address how job training satisfaction impacts on job satisfaction [32]. According to his findings, job training satisfaction was not only highly correlated with job satisfaction but also significantly related to the time spent in training, training methodology, and content. However, it was not related to age, gender, and race/ethnicity. Extended researches have been carried out to explore the impact of job training satisfaction on other work attitudes. Huang and Su found that there is a negative relationship between job training satisfaction and turnover intentions [103]. It is stated that, when employees are satisfied with job training, they are more likely to stay in the organization and have lower turnover intentions. The research results have also indicated that the relationship between job training satisfaction and turnover intentions can be mediated by job satisfaction. Mansour et al. showed that there is a positive relation between job training satisfaction and normative commitment [100]. Moreover, job training satisfaction was found to be positively related to organizational citizenship behavior [104, 105], organizational commitment (OC), and job involvement (JI) [105]. The relationship between JTS and OCB can also be partially mediated by OC and JI [105]. From these research results, job training satisfaction is found to be able to enhance employees’ work attitudes such as job satisfaction, commitment, job involvement, and organizational citizenship behavior, which leads to the increase of job performance.
\nBased on the above discussion, a revised comprehensive model of training effectiveness is proposed and shown in Figure 3. According to Schmidt’s definition, job training satisfaction measures the employees’ feelings about the whole job training activities such as identifying the training needs, designing the training program, delivering training contents, activating learning occurring, and assessing training evaluation. Thus, different from the original model shown in Figure 2, the variable of job training satisfaction was inserted after the variable of training transfer to influence job satisfaction and job performance. That is, if the learners are able to perceive positively toward training program, to learn the job required knowledge, skill, abilities, and attitudes through training, and to succeed in transferring the learned competencies to real workplace, their satisfaction level toward training program must be high. For instance, on-the-job training, especially structured OJT, has been perceived as an effective training approach to achieve transfer of training owing to its occurrence at or near the workplace using actual facilities, enhancing skills acquisition, and removing learning anxieties [6, 33]. This allows the employees to be able to perform the job well and, in turn, feel satisfied with the training. Such high satisfaction toward job training leads to high level of job satisfaction and further results in high job performance but low turnover intention. These findings are interesting and valuable. Jones et al. ever mentioned that training can have an indirect effect on performance if it increases job satisfaction by making it easier for employees to perform the job or feel more valued [96]. From a series of studies, the impact of training on job satisfaction, job performance, and turnover intention has been confirmed. The variable of job training satisfaction can serve as a predictor to the employees’ job satisfaction, job performance, and turnover intentions.
\nThe revised comprehensive model of training effectiveness with insertion of job training satisfaction and job satisfaction.
The central thesis of this chapter is to present how job training plays a role in influencing the employees’ job training satisfaction, which then impacts job satisfaction and subsequently affects job performance and turnover intentions. Although training is a critical strategy to help organizations gain competitive advantages and its purpose is to help employees learn job-related competencies, job training satisfaction cannot be achieved without a well-prepared and designed training program. That is, at the beginning of the training program design, it is necessary to carry out a needs assessment to make the learning occur, which consists of organizational analysis, person analysis, and task analysis. While conducting training design and delivery during training, the learner-centered learning paradigm which has been emphasized recently may be considered as a preferred approach owing to its increasing learners’ learning motivation and learning engagement. After training, the training effectiveness is evaluated by assessing not only learning performance of knowledge, skills, and job-related behaviors but also affective outcomes such as self-efficacy, attitude, and motivation. Research has indicated that possessing a pleasurable or positive emotional state with the whole job training program, employees will have higher job satisfaction and job performance. Other job attitudes such as organizational citizenship behavior, affective commitment, and normative commitment will increase, while turnover intention and absenteeism will decrease. In this chapter, the comprehensive model of training effectiveness was modified by inserting the job training satisfaction after training transfer. This not only better elaborate the relationship among training, job satisfaction, and job performance but also serves as a reminder for the human resource practitioners who should always bear in mind how to make the trainees satisfied with the training when designing and delivering a training program.
\nA proteoglycan-rich matrix, the perineuronal net (PNN) is a dense structure within the extracellular matrix (ECM), whose synapses form through gaps around many neuronal bodies and dendrites at a late stage in brain development. PNNs are formed at the end of a critical period of neurodevelopment, following the transformation of the central nervous system (CNS) from an environment conducive to neuronal growth and motility to one that is more restrictive, in response to several sensory inputs from both neurons and glia driving increased neuroplasticity [1]. The main components of the PNN matrix include several chondroitin sulfate proteoglycans (CSPGs), such as hyaluronan, link proteins, and tenascin-R and -C.
During mammalian development, hyaluronan binds to members of the lectican family originally produced in neurons, including versican V0 and V1 and neurocan [2], whereas aggrecan seems to be expressed by astroglial cells in the juvenile matrix [3]. Other lecticans include versican 2, brevican, phosphacan, tenascin-R and the link proteins HAPLN2/Bral1 and HAPLN4/Bral2 are only observed in more mature matrix environments approximately 2 weeks after birth [4, 5, 6], in contrast to the composition of the juvenile matrix. Following this period, shifts in brevican expression occur at the end of myelination, leading to white-matter precursor changes from an oligodendroglial to an astrocytic lineage [7], and resulting in a compact extracellular matrix forming the PPN [8].
PNNs have been observed 2–5 weeks after birth around parvalbumin (PV+)-expressing GABAergic interneurons in pyramidal cortex, and around large motor neurons of the brainstem and spinal cord. This period coincides with the end of experience-dependent refinement of the synaptic network [8], but marked by a still critical period of matrix turnover and proteoglycan degradation by ADAMTS metalloendopeptidases and matrix metalloproteinases (MMPs) [8, 9]. PNN formations can also be observed in several distinct areas of the CNS, such as other regions of the cerebral cortex, the hippocampus (HPC), thalamus, and cerebellum [8].
PNNs in the adult CNS secrete hyaluronan through the action of membrane-bound HA synthase, an enzyme linked to the action of link proteins, lecticans, tenascin-R and chondroitin sulphate proteoglycans (CSPGs), creating supramolecular aggregates on the surface of neurons [1]. Other relevant glycoproteins besides CSPGs include Reelin, mainly secreted by Cajal–Retzius cells and involved in the control of neuronal migration and the establishment of cell aggregation and dendrite formation during the embryonic and early postnatal stages of development [10]. In adulthood, Reelin signalling is involved in the modulation of synaptic function and binds to very-low-density lipoprotein receptors and apolipoprotein E receptor 2 [11]. Increased clustering of Reelin receptors leads to a build-up of DAB1 proteins on the neuron membrane, greater activation of Src/SFK family kinases, and tyrosine phosphorylation of N-methyl-D-aspartate receptors (NMDARs), resulting in a net increase of receptor activity (Figure 1) [12]. Reelin insufficiency may lead to alterations in NMDAR clustering and LTP, such as in dysfunctional GABA-ergic transmission in the cerebral cortex and hippocampus observed among the morphofunctional signalling changes in schizophrenia (SZ) [12].
Effect of Reelin concentrations in the ECM on NMDA signalling. Reelin activates adaptor protein disabled 1 (DAB1) by binding with its very-low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor type 2 (APOER2). DAB1 is phosphorylated by Src family kinases (SFK) at different sites on the protein - this phosphorylation occurs mainly through the action of a co-receptor, tyrosine kinase receptor (RTK or Trk), implicated in a variety of cellular processes including growth, differentiation, and regulation of energy metabolism in the neuron. DAB1 phosphorylation leads to inhibition of the serine/threonine kinase Gsk3β via protein kinase B (Akt), where a decrease in AKT phosphorylation levels with subsequent high levels of GSK-3β phosphorylation, has been observed in lymphocytes and brains of individuals with schizophrenia (SZ). Clustering of Reelin receptors via SKF activation also leads to greater tyrosine phosphorylation of N-methyl-D-aspartate receptors (NMDARs), resulting in a net increase of receptor activity following the induction of long-term potentiation via Ca2+ regulation. This signalling cascade appears to be an essential process for neurobiological regulation during neurodevelopment (modified from [
In fact, alterations of GABAergic signalling within a prenatal stress period have been identified as important factors in the development of SZ [13], autism spectrum disorder (ASD) [14], and epilepsy [15], often leading to an altered density of GABAergic cells and aberrant oscillatory activity. However, one functional model of brain development has proposed that prenatal stress involves DNA methylation, possibly inducing methylation of the gene responsible for Reelin promoter, with the consequent down-expression of Reelin resulting in abnormalities within the neuronal architecture of the prefrontal cortex, a reduction in dendritic complexity and a decreased number of GABAergic neurons, leading to altered developmental neuronal connectivity [13].
Animal studies have demonstrated that DNA methylation in the BDNF gene controls its expression during forebrain development in mice [16]. Furthermore, binding of BDNF and nerve growth factor (NGF) neurotrophins to their respective receptors (TrkB/A) triggers the PI-3kinase/AKT pathway, with activation of the mammalian target of rapamycin (mTOR) [17] and Akt-dependent inhibition of the serine/threonine kinase Gsk3β, resulting in decreased transcription of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) [18]. Since Reelin/lipoprotein receptors do not contain a cytoplasmic kinase domain, the core Reelin signalling pathway seems to be associated with tyrosine kinase receptor (RTK or Trk) activity [19], the most likely coreceptor candidate [20]. As such, Reelin signalling from the ECM in collaboration with TrkB/A receptor activation, leads to increased phosphorylation of serine-9 GSK3β, with the inhibition of GSK3β in glial cells and leukocytes resulting in more CREB being translocated from the cytoplasm to the nucleus, and an increase in the transcription of anti-inflammatory cytokines (IL-10) (Figure 2) [21].
Hypothetical signalling cascades for GSK3β modulation of the expression of pro-inflammatory and anti-inflammatory cytokines in glial cells. Receptor crosstalk between receptors TrkB/A and Reelin in the ECM (see
PNN development and the maturation of PV+ inhibitory cells, as well as processes such as myelination, mark the end of the critical period of human neurodevelopment [22]. Disruption or delay to the formation of the PNN results in the resumption or extension of the time window for neuroplasticity in the brain [23], wherein the nervous system is more sensitive to epigenetic, physical, biochemical, environmental, and nutritional factors. The effects of nutrition on individuals during gestational and early development have been extensively researched, leading many researchers to conclude that nutritional factors such as vitamins, folate and iodine can cause long-lasting impacts in neurodevelopment [24, 25]. As the foetus’ and newborn’s acquisition of vitamins like B12 and D, depends to a great extent on maternal diet, such research has increasingly focussed on the impact of the mothers’ vitamin deficiency on their offspring’s brain development during the foetal and exclusive breastfeeding stages.
S-adenosyl methionine (SAM) is a universal methyl donor for some of the main methylation reactions. Vitamin B12 is an important cofactor in the one-carbon cycle and is involved in the formation of SAM. Vitamin B12 supplements have been shown to improve pregnancy outcomes and reduce the risk of neurodevelopmental disorders in the developing child [26]. In rats, dose-dependent vitamin B12 supplementation was able to maintain the levels of docosahexaenoic acid (DHA) and BDNF in the hippocampus and cortex in pups at birth, and BDNF in the hippocampus at 3 months of age [17]. In addition, the combination of omega-3 fatty acid and vitamin B12 administration maintained spatial memory performance in neonates [17]. Experimental evidence suggests that DHA, together with greater levels of physical exercise, increases activated forms of CREB and synapsin I, reducing oxidative stress in the hippocampus [18].
Vitamin D deficiency may also reduce the integrity of PNNs and synaptic plasticity in neuropsychiatric disorders through the modulation of MMPs. Vitamin D deficiency has been associated with vulnerability to SZ [27], as well as ASD [28] and attention deficit and hyperactivity disorder (ADHD) [29], the two most common neurodevelopmental disorders. As mentioned earlier, ADAMTS and MMPs are two families of endogenous zinc-dependent proteases, secreted as inactive proenzymes that cleave ECM components. Alterations in the genes that encode MMP-16 and MMP-9 have been observed in patients with SZ [30]. High levels of MMP-9 can support the proteolytic cleavage of ECM with permissive synaptic plasticity but also lead to abnormal aggrecan degradation, abnormal development and neural excitability [30]. Chronic stress and neurological trauma can enhance MMP-9 levels in the brain [31, 32], and consequently raise the risk of SZ. A plausible proposal has been made that vitamin D deficiency leads to PNN degradation in patients with SZ [27]. In fact, vitamin D deficiency is associated with increased MMP-9 production [33] and calcium activity on the neuronal membrane, leading to increased nitric oxide (NO) formation and higher MMP-9 levels, and further appears to modulate its endogenous inhibitor TIMP1 (tissue inhibitor of MMP) [34]. Aggrecan-rich PNNs undergo restructuring leading to the occurrence of more synaptic anomalies and greater network dysfunction in GABAergic, glutamatergic, and dopaminergic neurotransmission, as evidenced by some forms of SZ (Figure 3) [34]. Cognitive deficits, such as spatial learning deficits, have been observed in adult mice with vitamin D deficiencies, with reduced density of PNNs and neural networks within the hippocampus [35].
Vitamin D deficiency and PNN formation during neurodevelopment. The figure above shows a neuron enveloped by a PNN. Vitamin D deficiency may induce a deficit in ECM organisation over the course of neurodevelopment, leading to the PNN loss and network-wide dysfunction in GABAergic, glutamatergic, and dopaminergic neurotransmission. Vitamin D deficiency is also linked to altered transcription of calcium channels (L-VGCC) potentially increasing the level of calcium input into the neuron, and to altered neuronal nitric oxide synthase (nNOS) activity, resulting in an increase of nitric oxide (NO) secretion into the extracellular space and elevated levels of MMP-9. This enhanced MMP-9 expression induces increased aggrecan synthesis, resulting in disruptions to the network of several neurotransmission systems important for normal cognitive function (spatial learning deficits), and SZ, autism and ADHD. Abbreviations: L-VGCC: L-type voltage-gated calcium channel; ECM: Extracellular matrix; MMP-9: Matrix metalloproteinase-9; nNOS: Neuronal nitric oxide synthase; NO: Nitric oxide; PNN: Perineuronal net; SZ: Schizophrenia; ADHD: Attention deficit and hyperactivity disorder (modified from [
Vitamin B12 is a member of the cobalamin family and can usually be obtained in sufficient quantities from meat, eggs, and dairy products. It is critical for the production of red blood cells, and the growth and maintenance of the nervous system.
Major causes of vitamin B12 deficiency include autoimmune pernicious anaemia, gastrectomy, ileal resection, pancreatic insufficiency, and malabsorption syndromes [36]. The human body is incapable of endogenous B12 production so it must be obtained from external sources in the individual’s diet [37, 38]. Currently, a nutritional B12 deficiency is common in vegans, a fast-growing eating trend in many Western countries [39]. Vitamin B12 deficiency is also common in developing countries, with more widespread occurrence over more widespread sections of society beginning in early life and persisting throughout adulthood [40].
Pregnant women require a greater amount of vitamin B12 (2.5 g/day) compared to the general adult population (2.4 g/day), to adequately meet the nutritional needs of the foetus via absorption through the placenta [41]. The lack of sufficient vitamin B12 ingestion by the mother during pregnancy results in its deficiency in breast milk and the foetal bloodstream [42, 43]. Indeed, several studies have linked maternal deficiency in vitamin B12 concentration to developmental complications, including spontaneous abortion [44], low birth weight [45, 46], intrauterine growth restriction [45], and neural tube defects [47]. Lack of sufficient vitamin B12 in the mother’s diet is reflected in similarly low concentrations of B12 in the bloodstream of breastfed babies during the period of exclusive breastfeeding, when the baby is dependent on breast milk for vitamin absorption, despite the relatively short window of this development period [48].
As in adults, vitamin B12 is mainly stored in the newborn’s liver and is used on demand. However, as newborns have limited hepatic reserves, even if they are born at a healthy weight and size, symptoms resulting from vitamin B12 deficiency may appear from as early as 2 months of age [49]. Such symptoms imply a clinical pattern including abnormal pigmentation, hypotonia, liver and spleen enlargement, anorexia and growth failure associated with poor brain growth, which were first described by Jadhav and colleagues in 1962 [50].
Cellular deficiency of vitamin B12 results in slower proliferation and a faster differentiation of neuroblastoma cells [51], which point to its pivotal role in cell division and differentiation. In addition, deficiency of vitamin B12 in rodents is associated with selective brain damage, vascular and cognitive impairment [52], long-lasting functional disabilities in exploratory behaviour, learning and memory functions, and a mild decrease in hippocampal neurogenesis [53]. Moreover, vitamin B12 seems to play an important role in myelination as its deficiency leads to demyelination and may cause severe retardation of myelination during prenatal development [54].
Different mechanisms have been proposed to account for the effects of vitamin B12 deficiency on general neural function, most especially in relation to neurodevelopment. The most well-understood mechanisms are related to the metabolic reactions in which vitamin B12 is the exclusive cofactor for mammalian cells [55], and the importance of the coenzyme forms of vitamin B12, methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl) to the methionine and methyl groups that are used for DNA synthesis, epigenetic and cellular division.
When vitamin B12 is in MeCbl form it is a cofactor for methionine synthetase, which promotes the methylation of homocysteine (HCY) to methionine required in cases of a reduced methionine status of dietary ingestion. The synthesised form of methionine is subsequently condensed into SAM, which is finally demethylated into S-adenosylhomocysteine (SAH) and is a methyl donor for the conversion of phosphatidylethanolamine to phosphatidylcholine [56]. The altered SAM:SAH ratio may be the result of B12 deficiency as SAH and HCY levels increase while SAM levels decrease. This decreased SAM:SAH ratio may impair the methylation that is necessary for the synthesis of proteins, lipids, and neurotransmitters [57, 58] and leads to inhibition of DNA synthesis and cell division, since folate is not being recycled [59]. These results show that without methionine, the myelin and neurotransmitters considered essential for neurodevelopment cannot be produced. Methionine is synthesised from homocysteine, increased levels of which are observed in many neurodegenerative diseases, and which are functionally linked to brain injury and cognitive impairment [60].
When vitamin B12 is found in adenosylcobalamin (AdoCbl) form, it is required as the cofactor of the enzyme L-methylmalonyl-CoA mutase (EC 5.4.99.2) in the mitochondria and promotes the conversion of methylmalonyl CoA to succinyl CoA. This pathway is important for the mitochondria to reuse propionyl CoA and the energy obtained through the Krebs cycle. In other instances, this pathway may be recruited in response to increased levels of SAM in which the elimination of HCY is necessary [61]. The inappropriate conversion of methylmalonyl CoA to succinyl CoA leads to excessive production of the precursor propionyl CoA, resulting in odd-chain fatty acid synthesis and subsequent incorporation of these abnormal fatty acids into the nerve sheaths, which leads to altered myelin formation, reduced quantities of ethanolamine, phospholipids, and sphingomyelin (Figure 4) [56]. In addition, the inefficient conversion of phosphatidylethanolamine to phosphatidylcholine may impair propionyl CoA production by the mitochondria and the myelination, or lead to demyelination [62]. Myelination, together with synaptic refinement and the physiological maturation of inhibitory neural networks, are key processes of brain development that seem to coincide with the appearance of PNNs. In fact, alterations in these processes are well described in disorders such as SZ and ASD [63, 64].
Cellular processing of vitamin B in normal and deficiency conditions. Transcobalamin (TC) binds to vitamin B12 with high affinity and transports it by TC receptor-mediated endocytosis. The TC undergoes degradation into the lysosome, liberating the vitamin B12, that can be in two forms, methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl). When the vitamin B is in MeCbl form, it participates in HCY cascade as a cofactor, promoting the methylation of HCY to methionine that is subsequently condensed into SAM, which is finally demethylated into S-adenosylhomocysteine (SAH) and it a methyl donor for the conversion of phosphatidylethanolamine (PE) to phosphatidylcholine. The propionate (propionic acid) reacts with coenzyme A yielding propionyl CoA that is converted first to D-methylmalonyl-CoA and then to L-methylmalonyl-CoA and finally to Succinyl-CoA with the participation of AdoCbl form of vitamin B12 in this step. The deficiency of vitamin B12 leads to an inappropriate conversion of methylmalonyl CoA to succinyl CoA resulting in excessive production of the propionyl CoA, and consequently an increase of odd-chain fatty acid synthesis, and the inefficient conversion of PE to PC may impair propionyl CoA production by the mitochondria, resulting in an altered myelin formation.
Vitamin D is known as the “neglected neurosteroid”, a term proposed by McGrath and colleagues in 2001 [65], and exerts a great variety of effects during brain development.
In 2005, a study conducted the first description of the distribution of 1,25-dihydroxyvitamin D3 receptors (VDR) and 1α-hydroxylase (1α-OHase), the enzyme responsible for the formation of the active vitamin D, in the human brain. They are found both in neurons and glial cells and show a region- and layer-specific pattern of expression in the brain. VDR receptors are absent in the macrocellular cells within the nucleus basalis of Meynert (NBM) and Purkinje cells in the cerebellum, while both VDRs and 1α-OHase have been identified in the substantia nigra and the hypothalamus [66]. VDRs can also be found in the developing brain during the critical period of cell proliferation, in the temporal lobe, cingulate, thalamus, cerebellum, amygdala and hippocampus [67].
Similarly to vitamin B12 deficiency, vitamin D deficiency during pregnancy appears to have serious consequences for foetal health. In the literature, abortions within the first trimester of gestation have been reported in association with the mothers’ lack of sufficient vitamin D concentration [68, 69, 70]. Moreover, as foetus are dependent on access to the mother’s supply of vitamin D, in conjunction with the large distribution of vitamin D receptors in the brain, there is a high probability that the vitamin D status of pregnant mothers may affect child neurocognitive development [67]. Among other sequelae, researchers have found cognitive and neural deficits in foetus and young infants due to maternal vitamin D deficiency during pregnancy, such as suboptimal neurocognitive development [71] and delays in the development of gross and fine motor function, problem-solving and communication [72]. However, a recent study analysed high-dosage vitamin D supplementation in the third trimester of pregnancy and its effects on child brain development and failed to report any improvements in the neurobiological mechanisms underlying developmental behaviour, such as motor milestones and cognitive and language development [73]. Few studies of the direct effects of vitamin D on brain development have been conducted to date in humans and many of them are inconclusive, probably because of differences in the timing of vitamin D exposure, the types of assessment used, and the age at which the assessment occurred.
Studies in rats have identified similar critical periods to vitamin B12 during neurodevelopment in which maternal vitamin D deficiency can result in neurodevelopmental alterations, such as abnormal cell proliferation and decreased expression of neuronal structure genes in the brain of mice offspring [74]. VDRs are temporally regulated in the rat brain during development, with the first VDR expression occurring in the mesencephalon on day 12 [75]. VDR expression continues across different areas throughout the course of development [75, 76] and is directly correlated to the onset of natural cell elimination [77]. Because of its key role in regulating developmental processes throughout the brain, altered levels of vitamin D or VDR dysfunction can result in long-lasting behavioural disruption in animal models [67]. Consistent with its role in PNN formation, altered vitamin D levels and VDR signalling during development have been associated with neuropsychiatric disorders such as SZ [78] and autism [79, 80].
The mechanisms by which vitamin D influences brain development are diverse. There is evidence that vitamin D modulates neurotrophic factors such as NGF and glial cell line-derived neurotrophic factor (GDNF), suggesting that it may have a neuroprotective function [81, 82]. Other neuroprotective functions of vitamin D include the reduction of the neurotoxicity of glutamate and reactive oxygen species (ROS), the upregulation of antioxidant molecules [83, 84], and the suppression of macrophage activity, leading to decreased neuroinflammation activity [85]. When used as an immune suppressant, vitamin D has been reported to suppress the concentration of proinflammatory cytokines in the brain [86, 87], to reduce blood–brain barrier disruption and macrophage/microglia activation in induced autoimmune encephalomyelitis [88], and to attenuate proinflammatory processes and up-regulate anti-inflammatory processes such as the M2 microglia phenotype, in a mouse model of Parkinson’s disease [89].
Vitamin D is known to reduce calcium levels in the brain, preventing cell death via excitotoxicity, and to downregulate or modulate L-type voltage-gated calcium channels (L-VGCCs) [90] (Figure 5). L-VGCCs are expressed in great quantity in the developing brain and have a critical role in synaptic plasticity and in regulating basal and burst firing activity in dopaminergic neurons within the ventral tegmental area [91]. Interestingly, disruption of L-VGCC function in hippocampal PV+ interneurons during development leads to significant morphological changes, such as reduced cell number and a decrease in dendritic arbour complexity [92, 93].
Effects of vitamin D in presynaptic transmission Vitamin D plays an important role in several neurodevelopmental processes, such as neurotransmission and calcium signalling, preventing cell damage, especially mitochondrial dysfunction. As mentioned above, vitamin D acts by regulating L-VGCC in order that, for example, prevent the accumulation of intracellular calcium and the concomitant activation of pathways that can lead to cell death. With vitamin D deficiency, L-VGCC becomes functionality altered, leading to increased intracellular calcium, mitochondrial dysfunction, and the consequent generation of free radicals such as reactive oxygen species (ROS) and inhibitory/excitatory synaptic imbalance, illustrated by the increase in glutamate release and GABA neurotransmitter decrease, resulting in excitotoxicity and neuroinflammation (modified from [
The association between vitamin D and L-VGCC function in the dopaminergic system and PV+ interneurons strengthen the hypothesis that vitamin D (dys) regulation plays a role in the onset of SZ [94]. Both epidemiological research and rodent models have shown a correlation between vitamin D deficiency and SZ. Alterations in the dopaminergic system have been frequently reported in response to vitamin D deficiency, consistent with increased VDR expression in brain areas primarily innervated by dopaminergic projections [95].
Associations have also been made between vitamin D receptors, calcium channels, PV+ interneurons and PNNs. L-VGCCs regulate PV+ expression and interneuron development [92] which are significantly disrupted in SZ. Curiously, the appearance of PNNs coincides with the synaptic refinement, myelination and maturation of inhibitory networks, and there is therefore strong evidence that PNNs have a pivotal role in the pathogenesis of SZ [63].
Following this same reasoning, vitamin D deficiency is considered a potential candidate for the development of several key alterations in ASD pathophysiology, most of them present mid to early development. John Cannell has been the main proponent of this hypothesis [96] and since its inception a number of studies have contributed to this line of research. The pathophysiology of ASD is multifactorial with solid evidence for both a genetic background and an environmental component. Some epidemiological findings have raised the additional hypothesis of specific genes which are environmentally responsive to the ASD, as epidemiological observations have pointed to changes in genotype expression. Cannell and others have cited neurosteroid pathway genes as good examples of environmentally responsive genes, since alterations in neurosteroid concentration may affect the genetic expression of the neural proteins regulated by steroids.
As already mentioned before, PNNs appear during postnatal development and surround cortical inhibitory GABA neurons expressing PV+, which control the output of mainly cortical and hippocampal neurons and are necessary for fast rhythmic neuronal synchrony during information processing in cognitive tasks [97, 98]. PNNs enveloping PV+-inhibitory interneurons are known to be vital for cognition [99]. These cortical PV+-inhibitory interneurons express specific NMDA receptor (NMDAR) subunits such as NR2A, and are targets of the NMDA receptor antagonist MK-801. MK-801 is the main component for studying an important hypothesis for our understanding of the aetiology of SZ, the cortical hypofunction of NMDA receptors (i.e. the glutamatergic hypothesis) [100]. This hypothesis is compatible with the concurrent descriptions provided by the neurodevelopmental hypothesis, with respect to the disruptions to the central nervous system over the course of development [101].
An animal model using MK-801 treatment revealed a critical postnatal period, specifically from 7 to 14 days after birth (P 7–14), resulting in SZ-like behaviour during adulthood, with a significant reduction in PV+-expressing cells in the PFC but not in the hippocampus, for mice treated with MK-801 from P 7–14 compared to matched controls [102]. In addition, mice in the treated group showed changes in performance on cognitive, social and behavioural tasks, while electrophysiological recordings from brain slices within the PFC showed significantly reduced frequency of up-states in MK-801-treated mice, but increased gamma activity in MK-801-treated mice compared to saline-treated mice [102]. Recent memory reactivation has been shown to occur in the presence of slow oscillatory up-states, contributing to memory consolidation [103]. This electrophysiological profile is altered in humans with SZ, with increased delta oscillations and irregular gamma rhythm [104, 105]. Moreover, PNN removal from visual cortex during a critical postnatal period alters the balance between excitatory and inhibitory PV+ spiking activity, inducing greater potentiation of gamma activity and restoring the neural network to an immature or juvenile ECM state, suggesting that the maturation of GABAergic fast spiking and PV+-inhibitory neurons suppresses the spontaneous activity of excitatory neurons [106].
Together with these electrophysiological findings, the metabolic requirements of PNN function have also been explored in fast-spiking cells, as well as their intrinsic vulnerability. In fact, PNNs appear to promote interneuron maturation and network stability and may also protect neurons against iron sequestration and oxidative stress [107, 108]. Oxidative stress has been observed in the PFC of SZ patients in conjunction with decreased levels of glutathione (GSH), an endogenous antioxidant and redox regulator [109]. This outcome can in turn be aggravated by the overexpression of truncated DISC1 that is associated with SZ in humans, causing mitochondrial dysfunction with decreased mitochondrial NADH dehydrogenase activity, diminished cellular ATP contents, and overactivity of mitochondrial Ca2+ mechanisms [110].
As mentioned previously with regards to the role of GSH, there are two metabolically active forms of vitamin B12, AdoCbl, and MeCbl: essential as a cofactor for the reaction necessary folate-dependent methylation of HCY by methionine synthase (MS) in the cytoplasm. As MS levels determine the ratio of methyl donor SAM to the endogenous methylation inhibitor SAH, the MeCbl reaction can influence SAM-dependent methylation reactions mainly through methylation of DNA and histones [111], an effect previously described with in relation to BDNF and epigenetic control. Zhang et al. 2016 analysed the postmortem human frontal cortex of autistic and schizophrenic individuals and 80-year-old individuals and found that the MeCbl form of vitamin B12 decreases with age, as well as to age of onset of ASD and SZ, as compared to age-matched controls. Additionally, they also observed an abnormally lower total cobalamin Cbl and MeCbl concentration in ASD and SZ subjects, leading the authors to propose a “Redox/Methylation Hypothesis of Autism” in light of the impaired GSH-dependent synthesis observed in the brains of autistic individuals [111]. In the same study, the authors further found that certain brain regions, as cerebellum and temporal cortex, in ASD, showed synthesis of reduced and oxidised glutathione (GSH/GSSG) (stable redox status), while other regions maintained SAM/SAH production (stable methylation status) [111], suggesting regional differences for metabolic disorders.
Concomitantly, several neurobiological changes found in ASD subjects or ASD animal models are consistent with an account of vitamin D deficiency. The main neurobiological processes mediated by vitamin D in neurodevelopment include neural cell proliferation [74], GABA, glutamate and serotonin neurotransmission [92], calcium signalling, mitochondrial regulation, oxidative stress and neuroinflammation (for review see [112]). Most of these processes are altered in ASD, resulting in the reduction of brain volume and changes in the number of glial and neuron cells, excitatory/inhibitory imbalance, disrupted calcium signalling, increased oxidative stress, the overactivation of microglia, and immune system dysregulation [113].
One of the best-studied hypotheses about the pathophysiology of ASD is the occurrence of changes in brain connectivity during development, which posits a reduced number of connections between distal brain regions and an increase in connections between proximal brain regions [114]. However, this hypothesis shows some inconsistencies in the light of several findings, such as reports of hyperconnectivity over long axonal fibres in autism or even mixed patterns of hypo- and hyper-connectivity [115, 116, 117, 118].
Another hypothesis regarding the pathophysiology of ASD is one of excitatory-inhibitory imbalance, caused both by the probable hyperactivity of excitatory cells and a reduction in the number, activity or even delay of inhibitory interneurons in the maturation process [119, 120, 121].
PV+-expressing interneurons are the main regulators of inhibitory/excitatory balance and orchestrate the coordinative function of brain microcircuitry via their fast-spiking inhibitory inputs onto pyramidal neurons [97, 122]. As such, the healthy maturation of PV+-interneurons is crucial for the establishment of optimal neural and behavioural development. Disruption to PV+ expression in PFC caused by early-life adversity leads to altered social interactions [123] and anxiety-related behaviour in rodents [124, 125]. Both forms of altered behaviour can be found in patients diagnosed with ASD [126, 127, 128].
As mentioned previously, the maturation of PV+ interneurons are mostly regulated by PNNs [129, 130]. Despite the protective actions of the PNN-PV+, the interneurons are very susceptible to oxidative stress [131, 132], and as such vitamin D deficiency represents a threat to the integrity of PNN function and consequently to the development of the GABAergic system.
Lastly, it is important to highlight the dysregulation of the immune system that is observed in ASD. ASD patients suffer from chronic systemic inflammation with a disbalance in cytokine expression, leading to increased production of proinflammatory cytokines. Vitamin D has been shown to contain immunomodulatory properties and may be an alternative treatment for slowing or minimising behavioural alterations in ASD (for review see [133]). Chronic systemic inflammation in early life may disrupt PV+ interneuron maturation and consequently lead to changes in PNNs. Taken together, these findings reveal the important role of vitamin D in maintaining the integrity of PNNs and the efficiency of synaptic transmission as a whole.
The ECM is one component of the tetrapartite synapse, together with the network of glial cells. The PNN is a dense ECM structure that enwraps inhibitory fast-spiking parvalbumin (PV+) interneurons, serving both as a protective barrier and to regulate synaptic plasticity. The destruction of those PNNs during the critical postnatal period of brain development alters the balance between excitatory and inhibitory PV+ spiking activity, inducing a greater potentiation of gamma-band activity, and reverting the firing pattern of the neural network to a so-called immature or juvenile ECM state. Studies have shown that a vitamin D deficiency in early development may lead to a reduction in the PNN integrity and synaptic plasticity through modulation of MMPs, contributing to increased risk of the onset of neuropsychiatric disorders, as SZ, ASD, and ADHD. Also, in preclinical studies, dose-dependent vitamin B12 supplements were sufficient to maintain the levels of DHA and BDNF in the hippocampus and cortex in neonates, and BDNF levels in the hippocampus at 3 months of age, considered a sensitive window or critical period during neurodevelopment. In addition, the ingestion and metabolism of vitamin B12 methylcobalamin (MeCbl) variants can influence S- adenosyl methionine and SAM-dependent methylation reactions, mainly through the methylation of DNA and histones, and the MeCbl deficiency can result in impairment of GSH-dependent synthesis, inducing oxidative stress in the PFC of schizophrenic patients, or with autism diagnosis. Thus, adequate levels of vitamin B12 and D appear to contribute to maintaining the integrity of PNNs, consequently lead to PV+ interneuron maturation.
The authors wish to thank IntechOpen for their support and payment of the Open Access Publishing Fee.
The authors declare no conflict of interest.
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\n\nAfter approval, you will proceed in submitting your full-length manuscript. 50-130 pages for compacts, 130-500 for Monographs & Edited Books.Your full-length manuscript must follow IntechOpen's Author Guidelines and comply with our publishing rules. Once the manuscript is submitted, but before it is forwarded for peer review, it will be screened for plagiarism.
\n\n3. PEER REVIEW RESULTS
\n\nExternal reviewers will evaluate your manuscript and provide you with their feedback. You may be asked to revise your draft, or parts of your draft, provide additional information and make any other necessary changes according to their comments and suggestions.
\n\n4. ACCEPTANCE AND PRICE QUOTE
\n\nIf the manuscript is formally accepted after peer review you will receive a formal Notice of Acceptance, and a price quote.
\n\nThe Open Access Publishing Fee of your IntechOpen Compacts, Monograph or Edited Book depends on the volume of the publication and includes: project management, editorial and peer review services, technical editing, language copyediting, cover design and book layout, book promotion and ISBN assignment.
\n\nWe will send you your price quote and after it has been accepted (by both the author and the publisher), both parties will sign a Statement of Work binding them to adhere to the agreed upon terms.
\n\nAt this step you will also be asked to accept the Copyright Agreement.
\n\n5. LANGUAGE COPYEDITING, TECHNICAL EDITING AND TYPESET PROOF
\n\nYour manuscript will be sent to Straive, a leader in content solution services, for language copyediting. You will then receive a typeset proof formatted in XML and available online in HTML and PDF to proofread and check for completeness. The first typeset proof of your manuscript is usually available 10 days after its original submission.
\n\nAfter we receive your proof corrections and a final typeset of the manuscript is approved, your manuscript is sent to our in house DTP department for technical formatting and online publication preparation.
\n\nAdditionally, you will be asked to provide a profile picture (face or chest-up portrait photograph) and a short summary of the book which is required for the book cover design.
\n\n6. INVOICE PAYMENT
\n\nThe invoice is generally paid by the author, the author’s institution or funder. The payment can be made by credit card from your Author Panel (one will be assigned to you at the beginning of the project), or via bank transfer as indicated on the invoice. We currently accept the following payment options:
\n\nIntechOpen will help you complete your payment safely and securely, keeping your personal, professional and financial information safe.
\n\n7. ONLINE PUBLICATION, PRINT AND DELIVERY OF THE BOOK
\n\nIntechOpen authors can choose whether to publish their book online only or opt for online and print editions. IntechOpen Compacts, Monographs and Edited Books will be published on www.intechopen.com. If ordered, print copies are delivered by DHL within 12 to 15 working days.
\n\nIf you feel that IntechOpen Compacts, Monographs or Edited Books are the right publishing format for your work, please fill out the publishing proposal form. For any specific queries related to the publishing process, or IntechOpen Compacts, Monographs & Edited Books in general, please contact us at book.department@intechopen.com
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Therefore, it is important to study the transcription and translation of genes involved in carbon metabolism in antibiotic-producing Streptomyces growing on various sugars.",book:{id:"10893",title:"Actinobacteria",coverURL:"https://cdn.intechopen.com/books/images_new/10893.jpg"},signatures:"Toshiko Takahashi, Jonathan Alanís, Polonia Hernández and María Elena Flores"},{id:"82757",title:"Seed Dormancy: Induction, Maintenance and Seed Technology Approaches to Break Dormancy",slug:"seed-dormancy-induction-maintenance-and-seed-technology-approaches-to-break-dormancy",totalDownloads:7,totalDimensionsCites:0,doi:"10.5772/intechopen.106153",abstract:"Dormancy is the major cause of erratic germination, patchy emergence and uneven seedling establishment in the field. These traits are exceedingly undesirable in crop production as future phases of growth and development are strongly linked to uniform seedling development at early growth phases. Variations in maturation time, and difficulty in managing abiotic and biotic stresses during pre- and postharvest are common consequences of uneven germination and seedling emergence. Minimizing this negative impact of dormancy in a seed lot is the major concern of all seed production companies. Generally, mature seeds show some considerable dormancy during which embryo growth is halted momentarily because one or more internal and external stimuli for growth resumption is/are absent. If the inhibition of seed germination is solely due to insufficient or complete absence of external signals, then the seed is in a state of quiescence. Otherwise, if linked to internal factors, then the seed is in a state of dormancy. Induction, maintenance, and release of dormancy are therefore related to Seed-dependent factors such as morphology, hormones, state of embryo maturity at seed dispersal and chemical inhibitors. This chapter focuses on species-dependent methods currently used to break dormancy, reduce germination time and improve emergence and seedling establishment.",book:{id:"11322",title:"Seed Biology Updates",coverURL:"https://cdn.intechopen.com/books/images_new/11322.jpg"},signatures:"Tabi Kingsley Mbi, Ntsomboh Godswill Ntsefong and Tatah Eugene Lenzemo"},{id:"79168",title:"Pulses: A Potential Source of Valuable Protein for Human Diet",slug:"pulses-a-potential-source-of-valuable-protein-for-human-diet",totalDownloads:4,totalDimensionsCites:0,doi:"10.5772/intechopen.99980",abstract:"Nutritional profile of pulses has significant importance in human diet with respect to protein and mineral quality and bioavailability. Protein energy malnutrition is widespread throughout the world especially among the developing countries. Pulses being rich in macronutrients such as protein from 20 to 26% and low in calories are most suitable for product development for target-oriented population. During last decade, the demand for pulse-based products with high protein and fiber, low glycemic index, and gluten free with more antioxidant showed increasing trend by the consumers. Drift of end-use application of pulses generated interest for research in all disciplines such as breeding, agronomy, food, and nutrition, etc. A great share of plant protein in human diet may be a critical step for reducing dependence on animal origin protein source. This chapter will review contribution or choice of plant-based protein from legumes or pulses with good-quality protein based on amino acid composition. Additionally, this overview can give insight into the development of new product with balanced nutritional quality and high protein contents as a potential protein supply for malnourished population.",book:{id:"12236",title:"Legumes Research- Volume 2",coverURL:"https://cdn.intechopen.com/books/images_new/12236.jpg"},signatures:"Saima Parveen, Amina Jamil, Imran Pasha and Farah Ahmad"},{id:"83043",title:"Applications of CRISPR/Cas9 for Selective Sequencing and Clinical Diagnostics",slug:"applications-of-crispr-cas9-for-selective-sequencing-and-clinical-diagnostics",totalDownloads:3,totalDimensionsCites:0,doi:"10.5772/intechopen.106548",abstract:"In this chapter, we will discuss the applications of CRISPR/Cas9 in the context of clinical diagnostics. We will provide an overview of existing methods and their use cases in the diagnostic field. Special attention will be given to selective sequencing approaches using third-generation sequencing and PAM-site requirements. As target sequences in an AT-rich environment cannot easily be accessed by the commercially available SpCas9 due to rarity of NGG PAM-sites, new enzymes such as ScCas9 with PAM-site requirements of NNG will be highlighted. Original research on CRISPR/Cas9 systems to determine molecular glioma markers by enriching regions of interest will be discussed in the context of potential future applications in clinical diagnostics.",book:{id:"11804",title:"CRISPR Technology",coverURL:"https://cdn.intechopen.com/books/images_new/11804.jpg"},signatures:"Maximilian Evers, Björn Brändl, Franz-Josef Müller, Sönke Friedrichsen and Stephan Kolkenbrock"},{id:"83012",title:"Cotton Based Cellulose Nanocomposites: Synthesis and Application",slug:"cotton-based-cellulose-nanocomposites-synthesis-and-application",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.106473",abstract:"Nanocellulose is a renewable natural biomaterial which has risen to prominence due to its biodegradability and physiochemical properties making it a promising candidate to replace non-biodegradable synthetic fibers. Due to its profound qualities, nanocellulose extracted from cotton fibers have tremendous application potential and have been intensively studied particularly in the generation of nanofillers and as reinforcement components in polymer matrixes. Deposition of inorganic nanoparticles on cotton fabric result in antimicrobial textiles with multifunctional use particularly in manufacture of PPE and as filtration devices against environmental pollutants and pathogens. This chapter compiles three main sections. The first section gives an overview of the extent of work done in the creation and application potential of cotton-based nanocomposites. The second section describes the in situ and ex situ methods of nanoparticle deposition and self assembly on cotton fabrics to generate multifunctional cotton-based nanocomposites with antimicrobial potential while the final section describes the incorporation of cotton nanofibers in polymer matrices, their reinforcing properties, as well as surface modification to assist their incorporation. 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