Summary of Autoimmune liver disease
\r\n\t"
",isbn:null,printIsbn:null,pdfIsbn:null,doi:null,price:0,priceEur:null,priceUsd:null,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"cc796459268324e827219d1d904e4265",bookSignature:"Prof. Moulay Tahar Lamchich",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/7196.jpg",keywords:"Induction motor, smart motor, electrical vehicles, energy generation, drives, electromechanical, hybrid transportation, smart control, high efficiency motor, variable speed drives, power electronic, energy efficiency.",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"July 4th 2018",dateEndSecondStepPublish:"July 25th 2018",dateEndThirdStepPublish:"September 23rd 2018",dateEndFourthStepPublish:"December 12th 2018",dateEndFifthStepPublish:"February 10th 2019",remainingDaysToSecondStep:"3 years",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"21932",title:"Prof.",name:"Moulay Tahar",middleName:null,surname:"Lamchich",slug:"moulay-tahar-lamchich",fullName:"Moulay Tahar Lamchich",profilePictureURL:"https://mts.intechopen.com/storage/users/21932/images/system/21932.png",biography:"Moulay Tahar Lamchich is a Professor at the Faculty of Sciences Semlalia at Marrakech (Morocco). He completed his thesis in electromechanics in September 1991 and received his third cycle degree. Dr. Lamchich received his Ph.D. from the same university in July 2001. His main activity is based on short-circuit mechanical effects in substation structures, control of different types of machine drives, static converters, active power filters. In the last decennia, his research interests have included renewable energies, particularly the control and supervision of hybrid and multiple source systems for decentralized energy production, and intelligent management of energy. He has published more than fifty technical papers in reviews and international conferences. With IntechOpen, he has published two chapters and was editor of the books “Torque Control” and “Harmonic Analysis”. He is also the director of the “Intelligent management of energy and information systems” laboratory and supervising more than ten thesis projects.",institutionString:"University Cadi Ayyad",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Cadi Ayyad University",institutionURL:null,country:{name:"Morocco"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"11",title:"Engineering",slug:"engineering"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"270941",firstName:"Sandra",lastName:"Maljavac",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/270941/images/7824_n.jpg",email:"sandra.m@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"108",title:"Torque Control",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"torque-control",bookSignature:"Moulay Tahar Lamchich",coverURL:"https://cdn.intechopen.com/books/images_new/108.jpg",editedByType:"Edited by",editors:[{id:"21932",title:"Prof.",name:"Moulay Tahar",surname:"Lamchich",slug:"moulay-tahar-lamchich",fullName:"Moulay Tahar Lamchich"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6173",title:"Compendium of New Techniques in Harmonic Analysis",subtitle:null,isOpenForSubmission:!1,hash:"39a6df08251bdf1771d2921b3b7386b6",slug:"compendium-of-new-techniques-in-harmonic-analysis",bookSignature:"Moulay Tahar Lamchich",coverURL:"https://cdn.intechopen.com/books/images_new/6173.jpg",editedByType:"Edited by",editors:[{id:"21932",title:"Prof.",name:"Moulay Tahar",surname:"Lamchich",slug:"moulay-tahar-lamchich",fullName:"Moulay Tahar Lamchich"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"48381",title:"A Concise Review of Autoimmune Liver Diseases",doi:"10.5772/60520",slug:"a-concise-review-of-autoimmune-liver-diseases",body:'Autoimmune liver disease (AILD) consists of autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). It is characterised by the immune mediated injury to the hepatocytes and bile ducts. Hepatocyte injury is the predominant features in autoimmune hepatitis and biliary injury is the hallmark of primary biliary cirrhosis (Intrahepatic bile duct injury), primary sclerosing cholangitis or Immunoglobulin (Ig) G4 mediated cholangitis (both intra and extra-hepatic bile duct injury). Overlap or variant syndrome indicates the presence of simultaneous injury to both hepatocytes and cholangiocytes during the course of the disease. Imbalance in effector and regulatory arm of adaptive immune cells had been described as the immunopathogenesis of AILD. Antigenic causative factors are still poorly understood across AILD but genetic, environmental factors and microbiota play a major role in disease pathology.
The aim of the chapter is to describe in depth of each disease entity in regard to their immuno-pathogenesis, diagnosis, investigations and management strategies including standardised care as well as future novel therapies.
Long term global immunosuppressive therapy in AIH with multiple side effects and lack of definitive treatment to tackle the underlying immunopathology in PBC and PSC are major challenging aspects in AILD. Thorough understanding of causative antigens, immuno-pathogenesis, OMIC profiles (genomic, metabolomics, proteomic and microbiomic) of AILD patients will direct clinicians for stratification and individualized personal care. Novel new immunological based cell and cytokines therapies are urgently warranted in defined unique group of AILD patients.
The diagnosis and management of AILD can be constantly challenging due to the presence of overlap features at diagnosis or gradual evolution in phenotype of diseases from one spectrum (typical AIH) to others (overlap of AIH/PBC and AIH/PSC) during the disease process. Therefore, the continuous assessment of the disease presentations are essential in follow up of patients with AILD.
An autoimmune liver disease (AILD) is an umbrella term for diseases caused by immune mediated reaction to either hepatocytes or bile ducts. Regulatory T cells (Treg) play an important and essential role in the maintenance of homeostasis and prevention of autoimmune responses [1]. Autoimmune hepatitis (AIH) is caused by an immune mediated injury of the hepatocytes and characterised by presence of lobular and interface hepatitis on liver histology, presence of hypergammaglobulinaemia and high titre of antinuclear antibodies (ANA) in the serum with transaminitis on liver biochemistry. The main aim of treatment is to suppress the immune system globally and the first line therapies used are prednisolone and azathioprine. Second line therapies such as tacrolimus and mycophenolate mofetil are also used in AIH patients. Two commonly used biologics in difficult-to-treat AIH patients are anti- tumour necrosis factor (anti-TNF) for example Infliximab and anti-CD20 monoclonal antibody therapy as in Rituximab. New novel antigen-specific autologous regulatory T cells therapy development is also in progress for future treatment of autoimmune hepatitis.
Primary biliary cirrhosis (PBC) is an injury to the intra-hepatic biliary ducts and tends of present in 4th to 6th decade of life. The main therapy is ursodeoxycholic acid (UDCA) but new therapies for PBC such as Obeticholic acid have been emerged recently. Patients with PBC tend to suffer with significant itch and management of itch can be challenging at times. There are therapies available for itch from the spectrum to cholestyramine to immunoglobulins infusion treatment.
Primary sclerosing cholangitis (PSC) is an immune mediated injury, mainly to biliary system either intrahepatic or extrahepatic or both. PSC is common in young, male patient and commonly associated with inflammatory bowel disease (IBD), especially ulcerative colitis. There is a significant risk of developing cancer such as cholangiocarcinoma or gall bladder cancer or bowel cancer in these groups of patients and hence surveillance is important. There are no targeted treatments available for PSC and liver transplantation is necessary in end stage PSC.
Detailed summary of three autoimmune liver disease (autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis) are documented in table 1.
Summary of Autoimmune liver disease
ANA: Anti-nuclear antibodies, ASMA: anti smooth muscle antibodies, LKM: Liver- kidney-microsomal antibodies, g G: Immunoglobulin G, Ig M: Immunoglobulin M, Anti-gp 210: Antibodies against the nuclear pore membrane glycoprotein (anti-gp210), Anti-Sp 100: Antibodies against the nuclear protein Sp100, ULN: Upper limit of normal, UDCA: Ursodeoxycholic acid
Adapted from 1) Trivedi, P.J. and G.M. Hirschfield, Review article: overlap syndromes and autoimmune liver disease. Aliment Pharmacol Ther, 2012. 36(6): p. 517-33. 2) Strassburg, C.P. and M.P. Manns, Therapy of autoimmune hepatitis. Best Pract Res Clin Gastroenterol, 2011. 25(6): p. 673-87.3) Yimam, K.K. and C.L. Bowlus, Diagnosis and classification of primary sclerosing cholangitis. Autoimmun Rev, 2014. 13(4-5): p. 445-50.
Autoimmune hepatitis (AIH) is an immune mediated, chronic inflammatory disease of unknown aetiology, mainly affecting the hepatocytes. It was first defined in 1950 by Waldenström when he described a chronic hepatitis in young woman which eventually lead to liver cirrhosis [2]. It is characterised by the morphological changes of interface hepatitis on liver biopsy, hypergammaglobulinaemia and the presence of high circulating ANA in the serum [3, 4]. It is more common in women (around 75%) and can affect at any age from young to elderly. It is also associated with other autoimmune conditions such as hypothyroidism, ulcerative colitis, type 1 diabetes mellitus, rheumatoid arthritis, coeliac disease or skin disorders such as vitiligo. Therefore, obtaining a detailed history especially family history of autoimmune conditions are important in the assessment of patients with potential AIH diagnosis.
There is limited evidence regarding the incidence and prevalence of AIH. From the data so far, it has been estimated that the prevalence of AIH is around 5 to 20 cases per 100,000 among the Caucasian population in Western Europe [5]. AIH accounts for up to 20% of chronic hepatitis among the Caucasian population of North America and Western Europe [5]. AIH prevalence and clinical expression appear to vary according to ethnicity. Previous studies showed that black patients tend to have more aggressive disease [6] whereas Hispanic populations had a higher prevalence of cirrhosis [7]. Asian patients develop the disease later in life and have a poorer survival [7] and Alaskan native patients presented more frequently with acute AIH [8].
Clinically, there are three forms of AIH. Type 1 AIH is common in adults and characterised by the presence of ANA and/or anti smooth muscle antibodies (ASMA) with raised Immunoglobulin-G (Ig G). Type 2 is seen mostly in children and characterised by the presence of anti-liver-kidney-microsomal (LKM) antibodies directed against cytochrome P450 (CYP-2D6) [9, 10] and with lower frequency against UDP-glucuronosyltransferases (UGT) [2, 11]. Antibodies against soluble liver or liver-pancreas (SLP) antigens are common in type 3 AIH. Around 19% of patients can present with seronegative disease at the time of diagnosis [12].
The exact aetiopathogenesis of AIH is still unknown. It is a complex process interlinking environmental and genetic factors in a susceptible host. The most common environmental trigger thought to cause AIH is viral infection. Drug induced AIH is a recognised entity and the commonly associated drugs are anti-TNF treatment such as Adalimumab, antibiotics such as minocycline or nitrofurantion or statins such as rosuvastatin [13-15]. Both T cells and B cells play an important role in the adaptive immune response to both self and non-self-antigen. T cells, both CD4 and CD8 T cells, play a major role in the immnuopathogenesis with effector responses mediated by Natural Killer (NK) cells and macrophages [16]. Regulatory T cells (Treg) play an essential role in the homeostasis and prevention of autoimmune conditions [1]. They are classified as CD4+ CD25high CD127Low and represent the 2 % of the CD3 subset [17]. Foxp3 (forkhead box P3) is a transcription factor which controls the phenotype, development and function of Treg [18]. Commitment to Treg lineage primary occurs in the thymus as a result of presenting self- antigens by medullary thymic epithelium. In AIH, the number of Tregs is normal but their function is impaired [19]. Reduction in frequency of Treg has also been reported [17, 20].
Type 1 AIH is associated with human leukocyte antigen (HLA) DR3 (HLA-DRB1*0301) and DR4 (HLA-DRB1*0401) in white North Europe and North American patients [21, 22]. It has been suggested the presence of DR3 is associated with poorer response to treatment and hence requires liver transplantation (LT) [21, 22]. On the other hand, patients with DR4 are usually older and more responsive to treatment with steroid [21]. A recent geno-wide association study of type 1 AIH in Netherlands showed that type 1 AIH is associated with the rs3184504*A allele in the SH2B3 gene [22]. These single nucleotide polymorphisms (SNP) represent the first genetic AIH locus outside the Major Histocompatibility Complex (MHC) region [22]. It encodes a missense variant in exon 3 of the Scr homology 2 adaptor protein 3 (SH2B3) genes located in the 12q24 region [22]. SH2B3 is a negative regulator of T-cell activation, tumour necrosis factor, and Janus kinase 2 and 3 signalling, and plays an essential role in normal haematopoiesis [22]. Capcase recruitment domain family member 10 (CARD 10) gene with allele rs6000782 has been shown to be associated with type 1 AIH [22]. CARD 10 is a scaffold protein and induces pro-inflammatory nuclear factor kB activation and it is widely expressed in a variety of non-haematopoietic tissue including hepatocytes [22].
Proposed pathway of pathogenesis in AIH has been shown in Figure 1.
Pathogenesis of Autoimmune hepatitis. Autoimmune hepatitis (AIH) is initiated by the presence of auto antigen peptide onto antigen presenting cells (APC) which activates T helper cells (Th0) due to interleukins (IL) 2 and 4. Upon activation of Th0, it can differentiate into Th1 and Th2 cellular pathway. Th1 produces IL2 and Interferon-gamma (IFN-r) which subsequently activates CD8 lymphocytes.
Most patients present with nonspecific symptoms such as fatigue, arthralgia and anorexia at the time of presentation. About 25% of patient present asymptomatically [23] and the majority of patients present late with symptoms of portal hypertension and decompensated cirrhosis. Recent systematic review mentioned that around 25 % of elderly patients (age 60 to 65) were more likely to present asymptomatically, they are more likely to be HLA-DR4 positive and cirrhotic at initial presentation [24]. They are less likely to be HLA-DR3-positive and to relapse after treatment withdrawal after complete remission [24]. AIH can also present during pregnancy or postpartum period. Physical examination can either be normal, or show hepatomegaly, splenomegaly or signs of chronic liver disease. In some patients, AIH present as acute severe hepatitis and rarely, they progress to fulminant form and require liver transplantation [2].
Blood tests can show signs of hepatitis with raised alanine transaminase (ALT, U/L) (usually less than 500 U/L), aspartate transaminase (AST, U/L) and occasionally bilirubin (umol/L). Typical immunology profile in AIH patients are raised Ig G with positive ANA, ASMA (in type 1 AIH) and LKM (in type 2 AIH). Patients with acute presentation of AIH should be monitored for synthetic function such as international normalised ratio (INR) and albumin as well as mental status or sign of hepatic encephalopathy since some patients can progress to acute liver failure rapidly and will need liver transplantation. Viral hepatitis, toxins, drugs should be excluded in patient presenting with acute or chronic form of hepatitis. Men with AIH appear to have a higher relapse rate and younger age of disease onset [25, 26]. Cirrhosis at presentation [27, 28] and presence of SLA antibodies are poor predictive outcomes in type 1 AIH patients [29, 30].
Liver biopsy is recommended at the time of presentation to establish the diagnosis as well as to guide the treatment, however in patients presenting with acute hepatitis who has suspicious diagnosis of AIH, the treatment should not be delayed [31]. The histological hallmarks of AIH is a lymphoplasmacytic peri-portal infiltrate invading the limiting plate, also called piecemeal necrosis or “interface hepatitis” and eventually lead to lobular hepatitis (Figure 2) [13]. Patients with chronic AIH usually have plasma cell- rich mononuclear infiltrate involving portal and peri-portal regions [16] which subsequently lead to peri-portal fibrosis. Up to 30% of patients with AIH had histological features of cirrhosis at the time of presentation [2]. In 17% of patients with peri-portal hepatitis whereas 82% of patients who had bridging fibrosis, cirrhosis develops within 5 years [2].
The diagnosis of AIH is based on multiple investigations and diagnostic criteria was proposed by the international AIH group in 1993 and subsequently updated in 1999 (Table 2) [13, 32, 33]. In 2008, the groups established the simplified scoring system which is more user friendly in day to day clinical care[13] (Table 3). The scoring is based on combination of the serum immunoglobulins titres (ANA, SMA or LKM), serum liver enzymes and liver histology features with absence of viral hepatitis.
Histology findings of autoimmune hepatitis
\n\t\t\t\tClinical features\n\t\t\t | \n\t\t\t\n\t\t\t\tScore\n\t\t\t | \n\t\t
\n\t\t\t\tFemale \n\t\t\t | \n\t\t\t+2 | \n\t\t
\n\t\t\t\tALP:AST ratio\n\t\t\t | \n\t\t\t\n\t\t |
• <1.5 • 1.5-3.0 • >3.0 | \n\t+2 0 -2 | \n
\n\t\tSerum globulin or Ig G above normal\n\t | \n\t\n |
• >2.0 • 1.5-2.0 • 1.0-1.5 • <1.0 | \n+3 +2 +1 0 | \n
\n\t\tANA, SMA or LKM 1\n\t | \n\t\n |
• >1:80 • 1:80 • 1:40 • <1:40 | \n+3 +2 +1 0 | \n
\n\t\tIllicit drug use\n\t | \n\t\n |
• Positive • Negative | \n\t-4 +1 | \n
\n\t\tAverage daily alcohol intake\n\t | \n\t\n |
• <25g/day • >60g/day | \n+2 -2 | \n
\n\t\tHistological findings\n\t | \n\t\n |
• Interface hepatitis • Lymphoplasmacytic infiltrate • Rosette formation • None of the above • Biliary changes • Other changes | \n\t+3 +1 +1 -5 -3 -2 +2 | \n
\n\t\tOther autoimmune disease\n\t | \n\t\n |
\n\t\tAMA positivity\n\t | \n\t-4 | \n
\n\t\tViral hepatitis markers\n\t | \n\t\n |
• Positive • Negative | \n\t-3 +3 | \n
Definite AIH Probable AIH | \n\t>15 10-15 | \n
Revised International Autoimmune Hepatitis Group Scoring System for the Diagnosis of Autoimmune Hepatitis (AIH) (Adapted from Alvarez et al [21] and Chandok et al [22])
ALP: alkaline phosphatase, AST: Aspartate transaminase, Ig: Immunoglobulin, ANA: Antinuclear antibodies, SMA: Smooth muscle antibodies, LKM: Liver kidney microsomal antibodies, AMA: Anti-mitochondrial antibod
\n\t\t\tVariables\n\t\t | \n\t\t\n\t\t\tCut off\n\t\t | \n\t\t\n\t\t\tPoints\n\t\t | \n\t
ANA or SMA | \n\t\t≥ 1;40 | \n\t\t1 | \n\t
\n\t\t | ≥ 1:80 | \n\t\t2 | \n\t
Or LKM 1 | \n\t\t≥ 1:40 | \n\t\t2 | \n\t
Or SLA | \n\t\tPositive | \n\t\t1 | \n\t
Ig G | \n\t\t>upper limit of normal | \n1 | \n
\n\t | >1.1x upper limit of normal | \n2 | \n
Liver histology | \n\tCompatible with AIH | \n\t1 | \n
\n\t | Typical of AIH | \n\t2 | \n
Absence of viral hepatitis | \n\tYes | \n\t2 | \n
Simplified scoring system for autoimmune hepatitis
ANA: anti-nuclear antibodies; SMA: anti-smooth-muscle antibodies; LKM1: liver/ kidney microsomal antibody type 1; SLA: anti-soluble liver antigen.
Definite AIH: A cumulative score ≥7
Probable AIH: A cumulative score =6
Liver histology typical of AIH: interface hepatitis, emperipolesis, hepatic rosette formation
Liver histology compatible with AIH: chronic hepatitis with lymphocytic infiltration, without typical features.
The main aim for treatment of AIH is to suppress the ongoing inflammation and the first line therapies used are steroids (either prednisolone or budesonide) with or without azathioprine (AZA). Steroid side effects such as cosmetic changes, osteopenia, hirsutism, steroid induced diabetes are seen in about 44% of patients within 12 months of treatment and 80% within 24 months of treatment [2]. Budesonide is a preferred choice of treatment for patients who do not tolerate prednisolone due to side effects and in patients with diabetes mellitus. It is a synthetic steroid with high first-pass metabolism in the liver, which is in principle capable of limiting systemic side effects compared to conventional steroids [2]. Due to those side effects mentioned above, the adherence to medication can be an issue and hence, compliance needs to be monitored throughout the treatment period. Patients who need long term steroid therapy (> 3 months) should be started on calcium and vitamin D3 supplements to prevent osteoporosis.
The combination regimen of prednisone and azathioprine is associated with a lower occurrence of corticosteroid-related side effects than the higher dose prednisone regimen (10% versus 44%), and it is the preferred treatment in patients with AIH. AZA side effects include abdominal discomforts, pancreatitis, nausea, cholestatic hepatitis, rashes and leukopenia and they can be seen in 15% of patients who received 50mg of AZA [2]. Azathioprine metabolite and Thiopurine S-Methyl Transferase (TPMT) levels will guide the optimal dose for individual patients. Some patients who cannot tolerate AZA benefit from Mercaptourine. The metabolism of AZA has been demonstrated in Figure 3.
Azathioprine metabolism
Around 90% of adult patients respond to therapy within first 2 weeks with improvement in serum immunoglobulins and liver enzymes levels [31]. Treatment should be continued until normalisation of serum immunological and, biological parameters as well as improvement in liver histology. Relapsed AIH is characterized by an increase in the serum aminotransferase levels to at least threefold normal and it occurs in 50% to 86% of patients who previously had complete remission of their disease and usually happens during the first 6 months after the termination of therapy [13, 31]. In patients who has sub-optimal response to initial therapy or relapsed AIH should be considered for more potent treatments such as tacrolimus or mycophenolate mofetil.
Alternative therapies include tacrolimus, mycophenolate mofetil (MMF), cyclosporine, methotrexate, cyclophosphamide, ursodeoxycholic acid (UDCA), infliximab and rituximab [14]. Although there are some encouraging results with each of the medications, the treatment has not been implemented into standard management due to lack of randomised control data. Most of the evidence is based on from small, retrospective, single centre case series [34]. Therefore, these treatments should be only commenced in the specialised centre with presence of experienced hepatologists.
Cyclosporine A is a lipophilic cyclic peptide of 11 residues produced by Tolypocladium inflatum that acts on calcium dependent signalling and inhibits T cell function via the interleukin 2 gene [2]. Use of cyclosporine is limited due to its side effects of hirsutism, hypertension, renal insufficiency, hyperlipidaemia, increased risk of infection and malignancy [2]. The evidence of cyclosporine in adult AIH is limited due to a small number of case series arising from single centres. In one study of six patients, cyclosporine normalised ALT in all patients and 3 patients had improvement with liver histology in follow up. Another study of 5 patients with cyclosporine treatment showed biochemical improvement in 4 patients who had not responded to standard therapy [35]. In a study of 8 patients, it showed that cyclosporine is safe and all patients achieved remission [36].
Tacrolimus (Tac) is a macrolide compound and its mechanism is similar to that of cyclosporine A but it binds to a different immunophilin [2]. The main side effect is renal toxicity. Both cyclosporine and tacrolimus are calcineurin inhibitors and can be used as a rescue therapy for difficult to treat AIH patients. Compliance can be monitored by drug level in both drugs. An open label preliminary study in which 21 AIH patients were treated with tacrolimus (Tac) showed reduction of liver enzymes (ALT and AST) in 70-80% of patients who received 3 months of therapy [37]. There are only few studies reported use of Tac in the treatment of AIH although wide experience use of this drug exist in cohort of AIH patients who had liver transplantation (LT) [34]
Mycophenolate Mofetil (MMF) is a non-competitive inhibitor of inosine monophosphate dehydrogenase, which blocks the rate-limiting enzymatic step in de novo purine synthesis. MMF has a selective action on lymphocyte activation, with marked reduction of both T and B lymphocyte proliferation [2]. Many patients experience headache, nausea, diarrhoea, dizziness and neutropenia with MMF therapy [14]. It is contraindicated in pregnancy due to its teratogenic side effects. Recent studies of 59 patients with treatment naïve AIH were treated with MMF and prednisolone as a first line therapies in which the study showed biochemical and immunological parameters improvements in 88% of patients in the first 3 months and 12% had partial response [38]. A study from Canadian group studied 16 patients who failed conventional therapy were given either tacrolimus or MMF [39] and complete response were seen in 50% of patients and 12.5 % had non response to treatment [39]. Another study looking at 36 patients with AIH who were treated with MMF and it showed remission in 39% of patients. The study mentioned in patients who does not respond to AZA, around 75% of those do not respond to MMF either [40].
Infliximab, a recombinant humanized chimeric antibody, has been used in other immunomodulatory conditions such as rheumatoid arthritis and inflammatory bowel disease. However, infliximab has been associated with de novo AIH in some patients with liver transplantation (LT) and therefore, it should be used by the experienced team in specialised centre. A retrospective, single centre review of 11 patients with difficult to treat AIH were treated with infliximab and it showed infliximab led to reduction of inflammation, evidenced by a decrease in transaminases and serum immunoglobulins [41].
Rituximab is an anti-CD20 chimeric monoclonal antibody, a surface marker expressed on B cells, from early pre-B to memory B lymphocytes [42]. Treatment with rituximab leads to B cell depletion through both complement- and antibody-dependent cellular cytotoxicity [42]. AIH is considered to be a T-cell–mediated disease; however, numerous observations would suggest that B cells are also involved in its pathogenesis [43]. Although there were good evidences to suggest that rituximab is effective in autoimmune haemolytic anaemia, cryoglobulinemia and systemic lupus erythematosus, the data on efficacy of rituximab in AIH are limited [44-46]. A study by Burak and colleague showed that Rituximab is well tolerated with no significant side effects and resulted in biochemical response in patients with refractory or intolerant to other treatment [47].
Patients with acute, severe AIH who are untreated have poorer short and long term survival compared to treated AIH patients [48-50]. For patients with the severe acute phenotype of AIH, failure to respond to treatment within the first 7–14 days after presentation is associated with a mortality of almost 50% [51]. For patients with established cirrhosis at presentation, treatment can induce remission and improve long-term outcome, with 10-year life expectancies of greater than 90% [52, 53]. Patient with cirrhosis due to AIH usually develop hepatocellular carcinoma at a mean of 9 to 10 years according to previous published case series and hence, routine surveillance with 6 monthly ultrasound scan and alpha feto protein (AFP) is recommended for these cohort of patients [54, 55]. Autoimmune hepatitis is an acceptable reason for liver transplantation, with frequency of survival exceeding 75% at 5 and 10 years after transplant [56, 57]. In summary, the overall prognosis of AIH is good for patient who are treated and responded to immunosuppressive therapy. Therefore, compliance is important which can be achieved by supporting patient and education to the patient. It is also crucial to recognise and treat the patients who are not responsive to standard immunosuppressive therapies with more novel treatments. It is essential to have smooth handover and transition between paediatric and adult hepatology team which will help young patients with AIH to continue with their treatment and follow up.
Primary biliary cirrhosis (PBC) is an autoimmune condition and causes a chronic and progressive destruction of intrahepatic bile ducts resulting in chronic cholestasis, portal inflammation, fibrosis and then gradually lead to cirrhosis and liver failure [58]. The disease is predominantly seen in women than men with a ratio of 10:1 [60] and had a prevalence of 1 in 1000 women over the age of 40 [59].
The highest prevalence and incidence rates have been reported in Great Britain, Scandinavia and the northern Midwest region of the USA [5, 61]. It has been suggested that the incidence of PBC is rising and in the United Kingdom (UK), the incidence rate rose from 2.05 cases per 100,000 populations per year in Sheffield from 1980 to 1999 [5, 62] and from 1.1 to 3.2 cases per 100,000 population per year in Newcastle- Upon- Tyne from 1976 to 1994 [63, 64].
Both genetic and environmental factors such as chemical substances, bacterial and viruses play an important role in the pathogenesis of PBC. In general, data indicate that 1 to 6% of PBC cases have at least one other family member presenting with the disease [60]. The concordance rate observed among monozygotic twins for PBC is 63%, among the highest reported in autoimmune diseases [60]. Prior to the advent of genome-wide association studies, only class II HLA loci (HLA-DRB1*08, *11, and *13) had been reproducibly shown to associate with disease [59]. With the application of genome-wide technology, HLA was confirmed as the strongest association and many other risk loci have been identified, with equivalent effect size to HLA, including IL12A, IL12RB2, STAT4, IRF5-TNPO3, 17q12.21, MMEL1, SPIB, and CTLA-4 [59]. These collectively support an important role for innate and adaptive immunity in development of disease [59].
There is an increased auto reactive CD4 pyruvate dehydrogenase complex (PDC)-E2 specific T cells in liver and regional lymph nodes in patients with PBC and CD8 PDC-E2 T cells infiltrates in the liver suggesting that anti-mitochondrial response is either directed to the aetiology or associated with other environmental or genetic trigger [65].
The majority of patients are asymptomatic at the time of diagnosis. With progression of the disease, patients usually develop fatigue and pruritus. Fatigue is the most common symptom and is present in up to 78% of patients with PBC [65]. Fatigue is not associated with disease severity or disease duration or histological findings and it is difficult to manage in most patients. Pruritus is a more specific symptom of PBC than fatigue and formerly occurred in 20%-70% of patients with PBC [65]. It can be local or diffuse, usually worse at night and tend to be in the palms and soles of the feet. Pruritus is often exacerbated by contact with wool, other fabrics, heat, or during pregnancy [65]. Sicca syndrome, hypothyroidism, vitamin D deficiency, osteopenia and hypercholesterolemia are commonly seen in patients with PBC and should be investigated and managed appropriately.
Individuals with abnormal cholestatic liver function tests such as raised alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) and elevated conjugated bilirubin should be investigated for underlying PBC [66]. Immunologically, the majority of patients (around 95%) have positive anti-mitochondrial antibodies (AMA) in their serum and raised levels of immunoglobulins-M (Ig M) [67].
AMA reactivity is classically studied by immunofluorescence and considered positive at a titre of ≥1:40 [66]. The targets of the disease-specific ant mitochondrial response are all members of a family of enzymes, the 2-oxo-acid dehydrogenase complexes and include PDC-E2, branched chain 2-oxo-acid dehydrogenase complex, and 2-oxo-glutaric acid dehydrogenase complex [65]. These enzymes catalyse the oxidative decarboxylation of keto acid substrates and are located in the inner mitochondrial membrane [65].
Patient who had raised ALP and high titre of AMA (tire of ≥ 1:40) or AMA type 2 (M2) can be diagnosed with PBC without liver biopsy as per EASL (European Association for the Study of the Liver) guideline [66]. Positive ANA titres are also found in 30–50% of individuals with PBC (more commonly in the few who are AMA negative), but in this setting ANA reactivity is, in contrast to AIH, often antigen specific (anti gp-210 and anti sp-100) [12, 68].
\n\t\t\tStage\n\t\t | \n\t\t\n\t\t\tFindings\n\t\t | \n\t
1 (Portal tract Inflammation) | \n\t\tPortal tract inflammation from mainly lymphoplasmacytic infiltrates with or without florid bile duct lesions resulting in septal and interlobular bile ducts. | \n\t
2 (Peri-portal fibrosis) | \n\t\tGradual increase of peri-portal lesions extending into the hepatic parenchyma- referred as interface hepatitis. | \n\t
3 (Bridging fibrosis) | \n\t\tDistortion of the hepatic architecture with numerous fibrous septa. Ductopenia (defined as loss of >50% of interlobular bile ducts) becomes more frequent at this stage. | \n
4 (Cirrhosis) | \n\tCirrhosis with the existence of regenerative nodules. | \n
Liver histology stages seen in primary biliary cirrhosis
The stages of PBC are shown in Figure 4.
(Adapted from Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ. Primary biliary cirrhosis. Hepatology 2009;50:291-308)
Liver biopsy is rarely needed in the diagnosis of PBC. However, in patients with overlap of AIH/PBC might need liver biopsy to access the degree of the liver injury. In PBC, liver histology is divided into 4 stages (Table 4, Figure 4). Nowadays, the degree of fibrosis can be determined by performing non-invasive procedure such as transient elastography or Fibroscan. Magnetic resonance cholangio-pancreatography (MRCP) and Endoscopic retrograde cholangio-pancreatography (ERCP) are sometimes required to exclude other biliary pathology or PSC.
Histology finding of Primary biliary cirrhosis (PBC)
Ursodeoxycholic acid (UDCA) is the only approved treatment for patients with PBC and shown to be associated with improvement in liver biochemistries, delayed histologic progression of disease, and delayed development of oesophageal varices and prolong transplant free survival [67, 69]. UDCA at a dose of 13-15 mg/kg is proven benefit. Various risk scores have been validated to access the response of UDCA in patients with PBC and these are Barcelona, Paris I and II, Rotterdam and Toronto criteria (table 5) [127-131].
\n\t\t\tCriteria\n\t\t | \n\t\t\n\t\t\tBiochemical response\n\t\t | \n\t
Barcelona | \n\t\tDecrease of serum ALP > 40% or ALP normalisation (after 1 year) | \n
Paris I | \n\tALP ≤ 3 x ULN, AST ≤ 2 x ULN and serum albumin ≤ 1mg/dl (after 1 year) | \n
Paris II | \n\tALP and AST < 1.5 x ULN, serum bilirubin <1mg/dl (after 1 year) | \n
Rotterdam | \n\tNormalisation of abnormal serum bilirubin and/or serum albumin (after 1 year) | \n
Toronto | \n\tALP < 1.67 x ULN (after 2 years) | \n
Assessment of response to UDCA in patients with PBC
ALP: alkaline phosphatase, AST: Aspartate transaminase, ULN: upper limit of normal
Ursodeoxycholic acid is a hydrophilic bile acid and normally present in about 3% of bile in humans [70]. In patient with cholestasis, there is a decrease in endogenous production of bile acids as well as reduction in the absorption of UDCA [70]. After oral administration of UDCA, it is absorbed in small intestine and colon and transported to liver via portal tract. The absorption of UDCA is increased after meal consumption due to alkaline pH status. Administration of 13-15 mg/kg of UDCA in PBC patients causes enrichment of 40 to 50 % in primary bile acids [70].
Other drugs have been tested, but none have been found as single agents to be of benefit. These include chlorambucil, penicillamine, cyclosporine, corticosteroids, azathioprine, mycophenolate mofetil, thalidomide, methotrexate, malotilate, and colchicine [65].
Fatigue can be difficult to manage and other underlying conditions such as anaemia, thyroid disorder should be investigated and ruled out. There is no proposed treatment for fatigue and it can sometime persist even after Liver transplantation. A study by Jones et al showed that Modafinil at a dose of 100 to 200 mg/day was associated with a significant improvement in fatigue and improved day time somnolence [71].
There are few effective treatments available for pruritus in PBC patients. Cholestyramine is a non-absorbable resin and it is the first line therapy in the management of pruritus. The recommended dose of cholestyramine is 4 g per dose to a maximum of 16 g/day given 2-4 hours before or after UDCA [65]. In general, cholestyramine is well tolerated, although some patients report bloating, constipation, and diarrhoea [65].
Rifampicin is a P450 enzyme inducer and used in treatment of pruritus for PBC patients. The recommended dose is 150 mg once daily or twice daily based on the level of bilirubin. Side effects of rifampicin remain a serious concern because cases of hepatitis and hepatic failure, haemolysis and renal impairment and therefore, patient should be closely monitored during the treatment [65]. It should not be used together with serotonin reuptake inhibitor (SSRI) in patient with severe depression since it decrease the effect of SSRI[65].
Opioid antagonist, Naltrexone 50 mg daily, has been shown to be effective in treatment of pruritus in PBC patients. Other agents are SSRI (sertraline), Etarnacept (TNF-alpha inhibitor), Amitriptyline, Anti histamine. Some patient with difficult to treat pruritus can be managed with plasmapheresis.
Several pilot studies and randomized controlled trials have evaluated various agents in PBC. Trials with mesenchymal stem cells, Rituximab, Ustekinumab, Moexipril which is an angiotensin-converting enzyme (ACE) inhibitor and Abatacept treatments in PBC is currently ongoing (www.clinicaltrials.gov).
There is a suggestion that beta retrovirus might be involved in the pathogenesis of PBC and hence, a randomised controlled trial with lamivudine and zidovudine was studied in PBC patients [72]. There is a good biochemical response seen in patient taking lamivudine and zidovudine but complete biochemical normalisation was not observed [72]. The study did not showed any correlation with virus and biochemical response and as a result, treatment is not recommended in PBC [72].
Recently, fibrates have been thought to be beneficial in PBC since it has anti-inflammatory effect via peroxisome proliferator activated receptor alpha (PPAR-a) [67]. Fenofibrate is a fibric acid and thought to modulate immune response and the cell proliferation and pilot study which treated 20 patients with fenofibrate and UDCA showed significant improvement in liver biochemistry (ALP and ALT) and Ig M although albumin and bilirubin remained unchanged [73]. Larger studies are needed in future. Similar findings were seen in study with bezafibrate.
Obeticholic acid (OCA) is a farnesoid X receptor (FXR) agonist [74]. FXR is expressed in liver, intestine, adrenal glands and kidneys and has an important role in the enterohepatic circulation of bile acids [74, 75]. FXR reduces bile acid synthesis by acting on the enzyme cholesterol 7a hydroxylase and also by down-regulating the expression of the sodium/taurocholate co-transporting peptide, a bile acid uptake protein[75]. Preliminary studies of OCA in patients with PBC have demonstrated marked biochemical improvement when administered in combination with UDCA and alone [74]. Pruritus is the most common side effects and seen at high dose. Currently, there is a phase 3 trial ongoing for OCA treatment in PBC patients.
There are many criteria used to assess biochemical response to UDCA (Table 5). The 1-year biochemical response to UDCA provides significant prognostic information even in the early stage of PBC [70]. Early-stage patients who show ALP and AST ⩽1.5× upper limit of normal (ULN), and normal bilirubin level after 1 year of treatment appear to be at very low or no risk of liver failure or progression to cirrhosis. In those patients, they had a 10-year transplant-free survival rate of 90% compared to 51% for those who did not (p <0.001) [76]. About 40% of patients have a suboptimal response to UDCA and subsequently need additional therapy. Liver transplantation is the treatment for patients with decompensated liver cirrhosis and recurrence of PBC is seen in 20% after LT [77].
Primary sclerosing cholangitis (PSC) is a rare autoimmune liver disease and primary affects larger bile ducts. It is caused by chronic inflammation which then leads to fibrotic strictures and dilatation of hepatic biliary system and leading to chronic cholestasis. Chronic cholestasis can subsequently lead to liver cirrhosis with portal hypertension and liver failure [78]. PSC can affect any part of the biliary system including the gallbladder [78].
It is more common in male with median age of around 40 and affects mostly Northern European descendants [79]. The most important underlying risk factor associated with PSC is inflammatory bowel disease and PSC is seen in 75 % of cases of patients with IBD [79]. Around 60 to 80% of patients with PSC have underlying ulcerative colitis, mainly on the right side of the colon and 4% of patients with UC have co-existing PSC [80].
A recent study in UK showed the incidence of PSC to be 0.41 cases per 100,000 populations [81], although the true incidence may be underestimated since it is a relatively rare diseases and needs expertise and invasive procedures to make the diagnosis [79].
The exact mechanism of pathogenesis in PSC is unknown but thought to be multifactorial. It has thought that PSC occurs in individuals with genetic predisposition triggers various environmental stimuli [80]. Patient who has first degree relative with PSC have 9 to 39 fold increased risk of developing PSC and the most associated HLA are HLA DRB1 and DRQ1 [80]. Gut and liver axis theory had been proposed in the pathogenesis of PSC [82]. Manipulation of the intestinal micro flora changes the immune and metabolic pathway [83]. There has been hypothesized that translocation of microbial flora across the inflamed, permeable gut via the portal system to liver and biliary system activate the immune system and cause inflammation of the biliary tree [84-86]. Homing of mucosal lymphocytes which possess (C-C motif chemokine receptor-9) CCR9 and alpha4beta7 in the liver leads to biliary damage in PSC [87, 88]. Recently mucosa associated innate T cells and innate lymphoid cells has been proposed in the pathogenesis of PSC [89]. Although the putative gut-derived trigger(s) of hepatobiliary pathobiology in PSC has not been determined, microbial metabolites or products (i.e., pathogen-associated molecular patterns, PAMPs) such as lipopolysaccharide (i.e., endotoxin, LPS) and peptidoglycan (i.e., a bacterial cell wall polymer, PG) have been proposed as likely candidates [90].
About 15-40% of patients are asymptomatic during the early stage of the clinical course and at later stage, the most common symptoms are jaundice, pruritus, fatigue and abdominal pain [79]. Any patient who has underlying IBD and abnormal liver blood tests especially raised ALP should be investigated for PSC. In 95 % of cases, ALP rose 3-10 times the upper limit of normal and other liver enzymes ALT and AST were 2-3 times above the normal limit [79]. Bilirubin tends to be within normal range in about 60% of patients. In 69-95% of patients with PSC, 50 to 80% of patients with UC and 10-20% of patients with Crohn’s colitis have positive perinuclear antineutrophil autoantibodies (pANCA) [79].
Mayo risk score is used in PSC and the score is calculated using age, bilirubin, albumin, liver transaminase, AST and varcieal bleed and it is used to estimate survival of patient with PSC for up to 4 years [132]. The Mayo Risk Score= (0.0295 * (age in years)) + (0.5373 * (total bilirubin in mg/dL)) - (0.8389 * (serum albumin in g/dL)) + (0.5380 * (AST in IU/L) + (1.2426 * (points for variceal bleeding; 0= No, 1=Yes)). The score of less than or equal to zero is regarded as low risk, between 0 and 2 as intermediate and above 2 as high risk groups.
The diagnosis is best confirmed by MRCP, which is a non-invasive and first line investigation for the diagnosis of PSC. ERCP is used mainly for therapeutic purposes such as stenting, balloon dilatation and biliary brushing in patient with PSC. Contrast cholangiography, which reveals characteristic features of diffuse, multifocal strictures and focal dilation of the bile ducts, leading to a beaded appearance [79]. Liver biopsy is rarely necessary due to good diagnostic yield with MRCP or ERCP investigations except in suspicion of small duct PSC or overlap with AIH. Periductal concentric (“onion-skin”) fibrosis is a classic histopathologic finding of PSC, but this observation is infrequent in PSC [91] (Figure 5).
Histology findings in Primary Sclerosing Cholangitis (PSC)
In addition to biliary cirrhosis, complications of PSC include dominant strictures of the bile ducts, cholangitis, cholangiocarcinoma, colon dysplasia and cancer in patients with IBD, gallbladder polyps, gallbladder cancer, and hepatic osteodystrophy [79]. Cholangitis occurs in 10 to 15 % of patients with PSC [80]. The cumulative lifetime risk for cholangiocarcinoma in PSC is estimated at 7 to 15% [67]. About half of those cholangiocarcinomas are diagnosed within one year of PSC diagnosis and the rate of cancer development is 0.5 to 1.5% per year subsequently after the first year[67]. Suspected dominant stricture should be investigated by Endoscopic ultrasound scan (EUS) and biopsy along with Positron Emission Tomography (PET) scan.
Immunoglobulin G4 (Ig-G4) associated cholangitis is similar to PSC and is characterized by the presence of biliary strictures, lymphoplasmacytic infiltration and elevated Ig G4 serum levels [92]. Ig G4 elevation is seen in 12% of PSC patients [92]. The biliary features are similar on the cholangiogram in these two conditions and hence, it is important to check Ig G4 level and review the anatomy of pancreas on imaging. Tissue from liver biopsy can be stained using monoclonal anti-human IgG4 antibody. It is important to differentiate between the two because Ig G4 associated cholangitis or pancreatitis responsive to steroids unlike PSC.
To date, there are no effective therapies for patients with PSC and the only treatment for end stage PSC is liver transplantation. Timing for liver transplantation is challenging in PSC as these patients sometimes do not fulfil MELD criteria MELD criteria but they can deteriorate rapidly thus early referral to experience centres is essential. UDCA has been used in cholestatic patients with PSC although the data suggested that the medication has not improved overall survival. Studies utilizing doses between 10–15 mg/kg/day were associated with biochemical and histologic improvement [93, 94]. Two previous studies looking at high dose UDCA at a dose of 17-23 mg/kg/day [95] and 28-30 mg/kg/day [96, 97] showed that there were no difference in mortality or LT but increased in adverse events. A recent meta-analysis found no difference in fatigue, mortality, histologic progression or development of cholangiocarcinoma for standard or high dose UDCA [92, 98] and therefore, high dose UDCA is not used in routine clinical practice.
Antibiotics are used in patients with biliary sepsis in the background of PSC and some clinicians used rotating antibiotics in patients with resistant bacteremia. Published data looking into vancomycin or metronidazole treatment suggests that both are efficient in treatment of infection but vancomycin achieved improvement in ALT more than metronidazole with less side effects [99]. A recent randomised pilot study of vancomycin or metronidazole treatment in PSC patients showed that both antibiotics are effective although only vancomycin group reached the primary end point of reduction in ALP at 12 weeks [99].
There are many ongoing clinical trials in PSC such as obeticholic acid, mitomycin, thalidomide, LUM001: an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTi), GS-6624: a Monoclonal Antibody against Lysyl Oxidase like 2 (LOXL2), Xifaxan, Cladribine and the combination of UDCA and all trans-retinoid acid (ATRA) (www.clnicaltrial.gov). There are ongoing phase 1 and 2 trials on anti-fibrotic therapies in PSC.
The term ‘overlap syndrome’ described co-existence of AIH with features of PBC or PSC [12]. The diagnosis can be challenging and there is no single test available to diagnose. Therefore, it is important to revisit clinical history or repeat investigation if there is in doubt with the diagnosis. The diagnosis can be made with combination of tests such as blood biochemistry, immunology with addition of radiology and tissue biopsy. It is assumed that overlap syndrome can be found in 5-20% of cases [12].
AIH/PBC should be considered in patients with mixed pattern of cholestastic and hepatitis features or anyone with suboptimal response to immunosuppressions. It has been reported that AIH/PC occurs in 8% of patients with either AIH or PBC. Some PBC patients express negative AMA with positive ANA serology or SMA serology and hence, diagnosis based on immunology alone can be tricky. In general, IgG elevation is common in AIH and IgM is manly observed in PBC. Treatment should be targeted both AIH and PBC in these patients.
In adults with both AIH and IBD, cholangiographic changes suggestive of PSC are present in up to 44% patients and may affect therapy and prognosis [13]. Those who develop AIH during childhood or Autoimmune sclerosing cholangitis are most common to develop into AIH/PSC overlap. MRCP and repeat liver biopsy is recommended. Treatment should be directed towards PSC and immunosuppression should be slowly weaned off unless they are indicated for inflammatory bowel disease.
Liver transplantation (LT) is the treatment for patients with end stage AIH, PBC or PSC disease. The common indications are decompensated liver cirrhosis as indicated by the presence of refractory or resistant ascites, hepatic encephalopathy or uncontrolled variceal bleeding. Hepatocellular carcinoma, hepatopulmonary syndrome and portopulmonary hypertension are the other indications for LT. Model for End Stage Liver Disease (MELD) score is calculated by using renal function (Creatinine), International Normalised ratio (INR) and Bilirubin. MELD score= [0.957x Loge (creatinine in mg/dL) + 0.378x Loge (bilirubin in mg/dL) + 1.120x Loge (INR) + 0.643) [133]. Patients with MELD score of above 16 with other indication is considered for liver transplant assessment. MELD score was initially developed to predict survival in patients undergoing Trans jugular Porto systemic shunt [100, 101]. In 2002, UNOS (the United Network of Organ Sharing) adapted a new approach to allocate organ giving priority to the sickest patient and the assessment is based on MELD score [102]. Implementation of MELD in 2002 led to an immediate reduction in LT waiting list registrations for the first time in history of LT (12% decrease in 2002) [103] as well as reduction in mortality on the waiting list [104].
Since 1996, listing for transplantation in the United Kingdom was based on the following principles: selecting patients if the expected survival without transplantation was 1 year or less or liver disease that was associated with an unacceptable quality of life and expecting that patients would have an at least 50% survival at 5 years with acceptable quality of life [105]. Serum sodium was associated with a higher risk of mortality independent of the MELD score in patients listed for orthotropic liver transplantation [106]. In United Kingdom, UKLED score (United Kingdom End Stage Liver Disease has been used since 2008 and it is calculated from patient’s INR, serum creatinine, serum bilirubin and serum sodium) has been used in assessment of liver transplantation. UKELD score of 49 is the baseline entry criteria for LT assessment. Patients with UKELD score of 49 have 9% one year mortality and score above 60 has mortality of 50% [105].
LT is required in about 10% of patients with AIH and in Europe; 4-6 % of LT are for the indication of AIH [2, 7]. Long-term survival is excellent in AIH patients with 5 year survival being up to 92 % [2]. Recurrence of AIH can occur post LT and the rate of recurrence is between 8-12 % at year 1 and higher after 5 years follow up with the rate of around 36-65% [107]. The treatment should be either increase with the ongoing immunosuppressive therapies or change to alternative therapies such as addition of MMF, replacement of tacrolimus with cyclosporine or the replacement of calcineurin inhibitor (CNI) with sirolimus [108].
In patients with PBC, LT is indicated for decompensated liver cirrhosis, hepatocellular carcinoma and intractable pruritus with unacceptable quality of life. Patient should be referred for LT assessment when the bilirubin reaches around 100 umol/L with MELD >12 and Mayo risk score of 7-8 [134]. PBC can recur in post LT and the median time is 3 to 5.5 years although it can happen within the first year of transplantation [108]. PBC recurs in 15 to 30% of patients after LT and most of the patients do not lose their graft [67]. The treatment of recurrence PBC is UDCA, which causes improvement with ALP and ALT but not the patient or graft survival [109].
In addition to above mentioned indication for LT, some patients with PSC will need LT due to intractable pruritus, recurrent cholangitis in the presence of dominant bile duct strictures that cannot be managed endoscopically and the presence of limited stage cholangiocarcinoma [108]. 5 year survival post LT is around 80%[92]. Recurrence of PSC have been documented among LT recipients and its prevalence ranges from 15 to 30% and the median time for recurrence is between 3 and 5 years post LT [108] and can be associated with poor survival and graft loss [67].
De novo autoimmune hepatitis (d-AIH) in LT patients whom were transplanted for other reasons than AIH was documented in late 1990 [110]. De novo autoimmune hepatitis occurs in 1-7 % of patients 0.1-9 years after transplantation, especially in children [135]. Risk factors for de novo-AIH had been associated with older age donor, female donor, acute cellular rejection and the use of tacrolimus [111, 112]. The disease is usually characterized by features of acute hepatitis in otherwise stable transplant recipients. The characteristic feature is a marked hypergammaglobulinaemia with positive ANA. Antibodies against glutathione S-transferase T1 (GSTT1) has been reported in patients with de novo immune hepatitis following liver transplantation, thus suggesting that immune system recognizes the Glutathione S-transferase theta-1 (GSTT1) protein as a non-self-antigen, and mount an allo-reactive immune response and molecular mimicries that override self-tolerance[113]. Antibodies against cytokeratin 8/18 in patient with de novo autoimmune hepatitis after living-donor liver transplantation had also been reported thus the changes in cytokeratin 8/18 in hepatocytes might be one of the sources of pathogenesis of de novo autoimmune hepatitis after liver transplantation[114]. A histologic pattern of centri-lobular injury including increased necroinflammatory activity and increased plasma cell infiltration correlates with measurements of autoimmunity in de novo AIH recipients [115]. Treatment with increased dose of steroids or Azathioprine results in an improved outcome. However, maintenance therapy is usually required [116]. Standard liver tests do not reflect the extent of these changes, so protocol liver biopsies may be required to detect these changes [117].
Pregnancy constitutes a major challenge to the maternal immune system. AIH tends to improve after the second trimester of pregnancy, allowing a decrease in immunosuppressive therapy. It is due to a variety of immunological alterations that are induced by pregnancy in order to protect the semi-allogeneic fetus from rejection. Immuno-regulation induced by pregnancy polarizes the immune system to T-Helper (TH)-2 predominant phenotype. The increase of circulating inhibitors of pro-inflammatory cytokines occurring in pregnancy could act as a potent anti-inflammatory agent in AIH. T regulatory (Treg) cells are a recently discovered subset of T-lymphocytes with potent suppressive activity and pivotal roles in curtailing destructive immune responses and preventing autoimmune disease[118]. Systemic expansion of the maternal T suppressor or CD4+CD25+ regulatory T cell pool during pregnancy suppress an aggressive allogeneic response directed against the fetus[119].
Premature birth is the greatest risk and fetal mortality is reported to be around 21%, perinatal mortality is 4% and maternal mortality is 3% [14]. Poor disease control in the year prior to pregnancy and the absence of drug therapy are associated with poor outcomes [120]. Adverse pregnancy outcomes were highly associated with the presence of antibodies against soluble liver antigen/liver-pancreas (SLA/LP) and Ro/SSA [121] Preconception advice and discussion is important and should be emphasised. More than half of the women reduced or stopped the immune suppression during pregnancy or breastfeeding. AZA is a Food and Drug Administration (FDA) category D drug and safety in pregnancy has not been well established in human studies [14] however, current pharmacological treatment including azathioprine appears to be safe during pregnancy and lactation. There are no reported increased in congenital malformations with AZA and it is safe to use in mother who plan to breast-feed the baby. AIH commonly exacerbates following delivery [122, 123] and therefore, vigilance is required during the postpartum period. Patients with AIH need to be monitored carefully during pregnancy and for several months post partum [124]. Women with advance cirrhosis and portal hypertension have an increased risk of variceal bleed during the pregnancy and therefore, eradication of varices either with banding or pharmaco-therapy are recommended prior to conception. Pregnant women with cirrhosis and portal hypertension should undergo upper GI endoscopy during the second trimester and careful discussion with obstetric team and fetal medicine team is required for the safety of mother and the baby.
There are limited data for pregnancy and PBC. It has been noted that early diagnosis of PBC and early used of UDCA have a favourable outcomes on the pregnancy [125]. PSC rarely occur in female but the condition does not seem to reduce fertility in both men and women according to case series [126].
AILD is a spectrum of autoimmune condition mainly affecting liver (in the case of AIH) and biliary system (in PBC and PSC). The diagnosis is guided by clinical, biochemical and immunological parameters, although liver biopsy is still useful especially in patients with AIH to diagnose as well as for the assessment and monitoring of the disease status. In AIH, the aim of the treatment is to suppress the immune system with long term immunosuppressive medications such as azathioprine. There are new therapies emerging on the horizon. In PBC, women are more affected and the current treatment used is UDCA although there are many trials running ongoing in the treatment of PBC and it is an exciting era. For PSC, the definitive treatment is liver transplantation and more research is needed to understand that pathogenesis and treatment in this field of subject.
The histology slides were kindly provided by Professor Stefan Hubscher, Liver Histology Department, University Hospital Birmingham NHS Trust, Birmingham, UK. N.N.T is funded by National Institute for Health Research (NIHR) and Y.H. O is funded by Medical research council (MRC).
College students’ mental health plays a very important role in their success and persistence at their institution [1]. When the students can manage their anxiety, they feel less pressure. If the students remain anxious, they may not follow through with their academic studies. Also, anxiety could complicate their physical and psychological states and persist after graduation, and it may negatively affect their capacity to work in the future [2]. Therefore, it is important to understand the factors that cause students’ anxiety at higher education institutions.
\nTo achieve the purposes of the study which focused to present the factors that cause students’ anxiety in higher education institutions and find the solutions to this issue, a literature review was used to describe students’ perception of anxiety feelings while they study in higher education institutions. Many studies that described students’ perceptions from different countries were used to present this issue.
\nThe researcher collected the researches that focus on students’ anxiety and grouped them in different subcategories and explained each category based on the availability of recent researches that belong to the topic and the experience of the researcher. Although there were many factors that may cause students’ anxiety, the researcher focused on some critical factors that presented in most higher education institutions in recent years.
\nStudying a new language is a major factor that causes anxiety among many students, especially those who follow their studies in a non-native language. Most students in higher education institutions study English as a foreign language or as a second language. Some of them may learn English before college. However, they may not able to meet the high level of English proficiency required at the college level. They face anxiety because if they cannot pass successfully, they may not be able to graduate from the institution.
\nTian [3] indicates Korean students face language anxiety when they must make presentations in class, and they lack language proficiency. Moreover, they feel anxiety because of their peers’ negative feedback. Charoensukmongkol [4] also indicates Thai students face language anxiety because they lack proficiency in the English language. Tsai and Lee [5] found Taiwanese students have anxiety when reading English because they do not understand the English vocabulary, the topics, or the long and complicated text structures, and they fear they will make mistakes when answering questions.
\nJawas [6] found Indonesian students also have English language anxiety because they lack proficiency in writing, and the instructors present them with class essay assignments that probably increase their anxiety because of the limited time in class to finish the assignment with the appropriate answer. Also, some Indonesian students have anxiety when giving a presentation. Some of them may not prepare well and do not like when someone asks them difficult questions about the presentation [7].
\nAbdala and Elnadeef [8] also indicate that Saudi Arabian students feel anxious about learning the English language specifically when they make mistakes in the class and lack writing proficiency. They are scared when they hear unwanted comments and jokes from their classmates while they are speaking. Some other students face anxiety in learning the Chinese language [9]. The Chinese language is not easy to learn, specifically in speaking and writing. Also, some Hispanic students have difficulties when studying Spanish, specifically in writing, spelling words, and using conjunctions [10].
\nCurriculum difficulties are also considered a factor that causes students’ anxiety in most higher education institutions. Some students cannot understand the curriculum and struggle to answer questions in the classroom, do assignments, and write research papers or reports. Some students may hesitate to ask the instructors for help; therefore, they become anxious because they are unable to meet the course requirements. Some difficult curriculums include mathematics [11, 12, 13], biology [14, 15], statistics [16], chemistry, physics, history [17], and law [18]. In addition, there are several medical specialization classes that cause students’ anxiety, such as dental and medical [19], medical and engineering [20], dentistry and veterinary [21], and pharmacy [22].
\nSome students face anxiety with midterm and final exams because they are not well prepared. Some students may not understand the exam questions and write the wrong answers as a result [17]. More importantly, sometimes there is not enough time to answer the exam questions. Some faculty members do not know the differences in the students’ abilities, and they make exams that do not fit with some students’ intelligence. As a result, students may fail the exams. Exam anxiety is widespread among college students [23, 24] in different majors like math, history, geography, chemistry, physics, engineering, arts, and music. For example, some students specializing in music have anxiety in exams where they must use a musical instrument [25]. Also, some pharmacy students have anxiety about their clinical exams [22].
\nSome students also face anxiety about online exams because some faculty members make the exams with a time limit, and some students may need more time. Also, the computer may not work well or Internet services may shutdown while students are taking the online exam. As a result, some students may not prefer online exams.
\nFinancial anxiety is considered an issue many students face when studying at higher education intuitions because they are responsible for paying for their studies, especially those at private institutions. Some of them may be in debt. This financial pressure leads students to feel anxiety, which causes them psychological distress [26] that results in a lower grade point average (GPA). Some students who face difficulties in understanding difficult subjects depend on costly private instructors. Students also need money for daily expenses such as food and transportation. When students feel they do not have enough money, they may be anxious and ask friends for money, which negatively affects students’ feelings, leading to stress and anxiety.
\nMany international students suffer from alienation and culture shock when they seek to continue studying in other countries. This shock causes them psychological crises such as anxiety because of the distance from their family and country, the difficulty of a new language and speaking with others, and the difficulty of adapting to the new culture, which requires patience.
\nSome university students have many family problems that cause them anxiety while they are studying. One of these problems is the illness of a family member, such as a parent, which requires the student to remain close to the patient. If the students are they have responsibility of the children and the husband. These problems affect the student academically because it hinders him in preparing well for tests, performing academic duties, and attending lectures, which causes him concern about how to balance his family and academic responsibilities.
\nSome students who suffer from a chronic illness have anxiety [27]. For example, a student who suffers diabetes is required to take daily insulin injections and go to the health center, and some may experience dizziness while at the university campus. Diabetes may hinder a student if his health condition relapses, and he may be absent from the university. Other illnesses include cancer, anemia, heart problems, asthma, and obesity. These diseases may negatively affect the academic level of the students, which causes them anxiety.
\nSome students who attend higher education institutions work off campus part or full time. Some of them may not be able to attend classes, specifically if they work in the mornings and their classes are scheduled for the same time. Some of them face anxiety if they cannot manage their time. They may fail their courses because of their absences or fail exams because they do not prepare well. As a result, they receive a lower GPA and an academic warning.
\nDiscrimination is a concern that many students face at higher education institutions. The institutions gather students and staff from different backgrounds, nationalities, ethnicities, religions, colors, cultures, and levels of intelligence. Some students feel anxiety because of unfair treatment from classmates, friends, and staff and faculty members. When the students feel they are not welcome and they are treated badly, this causes them to feel anxiety [28, 29].
\nSome disabled students enter higher education institutions to further their studies, despite the challenges they face. Some disabled students have anxiety because they are unable to major in some specializations they may need. Some specializations such as geology and biology need students to participate in course activities using labs and instruments, which is difficult for some disabled students. Also, they may not be able to socialize with other students and may prefer isolation. Some students are visually impaired and require specific resources like certain textbooks, handouts, and software [30]. However, these resources are not available for some courses. Also, some students may have psychiatric disabilities [31] and need special attention from the mental health center to help them succeed academically. Some students who have autism spectrum disorder have anxiety when trying to achieve success in their academic studies [32].
\nWhen students have anxiety, it affects their mind and body and causes several symptoms: cognitive, physical, and emotional.
\nMany students could experience symptoms along with their feelings of anxiety. They may have many negative and painful experiences, such as insomnia and other sleep disorders. Anxiety also negatively affects students’ memories. They may become unable to think correctly and make decisions; therefore they cannot participate in classroom discussions and cannot share their opinions and ideas with other classmates and faculty members. Some of them feel sadness, fear, and panic. As a result, their academic achievements are negatively affected.
\nStudents with anxiety can experience significant pain with symptoms like breathing problems, stomachaches, headaches, joint and muscle pain, and fatigue. These symptoms could make them unable to come to the university. Some students may fear from the faculty, so they upsent from the institution. Some students become fatigued when they have a lot of academic work to do on campus and feel anxious because they do not know how to manage this work. This academic anxiety badly affects students’ health; however, they should cope with anxiety. Some students have sensitive behaviors, which play a role in their tendency to become overwhelmed with anxiety. This needs change for students to cope with academic life.
\nSome students who suffer from anxiety experience painful emotional symptoms such as depression, sadness, nervousness, anger, and loneliness. Students may feel unhappy about coming to a university or become very nervous around people, such as friends and peers. Others feel worried and sad when they cannot overcome the challenges they face, such as having a low GPA. Some of them like to be alone when they have stressful feelings, which can lead to depression. Sometimes, these students may have negative thoughts about withdrawing from college, especially when their friends are successful and have good GPAs. Some students may feel tired from studying, the tough curriculum, and attending the university. They may have expected to be happy with university life but instead found it to be the opposite of what they wanted.
\nMental health problems are a social phenomenon that requires attention in many societies [33]. Anxiety is an aspect of a college student’s mental health. Attention must be paid to the means that help prevent students from falling into anxiety and reducing its severity and psychological impact on the students continuing their studies.
\nHaving human relationships between faculty members and students is very important. Communication between these groups plays an important role in reducing students’ anxiety. The faculty members should ask students if they need help to understand the curriculum, do assignments, and write reports. The faculty can design class activities related to the curriculum to make sure the students understand the content. For example, in teaching a language, the faculty should encourage group work in class to help students participate in communication to improve their speaking and their relationships with classmates to reduce the anxiety. Also, video games online can improve communication among students, increase students’ confidence, and reduce their anxiety [34]. Collaborative work among students can also reduce students’ anxiety, and they should be encouraged to use the strategies they prefer in learning [6].
\nThe faculty members can encourage students to answer questions, whether they are right or wrong, to reduce students’ fear. They should provide students with steps to do the assignments, write reports, and create projects. The faculty members should also understand that students differ in abilities and intelligence when they design exam questions. The exams should meet different students’ abilities to reduce their anxiety. Hull et al. [35] indicate the importance of changing evaluation tools and improving students’ self-efficacy.
\nThe faculty members have important roles in guiding students and giving them advice related to academic decisions, such as selecting a college or selecting a major, and helping them manage their time for studying multiple curriculums. In helping them deal with anxiety, adapt to the challenges, and improve their thinking, faculty members can reduce anxiety’s psychological side effects on students’ bodies and minds.
\nMany institutions provide students with mental health workers to help them cope with their negative feelings while they pursue their studies. To provide students with efficient mental services, the institutions should hire workers who specialize in psychology and counseling. This will provide students with effective strategies to reduce their anxiety. These mental health workers should be available to meet students on campus and, most importantly, give students a trusted and secure setting in which to improve their self-confidence when they seek help. They should provide students with a socialized atmosphere to reduce their isolation and fear, specifically students with psychiatric disabilities and autism spectrum disorder. These students need to manage their social emotions to adapt to university life [32]. Online social networks should be improved to help them socially [36].
\nAlso, it’s important to provide international students with mental health workers who can deal with their culture shock, speak different languages to meet various students’ needs, and provide them with social support and a friendly relationship. Different social and cultural activities on campus can help students communicate with others and reduce their anxiety as well. Shelton, Wang, and Zhu [37] indicate that cultural orientation is an appropriate way to keep students mentally healthy.
\nTo reduce students’ academic anxiety, institutions should provide students with effective academic services like a writing center, which helps students write in many subjects and improves their efficiency in using vocabulary and grammar. Tutorial services are also important in helping students reduce their anxiety. The tutorial should be provided by an effective staff specializing in the curriculum to help students understand the content of the courses, specifically in language courses, mathematics, statistics, and biology.
\nImproving library services can help students do research and experiments. According to Grandy [38], some adult students have library anxiety because they are unable to use the library services. Therefore, these students should be provided with information literacy courses to reduce their anxiety about using library resources, technology resources, and searching strategies.
\nMany students who suffer from anxiety can manage their negative feelings through exercises like walking, swimming, and playing tennis. Some students join sports clubs, which results in an improvement in their positivity and happiness. Taking part in physical activities can greatly reduce the negative psychological health impacts on a student’s body and mood [17], reduce mental difficulties, and improve their health well-being [39]. Other students may prefer to reduce their anxiety by reading books about mental health and dealing with anxiety to be aware of how they can manage their symptoms. Some of them may also read novels and magazines for relaxation [17].
\nStudents at higher education institutions face many kinds of challenges that affect negatively their psychology feeling, causing them anxiety. Its effects vary among students in how to deal with it, overcome its symptoms, and find solutions. The study found that the most important factor that causes anxiety is related to academic study. For example, many students who study a new language face challenges in understanding language words, speaking, and writing. This issue was found in many students in different countries such as Korea, Thailand, Indonesia, China, and Saudi Arabia, which reflect that this issue is widespread internationally among higher education institutions. This finding needs a special issue from the faculty members to dedicate efforts in helping students understand a new language without the feeling of anxiety.
\nThe finding also highlights that students in different colleges and specialization face anxiety. This finding may reflect that some students may have low academic competency to study in a specific specialization and not qualify to study high level of curriculum contents. However, some faculty members may not spend adequate time to explain to students the curriculums’ contents, which may affect negatively students’ feeling in searching and understanding. As it known that students vary in competencies, therefore the faculty members should focus in insuring that students understand the curriculum and how doing the assignments .
\nIn addition, most students in higher education institutions face anxiety of midterm and final exams in most specialization. This issue needs faculty members’ attention to focus on preparing students for exam and reduce their anxiety. As it is known, students attend the university or college to get knowledge and improve their abilities, not to feel anxiety and have a psychological sickness.
\nBesides academic factors, some students feel anxiety because of financial pressure and not being able to pay the tuitions and fees. This issue is widely spread among students specifically who study in a private institution. Actually the institution should consider the students’ financial level before admitting them in the institution to insure their ability to pay to reduce their anxiety.
\nSome students feel anxiety because of illness and not being able to attend class daily and doing assignments and preparing for exams. The medical staff in the institution should consider students with illness and disabilities and follow their health situations to insure their capability to follow their study and provide them with support services to reduce their anxiety. Most importantly some students hesitate to inform the support staff with their illness or disability situation; as a result they may not able to deal with the problems that they might face, and as a result they feel anxiety.
\nBecause the anxiety have several negative cognitive, physical, and emotional symptoms which negatively affect students’ mental health. Several solutions were suggested to alleviate students’ anxiety through developing human relationship between students and faculty members, which is an important factor in helping students reduce their anxiety feelings. It is important that faculty members recognize the importance of helping students in gaining knowledge and understanding curriculum contents to help them become qualified graduates in the work market with well body and mental health. As several researchers indicated, the negative effects of anxiety could have a continuous side effect on the students when they graduate and join the workforce. The workforce needs healthy and qualified graduates who can work without anxiety and stress.
\nMost students studying at higher education institutions face many challenges that give them a negative feeling and lead them to have anxiety. The most important factor that affects students is the academic challenges which are related to their persistence or retention in the institutions. Some of these academic factors include difficulty of studying new language, midterm and final exams, and curriculum. Some other students also face anxiety related to different reasons such as being ill or disabled students. Also some students feel discrimination which affects them negatively. International students also face culture shock anxiety which affects their persistence in the institutions. Students should learn managing this feeling to prevent their mental health from unwanted symptoms which may negatively affect their psychological behaviors. Also, students should understand how to improve their thinking and mind to adapt to the different challenges they face in their academic life. More importantly the university and college leadership should consider the importance of providing students with academic environment that encourage students’ learning and persistence at the institution and protect them from an unwanted anxiety feeling which probably may change students’ behaviors and attitudes negatively after graduation.
\nBook - collection of Works distributed in a book format, whose selection, coordination, preparation, and arrangement has been performed and published by IntechOpen, and in which the Work is included in its entirety in an unmodified form along with one or more other contributions, each constituting separate and independent sections, but together assembled into a collective whole.
",metaTitle:"Attribution Policy",metaDescription:"DEFINITION OF TERMS",metaKeywords:null,canonicalURL:"/page/attribution-policy",contentRaw:'[{"type":"htmlEditorComponent","content":"Work - a book Chapter (as well as Conference Papers), including any and all content, graphics, images and/or other materials forming part of, or accompanying, the Chapter/Conference Paper.
\\n\\nAttribution – appropriate credit for the used Work or book.
\\n\\nCreative Commons licenses – enable licensors to retain copyright while allowing others to use their Works in an appropriate way.
\\n\\nWith the purpose of protecting Authors' copyright and the transparent reuse of OA (Open Access) content, IntechOpen has developed Rules of Attribution of Works licensed under Creative Commons licenses.
\\n\\nIn case you reuse or republish any of the Works licensed under CC licenses, you must abide by the guidelines outlined below:
\\n\\nAll rights to Books and other compilations published on the IntechOpen platform and in print are reserved by IntechOpen. The Copyright to Books and other compilations is subject to a separate Copyright from any that exists in the included Works.
\\n\\nA Book in its entirety or a significant part of a Book cannot be translated freely without specific written consent by the publisher. Further information can be obtained at permissions@intechopen.com.
\\n\\nIn instances where permission is obtained from the publisher for reusing or republishing the Book, or significant parts of the Book, all of the following conditions apply:
\\n\\nEvery single Work that is used has to be attributed in the way described. If you are unsure about proper attribution, please write to permissions@intechopen.com.
\\n\\nIndividual Works originally published in IntechOpen books are licensed under Creative Commons licenses and can be freely used under terms of the respective CC license, if properly attributed. In order to properly attribute the Work you must respect all the conditions outlined below:
\\n\\nEvery single Work that is used has to be attributed in the way as described. If you are unsure about proper attribution, please contact Us at permissions@intechopen.com.
\\n\\nIn the event that you use more than one of IntechOpen's Works published in one or more books (but not a significant part of the book that is under separate Copyright), each of these have to be properly attributed in the way described.
\\n\\nIntechOpen does not have any claims on newly created copyrighted Works, but the Works originally published by IntechOpen must be properly attributed.
\\n\\nAll these rules apply to BOTH online and offline use.
\\n\\nParts of the Rules of Attribution are based on Work Attributing Creative Commons Materials published by the Australian Research Council Centre of Excellence for Creative Industries and Innovation, in partnership with Creative Commons Australia, which can be found at creativecommons.org.au licensed under Creative Commons Attribution 2.5 Australia license, and Best practices for attribution published by Creative Commons, which can be found at wiki.creativecommons.org under the Creative Commons Attribution 4.0 license.
\\n\\nAll the above rules are subject to change, IntechOpen reserves the right to take appropriate action if any of the conditions outlined above are not met.
\\n\\nPolicy last updated: 2016-06-09
\\n"}]'},components:[{type:"htmlEditorComponent",content:'Work - a book Chapter (as well as Conference Papers), including any and all content, graphics, images and/or other materials forming part of, or accompanying, the Chapter/Conference Paper.
\n\nAttribution – appropriate credit for the used Work or book.
\n\nCreative Commons licenses – enable licensors to retain copyright while allowing others to use their Works in an appropriate way.
\n\nWith the purpose of protecting Authors' copyright and the transparent reuse of OA (Open Access) content, IntechOpen has developed Rules of Attribution of Works licensed under Creative Commons licenses.
\n\nIn case you reuse or republish any of the Works licensed under CC licenses, you must abide by the guidelines outlined below:
\n\nAll rights to Books and other compilations published on the IntechOpen platform and in print are reserved by IntechOpen. The Copyright to Books and other compilations is subject to a separate Copyright from any that exists in the included Works.
\n\nA Book in its entirety or a significant part of a Book cannot be translated freely without specific written consent by the publisher. Further information can be obtained at permissions@intechopen.com.
\n\nIn instances where permission is obtained from the publisher for reusing or republishing the Book, or significant parts of the Book, all of the following conditions apply:
\n\nEvery single Work that is used has to be attributed in the way described. If you are unsure about proper attribution, please write to permissions@intechopen.com.
\n\nIndividual Works originally published in IntechOpen books are licensed under Creative Commons licenses and can be freely used under terms of the respective CC license, if properly attributed. In order to properly attribute the Work you must respect all the conditions outlined below:
\n\nEvery single Work that is used has to be attributed in the way as described. If you are unsure about proper attribution, please contact Us at permissions@intechopen.com.
\n\nIn the event that you use more than one of IntechOpen's Works published in one or more books (but not a significant part of the book that is under separate Copyright), each of these have to be properly attributed in the way described.
\n\nIntechOpen does not have any claims on newly created copyrighted Works, but the Works originally published by IntechOpen must be properly attributed.
\n\nAll these rules apply to BOTH online and offline use.
\n\nParts of the Rules of Attribution are based on Work Attributing Creative Commons Materials published by the Australian Research Council Centre of Excellence for Creative Industries and Innovation, in partnership with Creative Commons Australia, which can be found at creativecommons.org.au licensed under Creative Commons Attribution 2.5 Australia license, and Best practices for attribution published by Creative Commons, which can be found at wiki.creativecommons.org under the Creative Commons Attribution 4.0 license.
\n\nAll the above rules are subject to change, IntechOpen reserves the right to take appropriate action if any of the conditions outlined above are not met.
\n\nPolicy last updated: 2016-06-09
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. His current research interests include the areas of mobile communication systems and channel modeling in addition to atmospheric optical communications, adaptive optics and statistics",institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5774},{group:"region",caption:"Middle and South America",value:2,count:5240},{group:"region",caption:"Africa",value:3,count:1721},{group:"region",caption:"Asia",value:4,count:10411},{group:"region",caption:"Australia and Oceania",value:5,count:897},{group:"region",caption:"Europe",value:6,count:15812}],offset:12,limit:12,total:118381},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{hasNoEditors:"0",sort:"dateEndThirdStepPublish",topicId:"6,5"},books:[{type:"book",id:"9662",title:"Vegetation Index and Dynamics",subtitle:null,isOpenForSubmission:!0,hash:"0abf2a59ee63fc1ba4fb64d77c9b1be7",slug:null,bookSignature:"Dr. Eusebio Cano Carmona, Dr. Ricardo Quinto Canas, Dr. Ana Cano Ortiz and Dr. Carmelo Maria Musarella",coverURL:"https://cdn.intechopen.com/books/images_new/9662.jpg",editedByType:null,editors:[{id:"87846",title:"Dr.",name:"Eusebio",surname:"Cano Carmona",slug:"eusebio-cano-carmona",fullName:"Eusebio Cano Carmona"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9659",title:"Fibroblasts - Advances in Cancer, Autoimmunity and Inflammation",subtitle:null,isOpenForSubmission:!0,hash:"926fa6446f6befbd363fc74971a56de2",slug:null,bookSignature:"Ph.D. Mojca Frank Bertoncelj and Ms. Katja Lakota",coverURL:"https://cdn.intechopen.com/books/images_new/9659.jpg",editedByType:null,editors:[{id:"328755",title:"Ph.D.",name:"Mojca",surname:"Frank Bertoncelj",slug:"mojca-frank-bertoncelj",fullName:"Mojca Frank Bertoncelj"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8977",title:"Protein Kinase - New Opportunities, Challenges and Future Perspectives",subtitle:null,isOpenForSubmission:!0,hash:"6d200cc031706a565b554fdb1c478901",slug:null,bookSignature:"Dr. Rajesh Kumar Singh",coverURL:"https://cdn.intechopen.com/books/images_new/8977.jpg",editedByType:null,editors:[{id:"329385",title:"Dr.",name:"Rajesh",surname:"Singh",slug:"rajesh-singh",fullName:"Rajesh Singh"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10557",title:"Elaeis guineensis",subtitle:null,isOpenForSubmission:!0,hash:"79500ab1930271876b4e0575e2ed3966",slug:null,bookSignature:"Dr. Hesam Kamyab",coverURL:"https://cdn.intechopen.com/books/images_new/10557.jpg",editedByType:null,editors:[{id:"225957",title:"Dr.",name:"Hesam",surname:"Kamyab",slug:"hesam-kamyab",fullName:"Hesam Kamyab"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10218",title:"Flagellar Motility in Cells",subtitle:null,isOpenForSubmission:!0,hash:"5fcc15570365a82d9f2c4816f4e0ee2e",slug:null,bookSignature:"Prof. Yusuf Bozkurt",coverURL:"https://cdn.intechopen.com/books/images_new/10218.jpg",editedByType:null,editors:[{id:"90846",title:"Prof.",name:"Yusuf",surname:"Bozkurt",slug:"yusuf-bozkurt",fullName:"Yusuf Bozkurt"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10750",title:"Solanum tuberosum - a Promising Crop for Starvation Problem",subtitle:null,isOpenForSubmission:!0,hash:"516eb729eadf0d1a9d1d2e6bf31e8e9c",slug:null,bookSignature:"Prof. Mustafa Yildiz and Dr. Yasin Ozgen",coverURL:"https://cdn.intechopen.com/books/images_new/10750.jpg",editedByType:null,editors:[{id:"141637",title:"Prof.",name:"Mustafa",surname:"Yildiz",slug:"mustafa-yildiz",fullName:"Mustafa Yildiz"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10797",title:"Cell Culture",subtitle:null,isOpenForSubmission:!0,hash:"2c628f4757f9639a4450728d839a7842",slug:null,bookSignature:"Prof. Xianquan Zhan",coverURL:"https://cdn.intechopen.com/books/images_new/10797.jpg",editedByType:null,editors:[{id:"223233",title:"Prof.",name:"Xianquan",surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10772",title:"Parasitic Plants",subtitle:null,isOpenForSubmission:!0,hash:"31abd439b5674c91d18ad77dbc52500f",slug:null,bookSignature:"Dr. Ana Maria Gonzalez and Dr. Hector Sato",coverURL:"https://cdn.intechopen.com/books/images_new/10772.jpg",editedByType:null,editors:[{id:"281854",title:"Dr.",name:"Ana Maria",surname:"Gonzalez",slug:"ana-maria-gonzalez",fullName:"Ana Maria Gonzalez"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10737",title:"Equus",subtitle:null,isOpenForSubmission:!0,hash:"258ffafc92a7c9550bb85f004d7402e7",slug:null,bookSignature:"Associate Prof. Adriana Pires Neves",coverURL:"https://cdn.intechopen.com/books/images_new/10737.jpg",editedByType:null,editors:[{id:"188768",title:"Associate Prof.",name:"Adriana",surname:"Pires Neves",slug:"adriana-pires-neves",fullName:"Adriana Pires Neves"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10777",title:"Plant Reproductive Ecology - Recent Advances",subtitle:null,isOpenForSubmission:!0,hash:"3fbf391f2093649bcf3bd674f7e32189",slug:null,bookSignature:"Dr. Balkrishna Ghimire",coverURL:"https://cdn.intechopen.com/books/images_new/10777.jpg",editedByType:null,editors:[{id:"206647",title:"Dr.",name:"Balkrishna",surname:"Ghimire",slug:"balkrishna-ghimire",fullName:"Balkrishna Ghimire"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10749",title:"Legumes",subtitle:null,isOpenForSubmission:!0,hash:"49d3123cde96adbe706adadebebc5ebb",slug:null,bookSignature:"Dr. Jose Carlos Jimenez-Lopez",coverURL:"https://cdn.intechopen.com/books/images_new/10749.jpg",editedByType:null,editors:[{id:"33993",title:"Dr.",name:"Jose Carlos",surname:"Jimenez-Lopez",slug:"jose-carlos-jimenez-lopez",fullName:"Jose Carlos Jimenez-Lopez"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10751",title:"Bovine Science",subtitle:null,isOpenForSubmission:!0,hash:"9e3eb325f9fce20e6cefbce1c26d647a",slug:null,bookSignature:"Dr. Muhammad Abubakar",coverURL:"https://cdn.intechopen.com/books/images_new/10751.jpg",editedByType:null,editors:[{id:"112070",title:"Dr.",name:"Muhammad",surname:"Abubakar",slug:"muhammad-abubakar",fullName:"Muhammad Abubakar"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:19},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:5},{group:"topic",caption:"Business, Management and Economics",value:7,count:2},{group:"topic",caption:"Chemistry",value:8,count:8},{group:"topic",caption:"Computer and Information Science",value:9,count:6},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:7},{group:"topic",caption:"Engineering",value:11,count:21},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:4},{group:"topic",caption:"Materials Science",value:14,count:6},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:25},{group:"topic",caption:"Neuroscience",value:18,count:2},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:3},{group:"topic",caption:"Physics",value:20,count:3},{group:"topic",caption:"Psychology",value:21,count:4},{group:"topic",caption:"Robotics",value:22,count:1},{group:"topic",caption:"Social Sciences",value:23,count:3},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:1}],offset:12,limit:12,total:24},popularBooks:{featuredBooks:[{type:"book",id:"9521",title:"Antimicrobial Resistance",subtitle:"A One Health Perspective",isOpenForSubmission:!1,hash:"30949e78832e1afba5606634b52056ab",slug:"antimicrobial-resistance-a-one-health-perspective",bookSignature:"Mihai Mareș, Swee Hua Erin Lim, Kok-Song Lai and Romeo-Teodor Cristina",coverURL:"https://cdn.intechopen.com/books/images_new/9521.jpg",editors:[{id:"88785",title:"Prof.",name:"Mihai",middleName:null,surname:"Mares",slug:"mihai-mares",fullName:"Mihai Mares"}],equalEditorOne:{id:"190224",title:"Dr.",name:"Swee Hua Erin",middleName:null,surname:"Lim",slug:"swee-hua-erin-lim",fullName:"Swee Hua Erin Lim",profilePictureURL:"https://mts.intechopen.com/storage/users/190224/images/system/190224.png",biography:"Dr. Erin Lim is presently working as an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates and is affiliated as an Associate Professor to Perdana University-Royal College of Surgeons in Ireland, Selangor, Malaysia. She obtained her Ph.D. from Universiti Putra Malaysia in 2010 with a National Science Fellowship awarded from the Ministry of Science, Technology and Innovation Malaysia and has been actively involved in research ever since. Her main research interests include analysis of carriage and transmission of multidrug resistant bacteria in non-conventional settings, besides an interest in natural products for antimicrobial testing. She is heavily involved in the elucidation of mechanisms of reversal of resistance in bacteria in addition to investigating the immunological analyses of diseases, development of vaccination and treatment models in animals. She hopes her work will support the discovery of therapeutics in the clinical setting and assist in the combat against the burden of antibiotic resistance.",institutionString:"Abu Dhabi Women’s College",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Perdana University",institutionURL:null,country:{name:"Malaysia"}}},equalEditorTwo:{id:"221544",title:"Dr.",name:"Kok-Song",middleName:null,surname:"Lai",slug:"kok-song-lai",fullName:"Kok-Song Lai",profilePictureURL:"https://mts.intechopen.com/storage/users/221544/images/system/221544.jpeg",biography:"Dr. Lai Kok Song is an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates. He obtained his Ph.D. in Biological Sciences from Nara Institute of Science and Technology, Japan in 2012. Prior to his academic appointment, Dr. Lai worked as a Senior Scientist at the Ministry of Science, Technology and Innovation, Malaysia. His current research areas include antimicrobial resistance and plant-pathogen interaction. His particular interest lies in the study of the antimicrobial mechanism via membrane disruption of essential oils against multi-drug resistance bacteria through various biochemical, molecular and proteomic approaches. Ultimately, he hopes to uncover and determine novel biomarkers related to antibiotic resistance that can be developed into new therapeutic strategies.",institutionString:"Higher Colleges of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Higher Colleges of Technology",institutionURL:null,country:{name:"United Arab Emirates"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10020",title:"Operations Management",subtitle:"Emerging Trend in the Digital Era",isOpenForSubmission:!1,hash:"526f0dbdc7e4d85b82ce8383ab894b4c",slug:"operations-management-emerging-trend-in-the-digital-era",bookSignature:"Antonella Petrillo, Fabio De Felice, Germano Lambert-Torres and Erik Bonaldi",coverURL:"https://cdn.intechopen.com/books/images_new/10020.jpg",editors:[{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9560",title:"Creativity",subtitle:"A Force to Innovation",isOpenForSubmission:!1,hash:"58f740bc17807d5d88d647c525857b11",slug:"creativity-a-force-to-innovation",bookSignature:"Pooja Jain",coverURL:"https://cdn.intechopen.com/books/images_new/9560.jpg",editors:[{id:"316765",title:"Dr.",name:"Pooja",middleName:null,surname:"Jain",slug:"pooja-jain",fullName:"Pooja Jain"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10192",title:"Background and Management of Muscular Atrophy",subtitle:null,isOpenForSubmission:!1,hash:"eca24028d89912b5efea56e179dff089",slug:"background-and-management-of-muscular-atrophy",bookSignature:"Julianna Cseri",coverURL:"https://cdn.intechopen.com/books/images_new/10192.jpg",editors:[{id:"135579",title:"Dr.",name:"Julianna",middleName:null,surname:"Cseri",slug:"julianna-cseri",fullName:"Julianna Cseri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9644",title:"Glaciers and the Polar Environment",subtitle:null,isOpenForSubmission:!1,hash:"e8cfdc161794e3753ced54e6ff30873b",slug:"glaciers-and-the-polar-environment",bookSignature:"Masaki Kanao, Danilo Godone and Niccolò Dematteis",coverURL:"https://cdn.intechopen.com/books/images_new/9644.jpg",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9243",title:"Coastal Environments",subtitle:null,isOpenForSubmission:!1,hash:"8e05e5f631e935eef366980f2e28295d",slug:"coastal-environments",bookSignature:"Yuanzhi Zhang and X. San Liang",coverURL:"https://cdn.intechopen.com/books/images_new/9243.jpg",editors:[{id:"77597",title:"Prof.",name:"Yuanzhi",middleName:null,surname:"Zhang",slug:"yuanzhi-zhang",fullName:"Yuanzhi Zhang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7847",title:"Medical Toxicology",subtitle:null,isOpenForSubmission:!1,hash:"db9b65bea093de17a0855a1b27046247",slug:"medical-toxicology",bookSignature:"Pınar Erkekoglu and Tomohisa Ogawa",coverURL:"https://cdn.intechopen.com/books/images_new/7847.jpg",editors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoglu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9027",title:"Human Blood Group Systems and Haemoglobinopathies",subtitle:null,isOpenForSubmission:!1,hash:"d00d8e40b11cfb2547d1122866531c7e",slug:"human-blood-group-systems-and-haemoglobinopathies",bookSignature:"Osaro Erhabor and Anjana Munshi",coverURL:"https://cdn.intechopen.com/books/images_new/9027.jpg",editors:[{id:"35140",title:null,name:"Osaro",middleName:null,surname:"Erhabor",slug:"osaro-erhabor",fullName:"Osaro Erhabor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8558",title:"Aerodynamics",subtitle:null,isOpenForSubmission:!1,hash:"db7263fc198dfb539073ba0260a7f1aa",slug:"aerodynamics",bookSignature:"Mofid Gorji-Bandpy and Aly-Mousaad Aly",coverURL:"https://cdn.intechopen.com/books/images_new/8558.jpg",editors:[{id:"35542",title:"Prof.",name:"Mofid",middleName:null,surname:"Gorji-Bandpy",slug:"mofid-gorji-bandpy",fullName:"Mofid Gorji-Bandpy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5252},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9521",title:"Antimicrobial Resistance",subtitle:"A One Health Perspective",isOpenForSubmission:!1,hash:"30949e78832e1afba5606634b52056ab",slug:"antimicrobial-resistance-a-one-health-perspective",bookSignature:"Mihai Mareș, Swee Hua Erin Lim, Kok-Song Lai and Romeo-Teodor Cristina",coverURL:"https://cdn.intechopen.com/books/images_new/9521.jpg",editors:[{id:"88785",title:"Prof.",name:"Mihai",middleName:null,surname:"Mares",slug:"mihai-mares",fullName:"Mihai Mares"}],equalEditorOne:{id:"190224",title:"Dr.",name:"Swee Hua Erin",middleName:null,surname:"Lim",slug:"swee-hua-erin-lim",fullName:"Swee Hua Erin Lim",profilePictureURL:"https://mts.intechopen.com/storage/users/190224/images/system/190224.png",biography:"Dr. Erin Lim is presently working as an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates and is affiliated as an Associate Professor to Perdana University-Royal College of Surgeons in Ireland, Selangor, Malaysia. She obtained her Ph.D. from Universiti Putra Malaysia in 2010 with a National Science Fellowship awarded from the Ministry of Science, Technology and Innovation Malaysia and has been actively involved in research ever since. Her main research interests include analysis of carriage and transmission of multidrug resistant bacteria in non-conventional settings, besides an interest in natural products for antimicrobial testing. She is heavily involved in the elucidation of mechanisms of reversal of resistance in bacteria in addition to investigating the immunological analyses of diseases, development of vaccination and treatment models in animals. She hopes her work will support the discovery of therapeutics in the clinical setting and assist in the combat against the burden of antibiotic resistance.",institutionString:"Abu Dhabi Women’s College",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Perdana University",institutionURL:null,country:{name:"Malaysia"}}},equalEditorTwo:{id:"221544",title:"Dr.",name:"Kok-Song",middleName:null,surname:"Lai",slug:"kok-song-lai",fullName:"Kok-Song Lai",profilePictureURL:"https://mts.intechopen.com/storage/users/221544/images/system/221544.jpeg",biography:"Dr. Lai Kok Song is an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates. He obtained his Ph.D. in Biological Sciences from Nara Institute of Science and Technology, Japan in 2012. Prior to his academic appointment, Dr. Lai worked as a Senior Scientist at the Ministry of Science, Technology and Innovation, Malaysia. His current research areas include antimicrobial resistance and plant-pathogen interaction. His particular interest lies in the study of the antimicrobial mechanism via membrane disruption of essential oils against multi-drug resistance bacteria through various biochemical, molecular and proteomic approaches. Ultimately, he hopes to uncover and determine novel biomarkers related to antibiotic resistance that can be developed into new therapeutic strategies.",institutionString:"Higher Colleges of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Higher Colleges of Technology",institutionURL:null,country:{name:"United Arab Emirates"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10020",title:"Operations Management",subtitle:"Emerging Trend in the Digital Era",isOpenForSubmission:!1,hash:"526f0dbdc7e4d85b82ce8383ab894b4c",slug:"operations-management-emerging-trend-in-the-digital-era",bookSignature:"Antonella Petrillo, Fabio De Felice, Germano Lambert-Torres and Erik Bonaldi",coverURL:"https://cdn.intechopen.com/books/images_new/10020.jpg",editors:[{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9560",title:"Creativity",subtitle:"A Force to Innovation",isOpenForSubmission:!1,hash:"58f740bc17807d5d88d647c525857b11",slug:"creativity-a-force-to-innovation",bookSignature:"Pooja Jain",coverURL:"https://cdn.intechopen.com/books/images_new/9560.jpg",editors:[{id:"316765",title:"Dr.",name:"Pooja",middleName:null,surname:"Jain",slug:"pooja-jain",fullName:"Pooja Jain"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10192",title:"Background and Management of Muscular Atrophy",subtitle:null,isOpenForSubmission:!1,hash:"eca24028d89912b5efea56e179dff089",slug:"background-and-management-of-muscular-atrophy",bookSignature:"Julianna Cseri",coverURL:"https://cdn.intechopen.com/books/images_new/10192.jpg",editors:[{id:"135579",title:"Dr.",name:"Julianna",middleName:null,surname:"Cseri",slug:"julianna-cseri",fullName:"Julianna Cseri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9243",title:"Coastal Environments",subtitle:null,isOpenForSubmission:!1,hash:"8e05e5f631e935eef366980f2e28295d",slug:"coastal-environments",bookSignature:"Yuanzhi Zhang and X. San Liang",coverURL:"https://cdn.intechopen.com/books/images_new/9243.jpg",editors:[{id:"77597",title:"Prof.",name:"Yuanzhi",middleName:null,surname:"Zhang",slug:"yuanzhi-zhang",fullName:"Yuanzhi Zhang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9644",title:"Glaciers and the Polar Environment",subtitle:null,isOpenForSubmission:!1,hash:"e8cfdc161794e3753ced54e6ff30873b",slug:"glaciers-and-the-polar-environment",bookSignature:"Masaki Kanao, Danilo Godone and Niccolò Dematteis",coverURL:"https://cdn.intechopen.com/books/images_new/9644.jpg",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7847",title:"Medical Toxicology",subtitle:null,isOpenForSubmission:!1,hash:"db9b65bea093de17a0855a1b27046247",slug:"medical-toxicology",bookSignature:"Pınar Erkekoglu and Tomohisa Ogawa",coverURL:"https://cdn.intechopen.com/books/images_new/7847.jpg",editors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoglu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"9243",title:"Coastal Environments",subtitle:null,isOpenForSubmission:!1,hash:"8e05e5f631e935eef366980f2e28295d",slug:"coastal-environments",bookSignature:"Yuanzhi Zhang and X. San Liang",coverURL:"https://cdn.intechopen.com/books/images_new/9243.jpg",editedByType:"Edited by",editors:[{id:"77597",title:"Prof.",name:"Yuanzhi",middleName:null,surname:"Zhang",slug:"yuanzhi-zhang",fullName:"Yuanzhi Zhang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10020",title:"Operations Management",subtitle:"Emerging Trend in the Digital Era",isOpenForSubmission:!1,hash:"526f0dbdc7e4d85b82ce8383ab894b4c",slug:"operations-management-emerging-trend-in-the-digital-era",bookSignature:"Antonella Petrillo, Fabio De Felice, Germano Lambert-Torres and Erik Bonaldi",coverURL:"https://cdn.intechopen.com/books/images_new/10020.jpg",editedByType:"Edited by",editors:[{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9521",title:"Antimicrobial Resistance",subtitle:"A One Health Perspective",isOpenForSubmission:!1,hash:"30949e78832e1afba5606634b52056ab",slug:"antimicrobial-resistance-a-one-health-perspective",bookSignature:"Mihai Mareș, Swee Hua Erin Lim, Kok-Song Lai and Romeo-Teodor Cristina",coverURL:"https://cdn.intechopen.com/books/images_new/9521.jpg",editedByType:"Edited by",editors:[{id:"88785",title:"Prof.",name:"Mihai",middleName:null,surname:"Mares",slug:"mihai-mares",fullName:"Mihai Mares"}],equalEditorOne:{id:"190224",title:"Dr.",name:"Swee Hua Erin",middleName:null,surname:"Lim",slug:"swee-hua-erin-lim",fullName:"Swee Hua Erin Lim",profilePictureURL:"https://mts.intechopen.com/storage/users/190224/images/system/190224.png",biography:"Dr. Erin Lim is presently working as an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates and is affiliated as an Associate Professor to Perdana University-Royal College of Surgeons in Ireland, Selangor, Malaysia. She obtained her Ph.D. from Universiti Putra Malaysia in 2010 with a National Science Fellowship awarded from the Ministry of Science, Technology and Innovation Malaysia and has been actively involved in research ever since. Her main research interests include analysis of carriage and transmission of multidrug resistant bacteria in non-conventional settings, besides an interest in natural products for antimicrobial testing. She is heavily involved in the elucidation of mechanisms of reversal of resistance in bacteria in addition to investigating the immunological analyses of diseases, development of vaccination and treatment models in animals. She hopes her work will support the discovery of therapeutics in the clinical setting and assist in the combat against the burden of antibiotic resistance.",institutionString:"Abu Dhabi Women’s College",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Perdana University",institutionURL:null,country:{name:"Malaysia"}}},equalEditorTwo:{id:"221544",title:"Dr.",name:"Kok-Song",middleName:null,surname:"Lai",slug:"kok-song-lai",fullName:"Kok-Song Lai",profilePictureURL:"https://mts.intechopen.com/storage/users/221544/images/system/221544.jpeg",biography:"Dr. Lai Kok Song is an Assistant Professor in the Division of Health Sciences, Abu Dhabi Women\\'s College, Higher Colleges of Technology in Abu Dhabi, United Arab Emirates. He obtained his Ph.D. in Biological Sciences from Nara Institute of Science and Technology, Japan in 2012. Prior to his academic appointment, Dr. Lai worked as a Senior Scientist at the Ministry of Science, Technology and Innovation, Malaysia. His current research areas include antimicrobial resistance and plant-pathogen interaction. His particular interest lies in the study of the antimicrobial mechanism via membrane disruption of essential oils against multi-drug resistance bacteria through various biochemical, molecular and proteomic approaches. Ultimately, he hopes to uncover and determine novel biomarkers related to antibiotic resistance that can be developed into new therapeutic strategies.",institutionString:"Higher Colleges of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Higher Colleges of Technology",institutionURL:null,country:{name:"United Arab Emirates"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9560",title:"Creativity",subtitle:"A Force to Innovation",isOpenForSubmission:!1,hash:"58f740bc17807d5d88d647c525857b11",slug:"creativity-a-force-to-innovation",bookSignature:"Pooja Jain",coverURL:"https://cdn.intechopen.com/books/images_new/9560.jpg",editedByType:"Edited by",editors:[{id:"316765",title:"Dr.",name:"Pooja",middleName:null,surname:"Jain",slug:"pooja-jain",fullName:"Pooja Jain"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9669",title:"Recent Advances in Rice Research",subtitle:null,isOpenForSubmission:!1,hash:"12b06cc73e89af1e104399321cc16a75",slug:"recent-advances-in-rice-research",bookSignature:"Mahmood-ur- Rahman Ansari",coverURL:"https://cdn.intechopen.com/books/images_new/9669.jpg",editedByType:"Edited by",editors:[{id:"185476",title:"Dr.",name:"Mahmood-Ur-",middleName:null,surname:"Rahman Ansari",slug:"mahmood-ur-rahman-ansari",fullName:"Mahmood-Ur- Rahman Ansari"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10192",title:"Background and Management of Muscular Atrophy",subtitle:null,isOpenForSubmission:!1,hash:"eca24028d89912b5efea56e179dff089",slug:"background-and-management-of-muscular-atrophy",bookSignature:"Julianna Cseri",coverURL:"https://cdn.intechopen.com/books/images_new/10192.jpg",editedByType:"Edited by",editors:[{id:"135579",title:"Dr.",name:"Julianna",middleName:null,surname:"Cseri",slug:"julianna-cseri",fullName:"Julianna Cseri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9550",title:"Entrepreneurship",subtitle:"Contemporary Issues",isOpenForSubmission:!1,hash:"9b4ac1ee5b743abf6f88495452b1e5e7",slug:"entrepreneurship-contemporary-issues",bookSignature:"Mladen Turuk",coverURL:"https://cdn.intechopen.com/books/images_new/9550.jpg",editedByType:"Edited by",editors:[{id:"319755",title:"Prof.",name:"Mladen",middleName:null,surname:"Turuk",slug:"mladen-turuk",fullName:"Mladen Turuk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editedByType:"Edited by",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9313",title:"Clay Science and Technology",subtitle:null,isOpenForSubmission:!1,hash:"6fa7e70396ff10620e032bb6cfa6fb72",slug:"clay-science-and-technology",bookSignature:"Gustavo Morari Do Nascimento",coverURL:"https://cdn.intechopen.com/books/images_new/9313.jpg",editedByType:"Edited by",editors:[{id:"7153",title:"Prof.",name:"Gustavo",middleName:null,surname:"Morari Do Nascimento",slug:"gustavo-morari-do-nascimento",fullName:"Gustavo Morari Do Nascimento"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9888",title:"Nuclear Power Plants",subtitle:"The Processes from the Cradle to the Grave",isOpenForSubmission:!1,hash:"c2c8773e586f62155ab8221ebb72a849",slug:"nuclear-power-plants-the-processes-from-the-cradle-to-the-grave",bookSignature:"Nasser Awwad",coverURL:"https://cdn.intechopen.com/books/images_new/9888.jpg",editedByType:"Edited by",editors:[{id:"145209",title:"Prof.",name:"Nasser",middleName:"S",surname:"Awwad",slug:"nasser-awwad",fullName:"Nasser Awwad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"16",title:"Medicine",slug:"medicine",parent:{title:"Health Sciences",slug:"health-sciences"},numberOfBooks:1511,numberOfAuthorsAndEditors:39573,numberOfWosCitations:21767,numberOfCrossrefCitations:11544,numberOfDimensionsCitations:29307,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"medicine",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"10192",title:"Background and Management of Muscular Atrophy",subtitle:null,isOpenForSubmission:!1,hash:"eca24028d89912b5efea56e179dff089",slug:"background-and-management-of-muscular-atrophy",bookSignature:"Julianna Cseri",coverURL:"https://cdn.intechopen.com/books/images_new/10192.jpg",editedByType:"Edited by",editors:[{id:"135579",title:"Dr.",name:"Julianna",middleName:null,surname:"Cseri",slug:"julianna-cseri",fullName:"Julianna Cseri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9027",title:"Human Blood Group Systems and Haemoglobinopathies",subtitle:null,isOpenForSubmission:!1,hash:"d00d8e40b11cfb2547d1122866531c7e",slug:"human-blood-group-systems-and-haemoglobinopathies",bookSignature:"Osaro Erhabor and Anjana Munshi",coverURL:"https://cdn.intechopen.com/books/images_new/9027.jpg",editedByType:"Edited by",editors:[{id:"35140",title:null,name:"Osaro",middleName:null,surname:"Erhabor",slug:"osaro-erhabor",fullName:"Osaro Erhabor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9406",title:"Clinical Implementation of Bone Regeneration and Maintenance",subtitle:null,isOpenForSubmission:!1,hash:"875a140c01518fa7a9bceebd688b0147",slug:"clinical-implementation-of-bone-regeneration-and-maintenance",bookSignature:"Mike Barbeck, Nahum Rosenberg, Patrick Rider, Željka Perić Kačarević and Ole Jung",coverURL:"https://cdn.intechopen.com/books/images_new/9406.jpg",editedByType:"Edited by",editors:[{id:"204918",title:"Dr.",name:"Mike",middleName:null,surname:"Barbeck",slug:"mike-barbeck",fullName:"Mike Barbeck"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9122",title:"Cosmetic Surgery",subtitle:null,isOpenForSubmission:!1,hash:"207026ca4a4125e17038e770d00ee152",slug:"cosmetic-surgery",bookSignature:"Yueh-Bih Tang",coverURL:"https://cdn.intechopen.com/books/images_new/9122.jpg",editedByType:"Edited by",editors:[{id:"202122",title:"Prof.",name:"Yueh-Bih",middleName:null,surname:"Tang",slug:"yueh-bih-tang",fullName:"Yueh-Bih Tang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9134",title:"Recent Advances in Digital System Diagnosis and Management of Healthcare",subtitle:null,isOpenForSubmission:!1,hash:"ff00a5718f23cb880b7337b1c36b5434",slug:"recent-advances-in-digital-system-diagnosis-and-management-of-healthcare",bookSignature:"Kamran Sartipi and Thierry Edoh",coverURL:"https://cdn.intechopen.com/books/images_new/9134.jpg",editedByType:"Edited by",editors:[{id:"29601",title:"Dr.",name:"Kamran",middleName:null,surname:"Sartipi",slug:"kamran-sartipi",fullName:"Kamran Sartipi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9569",title:"Methods in Molecular Medicine",subtitle:null,isOpenForSubmission:!1,hash:"691d3f3c4ac25a8093414e9b270d2843",slug:"methods-in-molecular-medicine",bookSignature:"Yusuf Tutar",coverURL:"https://cdn.intechopen.com/books/images_new/9569.jpg",editedByType:"Edited by",editors:[{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9157",title:"Neurodegenerative Diseases",subtitle:"Molecular Mechanisms and Current Therapeutic Approaches",isOpenForSubmission:!1,hash:"bc8be577966ef88735677d7e1e92ed28",slug:"neurodegenerative-diseases-molecular-mechanisms-and-current-therapeutic-approaches",bookSignature:"Nagehan Ersoy Tunalı",coverURL:"https://cdn.intechopen.com/books/images_new/9157.jpg",editedByType:"Edited by",editors:[{id:"82778",title:"Ph.D.",name:"Nagehan",middleName:null,surname:"Ersoy Tunalı",slug:"nagehan-ersoy-tunali",fullName:"Nagehan Ersoy Tunalı"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9839",title:"Outdoor Recreation",subtitle:"Physiological and Psychological Effects on Health",isOpenForSubmission:!1,hash:"5f5a0d64267e32567daffa5b0c6a6972",slug:"outdoor-recreation-physiological-and-psychological-effects-on-health",bookSignature:"Hilde G. Nielsen",coverURL:"https://cdn.intechopen.com/books/images_new/9839.jpg",editedByType:"Edited by",editors:[{id:"158692",title:"Ph.D.",name:"Hilde G.",middleName:null,surname:"Nielsen",slug:"hilde-g.-nielsen",fullName:"Hilde G. Nielsen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editedByType:"Edited by",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editedByType:"Edited by",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9018",title:"Some RNA Viruses",subtitle:null,isOpenForSubmission:!1,hash:"a5cae846dbe3692495fc4add2f60fd84",slug:"some-rna-viruses",bookSignature:"Yogendra Shah and Eltayb Abuelzein",coverURL:"https://cdn.intechopen.com/books/images_new/9018.jpg",editedByType:"Edited by",editors:[{id:"278914",title:"Ph.D.",name:"Yogendra",middleName:null,surname:"Shah",slug:"yogendra-shah",fullName:"Yogendra Shah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9523",title:"Oral and Maxillofacial Surgery",subtitle:null,isOpenForSubmission:!1,hash:"5eb6ec2db961a6c8965d11180a58d5c1",slug:"oral-and-maxillofacial-surgery",bookSignature:"Gokul Sridharan",coverURL:"https://cdn.intechopen.com/books/images_new/9523.jpg",editedByType:"Edited by",editors:[{id:"82453",title:"Dr.",name:"Gokul",middleName:null,surname:"Sridharan",slug:"gokul-sridharan",fullName:"Gokul Sridharan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:1511,mostCitedChapters:[{id:"19013",doi:"10.5772/21983",title:"Cell Responses to Surface and Architecture of Tissue Engineering Scaffolds",slug:"cell-responses-to-surface-and-architecture-of-tissue-engineering-scaffolds",totalDownloads:9697,totalCrossrefCites:109,totalDimensionsCites:230,book:{slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",title:"Regenerative Medicine and Tissue Engineering",fullTitle:"Regenerative Medicine and Tissue Engineering - Cells and Biomaterials"},signatures:"Hsin-I Chang and Yiwei Wang",authors:[{id:"45747",title:"Dr.",name:"Hsin-I",middleName:null,surname:"Chang",slug:"hsin-i-chang",fullName:"Hsin-I Chang"},{id:"53659",title:"Ms.",name:"Yiwei",middleName:null,surname:"Wang",slug:"yiwei-wang",fullName:"Yiwei Wang"}]},{id:"46479",doi:"10.5772/57353",title:"Floating Drug Delivery Systems for Eradication of Helicobacter pylori in Treatment of Peptic Ulcer Disease",slug:"floating-drug-delivery-systems-for-eradication-of-helicobacter-pylori-in-treatment-of-peptic-ulcer-d",totalDownloads:1995,totalCrossrefCites:79,totalDimensionsCites:180,book:{slug:"trends-in-helicobacter-pylori-infection",title:"Trends in Helicobacter pylori Infection",fullTitle:"Trends in Helicobacter pylori Infection"},signatures:"Yousef Javadzadeh and Sanaz Hamedeyazdan",authors:[{id:"94276",title:"Prof.",name:"Yousef",middleName:null,surname:"Javadzadeh",slug:"yousef-javadzadeh",fullName:"Yousef Javadzadeh"},{id:"98229",title:"Dr.",name:"Sanaz",middleName:null,surname:"Hamedeyazdan",slug:"sanaz-hamedeyazdan",fullName:"Sanaz Hamedeyazdan"}]},{id:"25512",doi:"10.5772/30872",title:"Epidemiology of Psychological Distress",slug:"epidemiology-of-psychological-distress",totalDownloads:8066,totalCrossrefCites:57,totalDimensionsCites:145,book:{slug:"mental-illnesses-understanding-prediction-and-control",title:"Mental Illnesses",fullTitle:"Mental Illnesses - Understanding, Prediction and Control"},signatures:"Aline Drapeau, Alain Marchand and Dominic Beaulieu-Prévost",authors:[{id:"84582",title:"Dr.",name:"Aline",middleName:null,surname:"Drapeau",slug:"aline-drapeau",fullName:"Aline Drapeau"},{id:"84605",title:"Dr.",name:"Alain",middleName:null,surname:"Marchand",slug:"alain-marchand",fullName:"Alain Marchand"},{id:"84606",title:"Dr.",name:"Dominic",middleName:null,surname:"Beaulieu-Prévost",slug:"dominic-beaulieu-prevost",fullName:"Dominic Beaulieu-Prévost"}]}],mostDownloadedChaptersLast30Days:[{id:"43758",title:"Anxiety Disorders in Pregnancy and the Postpartum Period",slug:"anxiety-disorders-in-pregnancy-and-the-postpartum-period",totalDownloads:39763,totalCrossrefCites:11,totalDimensionsCites:20,book:{slug:"new-insights-into-anxiety-disorders",title:"New Insights into Anxiety Disorders",fullTitle:"New Insights into Anxiety Disorders"},signatures:"Roberta Anniverno, Alessandra Bramante, Claudio Mencacci and Federico Durbano",authors:[{id:"157077",title:"Dr.",name:"Federico",middleName:null,surname:"Durbano",slug:"federico-durbano",fullName:"Federico Durbano"},{id:"166382",title:"Dr.",name:"Roberta",middleName:null,surname:"Anniverno",slug:"roberta-anniverno",fullName:"Roberta Anniverno"}]},{id:"70711",title:"Fetal Growth Restriction",slug:"fetal-growth-restriction",totalDownloads:1706,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"growth-disorders-and-acromegaly",title:"Growth Disorders and Acromegaly",fullTitle:"Growth Disorders and Acromegaly"},signatures:"Edurne Mazarico Gallego, Ariadna Torrecillas Pujol, Alex Joan Cahuana Bartra and Maria Dolores Gómez Roig",authors:[{id:"202446",title:"Ph.D.",name:"Maria Dolores",middleName:null,surname:"Gómez Roig",slug:"maria-dolores-gomez-roig",fullName:"Maria Dolores Gómez Roig"},{id:"311835",title:"Dr.",name:"Edurne",middleName:null,surname:"Mazarico",slug:"edurne-mazarico",fullName:"Edurne Mazarico"}]},{id:"70405",title:"Hemostasis in Cardiac Surgery: How We Do it with Limited Resources",slug:"hemostasis-in-cardiac-surgery-how-we-do-it-with-limited-resources",totalDownloads:2694,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:null,title:"Contemporary Applications of Biologic Hemostatic Agents across Surgical Specialties - Volume 1",fullTitle:"Contemporary Applications of Biologic Hemostatic Agents across Surgical Specialties - Volume 1"},signatures:"Fevzi Sarper Türker",authors:null},{id:"64851",title:"Herbal Medicines in African Traditional Medicine",slug:"herbal-medicines-in-african-traditional-medicine",totalDownloads:9954,totalCrossrefCites:10,totalDimensionsCites:17,book:{slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Ezekwesili-Ofili Josephine Ozioma and Okaka Antoinette Nwamaka\nChinwe",authors:[{id:"191264",title:"Prof.",name:"Josephine",middleName:"Ozioma",surname:"Ezekwesili-Ofili",slug:"josephine-ezekwesili-ofili",fullName:"Josephine Ezekwesili-Ofili"},{id:"211585",title:"Prof.",name:"Antoinette",middleName:null,surname:"Okaka",slug:"antoinette-okaka",fullName:"Antoinette Okaka"}]},{id:"59779",title:"Effective Communication in Nursing",slug:"effective-communication-in-nursing",totalDownloads:6504,totalCrossrefCites:2,totalDimensionsCites:4,book:{slug:"nursing",title:"Nursing",fullTitle:"Nursing"},signatures:"Maureen Nokuthula Sibiya",authors:[{id:"73330",title:"Dr.",name:"Nokuthula",middleName:null,surname:"Sibiya",slug:"nokuthula-sibiya",fullName:"Nokuthula Sibiya"}]},{id:"64858",title:"The Neurobiology of Anorexia Nervosa",slug:"the-neurobiology-of-anorexia-nervosa",totalDownloads:892,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"anorexia-and-bulimia-nervosa",title:"Anorexia and Bulimia Nervosa",fullTitle:"Anorexia and Bulimia Nervosa"},signatures:"Ashley Higgins",authors:null},{id:"63771",title:"The Role of Catheter Reshaping at the Angiographic Success",slug:"the-role-of-catheter-reshaping-at-the-angiographic-success",totalDownloads:536,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"angiography",title:"Angiography",fullTitle:"Angiography"},signatures:"Yakup Balaban",authors:[{id:"252647",title:"Associate Prof.",name:"Yakup",middleName:null,surname:"Balaban",slug:"yakup-balaban",fullName:"Yakup Balaban"}]},{id:"61866",title:"Plants Secondary Metabolites: The Key Drivers of the Pharmacological Actions of Medicinal Plants",slug:"plants-secondary-metabolites-the-key-drivers-of-the-pharmacological-actions-of-medicinal-plants",totalDownloads:5564,totalCrossrefCites:13,totalDimensionsCites:32,book:{slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Rehab A. Hussein and Amira A. El-Anssary",authors:[{id:"212117",title:"Dr.",name:"Rehab",middleName:null,surname:"Hussein",slug:"rehab-hussein",fullName:"Rehab Hussein"},{id:"221140",title:"Dr.",name:"Amira",middleName:null,surname:"El-Anssary",slug:"amira-el-anssary",fullName:"Amira El-Anssary"}]},{id:"17956",title:"Sexual and Reproductive Function in Chronic Kidney Disease and Effect of Kidney Transplantation",slug:"sexual-and-reproductive-function-in-chronic-kidney-disease-and-effect-of-kidney-transplantation",totalDownloads:11790,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"after-the-kidney-transplant-the-patients-and-their-allograft",title:"After the Kidney Transplant",fullTitle:"After the Kidney Transplant - The Patients and Their Allograft"},signatures:"Mahboob Lessan-Pezeshki and Shirin Ghazizadeh",authors:[{id:"26564",title:"Prof.",name:"Mahboob",middleName:null,surname:"Lessan Pezeshki",slug:"mahboob-lessan-pezeshki",fullName:"Mahboob Lessan Pezeshki"},{id:"26571",title:"Prof.",name:"Shirin",middleName:null,surname:"Ghazizadeh",slug:"shirin-ghazizadeh",fullName:"Shirin Ghazizadeh"}]},{id:"64747",title:"Bone Development and Growth",slug:"bone-development-and-growth",totalDownloads:3711,totalCrossrefCites:6,totalDimensionsCites:9,book:{slug:"osteogenesis-and-bone-regeneration",title:"Osteogenesis and Bone Regeneration",fullTitle:"Osteogenesis and Bone Regeneration"},signatures:"Rosy Setiawati and Paulus Rahardjo",authors:null}],onlineFirstChaptersFilter:{topicSlug:"medicine",limit:3,offset:0},onlineFirstChaptersCollection:[{id:"75604",title:"Normal Puerperium",slug:"normal-puerperium",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.96348",book:{title:"Midwifery"},signatures:"Subrat Panda, Ananya Das, Arindam Mallik and Surajit Ray Baruah"},{id:"75596",title:"The Use of a Dynamic Elastomeric Fabric Orthotic Intervention in Adolescents and Adults with Scoliosis",slug:"the-use-of-a-dynamic-elastomeric-fabric-orthotic-intervention-in-adolescents-and-adults-with-scolios",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.96391",book:{title:"Spinal Deformities in Adolescents, Adults and Older Adults"},signatures:"Martin Matthews and James Wynne"},{id:"75582",title:"Elimination of Plasmodium vivax Malaria: Problems and Solutions",slug:"elimination-of-plasmodium-vivax-malaria-problems-and-solutions",totalDownloads:1,totalDimensionsCites:null,doi:"10.5772/intechopen.96604",book:{title:"Current Topics and Emerging Issues in Malaria Elimination"},signatures:"Liwang Cui, Awtum Brashear, Lynette Menezes and John Adams"}],onlineFirstChaptersTotal:652},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"10176",title:"Microgrids and Local Energy Systems",subtitle:null,isOpenForSubmission:!0,hash:"c32b4a5351a88f263074b0d0ca813a9c",slug:null,bookSignature:"Prof. Nick Jenkins",coverURL:"https://cdn.intechopen.com/books/images_new/10176.jpg",editedByType:null,editors:[{id:"55219",title:"Prof.",name:"Nick",middleName:null,surname:"Jenkins",slug:"nick-jenkins",fullName:"Nick Jenkins"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:1},route:{name:"profile.detail",path:"/profiles/304306/dionysios-karavyrakis",hash:"",query:{},params:{id:"304306",slug:"dionysios-karavyrakis"},fullPath:"/profiles/304306/dionysios-karavyrakis",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()