Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
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This achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
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We are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
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Thank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
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1. Introduction
From the offset of Coronavirus disease (COVID-19), groups that are more vulnerable to COVID-19 were identified. Presence of diabetes mellitus (DM), both type 1 (T1DM) and type 2 (T2DM) independently increases the adverse effects of COVID-19 [1]. A meta-analysis found that the proportion of diabetes in COVID-19 patients was 9.7% and that having cardiac disease and diabetes increased the risk of death by twice as much as the other risk factors [2]. The purpose of this chapter is to discuss in detail the current evidence available regarding type 2 diabetes mellitus and COVID-19.
2. Pathophysiology of T2D and COVID-19
There has been some insight into the pathophysiological mechanisms of COVID-19 infection and diabetes, but much remains to be investigated. The SARS-CoV2 utilizes angiotensin converting enzyme 2 (ACE2) to gain entry into infected cells and reduces expression of ACE2, and over activation of renin angiotensin aldosterone system (RAAS) is proposed to contribute to adverse effects in patients with diabetes (PWD) and COVID-19 infection [3].
Mechanisms accentuated in PWD include increased inflammatory cytokines, increased lipopolysaccharides, and increased RAAS (angiotensin 2) which results in vascular endothelial damage, increased ROS and IL-6 in increased insulin resistance (due to exaggerated angiotensin 2 activity) which results in hyperglycaemia [4]. There is increased blood viscosity due to increased fibrinogen and d-dimer [4]. The S1 spike protein of SARS-Cov2 is predicted to bind to DPP4 which may facilitate epithelial infection [1, 5].
It has been noted that infection with SARS-Cov-2 virus results in damage to pancreatic beta-cells [6]. Apart from COVID-19 related impaired insulin production [7], COVID-19 can cause insulin resistance due to activation of integrated stress response (ISR) initiating serine/threonine kinases which can induce IRS-1 serine phosphorylation. Hence, patients with COVID-19 infection can present with hyperglycaemia for the first time and may require insulin for insulin naïve patients or the one on insulin may have increased requirements [8].
Patients with type 2 diabetes (T2D) have a dysregulated immune response with higher ratio of lymphopenia, and increased levels of neutrophils, CRP and IL-6 have been noted in PWD with COVID-19 infections. T2D is associated with activation of the RAAS in different tissues [3]. In PWD pulmonary dysfunction has been reported involving changes in lung volume, lung diffusing capacity, ventilation, bronchomotor tone and neuroadrenergic bronchial innervation [3].
Increased metabolic rate, dysregulation of glucose metabolism, aggravation of inflammation and immune modulation result in increased oxidative stress, cytokine production, endothelial damage, increased glucotoxicity which ultimately can result in increased severity of COVID-19 and rapid progression of cardiorespiratory failure [4].
3. Clinical manifestations
The most common symptoms of COVID-19 infection are fever, cough [9], fatigue and shortness of breath [10]. Other symptoms such as sore throat, rhinorrhoea, ageusia, anosmia, vomiting and diarrhea have also been reported [11]. An observational study noted that male patients were more vulnerable than female patients to COVID-19 infection [9]. Common comorbidities include diabetes mellitus, hypertension obesity and cardiovascular disease [10].
Multiple comorbidities are associated with more severe disease and higher mortality [9]. Patients with T2D are more likely to develop severe COVID-19 infection as compared with patients without diabetes [12]. An increased prevalence of chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD) has been noted in patients with T2D and COVID-19 infection [11]. COVID-19 infection may result in severe insulin resistance and insulin deficiency precipitating diabetic ketoacidosis (DKA) in patients with T1DM and not commonly but still possible in T2DM, result in new onset diabetes, or in PWD result in new or increased insulin therapy at times with very high dose requirements. Dexamethasone therapy which has been found to be beneficial in COVID-19 infection, can result in further hyperglycaemia and has the potential of precipitating Hyperosmolar hyperglycaemic state (HHS) and DKA [7]. Regular monitoring of capillary blood glucose (CBGs) is warranted for inpatients. As hyperglycaemia with ketosis may occur in COVID-19 infection, ketones should be checked in all patients with diabetes initially or if CBG > 12 mmol/L [13].
Laboratory findings include lymphopenia, thrombocytopenia, raised CRP, raised ALT and other markers of inflammation such as ferritin [10]. Compared with patients without diabetes, patients with T2DM were found to have a higher ESR, CRP, IL-6, TNF-α and procalcitonin but lower lymphocyte and T lymphocyte subsets [12]. HbA1C, IL-6 and lymphocyte count have been proposed as risk factors for the severity of COVID-19 infection and T2DM [12]. CT scan changes are common and include ground glass abnormalities, lung lesions and enlargement of lymph nodes [10].
4. Management of type 2 diabetes and COVID-19 infection
Diabetes UK, a British-based patient, healthcare professional and research charity, has provided advice for healthcare professionals on COVID-19 and inpatient diabetes care on their website and topics include front door guidance, managing inpatient hyperglycaemia, dexamethasone therapy and safe discharge endorsed by the Joint British Diabetes Society (JBDS) and Association of British Clinical Diabetologists (ABCD) [14].
Front door guidance is available for inpatients [13]. An ABCDE (Airway, breathing, circulation, disability and exposure) approach is warranted initially if patient is unwell, CBG> 12 mmol/L or known diabetes. Aim is rule out DKA, HHS and watch out for new presentation of diabetes, sepsis, steroid use, uncontrolled diabetes or delayed and missed treatment of diabetes [13]. Be aware of the possibility of euglycaemic DKA. Stop Metformin and SGLT2 inhibitors on admission. Fluid requirements may differ in patients with COVID-19 infection and have to be tailored individually due to ARDS, cardiac involvement or AKI. Contact the diabetes specialist team and early involvement of critical care team where appropriate.
Target glucose levels are 6–10 mmol/L, and up to 12 mmol/L is acceptable. The guidance for managing inpatient hyperglycaemia should be used if glucose levels are >12 mmol/L and a corrective dose is appropriate and the patient is not in DKA or HHS [14]. It provides information for patients on insulin and insulin naïve patients too, regarding insulin dose adjustment as while recovering from COVID-19 related insulin resistance, doses may require rapid reduction to avoid hyperglycemia [14]. Initiation of IV insulin with monitoring of blood glucose, electrolytes, pH and ketones should be done as appropriate. Blood ketones <0.6 mmol/L is safe, blood ketones 1.5–2.9 mmol/L signifies increased risk of DKA [13], and if 3 mmol/L or greater, then check pH and bicarbonate for possibility of DKA [13].
If patients unable to manage insulin pump start on variable rate intravenous insulin infusion (VRII) or subcutaneous (S/C) insulin. For S/C insulin find out the total daily insulin dose and if not available can be calculated as 0.5 units multiplied by weight. Half this dose is given as basal and remaining half as bolus dose divided by 3 to give the meal time dose [13]. If patient is placed in prone position, feeding may be affected and that needs to be taken into account while dosing insulin.
Continuous glucose monitors (CGMs) and flash glucose monitoring (FGM) can be left on but capillary blood glucose monitoring must still continue. For magnetic imaging such as MRIs, these devices including pumps should be removed [13]. Always check the feet on admission to look for foot infection and rule out critical limb ischaemia.
4.1 Medications used in diabetes
As it was not feasible to conduct RCTs initially, expert opinion and observational studies regarding treatment with medication for T2D suggest the following [15]:
Regular monitoring blood glucose of patients on insulin should be encouraged [15]. A retrospective study in patients in China found that patients with T2D required more medical interventions and had a significantly higher mortality and multiple organ injury than the non-diabetic individuals [3]. Within PWD they found that well controlled BG (CBG 3.9–10 mmol/L) was associated with reduction in adverse outcomes including lower mortality as compared with poorly controlled BG while in hospital. Hence correlation of improved glycaemic control with better outcomes was made and aggressive blood glucose lowering treatment with tablets and insulin was advocated.
4.1.1 Insulin
Insulin therapy is the mainstay in acute unwell PWD admitted to hospital where oral tablets have been stopped or not enough to control the hyperglycaemia. However, there is some evidence that insulin treatment is associated with adverse clinical outcomes in patients with T2D and COVID-19, including increased mortality. Use of insulin was associated with enhanced inflammation (increased IL-1β-dependent CRP and IL-6) and injury of vital organs (acute cardiac injury and acute kidney injury) during the progression of COVID-19 in patients with T2D [16]. Hypoglycaemia was higher in patients on insulin and may have contributed to the increased mortality although a sub-group without hypoglycaemia still had increased mortality. Insulin has been the mainstay in ill PWD and if hyperglycaemia and insulin result in adverse outcomes, there is a difficult dilemma for clinicians [17]. A UK study of 2.85 million PWD, a higher risk of COVID-19 related mortality was seen in patients on insulin, but the higher risk was thought to be due to residual confounding factors rather than direct drug effects [18]. Currently guidelines continue to endorse insulin in unwell PWD. Caution and close monitoring is to be exerted while using insulin treatment in PWD and COVID-19.
4.1.2 Metformin
Metformin, a lipophilic biguanide, has been associated with reduced mortality in women with obesity or T2D admitted to hospital with COVID-19 infection [19]. Several explanations have been provided including decreased inflammatory factors. Retrospective studies evaluating use of Metformin in T2D and COVID-19 infection have mainly suggested some benefit or no harm or benefit whereas a single study has suggested some harm, but overall use of Metformin is considered to be safe [20]. The CORONADO study which was a prospective study noted that Metformin was associated with a lower risk of death in PWD hospitalized with COVID-19 infection [21]. Dehydration with Covid-19 may increase the risk of lactic acidosis in patients taking metformin, hence temporary cessation of the drug along with usual sick day rules should be followed. Renal function should be monitored closely [15]. As metformin may reduce progression to severe COVID-19 infection, after initial cessation and review of clinical parameters including hypoxic state, lactate and renal parameters, metformin may be re-introduced if appropriate [13]. The MET-Covid Trial is an RCT designed to evaluate use of Metformin versus placebo for outpatient treatment and post exposure prophylaxis of COVID-19 infection [22].
4.1.3 Sodium glucose co-transporter 2 inhibitors
Sodium glucose co-transporter 2 inhibitors (SGLT2i) primarily act on the proximal tubule to block sodium and glucose absorption. Given that the mechanisms that are attributed to the protective effects of SGLT2i overlap with the mechanisms that are activated in COVID-19 infection, SGLT2i seem to have the potential to protect against end organ damage through cardio-renal protection [23]. Initiation of this medication should not be done during any likely infection, and for patients with T2D with COVID-19 infection, on SGLT2I, risk of dehydration and euglycemic DKA remains and should temporarily stop this medication and follow sick day rules. Renal function should be monitored closely [15]. A retrospective study to evaluate SGLT2i and COVID19 infection in a large UK based primary care dataset concluded that as compared to DPP4i, SGLT2i did not confer an increased risk of COVID-19 infection [24]. They deemed that clinicians can safely use SGLT2i the everyday care of PWD during COVID-19. DARE-19, is the first randomized controlled multi-centre trial investigating the use of Dapagliflozin, and the goals are to prevent COVID-19 related organ dysfunction or mortality and to improve clinical recovery [23].
4.1.4 Glucagon like peptide receptor agonists
Glucagon like peptide receptor agonist (GLP-1 RA) in animal studies has shown to activate ACE-2 expression and there have been speculations if this accelerated virus entrance into host cells but also if this expression neutralizes the virus limiting infection [25]. There is support for the hypothesis that GLP-1 RA may mitigate a more adverse clinical course in PWD and COVID-19 infection [26]. GLP-1 RA also are beneficial with weight loss. There are a few studies on GLP1RA and COVID-19 infection and even the final report of the CORONADO study did not find any benefit or harm with its use [27]. Dehydration is likely to lead to serious illness so patients on GLP1RA with COVID-19 should be monitored [15]. Regular meals and adequate hydration should be encouraged [15].
4.1.5 Dipeptidyl peptidase-4 inhibitors
It has been proposed that SARS Cov-2 binds to Dipeptidyl peptidase-4 inhibitors (DPP4), but the clinical implications are not known. Dipeptidyl peptidase-4 inhibitors (DPP4i) are well tolerated in COVID-19 infection [15]. The majority of studies have shown either benefit with DPP4i in PWD and COVID-19, or no harm or benefit [20], Although DPP4 inhibitors appear to be safe in T2D and COVID-19 infection [4], in an observational study of 717 patients, in the diabetes sub-group, patients on DPP4I were at a higher risk of ICU admission [5]. As study that compared GLP-1 RA or DPP4i with SGLT2i did not note associated improved outcomes in patients with COVID-19 infection [28]. As DPP4 upregulation may be an indicator for severity of COVID-19 infection, there is interest regarding the use of DPP4i in COVID-19 infection and available information may form the path to discovering novel therapies [29]. RCTs involving Linagliptin versus placebo and Sitagliptin versus placebo have been registered [30, 31].
4.1.6 Sulphonylureas
The use of sulphonylureas with regard to COVID-19 infection has not shown any harm or benefit according to some retrospective studies [20]. If there is a risk of hypoglycaemia, they may be stopped. Sulphonylureas are not recommended in the context of dexamethasone induced hyperglycaemia as beta cell function maybe impaired with COVID-19 infection and there is insulin resistance too [7].
4.1.7 Thiazolidinediones
Several studies have shown a reduction in proinflammatory cytokines with pioglitazone, but no studies have reported outcomes in pioglitazone users with COVID-19 infection, and due to small numbers of users meaningful data is unlikely to be available soon [20].
4.1.8 Steroid induced hyperglycaemia
Dexamethasone has been proven to reduce mortality in patients dependent on oxygen therapy and ventilation. However, recommended dose of 6 mg orally or intravenously are bound to affect glucose metabolism and guidance for glucocorticoid therapy in patients with and without diabetes is provided by DUK [14].
4.2 Hypertension
Treatment with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) could increase the expression of ACE2 and accelerate entry of the virus into the cells. However, in COVID-19 infection, impairment of the ACE2/Mas receptor pathway and increase in angiotensin-2 activity could occur, and RAAS blockade may protect against this serious lung injury. Thus it is recommended that ACEI and ARBs should continue [15].
4.3 Lipid medications
Reduction on ACE2 by hyperlipidemia is restored by statins. It is believed that statins should not be discontinued in patients with COVID-19 infection due to it pleiotropic effects and potential for a cytokine storm due to rebound increase in interleukins [15].
4.4 Renal transplant recipients
Potential effect of COVID-19 on pancreatic function of patients with solid organ transplants is not known. Monitoring is required for patients with PTDM and without diabetes at risk of PTDM [15].
4.5 Fatty liver disease
Should be considered at an increased risk of cytokine storm and should be considered at risk of severe disease. Hence patients at risk of a cytokine storm and are to be considered at an increased risk of severe disease. There may be some benefit of screening and monitoring tests for hyperinflammation [15].
4.6 Discharge
Advice regarding safe and supported discharge is available [14]. Patients using insulin pumps or wearable diabetes technology should have them returned to the patient if not being used and ensure enough consumables are available at home. If a patient has had DKA, SGLT2i should not be used. Metformin can be re-started once the patient is well, eGFR>30 ml/min and lactate is normal. Sulphonylureas may have been withheld due to risk of hypoglycaemia, and assessment should be made if re-starting it is appropriate.
4.7 Outpatient management
It is suggested that patients with diabetes (PWD) not yet infected with the SARS-CoV-2 virus should intensify their treatment to prevent COVID-19 infection including glycaemic control, management of hypertension and raised cholesterol. Tele medicine and virtual appointments should continue to ensure adequate follow up [15]. The priority was to contain spread of COVID-19 but health care services need to ensure that the needs of PWD are met is imperative which includes continuous supply of medications and available healthcare services in the primary care [32].
4.8 Prevention
Patients with COVID-19 infection without diabetes should be monitored for new onset diabetes especially if on steroids. PWD and COVID-19 infection should have good glycaemic control [15].
4.9 Lifestyle management
While lockdown was the best armamentarium we had while the vaccination program was established and rolled out, it lead to potential for more sedentary activity, unhealthy diet, mental health related issues and possible delay in seeking care due to fear of contracting COVID-19 especially for patients with chronic conditions. Maintaining a healthy lifestyle is important now more than ever [32]. Adoption of dietary advice and restriction of dietary carbohydrates has been proposed for people with metabolic syndrome [33]. Smoking was associated with a higher mortality rate in hospitalized patients and advice regarding smoking cessation should be given [9].
4.10 Prediabetes
Prediabetes is associated with increased CRP and IL-6, and hospitalized patients with moderate to severe COVID-19 infection have been noted to have prediabetes, hence it has been proposed that pre-diabetes be treated as a comorbidity for COVID-19 infection [34]. Whether screening of all COVID-19 infected patients for prediabetes to improve patient care is feasible or beneficial remains to be seen as there is currently no therapeutic drug approved for prediabetes.
5. Complications
Apart from the known pulmonary complications, extra pulmonary complications from COVID-19 include neurological, cardiovascular, gastro-intestinal, renal, endocrine and dermatological complications are being reported [35]. Due to COVID-19 infection, there have been increased risk of hyperglycaemia, euglycaemic ketosis and diabetic ketoacidosis (DKA) [35]. With COVID-19 infection, there is a risk of atypical presentations of complications such as DKA or mixed hyperosmolar states with associated increased mortality. A retrospective case series confirmed that PWD are at a risk of combined DKA and HHs with COVID-19 infection [36]. Data from our own centre has shown that DKA in T2DM is increased significantly and that the frequency of HHS increased seven fold during the first Covid pandemic in the UK [37]. Fluid management is a challenge in such patients especially in case of renal impairment and ARDS should be avoided. Guidelines for management of DKA is available on the Diabetes UK website and it is worth remembering that euglycaemic DKA can occur in patients taking SGLT2i or in pregnancy [14]. In a whole population study assessing risks of in-hospital death in England, people with T1DM were found to be three-and-a-half times more at risk of dying from COVID-19 infection, while people with T2D are at twice the risk of dying than people without diabetes [38]. Hence, continued measures to mitigate the risks of people with diabetes of becoming seriously ill or dying due to COVID-19 infection is warranted.
6. Conclusion
COVID-19 infection and diabetes mellitus have important and clinically relevant interactions. It is important for all physicians to be aware of these, particularly in view of likely further COVID-19 pandemics.
\n',keywords:"COVID-19, SARS-COV-2, diabetes mellitus, hyperglycaemia, type 2 diabetes",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/78277.pdf",chapterXML:"https://mts.intechopen.com/source/xml/78277.xml",downloadPdfUrl:"/chapter/pdf-download/78277",previewPdfUrl:"/chapter/pdf-preview/78277",totalDownloads:123,totalViews:0,totalCrossrefCites:0,dateSubmitted:"July 12th 2021",dateReviewed:"July 26th 2021",datePrePublished:"November 8th 2021",datePublished:"December 8th 2021",dateFinished:"August 26th 2021",readingETA:"0",abstract:"COVID-19 pandemic caused by SARS-COV-2 virus has evolved into a global crisis and is a major concern especially for the diabetes community. People with diabetes mellitus have increased morbidity and mortality associated with COVID-19 infection. Conversely, COVID-19 infection and treatment may predispose to hyperglycemia. Potentially modifiable risk factors have been discussed and urgent need to mitigate the risks is warranted. In this book chapter we summarize the available evidence on COVID-19 and type 2 diabetes mellitus including link between COVID-19 and type 2 diabetes, pathophysiology, clinical manifestations, management and complications.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/78277",risUrl:"/chapter/ris/78277",signatures:"Ritwika Mallik and Mohammed S.B. Huda",book:{id:"10706",type:"book",title:"Fighting the COVID-19 Pandemic",subtitle:null,fullTitle:"Fighting the COVID-19 Pandemic",slug:"fighting-the-covid-19-pandemic",publishedDate:"December 8th 2021",bookSignature:"Manal Mohammad Baddour",coverURL:"https://cdn.intechopen.com/books/images_new/10706.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83968-217-9",printIsbn:"978-1-83968-216-2",pdfIsbn:"978-1-83968-246-9",isAvailableForWebshopOrdering:!0,editors:[{id:"174598",title:"Dr.",name:"Manal Mohammad",middleName:null,surname:"Baddour",slug:"manal-mohammad-baddour",fullName:"Manal Mohammad Baddour"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"356482",title:"Dr.",name:"Mohammed S.B.",middleName:null,surname:"Huda",fullName:"Mohammed S.B. Huda",slug:"mohammed-s.b.-huda",email:"bobby.huda1@nhs.net",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"428233",title:"Dr.",name:"Ritwika",middleName:null,surname:"Mallik",fullName:"Ritwika Mallik",slug:"ritwika-mallik",email:"r.mallik@qmul.ac.uk",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Pathophysiology of T2D and COVID-19",level:"1"},{id:"sec_3",title:"3. Clinical manifestations",level:"1"},{id:"sec_4",title:"4. Management of type 2 diabetes and COVID-19 infection",level:"1"},{id:"sec_4_2",title:"4.1 Medications used in diabetes",level:"2"},{id:"sec_4_3",title:"4.1.1 Insulin",level:"3"},{id:"sec_5_3",title:"4.1.2 Metformin",level:"3"},{id:"sec_6_3",title:"4.1.3 Sodium glucose co-transporter 2 inhibitors",level:"3"},{id:"sec_7_3",title:"4.1.4 Glucagon like peptide receptor agonists",level:"3"},{id:"sec_8_3",title:"4.1.5 Dipeptidyl peptidase-4 inhibitors",level:"3"},{id:"sec_9_3",title:"4.1.6 Sulphonylureas",level:"3"},{id:"sec_10_3",title:"4.1.7 Thiazolidinediones",level:"3"},{id:"sec_11_3",title:"4.1.8 Steroid induced hyperglycaemia",level:"3"},{id:"sec_13_2",title:"4.2 Hypertension",level:"2"},{id:"sec_14_2",title:"4.3 Lipid medications",level:"2"},{id:"sec_15_2",title:"4.4 Renal transplant recipients",level:"2"},{id:"sec_16_2",title:"4.5 Fatty liver disease",level:"2"},{id:"sec_17_2",title:"4.6 Discharge",level:"2"},{id:"sec_18_2",title:"4.7 Outpatient management",level:"2"},{id:"sec_19_2",title:"4.8 Prevention",level:"2"},{id:"sec_20_2",title:"4.9 Lifestyle management",level:"2"},{id:"sec_21_2",title:"4.10 Prediabetes",level:"2"},{id:"sec_23",title:"5. 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Diabetes Metab. 2020 Dec 10;47(5):101216. DOI: 10.1016/j.diabet.2020.101216.'},{id:"B22",body:'Met-Covid: Outpatient Metformin Use for Covid 19 [Internet]. Available from: https://clinicaltrials.gov/ct2/show/NCT045110194 [Accessed on 2021-06-28].'},{id:"B23",body:'Kosiborod M, Berwanger O, Koch GG, Martinez F, Mukhtar O, Verma S, Chopra V, Javaheri A, Ambery P, Gasparyan SB, Buenconsejo J, Sjöström CD, Langkilde AM, Oscarsson J, Esterline R. Effects of dapagliflozin on prevention of major clinical events and recovery in patients with respiratory failure because of COVID-19: Design and rationale for the DARE-19 study. Diabetes Obes Metab. 2021 Apr;23(4):886-896. DOI: 10.1111/dom.14296.'},{id:"B24",body:'Sainsbury C, Wang J, Gokhale K, Acosta-Mena D, Dhalla S, Byne N, Chandan JS, Anand A, Cooper J, Okoth K, Subramanian A, Bangash MN, Taverner T, Hanif W, Ghosh S, Narendran P, Cheng KK, Marshall T, Gkoutos G, Toulis K, Thomas N, Tahrani A, Adderley NJ, Haroon S, Nirantharakumar K. Sodium-glucose co-transporter-2 inhibitors and susceptibility to COVID-19: A population-based retrospective cohort study. Diabetes Obes Metab. 2021 Jan;23(1):263-269. DOI: 10.1111/dom.14203.'},{id:"B25",body:'Pang J, Liu M, Ling W, Jin T. Friend or foe? ACE2 inhibitors and GLP-1R agonists in COVID-19 treatment. Obes Med. 2021 Mar;22:100312. DOI: 10.1016/j.obmed.2020.100312.'},{id:"B26",body:'Monda VM, Porcellati F, Strollo F, Gentile S. ACE2 and SARS-CoV-2 infection: Might GLP-1 receptor agonists play a role? Diabetes Ther. 2020 Sep;11(9):1909-1914. 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Legumes are nutritionally valuable, providing proteins (20–45%) with essential amino acids, complex carbohydrates (±60%) and dietary fibre (5–37%). Legumes also have no cholesterol and are generally low in fat, with ±5% energy from fat, with the exception of peanuts (±45%), chickpeas (±15%) and soybeans (±47%) and provide essential minerals and vitamins. In addition to their nutritional superiority, legumes have also been ascribed economical, cultural, physiological and medicinal roles owing to their possession of beneficial bioactive compounds. Research has shown that most of the bioactive compounds in legumes possess antioxidant properties, which play a role in the prevention of some cancers, heart diseases, osteoporosis and other degenerative diseases. Because of their composition, legumes are attractive to health conscious consumers, celiac and diabetic patients as well as consumers concerned with weight management. The incorporation of legumes in diets, especially in developing countries, could play a major role in eradicating protein-energy malnutrition especially in developing Afro-Asian countries. Legumes could be a base for the development of many functional foods to promote human health.",book:{id:"5963",slug:"functional-food-improve-health-through-adequate-food",title:"Functional Food",fullTitle:"Functional Food - Improve Health through Adequate Food"},signatures:"Yvonne Maphosa and Victoria A. 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The main global health organizations have incorporated patient safety in their review of work practices. The data provided by the medical laboratories have a direct impact on patient safety and a fault in any of processes such as strategic, operational and support, could affect it. To provide appreciate and reliable data to the physicians, it is important to emphasize the need to design risk management plan in the laboratory. Failure Mode and Effect Analysis (FMEA) is an efficient technique for error detection and reduction. Technical Committee of the International Organization for Standardization (ISO) licensed a technical specification for medical laboratories suggesting FMEA as a method for prospective risk analysis of high-risk processes. FMEA model helps to identify quality failures, their effects and risks with their reduction/elimination, which depends on severity, probability and detection. Applying FMEA in clinical approaches can lead to a significant reduction of the risk priority number (RPN).",book:{id:"9808",slug:"contemporary-topics-in-patient-safety-volume-1",title:"Contemporary Topics in Patient Safety",fullTitle:"Contemporary Topics in Patient Safety - Volume 1"},signatures:"Hoda Sabati, Amin Mohsenzadeh and Nooshin Khelghati",authors:[{id:"340486",title:"M.Sc.",name:"Hoda",middleName:null,surname:"Sabati",slug:"hoda-sabati",fullName:"Hoda Sabati"},{id:"348872",title:"M.Sc.",name:"Amin",middleName:null,surname:"Mohsenzadeh",slug:"amin-mohsenzadeh",fullName:"Amin Mohsenzadeh"},{id:"348874",title:"MSc.",name:"Nooshin",middleName:null,surname:"Khelghati",slug:"nooshin-khelghati",fullName:"Nooshin Khelghati"}]},{id:"69876",title:"Leadership Styles in Nursing",slug:"leadership-styles-in-nursing",totalDownloads:2963,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Recent developments in the field of management-organization and organizational behavior and new concepts have also led to the emergence of new leadership styles in leadership. Leadership in health services is important for following innovations and adapting to current situations. Nurses working together with other health personnel in hospitals providing health services constitute an important group in leadership. Nursing, which is a key force for patient safety and safe care, is a human-centered profession, and therefore leadership is a key skill for nurses at all levels. The leadership styles of nurse managers are believed to be an important determinant of job satisfaction and persistence of nurses. The need for nurses with leadership skills and the need for nurses to develop their leadership skills are increasing day by day. There are several leadership styles defined in nursing literature. These leadership styles are examined under the titles of relational leadership style, transformational leadership, resonant leadership, emotional intelligence leadership, and participatory leadership. The task-focused leadership style is explored under the headings of transactional and autocratic leadership, laissez-faire leadership, and instrumental leadership.",book:{id:"9047",slug:"nursing-new-perspectives",title:"Nursing",fullTitle:"Nursing - New Perspectives"},signatures:"Serpil Çelik Durmuş and Kamile Kırca",authors:null},{id:"58916",title:"Factors Affecting the Attitudes of Women toward Family Planning",slug:"factors-affecting-the-attitudes-of-women-toward-family-planning",totalDownloads:8485,totalCrossrefCites:9,totalDimensionsCites:18,abstract:"Everyone has the right to decide on the number and timing of children without discrimination, violence and oppression, to have the necessary information and facilities for it, to access sexual and reproductive health services at the highest standard. Deficient or incorrect family planning methods, wrong attitudes and behaviors toward the methods and consequent unplanned pregnancies, increased maternal and infant mortality rates are the main health problems in most countries. Individuals’ learning modern family planning methods and having positive attitude for these methods may increase the usage of these methods and contributes the formation of healthy communities. It is considered important to examine the current attitudes and determinants in order to spread the choice of effective method.",book:{id:"6142",slug:"family-planning",title:"Family Planning",fullTitle:"Family Planning"},signatures:"Nazli Sensoy, Yasemin Korkut, Selcuk Akturan, Mehmet Yilmaz,\nCanan Tuz and Bilge Tuncel",authors:[{id:"216377",title:"Prof.",name:"Nazli",middleName:null,surname:"Sensoy",slug:"nazli-sensoy",fullName:"Nazli Sensoy"},{id:"216589",title:"Dr.",name:"Yasemin",middleName:null,surname:"Korkut",slug:"yasemin-korkut",fullName:"Yasemin Korkut"},{id:"216595",title:"Dr.",name:"Selcuk",middleName:null,surname:"Akturan",slug:"selcuk-akturan",fullName:"Selcuk Akturan"},{id:"216596",title:"Dr.",name:"Canan",middleName:null,surname:"Tuz",slug:"canan-tuz",fullName:"Canan Tuz"},{id:"216598",title:"Dr.",name:"Bilge",middleName:null,surname:"Tuncel",slug:"bilge-tuncel",fullName:"Bilge Tuncel"},{id:"216599",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yilmaz",slug:"mehmet-yilmaz",fullName:"Mehmet Yilmaz"}]},{id:"69631",title:"Cultural Practices and Health Consequences: Health or Habits, the Choice Is Ours",slug:"cultural-practices-and-health-consequences-health-or-habits-the-choice-is-ours",totalDownloads:845,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Human beings are social animals with an innate desire to conform to socially accepted norms and values. Over periods of time, some of these norms become standards that all members of the community are expected to adhere to. Deviance from these standards is seen as absurd, wrong, or frankly abnormal. However, many of these cultural mores have no scientific basis and, some of them actually promote behaviors with negative health consequences. This chapter examines the cultural practices of some communities in Africa and their health consequences and, explores ways to address the challenges.",book:{id:"9138",slug:"public-health-in-developing-countries-challenges-and-opportunities",title:"Public Health in Developing Countries",fullTitle:"Public Health in Developing Countries - Challenges and Opportunities"},signatures:"Radiance Ogundipe",authors:[{id:"302308",title:"Dr.",name:"Radiance",middleName:null,surname:"Ogundipe",slug:"radiance-ogundipe",fullName:"Radiance Ogundipe"}]},{id:"55808",title:"The Role of Legumes in Human Nutrition",slug:"the-role-of-legumes-in-human-nutrition",totalDownloads:5378,totalCrossrefCites:59,totalDimensionsCites:100,abstract:"Legumes are valued worldwide as a sustainable and inexpensive meat alternative and are considered the second most important food source after cereals. Legumes are nutritionally valuable, providing proteins (20–45%) with essential amino acids, complex carbohydrates (±60%) and dietary fibre (5–37%). Legumes also have no cholesterol and are generally low in fat, with ±5% energy from fat, with the exception of peanuts (±45%), chickpeas (±15%) and soybeans (±47%) and provide essential minerals and vitamins. In addition to their nutritional superiority, legumes have also been ascribed economical, cultural, physiological and medicinal roles owing to their possession of beneficial bioactive compounds. Research has shown that most of the bioactive compounds in legumes possess antioxidant properties, which play a role in the prevention of some cancers, heart diseases, osteoporosis and other degenerative diseases. Because of their composition, legumes are attractive to health conscious consumers, celiac and diabetic patients as well as consumers concerned with weight management. The incorporation of legumes in diets, especially in developing countries, could play a major role in eradicating protein-energy malnutrition especially in developing Afro-Asian countries. Legumes could be a base for the development of many functional foods to promote human health.",book:{id:"5963",slug:"functional-food-improve-health-through-adequate-food",title:"Functional Food",fullTitle:"Functional Food - Improve Health through Adequate Food"},signatures:"Yvonne Maphosa and Victoria A. 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Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:36,paginationItems:[{id:"82195",title:"Endoplasmic Reticulum: A Hub in Lipid Homeostasis",doi:"10.5772/intechopen.105450",signatures:"Raúl Ventura and María Isabel Hernández-Alvarez",slug:"endoplasmic-reticulum-a-hub-in-lipid-homeostasis",totalDownloads:2,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"82409",title:"Purinergic Signaling in Covid-19 Disease",doi:"10.5772/intechopen.105008",signatures:"Hailian Shen",slug:"purinergic-signaling-in-covid-19-disease",totalDownloads:3,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82374",title:"The Potential of the Purinergic System as a Therapeutic Target of Natural Compounds in Cutaneous Melanoma",doi:"10.5772/intechopen.105457",signatures:"Gilnei Bruno da Silva, Daiane Manica, Marcelo Moreno and Margarete Dulce Bagatini",slug:"the-potential-of-the-purinergic-system-as-a-therapeutic-target-of-natural-compounds-in-cutaneous-mel",totalDownloads:9,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82103",title:"The Role of Endoplasmic Reticulum Stress and Its Regulation in the Progression of Neurological and Infectious Diseases",doi:"10.5772/intechopen.105543",signatures:"Mary Dover, Michael Kishek, Miranda Eddins, Naneeta Desar, Ketema Paul and Milan Fiala",slug:"the-role-of-endoplasmic-reticulum-stress-and-its-regulation-in-the-progression-of-neurological-and-i",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}}]},overviewPagePublishedBooks:{paginationCount:32,paginationItems:[{type:"book",id:"7006",title:"Biochemistry and Health Benefits of Fatty Acids",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7006.jpg",slug:"biochemistry-and-health-benefits-of-fatty-acids",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Viduranga Waisundara",hash:"c93a00abd68b5eba67e5e719f67fd20b",volumeInSeries:1,fullTitle:"Biochemistry and Health Benefits of Fatty Acids",editors:[{id:"194281",title:"Dr.",name:"Viduranga Y.",middleName:null,surname:"Waisundara",slug:"viduranga-y.-waisundara",fullName:"Viduranga Y. 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She is also the Global Harmonization Initiative (GHI)",institutionString:"Australian College of Business & Technology",institution:null}]},{type:"book",id:"6820",title:"Keratin",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6820.jpg",slug:"keratin",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Miroslav Blumenberg",hash:"6def75cd4b6b5324a02b6dc0359896d0",volumeInSeries:2,fullTitle:"Keratin",editors:[{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. 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She is now a lecturer at the University of Witwatersrand, South Africa, and a principal researcher at the Health Economics and Epidemiology Research Office (HE2RO), South Africa. Dr. Moolla holds a Ph.D. in Psychology with her research being focused on mental health and resilience. In her professional work capacity, her research has further expanded into the fields of early childhood development, mental health, the HIV and TB care cascades, as well as COVID. She is also a UNESCO-trained International Bioethics Facilitator.",institutionString:"University of the Witwatersrand",institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419588",title:"Ph.D.",name:"Sergio",middleName:"Alexandre",surname:"Gehrke",slug:"sergio-gehrke",fullName:"Sergio Gehrke",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038WgMKQA0/Profile_Picture_2022-06-02T11:44:20.jpg",biography:"Dr. Sergio Alexandre Gehrke is a doctorate holder in two fields. The first is a Ph.D. in Cellular and Molecular Biology from the Pontificia Catholic University, Porto Alegre, Brazil, in 2010 and the other is an International Ph.D. in Bioengineering from the Universidad Miguel Hernandez, Elche/Alicante, Spain, obtained in 2020. In 2018, he completed a postdoctoral fellowship in Materials Engineering in the NUCLEMAT of the Pontificia Catholic University, Porto Alegre, Brazil. He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,institution:{name:"Universidad Católica San Antonio de Murcia",country:{name:"Spain"}}},{id:"342152",title:"Dr.",name:"Santo",middleName:null,surname:"Grace Umesh",slug:"santo-grace-umesh",fullName:"Santo Grace Umesh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/342152/images/16311_n.jpg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"333647",title:"Dr.",name:"Shreya",middleName:null,surname:"Kishore",slug:"shreya-kishore",fullName:"Shreya Kishore",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333647/images/14701_n.jpg",biography:"Dr. Shreya Kishore completed her Bachelor in Dental Surgery in Chettinad Dental College and Research Institute, Chennai, and her Master of Dental Surgery (Orthodontics) in Saveetha Dental College, Chennai. She is also Invisalign certified. She’s working as a Senior Lecturer in the Department of Orthodontics, SRM Dental College since November 2019. She is actively involved in teaching orthodontics to the undergraduates and the postgraduates. Her clinical research topics include new orthodontic brackets, fixed appliances and TADs. She’s published 4 articles in well renowned indexed journals and has a published patency of her own. Her private practice is currently limited to orthodontics and works as a consultant in various clinics.",institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"323731",title:"Prof.",name:"Deepak M.",middleName:"Macchindra",surname:"Vikhe",slug:"deepak-m.-vikhe",fullName:"Deepak M. Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Univeristy of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:null},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\nHer topics of interest are biomaterials science and cell culture studies. 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After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. 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