\r\n\tb. The growth of digital environments which can educate and empower as well as exploit and destroy (mobile learning, STEM education, tablets, etc.).
\r\n\tc. Social, racial, class, and gender-based discriminations that restrict the developmental potential and the prosperity perspectives
\r\n\td. Health hazards and illnesses such as the laters COVID-19 pandemic.
\r\n\te. Armed conflicts with casualties and displacements of populations seeking refuge
\r\n\tf. Lack of physical spaces that will support and nourish development and learning, etc.
\r\n\tEducation in the post-modern era strives to address the above issues and develop policies, curricula, methodologies, and strategies to contribute to an environmentally and socially sustainable future. It embraces multiple perspectives and worldviews and seeks to touch on inequalities and discriminations in favor of equity. In this direction, children’s s agency lies at the heart of democratic approaches. Educational processes adopt forms of interactions that actualize learning as “becoming” and place it in a continuum between past, present, and future. This book intends to feature innovative approaches that employ transformative elements (targets, methods, materials, ideas, etc.) and embrace the concept of child development as “becoming” in an ever-changing and challenging world.
\r\n\r\n\tWe invite authors to contribute original research or research review papers that present innovative approaches addressing personal and social transformation. All aspects of early childhood education will be considered, including research methodology for the early years.
",isbn:"978-1-80355-949-0",printIsbn:"978-1-80355-948-3",pdfIsbn:"978-1-80355-950-6",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"351c41dca5c8c997f15e758f2e035178",bookSignature:"Dr. Maria Ampartzaki and Associate Prof. Michail Kalogiannakis",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11281.jpg",keywords:"Early Childhood Education, Preschool, STEAM, Environmental Sustainability, Social Sciences, Social Sustainability, ICT, Digital Devices, Education for Equity, Gender Issues, Post-modern Epistemology, Social Constructivism",numberOfDownloads:65,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 16th 2021",dateEndSecondStepPublish:"December 14th 2021",dateEndThirdStepPublish:"February 12th 2022",dateEndFourthStepPublish:"May 3rd 2022",dateEndFifthStepPublish:"July 2nd 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"8 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:"Dr. Maria Ampartzaki is an Assistant Professor in Early Childhood Education in the Department of Preschool Education at the University of Crete. Her research interests include ICT in education, science education in the early years, inquiry-based and art-based learning, teachers’ professional development, action research, and the Pedagogy of Multiliteracies, among others. She has run and participated in several funded and non-funded projects on the teaching of Science, Social Sciences, and ICT in education.",coeditorOneBiosketch:"Michail Kalogiannakis is an Associate Professor of the Department of Preschool\r\nEducation, University of Crete in Greece. He graduated from the Physics Department\r\nof the University of Crete and continued his post-graduate studies at the University\r\nParis-7 and University Paris-5 and received his Ph.D. degree at the University Paris 5.\r\nHis research interests include science education in early childhood, science teaching\r\nand learning, e-learning, the use of ICT in science education, and games simulations.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"422488",title:"Dr.",name:"Maria",middleName:null,surname:"Ampartzaki",slug:"maria-ampartzaki",fullName:"Maria Ampartzaki",profilePictureURL:"https://mts.intechopen.com/storage/users/422488/images/system/422488.jpg",biography:"Dr Maria Ampartzaki is an Assistant Professor in Early Childhood Education in the Department of Preschool Education at the University of Crete. Her research interests include ICT in education, science education in the early years, inquiry-based and art-based learning, teachers’ professional development, action research, and the Pedagogy of Multiliteracies, among others. She has run and participated in several funded and non-funded projects on the teaching of Science, Social Sciences, and ICT in education. She also has the experience of participating in five Erasmus+ projects.",institutionString:"University of Crete",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Crete",institutionURL:null,country:{name:"Greece"}}}],coeditorOne:{id:"260066",title:"Associate Prof.",name:"Michail",middleName:null,surname:"Kalogiannakis",slug:"michail-kalogiannakis",fullName:"Michail Kalogiannakis",profilePictureURL:"https://mts.intechopen.com/storage/users/260066/images/system/260066.jpg",biography:"Michail Kalogiannakis is an Associate Professor of the Department of Preschool Education, University of Crete, and an Associate Tutor at School of Humanities at the Hellenic Open University. He graduated from the Physics Department of the University of Crete and continued his post-graduate studies at the University Paris 7-Denis Diderot (D.E.A. in Didactic of Physics), University Paris 5-René Descartes-Sorbonne (D.E.A. in Science Education) and received his Ph.D. degree at the University Paris 5-René Descartes-Sorbonne (PhD in Science Education). His research interests include science education in early childhood, science teaching and learning, e-learning, the use of ICT in science education, games simulations, and mobile learning. 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As a result, sensitive and specific indicators of infection that can be collected easily and that accurately reflect infection severity and prognosis are highly coveted and are clinically important. Currently, common clinical indicators of infection include pyrexia, white blood cell (WBC) counts, C-reactive protein (CRP), and procalcitonin (PCT). However, in clinical settings, the limitation of CRP and PCT for assessing the severity and predicting prognosis may affect the clinician’s ability to effectively evaluate the change in septic patients’ general condition that would indicate deterioration and even impending death. Therefore, looking for new biomarkers with high sensitivity and specificity is one of the main research fields in sepsis. The objective of this paper is to review new biomarkers that are ….
Triggering receptor expressed on myeloid cells-1 (TREM-1) is a recently discovered member of the immunoglobulin superfamily of receptors that is expressed on polymorphonuclear granulocytes and mature monocytes. Bacterial or fungal infections may induce its expression.
sTREM-1 is a soluble form of TREM-1 that may be released into body fluids upon the upregulated expression of TREM-1(Bouchon A,et al. 2001). An increasing number of studies indicate that there are increased levels of sTREM-1 in body fluid samples for the following diseases and conditions: sepsis, pneumonia, pleural effusion, septic arthritis, meningitis, peritonitis, and uterine cavity infection (Gibot S, et al. 2004) (Gibot S, et al. 2004) (Liu CL, et al. 2007) (Collins CE,et al. 2009) (Determann RM, et al. 2006) (Kusanovic JP, et al.2010) (Determann RM, et al. 2009). This suggests that sTREM-1 may be a valuable diagnostic indicator for making distinctions between infectious and non-infectious diseases. It has also been found that septic shock patients have high levels of serum sTREM-1 that are closely related to the severity of infection, and sTREM-1 has a good positive correlation with the Sequential Organ Failure Assessment (SOFA) score (Gibot S, et al. 2004) (Dimopoulou I, et al. 2009). With regard to sepsis prognosis, dynamic changes in serum sTREM-1 may provide warnings concerning the life or death of patients (Zhang J, et al. 2011) (Gibot S, et al. 2005).
Urine sTREM-1 is more sensitive than WBC counts, serum CRP, and serum PCT for the early diagnosis of sepsis, as well as for dynamic assessments of severity and prognosis. It can also provide an early warning of possible secondary acute kidney injury (AKI) in sepsis patients (Su LX, et al. 2011).
In terms of diagnostic value for ventilator-associated pneumonia (VAP), the combination of sTREM-1 plus Clinical Pulmonary Infection Score (CPIS) improved the ability to diagnose VAP. Moreover, logistic regression analysis showed that sTREM-1 is an independent risk factor for VAP (Su LX, et al. for publication). We also found that sTREM-1 is of no use in determining bacteremia-caused, new fever in ICU patients, but sTREM-1 levels correlate with the prognosis of patients with bacteremia (Su LX, et al. for publication).
More and more studies have confirmed that sepsis is caused by factors both environmental and genetic and that from the pathological point of view, genetic factors outweigh environmental factors. Therefore, clarification of how genetic factors are associated with sepsis may increase the awareness of susceptibility and prognosis concerning the disease. A study investigating an association between TREM-1 gene polymorphisms and severe sepsis concluded that 3 studied common polymorphisms within the TREM-1 gene (rs7768162, rs9471535, and rs2234237) may not play a major role in the predisposition to severe sepsis in a Chinese Han cohort (Chen Q, et al. 2008). However, Jung et al (Jung ES,et al. 2011) proved that TREM-1 SNPs (rs7768162, rs9471535, and rs2234237) may play a significant role in the development of intestinal Behcet\'s disease and may have modest effects on disease severity. Recently, in our study, we found that 2 variations (rs2234246 and rs2234237) within the TREM-1 gene are not correlated with susceptibility to sepsis. However, the TREM-1 rs2234237 polymorphism is associated with high 28-day mortality among sepsis patients, constituting a risk factor affecting prognosis (Su LX, et al. for publication). Therefore, TREM-1 could be a fairly ideal genetic biomarker for the diagnosis and prognosis of sepsis.
CD163 is a transmembrane molecule, hitherto only discovered on the membrane of mononuclear phagocytes. As a specific scavenger receptor for hemoglobin/heme inside the body, it is capable of specific recognition of the hemoglobin-haptoglobin complex. Studies in recent years have found that CD163 regulates the expression of anti-inflammatory molecules, such as Interleukin-10 (IL-10) and Hemeoxigenase-1 (HO-1) (Moestrup SK, et al.2004) (Graversen JH, et al.2002).
Soluble CD163 (sCD163) comes from CD163 molecules that peel off the membrane of mononuclear cells (Moestrup SK, et al.2004) (Hogger P, et al. 2001). Blood levels of sCD163 have prognostic value for several inflammatory diseases and may have use in clinical applications as a biomarker of inflammatory diseases. Our prospective, clinical study confirmed that the serum sCD163 level might have potential value for the diagnosis of sepsis and severe sepsis, and its performance was superior to PCT and CRP levels. sCD163 also would have advantages for the dynamic monitoring of sepsis development and prognosis and have favorable prospects for use in clinical applications (Feng L, et al. for publication).
We compared sTREM-1, sCD163 and other clinical parameters for their assessment value for sepsis (Su LX, et al, for publication). On the day of ICU admission, the sepsis group displayed higher levels of serum sTREM-1, sCD163, PCT, and CRP than the Systemic Inflammatory Response Syndrome (SIRS) group (
Some studies in patients with bacteremia report high serum sCD163 expression, which has prognostic value (Gaini S, et al. 2008) (Moller HJ, et al. 2006), and high serum sCD163 expression also occurs in people with chronic kidney diseases (Axelsson J, et al. 2006). The CD163-hemoglobin scavenger receptor plays an important role in the process of the clearance and conversion of hemoglobin/heme in chronic kidney disease (Simoni J, et al. 2006). At present, it is unknown whether sCD163 can be detected in urine and what value it may possess for sepsis and secondary AKI. Recently, our team evaluated for the first time the potential value of urine sCD163 for sepsis and secondary AKI diagnosis, as well as for early assessment of prognosis. Our results demonstrated in an indirect manner the causes behind urine phagocyte increase and revealed a possible mechanism therein (Su LX, et al. for publication). Perhaps this new discovery of a noninvasive detection index may have potential clinical value for sepsis-related multiple organ dysfunction.
MicroRNAs (miRNAs) are a type of endogenous non-coding small RNAs that are about 22 nucleotides in length (Lagos-Quintana et al. 2001) (Ambros 2004). They play important biological roles by inhibiting the expressions of messenger RNAs (mRNAs) (Krutzfeldt et al. 2006). As with mRNAs, some miRNAs are differentially expressed among tissues or developmental stages. Unlike some widely expressed miRNAs, these tissue- or developmental stage-specific miRNAs likely play key roles in regulating specific processes involved in the development or function of individual tissues (Etheridge et al. 2011). The liver-specific miR-122 has been applied in lipid and cholesterol metabolism, which are both known to be important functions of the liver (Bolmeson et al. 2011; Fernandez-Hernando et al. 2011). Because of their unique expression profiles, these miRNAs hold promise as diagnostic markers or therapeutic targets for many diseases. For example, miR-122 is required in hepatitis C virus (HCV) replication (Cermelli et al. 2011) and reagents that can modulate the level of miR-122 have moved into clinical development for HCV treatment (Pan et al. 2007; Said 2010; Zhang et al. 2010). miRNAs play an essential role in many physical and biological processes; thus, altered miRNA expression levels are associated with the occurrence and progression of disease.
A significant number of miRNAs have been observed outside of cells, within various body fluids. These cell-free miRNAs in body fluids are stable under harsh conditions including boiling, low or high pH and multiple freeze-thaw cycles (Chen et al. 2008; Mitchell et al. 2008). At present, there are 2 possible hypotheses for the stability and origin of circulating miRNAs. One hypothesis is that passive release occurs during tissue injury. For example, miRNA-216a was differentially expressed in the plasma of a pancreatic injury model in rat (Kong et al. 2010). miR-122 was also a biomarker for drug-induced liver injury (Wang et al. 2009). Alternatively, miRNAs are contained in small particles and are, therefore, protected against RNase activity. Recently, it has been shown that a transfer of mRNA and miRNA between cells can be accomplished through microvesicles (Valadi et al. 2007). These are small particles, which are derived from the cell plasma membrane into the extracellular space and released into the circulation (Caby et al. 2005; van Niel et al. 2006). Microvesicles are derived from various cell types, e.g. reticulocytes, dendritic cells, B and T cells and mast cells (Escola et al. 1998; Valenti et al. 2006; Brase et al. 2010). And in the peripheral blood, two-thirds of microvesicles are derived from platelets. Platelet-derived microvesicles play a role in angiogenesis and the metastatic spread of cancers (Janowska-Wieczorek et al. 2005). Platelet-derived microvesicles induce an immune response upon regulating gene expression in hematopoietic, endothelial, and monocytic cells (Setzer et al. 2006; Majka et al. 2007). Notably, platelet-derived microvesicle subpopulations are increased in patients with sepsis (Janiszewski et al. 2004). However it is currently unknown whether microvesicle content changes in these diseases (Hunter et al. 2008).
Circulating miRNAs have been recently identified as biomarkers for sepsis. miR-150 was firstly identified as a prognostic marker for sepsis, and levels of miR-150, as detected by microarrays, were significantly different between the leukocytes of healthy controls and sepsis patients. In sepsis patients’ plasma, levels of miR-150 were correlated with the level of SOFA score, and the plasma level ratio for miR-150/interleukin-18 can be used to evaluate sepsis severity (Vasilescu et al. 2009). A recent study demonstrated that miR-150 differentially controls the development of natural killer (NK) and invariant NKT cell (iNKT) lineages by targeting the transcription factor c-Myb (Bezman et al. 2011). Few other functional studies about miR-150 in sepsis have been published. However, it has been demonstrated that the coding genes of tumor necrosis factor alpha (TNF-a), interleukin-10 (IL-10), and interleukin-18 (IL-18) have sequence complementarity to miR-150 (Vasilescu, Rossi et al. 2009). This finding suggests that miR-150 might be correlated with some of the immune system dysfunctions in sepsis patients, and it provides a new potential pathogenetic mechanism of sepsis. Hence, additional functional studies of miR-150 are required.
Sepsis is a complex disease that involves various tissues and organs. A simple screen for miRNAs differentially expressed in leukocytes may have missed many miRNAs secreted by other cell types. Hence, a genome-wide method was used to screen for differentially expressed miRNAs between the surviving and non-surviving groups of sepsis patients. Then, two novel prognostic biomarkers, miR-297 and miR-574-5p, were identified by microarray screening and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) confirmation (Wang et al. 2012). miR-297 was more closely correlated with survival from sepsis, whereas miR-574-5p was correlated with death from sepsis. After analysis in a multivariable logistic regression model, results showed that a combination of sepsis stage, SOFA scores, and miR-574-5p were correlated with the death of sepsis patients. The predictive capability of these 3 combined variables was analyzed by a ROC curve; the area under the curve was 0.932 (95% CI, 0.887-0.977). When the cutoff point was set at 0.288, these 3 combined variables provided 78.13% sensitivity and 91.84% specificity.
In summary, a genome-wide scan of sepsis patients’ sera demonstrated that 2 miRNAs, miR-297 and miR-574-5p, might be related to the prognosis of sepsis in a genetic way. Identification of these miRNAs could provide more therapeutic targets for sepsis.
As diagnostic biomarkers for sepsis, levels of these markers should be not only differentially expressed between sepsis patients and healthy controls, but also between sepsis patients and SIRS patients. Levels of miR-146a and miR-223 in sepsis patients’ sera were significantly decreased compared to SIRS patients and healthy controls. These levels were evaluated by qRT-PCR in 50 sepsis patients and 30 SIRS patients. The areas under the ROC curve for miR-146a and miR-223 were 0.858 and 0.804, respectively, which were both higher than IL-6 with an AUC of 0.785 (Wang et al. 2010). miR-146a regulates a pathway that promotes the binding of transcription repressor RelB to the TNF-α promoter, which generates facultative heterochromatin to silence acute proinflammatory genes (El Gazzar et al. 2011). This mechanism was proved in the THP-1 sepsis cell model of bacterial LPS/endotoxin tolerance. During LPS tolerance, transcriptional- and translation-repressive events combine to tightly regulate proinflammatory genes, which was a common feature of severe systemic inflammation (El Gazzar and McCall 2010). Hence, miR-146a was an important regulator during sepsis. Although the source and the release mechanism of miR-146a remain unknown, its clinical value is undeniable.
miR-15a and miR-16 are also newly identified diagnostic markers for sepsis. Levels of these 2 miRNAs in sepsis and SIRS patients were both significantly higher than in normal controls. And miR-15a can be used to distinguish sepsis patients from SIRS patients. The area under the ROC curve for miR-15a was 0.858, which was much higher than the curves for CRP and PCT. These results were obtained from 166 sepsis patients and 32 SIRS patients (Wang et al, 2012). miR-15a and miR-16 were initially identified as tumor suppressors, and the dysregulation of these two miRNAs has been found to occur in many types of cancer (Calin et al. 2002; Bottoni et al. 2005; Bhattacharya et al. 2009; Yang et al. 2010; Bandi and Vassella 2011). Recently, decreases in miR-15a, miR-16 and miR-223 were found to be associated with the innate immune system by targeting IκB kinase alpha (IKKα) mRNA, which is involved in the non-canonical NF-κB signaling pathway (Li et al. 2010). IκB kinase (IKK) is an enzyme complex that is part of the upstream NF-κB pathway. IκBα (inhibitor of kappa B) protein can inactivate NF-κB, and IKK can phosphorylate the inhibitory IκBα protein. Besides that, there is still no direct evidence for the correlations between miR-15a and miR-16 and sepsis. Hence, more functional studies of miR-15a and miR-16 need to be done.
For sepsis patients, timely diagnosis and early treatment are very important factors to improve their prognosis. miRNAs are newly identified as the main regulators of the immune system, and altered expression profiles in circulation can be used as diagnostic and prognostic biomarkers for sepsis. Although the functions of these miRNAs are not completely understood, their clinical value has been confirmed. New biomarkers also mean novel treatment targets. Hence, target genes of these miRNAs may emerge as potential treatment targets for sepsis patients.
A single nucleotide polymorphism (SNP) is the most common type of stable genetic variation in the population. Thus, SNPs explain different sequence alternatives (alleles) existing at single base pair positions in genomic DNA in normal individuals in some populations. They are distinguished from rare variations by a requirement for the least abundant allele to have a frequency of 1% or more.(Brookes 1999)
A SNP occurs in approximately 1 of 1000 base pairs, with the most frequent being a C to T substitution. Polymorphisms, which occur both in the coding and non-coding genome regions, involve replacement of a nucleotide with another one, or insertion or deletion of 1 or more nucleotides. Because of a higher degree of preservation of exons to assure the functionality of genes, the frequency of polymorphisms in the non-coding regions is much higher compared with the coding ones. But changes in non-coding regions interfere with the structure and process of transcription and gene expression; thus, polymorphisms and mutations in non-coding regions may also produce a marked effect on phenotype presentations.(Prucha et al. 2008)
SNPs are divided into two main categories, linked SNPs and causative SNPs. Linked SNPs (also called indicative SNPs) are located outside genes and do not affect protein function. Nevertheless, they are associated with a particular drug response or with the risk for getting a certain disease.
Causative SNPs affect the function of protein, correlating with a disease or influencing a person\'s response to medication. There are 2 forms of causative SNPs, coding SNPs (cSNPs) and non-coding SNPs. Coding SNPs, located in the coding region of a gene, can change the amino acid sequence of a gene\'s protein product; this type of SNP attracts more research than non-coding SNPs. Non-synonymous cSNPs (nsSNPs), which change the amino acid sequence of proteins and are likely to affect the structure and function of the proteins, are good candidates for disease-modifying alleles.(Jegga et al. 2007) And non-coding SNPs, located in the gene\'s regulatory sequences, also can change the level of gene expression. Because only about 3% to 5% of a person\'s DNA sequence codes for the production of proteins, most SNPs are found outside of coding sequences.
Single nucleotide substitutions may influence complex diseases by a variety of mechanisms. First, the amino acid sequence of some proteins whose functions include DNA binding, catalytic activity and receptor–ligand contact may be reduced or abolished by SNPs. Second, SNPs can interfere with the initiation or the termination codon or introduce errors in the reading frameshift. Third, mutations in known promoter motifs that alter DNA binding of transcription factors have the potential for decreasing or increasing gene expression. Finally, RNA cleavage-polyadenylation mutants in the untranslated region of the 5\' UTR are thought to play a role in controlling mRNA translation while sequence variants in the 3\' UTR control RNA cleavage, stability, export and intracellular localization.(Wjst 2004) It is reported that only 10% of all gene-based SNPs have sequence-predicted functional relevance making them a primary target for genotyping in association studies. (Wjst 2004) There has been an effort to explain the potential causal relationship between the genetic changes and the development and course of diseases in order to modulate a patient’s response to administration of drugs.(Sachidanandam et al. 2001)
Genome-wide association (GWA) studies have been used to compare patient populations. The International HapMap Project and the arrival of technologies that type more than 100,000 SNPs in a single experiment have made genome-wide single nucleotide polymorphism (GW-SNP) assay a realistic endeavor. (Gibbs and Singleton 2006)
More than 20 years ago, Sorensen and colleagues reported that if one of an adult adoptee’s biologic parents died of infection before the age of 50, the adoptee had a 5.81-fold increased risk of dying from infection.(Sorensen et al. 1988) Current sepsis-related polymorphism studies have most commonly focused on one or more polymorphisms for specific genes whose protein products are elements of biologic pathways implicated in sepsis. Many of these studies are association studies where various proinflammatory cytokines and their receptors, novel biomarkers, enzymes and mediators were compared with the development and clinical outcomes of sepsis, severe sepsis and organ dysfunction. In particular, identification of genetic variation in the Toll-like receptors (TLRs) and proinflammatory cytokines has provided valuable insights into the influence of genetic heterogeneity on the response to bacterial infection. And sometimes, different conclusions were given in researching the same SNP. Analyzing the variation in genes and associated differences in response to infection may contribute to the development of new gene diagnosis and therapeutic interventions that will improve outcome in this patient population.
Expressed by macrophages, dendritic cells, neutrophils, and other cell populations, TLRs play a central role in the innate immune response to infection through the recognition of distinct bacterial antigens. (Leulier and Lemaitre 2008) TLR4 is crucial for the recognition of lipopolysaccharide (LPS), while TLR2 is essential in the recognition of Gram-positive bacterial components.(Martin 2000; Opal and Huber 2002) In an American research study, human subjects with 2 TLR mutations (299 Asp→Gly and 399 Thr→Ile) were compared to subjects with TLR4 wild type for response to inhaled toxins. The changes in 299 Asp→Gly, but not 399 Thr→Ile, significantly reduced nuclear levels of NF-kB in LPS-stimulated THP-1 cells. The 299/399 polymorphisms had reduced levels of IL-1a associated with hyporesponsiveness to inhaled endotoxin in humans. (Arbour et al. 2000) Patients with septic shock with the TLR4 Asp299Gly/Thr399Ile alleles had a higher prevalence of gram-negative infections.(Lorenz et al. 2002) Furthermore, the TLR4 299 polymorphism has been reported to be associated with severe sepsis, septic shock and a higher mortality in septic patients with SIRS. (Lorenz, Mira et al. 2002; Child et al. 2003; Barber et al. 2004) Some studies illustrate that TLR2 753 Arg→Gln and 677 Arg→Trp may predispose individuals to certain gram-positive infections such as tuberculosis or leprosy.(Ben-Ali et al. 2004; Ogus et al. 2004)
A key role in the pathogenesis of sepsis is the balance or imbalance of pro- and anti-inflammatory cytokines. Disorders of coagulation are common in sepsis, and 30% to 50% of patients have the more severe clinical form, disseminated intravascular coagulation.(Levi et al. 2000)
TNF-αTNF-α, a pleiotropic cytokine mainly produced by activated monocytes and macrophages, plays a key role in the inflammatory response, and its overexpression can lead to the progression of inflammatory and autoimmune diseases.(Locksley et al. 2001; O\'Shea et al. 2002) But the association between TNF gene polymorphisms and morbidity or clinical outcome of sepsis was not so clearly defined. An association between development of sepsis, but not mortality from sepsis, and the TNF2 genotype in the overall population was found.(Teuffel et al. 2010) An Austrian study discovered that peak values of inflammatory and coagulation markers were not different between wild-type TNF- -308 individuals (GG) and carriers of the TNF- -308 mutant allele (GA and AA).(Kovar et al. 2007)
The interleukin-1 (IL-1) receptor-associated kinase 1 (IRAK1) is believed to play an important role in TLR2- and TLR4-induced activation of NF-ĸB, a critical event in the transcriptional regulation of many sepsis-associated proinflammatory mediators.(Arcaroli et al. 2006) Alleles A2, B2 and RN2 in the IL-1 gene might be important high-risk genetic markers for sepsis.(Ma et al. 2002) IRAK1 might be a genetic risk factor for the occurrence and development of sepsis in the Chinese population. (Arcaroli, Silva et al. 2006)
IL-10Interleukin-10 (IL-10) is an anti-inflammatory cytokine produced by macrophages and T-helper-type II (TH2) lymphocytes that can downregulate inflammatory production, which plays a very important role in the process of induction of immunoparalysis. (Nicod et al. 1995; Thomassen et al. 1996) Three SNPs (–1082, –819, and –592) were found in the regulatory region of the IL-10 gene. The A allele of the -1082 polymorphism in the IL-10 gene promoter is associated with late blood stream infections in ventilated, very low-birth-weight infants and with sepsis susceptibility, whereas the G allele is associated with higher stimulated IL-10 production and increased mortality in severe sepsis.(Shu et al. 2003; Stanilova et al. 2006) Otherwise, the -1082G/G genotype has been associated with lower mortality and organ failure among the subjects with acute respiratory distress syndrome.(Gong et al. 2006) The A allele of the single nucleotide polymorphism at -592 base pairs was associated with higher mortality in sepsis.(Lowe et al. 2003)
Sepsis, an increasing cause of mortality in patients with infectious diseases, especially in seriously ill patients in the ICU, requires rapid diagnosis and treatment. Because SNPs occur frequently throughout the genome and tend to be relatively stable genetically, they can be used as excellent biological markers in sepsis. Depending on rapid advances in technology and informatics, the primary goal in the management of sepsis may change from rapid treatment to prevention for those most at risk. The health care cost savings from such changes could be substantial.
In conclusion, the search for new biomarkers for assessing the severity of sepsis patients and predicting prognosis is very important, interesting, and challenging work, providing new insights to confront sepsis.
Authors are listed below with their open access chapters linked via author name:
",metaTitle:"IntechOpen authors on the Global Highly Cited Researchers 2018 list",metaDescription:null,metaKeywords:null,canonicalURL:null,contentRaw:'[{"type":"htmlEditorComponent","content":"New for 2018 (alphabetically by surname).
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\\n\\nFei Wei 2016-18
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\\n\\nQi Xie 2016-18
\\n\\nXin-She Yang 2017, 2018
\\n\\nYulong Yin 2015, 2017, 2018
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Over the past few decades, no major new types of antibiotics have been produced and almost all known antibiotics are increasingly losing their activity against pathogenic microorganisms. The levels of multi-drug resistant bacteria have also increased. It is known that worldwide, more than 60% of all antibiotics that are produced find their use in animal production for both therapeutic and non-therapeutic purposes. The use of antimicrobial agents in animal husbandry has been linked to the development and spread of resistant bacteria. Poultry products are among the highest consumed products worldwide but a lot of essential antibiotics are employed during poultry production in several countries; threatening the safety of such products (through antimicrobial residues) and the increased possibility of development and spread of microbial resistance in poultry settings. This chapter documents some of the studies on antibiotic usage in poultry farming; with specific focus on some selected bacterial species, their economic importance to poultry farming and reports of resistances of isolated species from poultry settings (farms and poultry products) to essential antibiotics.",book:{id:"6978",slug:"antimicrobial-resistance-a-global-threat",title:"Antimicrobial Resistance",fullTitle:"Antimicrobial Resistance - A Global Threat"},signatures:"Christian Agyare, Vivian Etsiapa Boamah, Crystal Ngofi Zumbi and\nFrank Boateng Osei",authors:[{id:"182058",title:"Dr.",name:"Christian",middleName:null,surname:"Agyare",slug:"christian-agyare",fullName:"Christian Agyare"},{id:"261271",title:"MSc.",name:"Crystal Ngofi",middleName:null,surname:"Zumbi",slug:"crystal-ngofi-zumbi",fullName:"Crystal Ngofi Zumbi"},{id:"261272",title:"MSc.",name:"Frank Boateng",middleName:null,surname:"Osei",slug:"frank-boateng-osei",fullName:"Frank Boateng Osei"},{id:"261273",title:"Dr.",name:"Vivian Etsiapa",middleName:null,surname:"Boamah",slug:"vivian-etsiapa-boamah",fullName:"Vivian Etsiapa Boamah"}]},{id:"49246",doi:"10.5772/61300",title:"Chitosan as a Biomaterial — Structure, Properties, and Electrospun Nanofibers",slug:"chitosan-as-a-biomaterial-structure-properties-and-electrospun-nanofibers",totalDownloads:4727,totalCrossrefCites:27,totalDimensionsCites:63,abstract:"Chitosan is a polysaccharide derived from chitin; chitin is the second most abundant polysaccharide in the world, after cellulose. Chitosan is biocompatible, biodegradable and non-toxic, so that it can be usedin medicalapplications such as antimicrobial and wound healing biomaterials. It also used as chelating agent due to its ability to bind with cholesterol, fats, proteins and metal ions.",book:{id:"4648",slug:"concepts-compounds-and-the-alternatives-of-antibacterials",title:"Concepts, Compounds and the Alternatives of Antibacterials",fullTitle:"Concepts, Compounds and the Alternatives of Antibacterials"},signatures:"H. M. Ibrahim and E.M.R. El- Zairy",authors:[{id:"90645",title:"Dr.",name:"Hassan",middleName:null,surname:"Ibrahim",slug:"hassan-ibrahim",fullName:"Hassan Ibrahim"},{id:"175694",title:"Dr.",name:"Enas",middleName:null,surname:"El- Zairy",slug:"enas-el-zairy",fullName:"Enas El- Zairy"}]},{id:"70919",doi:"10.5772/intechopen.90891",title:"Antimicrobial Effect of Titanium Dioxide Nanoparticles",slug:"antimicrobial-effect-of-titanium-dioxide-nanoparticles",totalDownloads:1817,totalCrossrefCites:21,totalDimensionsCites:47,abstract:"The widespread use of antibiotics has led to the emergence of multidrug-resistant bacterial strains, and therefore a current concern for food safety and human health. The interest for new antimicrobial substances has been focused toward metal oxide nanoparticles. Specifically, titanium dioxide (TiO2) has been considered as an attractive antimicrobial compound due to its photocatalytic nature and because it is a chemically stable, non-toxic, inexpensive, and Generally Recognized as Safe (GRAS) substance. Several studies have revealed this metal oxide demonstrates excellent antifungal and antibacterial properties against a broad range of both Gram-positive and Gram-negative bacteria. These properties were significantly improved by titanium dioxide nanoparticles (TiO2 NPs) synthesis. In this chapter, latest developments on routes of synthesis of TiO2 NPs and antimicrobial activity of these nanostructures are presented. Furthermore, TiO2 NPs favor the inactivation of microorganisms due to their strong oxidizing power by free radical generation, such as hydroxyl and superoxide anion radicals, showing reductions growth against several microorganisms, such as Escherichia coli and Staphylococcus aureus. Understanding the main mechanisms of antimicrobial action of these nanoparticles was the second main purpose of this chapter.",book:{id:"9521",slug:"antimicrobial-resistance-a-one-health-perspective",title:"Antimicrobial Resistance",fullTitle:"Antimicrobial Resistance - A One Health Perspective"},signatures:"Carol López de Dicastillo, Matias Guerrero Correa, Fernanda B. Martínez, Camilo Streitt and Maria José Galotto",authors:[{id:"244902",title:"Dr.",name:"Carol",middleName:null,surname:"Lopez De Dicastillo",slug:"carol-lopez-de-dicastillo",fullName:"Carol Lopez De Dicastillo"},{id:"315494",title:"Mr.",name:"Matias",middleName:null,surname:"Guerrero Correa",slug:"matias-guerrero-correa",fullName:"Matias Guerrero Correa"},{id:"315495",title:"Ms.",name:"Fernanda",middleName:null,surname:"B. Martínez",slug:"fernanda-b.-martinez",fullName:"Fernanda B. Martínez"},{id:"315496",title:"Mr.",name:"Camilo",middleName:null,surname:"Zuñiga",slug:"camilo-zuniga",fullName:"Camilo Zuñiga"},{id:"315497",title:"Dr.",name:"Maria José",middleName:null,surname:"Galotto",slug:"maria-jose-galotto",fullName:"Maria José Galotto"}]},{id:"65613",doi:"10.5772/intechopen.84411",title:"The Methods for Detection of Biofilm and Screening Antibiofilm Activity of Agents",slug:"the-methods-for-detection-of-biofilm-and-screening-antibiofilm-activity-of-agents",totalDownloads:9283,totalCrossrefCites:15,totalDimensionsCites:26,abstract:"Biofilm producer microorganisms cause nosocomial and recurrent infections. Biofilm that is a sticky exopolysaccharide is the main virulence factor causing biofilm-related infections. Biofilm formation begins with attachment of bacteria to biotic surface such as host cell or abiotic surface such as prosthetic devices. After attachment, aggregation of bacteria is started by cell-cell adhesion. Aggregation continues with the maturation of biofilm. Dispersion is started by certain conditions such as phenol-soluble modulins (PSMs). By this way, sessile bacteria turn back into planktonic form. Bacteria embedded in biofilm (sessile form) are more resistant to antimicrobials than planktonic bacteria. So it is hard to treat biofilm-embedded bacteria than planktonic forms. For this reason, it is important to detect biofilm. There are a few biofilm detection and biofilm production methods on prosthetics, methods for screening antibacterial effect of agents against biofilm-embedded microorganism and antibiofilm effect of agents against biofilm production and mature biofilm. The aim of this chapter is to overview direct and indirect methods such as microscopy, fluorescent in situ hybridization, and Congo red agar, tube method, microtiter plate assay, checkerboard assay, plate counting, polymerase chain reaction, mass spectrometry, MALDI-TOF, and biological assays used by antibiofilm researches.",book:{id:"8427",slug:"antimicrobials-antibiotic-resistance-antibiofilm-strategies-and-activity-methods",title:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods",fullTitle:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods"},signatures:"Sahra Kırmusaoğlu",authors:[{id:"179460",title:"Associate Prof.",name:"Sahra",middleName:null,surname:"Kırmusaoğlu",slug:"sahra-kirmusaoglu",fullName:"Sahra Kırmusaoğlu"}]},{id:"63397",doi:"10.5772/intechopen.80624",title:"Antibiotic Resistance in Lactic Acid Bacteria",slug:"antibiotic-resistance-in-lactic-acid-bacteria",totalDownloads:2486,totalCrossrefCites:12,totalDimensionsCites:21,abstract:"Most starter cultures belong to the lactic acid bacteria group (LAB) and recognized as safe by the US Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA). However, LAB may act as intrinsic or extrinsic reservoirs for antibiotic resistance (AR) genes. This fact may not constitute a safety concern itself, as the resistance gene transfer is vertical. Nevertheless, external genetic elements may induce changes that favor the horizontal transfer transmission of resistance from pathogens as well as from the human intestinal microbiota, which represents a severe safety issue. Some genus of AR LAB includes Enterococcus, Lactobacillus, Lactococcus, Leuconostoc, Pediococcus, and Streptococcus isolated from fermented meat and milk products. Currently, the WHO recommends that LAB used in the food industry should be free of resistance. Therefore, the objective of this chapter is to present an overview of the LAB antibiotic resistance and some methods to determine the same.",book:{id:"6978",slug:"antimicrobial-resistance-a-global-threat",title:"Antimicrobial Resistance",fullTitle:"Antimicrobial Resistance - A Global Threat"},signatures:"Yenizey M. 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After attachment, aggregation of bacteria is started by cell-cell adhesion. Aggregation continues with the maturation of biofilm. Dispersion is started by certain conditions such as phenol-soluble modulins (PSMs). By this way, sessile bacteria turn back into planktonic form. Bacteria embedded in biofilm (sessile form) are more resistant to antimicrobials than planktonic bacteria. So it is hard to treat biofilm-embedded bacteria than planktonic forms. For this reason, it is important to detect biofilm. There are a few biofilm detection and biofilm production methods on prosthetics, methods for screening antibacterial effect of agents against biofilm-embedded microorganism and antibiofilm effect of agents against biofilm production and mature biofilm. The aim of this chapter is to overview direct and indirect methods such as microscopy, fluorescent in situ hybridization, and Congo red agar, tube method, microtiter plate assay, checkerboard assay, plate counting, polymerase chain reaction, mass spectrometry, MALDI-TOF, and biological assays used by antibiofilm researches.",book:{id:"8427",slug:"antimicrobials-antibiotic-resistance-antibiofilm-strategies-and-activity-methods",title:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods",fullTitle:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods"},signatures:"Sahra Kırmusaoğlu",authors:[{id:"179460",title:"Associate Prof.",name:"Sahra",middleName:null,surname:"Kırmusaoğlu",slug:"sahra-kirmusaoglu",fullName:"Sahra Kırmusaoğlu"}]},{id:"62553",title:"Antibiotic Use in Poultry Production and Its Effects on Bacterial Resistance",slug:"antibiotic-use-in-poultry-production-and-its-effects-on-bacterial-resistance",totalDownloads:7327,totalCrossrefCites:43,totalDimensionsCites:92,abstract:"A surge in the development and spread of antibiotic resistance has become a major cause for concern. Over the past few decades, no major new types of antibiotics have been produced and almost all known antibiotics are increasingly losing their activity against pathogenic microorganisms. The levels of multi-drug resistant bacteria have also increased. It is known that worldwide, more than 60% of all antibiotics that are produced find their use in animal production for both therapeutic and non-therapeutic purposes. The use of antimicrobial agents in animal husbandry has been linked to the development and spread of resistant bacteria. Poultry products are among the highest consumed products worldwide but a lot of essential antibiotics are employed during poultry production in several countries; threatening the safety of such products (through antimicrobial residues) and the increased possibility of development and spread of microbial resistance in poultry settings. This chapter documents some of the studies on antibiotic usage in poultry farming; with specific focus on some selected bacterial species, their economic importance to poultry farming and reports of resistances of isolated species from poultry settings (farms and poultry products) to essential antibiotics.",book:{id:"6978",slug:"antimicrobial-resistance-a-global-threat",title:"Antimicrobial Resistance",fullTitle:"Antimicrobial Resistance - A Global Threat"},signatures:"Christian Agyare, Vivian Etsiapa Boamah, Crystal Ngofi Zumbi and\nFrank Boateng Osei",authors:[{id:"182058",title:"Dr.",name:"Christian",middleName:null,surname:"Agyare",slug:"christian-agyare",fullName:"Christian Agyare"},{id:"261271",title:"MSc.",name:"Crystal Ngofi",middleName:null,surname:"Zumbi",slug:"crystal-ngofi-zumbi",fullName:"Crystal Ngofi Zumbi"},{id:"261272",title:"MSc.",name:"Frank Boateng",middleName:null,surname:"Osei",slug:"frank-boateng-osei",fullName:"Frank Boateng Osei"},{id:"261273",title:"Dr.",name:"Vivian Etsiapa",middleName:null,surname:"Boamah",slug:"vivian-etsiapa-boamah",fullName:"Vivian Etsiapa Boamah"}]},{id:"65914",title:"Introductory Chapter: The Action Mechanisms of Antibiotics and Antibiotic Resistance",slug:"introductory-chapter-the-action-mechanisms-of-antibiotics-and-antibiotic-resistance",totalDownloads:4428,totalCrossrefCites:6,totalDimensionsCites:10,abstract:null,book:{id:"8427",slug:"antimicrobials-antibiotic-resistance-antibiofilm-strategies-and-activity-methods",title:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods",fullTitle:"Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods"},signatures:"Sahra Kırmusaoğlu, Nesrin Gareayaghi and Bekir S. Kocazeybek",authors:[{id:"179460",title:"Associate Prof.",name:"Sahra",middleName:null,surname:"Kırmusaoğlu",slug:"sahra-kirmusaoglu",fullName:"Sahra Kırmusaoğlu"},{id:"248288",title:"Prof.",name:"Bekir",middleName:null,surname:"Kocazeybek",slug:"bekir-kocazeybek",fullName:"Bekir Kocazeybek"},{id:"406463",title:"Dr.",name:"Nesrin",middleName:null,surname:"Gareayaghi",slug:"nesrin-gareayaghi",fullName:"Nesrin Gareayaghi"}]},{id:"63397",title:"Antibiotic Resistance in Lactic Acid Bacteria",slug:"antibiotic-resistance-in-lactic-acid-bacteria",totalDownloads:2486,totalCrossrefCites:12,totalDimensionsCites:21,abstract:"Most starter cultures belong to the lactic acid bacteria group (LAB) and recognized as safe by the US Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA). However, LAB may act as intrinsic or extrinsic reservoirs for antibiotic resistance (AR) genes. This fact may not constitute a safety concern itself, as the resistance gene transfer is vertical. Nevertheless, external genetic elements may induce changes that favor the horizontal transfer transmission of resistance from pathogens as well as from the human intestinal microbiota, which represents a severe safety issue. Some genus of AR LAB includes Enterococcus, Lactobacillus, Lactococcus, Leuconostoc, Pediococcus, and Streptococcus isolated from fermented meat and milk products. Currently, the WHO recommends that LAB used in the food industry should be free of resistance. Therefore, the objective of this chapter is to present an overview of the LAB antibiotic resistance and some methods to determine the same.",book:{id:"6978",slug:"antimicrobial-resistance-a-global-threat",title:"Antimicrobial Resistance",fullTitle:"Antimicrobial Resistance - A Global Threat"},signatures:"Yenizey M. Álvarez-Cisneros and Edith Ponce-Alquicira",authors:[{id:"256345",title:"Dr.",name:"Yenizey Merit",middleName:null,surname:"Alvarez Cisneros",slug:"yenizey-merit-alvarez-cisneros",fullName:"Yenizey Merit Alvarez Cisneros"},{id:"256347",title:"Dr.",name:"Edith",middleName:null,surname:"Ponce-Alquicira",slug:"edith-ponce-alquicira",fullName:"Edith Ponce-Alquicira"}]},{id:"49246",title:"Chitosan as a Biomaterial — Structure, Properties, and Electrospun Nanofibers",slug:"chitosan-as-a-biomaterial-structure-properties-and-electrospun-nanofibers",totalDownloads:4726,totalCrossrefCites:27,totalDimensionsCites:63,abstract:"Chitosan is a polysaccharide derived from chitin; chitin is the second most abundant polysaccharide in the world, after cellulose. Chitosan is biocompatible, biodegradable and non-toxic, so that it can be usedin medicalapplications such as antimicrobial and wound healing biomaterials. It also used as chelating agent due to its ability to bind with cholesterol, fats, proteins and metal ions.",book:{id:"4648",slug:"concepts-compounds-and-the-alternatives-of-antibacterials",title:"Concepts, Compounds and the Alternatives of Antibacterials",fullTitle:"Concepts, Compounds and the Alternatives of Antibacterials"},signatures:"H. M. Ibrahim and E.M.R. El- Zairy",authors:[{id:"90645",title:"Dr.",name:"Hassan",middleName:null,surname:"Ibrahim",slug:"hassan-ibrahim",fullName:"Hassan Ibrahim"},{id:"175694",title:"Dr.",name:"Enas",middleName:null,surname:"El- Zairy",slug:"enas-el-zairy",fullName:"Enas El- Zairy"}]}],onlineFirstChaptersFilter:{topicId:"897",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81704",title:"Quorum Sensing Inhibition Based Drugs to Conquer Antimicrobial Resistance",slug:"quorum-sensing-inhibition-based-drugs-to-conquer-antimicrobial-resistance",totalDownloads:22,totalDimensionsCites:0,doi:"10.5772/intechopen.104125",abstract:"Quorum sensing is the cell to cell communication mechanism in microorganism through signalling molecules. Regulation of virulence factor, sporulation, proteolytic enzymes production, biofilm formation, auto-inducers, cell population density are key physiological process mediated through quorum-sensing (QS) signalling. Elevation of innate immune system and antibiotic tolerance of pathogens is highly increased with perspective of quorum-sensing (QS) activity. Development of novel drugs is highly attractive scenario against cell-cell communication of microbes. Design of synthetic drugs and natural compounds against QS signal molecules is vital combat system to attenuate microbial pathogenicity. Quorum sensing inhibitors (QSIs), quorum quenchers (QQs), efflux pump inhibitors (EPIs) act against multi-drug resistance strains (MDR) and other pathogenic microbes through regulation of auto-inducers and signal molecule with perceptive to growth arrest both in-vitro and in-vivo. QQs, QSIs and EPIs compounds has been validated with various animal models for high selection pressure on therapeutics arsenal against microbe’s growth inhibition. Promising QSI are phytochemicals and secondary metabolites includes polyacetylenes, alkaloids, polyphenols, terpenoids, quinones.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Kothandapani Sundar, Ramachandira Prabu and Gopal Jayalakshmi"},{id:"82372",title:"Unlocking the Potential of Ghost Probiotics in Combating Antimicrobial Resistance",slug:"unlocking-the-potential-of-ghost-probiotics-in-combating-antimicrobial-resistance",totalDownloads:20,totalDimensionsCites:0,doi:"10.5772/intechopen.104126",abstract:"Antimicrobial resistance is a global concern that requires immediate attention. Major causes of development of antimicrobial resistance in microbial cells are overuse of antimicrobials along the food chain especially in livestock, in preventing infections as well as misuse of antimicrobials by patients. Probiotics could be a viable alternative to antibiotics in the fight against antimicrobial resistance. Probiotic strains can act as a complement to antimicrobial therapy, improving antimicrobial function and enhancing immunity. However, there are safety concerns regarding the extensive use of live microbial cells especially in immunocompromised individuals; these include microbial translocation, inhibition of other beneficial microorganisms and development of antimicrobial resistance, among other concerns. Inevitably, ghost probiotics have become the favored alternative as they eliminate the safety and shelf-life problems associated with use of probiotics. Ghost probiotics are non-viable microbial cells (intact or broken) or metabolic products from microorganisms, which when administered in adequate amounts have biologic activity in the host and confer health benefits. Ghost probiotics exert biological effects similar to probiotics. However, the major drawback of using ghost probiotics is that the mechanism of action of these is currently unknown, hence more research is required and regulatory instruments are needed to assure the safety of consumers.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Abigarl Ndudzo, Sakhile Ndlovu, Nesisa Nyathi and Angela Sibanda Makuvise"},{id:"82178",title:"Managing Antimicrobial Resistance beyond the Hospital Antimicrobial Stewardship: The Role of One Health",slug:"managing-antimicrobial-resistance-beyond-the-hospital-antimicrobial-stewardship-the-role-of-one-heal",totalDownloads:16,totalDimensionsCites:0,doi:"10.5772/intechopen.104170",abstract:"Infections caused by micro-organisms affect the health of people and animals, causing morbidity and mortality, with Asia and Africa as the epicenters. Some of the infectious diseases are emerging and re-emerging in nature. Examples include viral hepatitis, Lassa fever, Ebola, yellow fever, tuberculosis, covid-19, measles, and malaria, among others. Antimicrobials have been playing an important role in the treatment of infections by these microbes. However, there has been a development of resistance to these antimicrobials as a result of many drivers. This write-up used secondary data to explore the management of antimicrobial resistance (AMR) beyond the hospital antimicrobial resistance steward using the one health concept. The findings showed AMR to be a transboundary, multifaceted ecosystem problem affecting both the developed and developing countries. It is also one of the top ten global public health threats facing mankind. Globally, AMR will cost over US$100 trillion in output loss by 2050, about 700,000 deaths a year, and 4,150,000 deaths in Africa by 2050. About 2.4 million people could die in high-income countries between 2015 and 2050 without a sustained effort to contain AMR. The drivers of AMR are beyond the hospital and hospital AMR stewardship. Therefore, the need for one health concept to manage it.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Istifanus Anekoson Joshua, Mathew Bobai and Clement Sokfa Woje"},{id:"81918",title:"Machine Learning for Antimicrobial Resistance Research and Drug Development",slug:"machine-learning-for-antimicrobial-resistance-research-and-drug-development",totalDownloads:53,totalDimensionsCites:0,doi:"10.5772/intechopen.104841",abstract:"Machine learning is a subfield of artificial intelligence which combines sophisticated algorithms and data to develop predictive models with minimal human interference. This chapter focuses on research that trains machine learning models to study antimicrobial resistance and to discover antimicrobial drugs. An emphasis is placed on applying machine learning models to detect drug resistance among bacterial and fungal pathogens. The role of machine learning in antibacterial and antifungal drug discovery and design is explored. Finally, the challenges and prospects of applying machine learning to advance basic research on and treatment of antimicrobial resistance are discussed. Overall, machine learning promises to advance antimicrobial resistance research and to facilitate the development of antibacterial and antifungal drugs.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Shamanth A. Shankarnarayan, Joshua D. Guthrie and Daniel A. Charlebois"},{id:"81891",title:"Alternatives to Antibiotics in Semen Extenders Used in Artificial Insemination",slug:"alternatives-to-antibiotics-in-semen-extenders-used-in-artificial-insemination",totalDownloads:29,totalDimensionsCites:0,doi:"10.5772/intechopen.104226",abstract:"Antimicrobial resistance is a serious global threat requiring a widespread response. Both veterinarians and medical doctors should restrict antibiotic usage to therapeutic use only, after determining the sensitivity of the causal organism. However, the addition of antibiotics to semen extenders for animal artificial insemination represents a hidden, non-therapeutic use of antimicrobial substances. Artificial insemination for livestock breeding is a huge global enterprise with hundreds of million sperm doses prepared annually. However, reporting of antimicrobial resistance in semen is increasing. This review discusses the consequences of bacteria in semen samples, as well as the effect of antimicrobial substances in semen extenders on bacteria in the environment and even on personnel. Alternatives to antibiotics have been reported in the scientific literature and are reviewed here. The most promising of these, removal of the majority of bacteria by colloid centrifugation, is considered in detail, especially results from an artificial insemination study in pigs. In conclusion, colloid centrifugation is a practical method of physically removing bacteria from semen, which does not induce antibiotic resistance. Sperm quality in stored semen samples may be improved at the same time.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Jane M. Morrell, Pongpreecha Malaluang, Aleksandar Cojkic and Ingrid Hansson"},{id:"81699",title:"Efflux Pumps among Urinary E. coli and K. pneumoniae Local Isolates in Hilla City, Iraq",slug:"efflux-pumps-among-urinary-e-coli-and-k-pneumoniae-local-isolates-in-hilla-city-iraq",totalDownloads:13,totalDimensionsCites:0,doi:"10.5772/intechopen.104408",abstract:"Urinary tract infections (UTI) are the most common bacterial infections affecting humans. Escherichia coli and Klebsiella pneumoniae were common enterobacteria engaged with community-acquired UTIs. Efflux pumps were vital resistance mechanisms for antibiotics, especially among enterobacteria. Overexpression of an efflux system, which results in a decrease in antibiotic accumulation, is an effective mechanism for drug resistance. The ATP-binding cassette (ABC) transporters, small multidrug resistance (SMR), and multidrug and toxic compound extrusion (MATE) families, the major facilitator superfamily (MFS), and the resistance-nodulation- cell division (RND) family are the five superfamilies of efflux systems linked to drug resistance. This chapter highlights the results of studying the prevalence of efflux pump genes among local isolates of E. coli and K. pneumoniae in Hilla City, Iraq. class RND AcrAB-TolC, AcrAD-TolC, and AcrFE-TolC genes detected by conventional PCR of E. coli and K. pneumoniae respectively. The result revealed approximately all studied efflux transporter were found in both E. coli and K. pneumoniae in different percentages. Biofilm formation were observed in 50(100%) of K. pneumoniae and 49(98%) of E. coli isolates were biofilm former and follow: 30(60%), 20(40%) were weak, 12(24%), 22(44%) were moderate and 7(14%) and 8(16%) were Strong biofilm former for E. coli and K. pneumoniae, respectively.",book:{id:"11373",title:"The Global Antimicrobial Resistance Epidemic - Innovative Approaches and Cutting-Edge Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11373.jpg"},signatures:"Hussein Al-Dahmoshi, Sahar A. Ali and Noor Al-Khafaji"}],onlineFirstChaptersTotal:13},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:141,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:124,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:7,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"13633",title:"Prof.",name:"Abdelhamid",middleName:null,surname:"Mellouk",slug:"abdelhamid-mellouk",fullName:"Abdelhamid Mellouk",profilePictureURL:"https://mts.intechopen.com/storage/users/13633/images/1567_n.jpg",institutionString:null,institution:{name:"Paris 12 Val de Marne University",institutionURL:null,country:{name:"France"}}},{id:"109268",title:"Dr.",name:"Ali",middleName:null,surname:"Al-Ataby",slug:"ali-al-ataby",fullName:"Ali Al-Ataby",profilePictureURL:"https://mts.intechopen.com/storage/users/109268/images/7410_n.jpg",institutionString:null,institution:{name:"University of Liverpool",institutionURL:null,country:{name:"United Kingdom"}}},{id:"3807",title:"Dr.",name:"Carmelo",middleName:"Jose Albanez",surname:"Bastos-Filho",slug:"carmelo-bastos-filho",fullName:"Carmelo Bastos-Filho",profilePictureURL:"https://mts.intechopen.com/storage/users/3807/images/624_n.jpg",institutionString:null,institution:{name:"Universidade de Pernambuco",institutionURL:null,country:{name:"Brazil"}}},{id:"38850",title:"Dr.",name:"Efren",middleName:null,surname:"Gorrostieta Hurtado",slug:"efren-gorrostieta-hurtado",fullName:"Efren Gorrostieta Hurtado",profilePictureURL:"https://mts.intechopen.com/storage/users/38850/images/system/38850.jpg",institutionString:null,institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}},{id:"239041",title:"Dr.",name:"Yang",middleName:null,surname:"Yi",slug:"yang-yi",fullName:"Yang Yi",profilePictureURL:"https://mts.intechopen.com/storage/users/239041/images/system/239041.jpeg",institutionString:null,institution:{name:"Virginia Tech",institutionURL:null,country:{name:"United States of America"}}}]},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant 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