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Okedu, Roland Uhunmwangho, Ngang Bassey Ngang\nand Richard Azubuike John",authors:[{id:"172580",title:"Dr.",name:"Kenneth Eloghene",middleName:null,surname:"Okedu",fullName:"Kenneth Eloghene Okedu",slug:"kenneth-eloghene-okedu"},{id:"172664",title:"Dr.",name:"Roland",middleName:null,surname:"Uhunmwangho",fullName:"Roland Uhunmwangho",slug:"roland-uhunmwangho"}]},{id:"47648",title:"Increasing Energy Efficiency by Reducing Losses and Promoting Value Propositions",slug:"increasing-energy-efficiency-by-reducing-losses-and-promoting-value-propositions",signatures:"Rune Gustavsson and Leif Marcusson",authors:[{id:"119892",title:"Prof.",name:"Rune",middleName:"E",surname:"Gustavsson",fullName:"Rune Gustavsson",slug:"rune-gustavsson"},{id:"173171",title:"Dr.",name:"Leif",middleName:null,surname:"Marcusson",fullName:"Leif Marcusson",slug:"leif-marcusson"}]},{id:"47979",title:"Heuristic Optimization Method for Power System Protection Coordination — An Intelligent Tool for Energy Efficiency Improvement",slug:"heuristic-optimization-method-for-power-system-protection-coordination-an-intelligent-tool-for-energ",signatures:"Rabah Benabid and Mohamed Boudour",authors:[{id:"113243",title:"Dr.",name:"Rabah",middleName:null,surname:"Benabid",fullName:"Rabah Benabid",slug:"rabah-benabid"},{id:"173270",title:"Prof.",name:"Mohamed",middleName:null,surname:"Boudour",fullName:"Mohamed Boudour",slug:"mohamed-boudour"}]},{id:"47647",title:"Recent Developments on Silicon Based Solar Cell Technologies and their Industrial Applications",slug:"recent-developments-on-silicon-based-solar-cell-technologies-and-their-industrial-applications",signatures:"Jiahe Chen",authors:[{id:"123054",title:"Prof.",name:"Jiahe",middleName:null,surname:"Chen",fullName:"Jiahe Chen",slug:"jiahe-chen"}]},{id:"48018",title:"High Throughput Quantum Dot Based LEDs",slug:"high-throughput-quantum-dot-based-leds",signatures:"P. Amini, M. Dolatyari, G. Rostami and A. Rostami",authors:[{id:"4761",title:"Prof.",name:"Ali",middleName:null,surname:"Rostami",fullName:"Ali Rostami",slug:"ali-rostami"},{id:"172301",title:"Dr.",name:"Mahboubeh",middleName:null,surname:"Dolatyari",fullName:"Mahboubeh Dolatyari",slug:"mahboubeh-dolatyari"},{id:"172313",title:"Dr.",name:"Ghasem",middleName:null,surname:"Rostami",fullName:"Ghasem Rostami",slug:"ghasem-rostami"},{id:"172314",title:"Ms.",name:"Pegah",middleName:null,surname:"Amini",fullName:"Pegah Amini",slug:"pegah-amini"}]},{id:"47418",title:"Experimental Research on Development Energy Efficiency of Non-Thermal Plasma Technology",slug:"experimental-research-on-development-energy-efficiency-of-non-thermal-plasma-technology",signatures:"Tao Zhu",authors:[{id:"171042",title:"Dr.",name:"Tao",middleName:null,surname:"Zhu",fullName:"Tao Zhu",slug:"tao-zhu"}]}]}],publishedBooks:[{type:"book",id:"8871",title:"Renewable Energy",subtitle:"Resources, Challenges and Applications",isOpenForSubmission:!1,hash:"e00c59554fb355c16623c62064ecc3bb",slug:"renewable-energy-resources-challenges-and-applications",bookSignature:"Mansour Al Qubeissi, Ahmad El-kharouf and Hakan Serhad Soyhan",coverURL:"https://cdn.intechopen.com/books/images_new/8871.jpg",editedByType:"Edited by",editors:[{id:"241686",title:"Dr.",name:"Mansour",surname:"Al Qubeissi",slug:"mansour-al-qubeissi",fullName:"Mansour Al Qubeissi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8896",title:"Sustainable Mobility",subtitle:null,isOpenForSubmission:!1,hash:"c5b28b438521dcd383df9b6e797ec462",slug:"sustainable-mobility",bookSignature:"Bernardo Llamas, Marcelo F. Ortega Romero and Eugenia Sillero",coverURL:"https://cdn.intechopen.com/books/images_new/8896.jpg",editedByType:"Edited by",editors:[{id:"169368",title:"Dr.",name:"Bernardo",surname:"Llamas",slug:"bernardo-llamas",fullName:"Bernardo Llamas"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{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",editedByType:"Edited by",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari"},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun"},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"295",title:"Solar Cells",subtitle:"Thin-Film Technologies",isOpenForSubmission:!1,hash:"ad5cda9b208fbf385f7cdf7a5c16baae",slug:"solar-cells-thin-film-technologies",bookSignature:"Leonid A. 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Together with hypertension, dyslipidemia is among the most prevalent risk factors leading to CVD. Thus, treatment of dyslipidemia is crucial in reducing CVD events and the morbidity and mortality associated with them. Studies in the last decade have confirmed a causal relationship between low-density lipoprotein cholesterol (LDL-C) and the risk of atherosclerotic cardiovascular diseases (ASCVD) [1]. LDL-C can be lowered by diet restriction and lifestyle changes or by various lipid-lowering therapies, among which statins (3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase inhibitors) are currently considered the cornerstone medication. Based on the 2018 guidelines published by the American College of Cardiology (ACC) and the American Heart Association (AHA), multiple recommendations have been made for patients with or at risk of developing cardiovascular disease [2].
Under certain circumstances, non-statin medications like ezetimibe and PCSK9 inhibitors are found to be useful particularly in combination with statin therapy. Clinical trials pertaining to these novel therapies have shown great benefits with significant LDL-C-lowering potential and decrease in cardiovascular risk. These agents are generally well tolerated, but long-term safety and cost remain to be proven.
PCSK9 gene was initially discovered as part of a search for members of the protein convertase family of serine proteases [3]. It was initially named as neural apoptosis-regulated convertase-1 (NARC1) due to its upregulation in apoptosis of primary cultures of cerebellar neurons. Subsequent studies classified it as a member of the proteinase K family of subtilases, and it was renamed as (proprotein convertase subtilisin/kexin type 9 (PCSK9)). The gene mapped to chromosome 1p32 comprises 12 exons, and it is translated into a protein of 692 amino acids (NM-174936.3) and is mainly expressed in the liver [3]. Interestingly, the gene coding for PCSK9 coincides with a region linked to dominant inheritance of hypercholesterolemia in American and French families who had no mutations in either LDL-R or APOB genes [4, 5]. Loss-of-function mutations in the later are the two main culprits that comprise 99% of cases with familial hypercholesterolemia (FH). Further genetic analysis of these index families identified a few rare heterozygous missense mutations in PCSK9 gene, all coinciding with hypercholesterolemia [6]. Thus, PCSK9 is now recognized as the third gene causing FH and currently accounts for <1% of FH cases [7].
A crucial step in further understanding the role of this gene in cholesterol metabolism was achieved by Maxwell and Breslow, who showed that transgenic overexpression of PCSK9 in mice caused a FH-like phenotype due to increased intracellular degradation of the LDL-receptor (LDL-R) [8, 9]. This observation shed light into the physiological implication of PCSK9 gene in the lipid metabolism and dyslipidemia. It became clear that gain-of-function rather than loss-of-function mutations in PCSK9 lead to hypercholesterolemia. In the last decade, many disease-causing mutations, occurring in various domains of the protein and leading to either increased transcription or impaired autocatalysis, have confirmed the above findings [10, 11, 12, 13].
It was not until 2005 when studies in individuals with extremely low LDL-C levels revealed some PCSK9 coding variants that were not seen in individuals with high levels of LDL-C. Some of these variants encoded truncated version of the protein that was clearly predicted to cause loss-of-function of PCSK9 [14, 15]. Mendelian randomization experiments clearly revealed that individuals with PCSK9 loss-of-function variants had lifelong depressed LDL-C levels as well as reduced ASCVD risk [16]. In these initial studies, of 3363 blacks, 2.6% carried heterozygous PCSK9 nonsense variants and were associated with 28 and 88% reductions in LDL-C and ASCVD risk, respectively. Of the 9524 white subjects examined, 3.2% had a PCSK9 mutation and were associated with 15 and 47% reductions in LDL-C and ASCVD risk, respectively. The above results were then confirmed in subsequent larger cohort studies [17, 18].
Taken together, the findings in either gain-of-function or loss-of-function mutations in PCSK9 gene have provided very strong evidence for the potential pharmacological use of targeted reduction of PCSK9 protein. Additionally, studies of complete human knockouts of PCSK9 (biallelic loss-of-function mutations) revealed only isolated decreased LDL-C levels with no deleterious health complications [19, 20]. This supports the potential safety of pharmacologically targeting PCSK9. However, it is worth mentioning that carriers of PCSK9 loss-of-function mutations showed an increased risk of developing type 2 diabetes mellitus (T2DM) [21, 22]. This finding would suggest that a similar side effect may be encountered in potential pharmacological inhibitors of PCSK9 (an increase of T2DM has been reported in statin drugs) [23]. However, no such association was found in clinical trials with human monoclonal anti-PCSK9 [24]. An increased risk of T2DM was also observed in a phenome-wide association study performed in >337,000 individuals with PCSK9 p.R46L mutation [25]. The same mutation was found to have a protective effect on hyperlipidemia, coronary heart disease (CHD), ischemic stroke, and cerebral infarction. No association with cataracts, heart failure, atrial fibrillation, or cognitive dysfunction was reported.
PCSK9 is a serine protease involved in cholesterol metabolism. In the liver, it binds to the LDL-receptor (LDL-R), inducing intracellular degradation, thus reducing serum LDL clearance. Generally, PCSK9 molecule is absent allowing repeated recycling of the LDL-R receptor. One study also suggests that intracellular PCSK9 may be recycled so that a single molecule might contribute multiple times to receptor degradation [26]. Under physiological conditions, PCSK9 expression is very low compared to LDL-R, thus allowing continuous recycling of the receptor (Figure 1A). In the case of low intracellular levels of cholesterol, both LDL-R and PCSK9 are transcribed (Figure 1B). Once secreted in the plasma, PCSK9 serves as one of the many potential ligands for LDL-R. After endocytosis, LDL-R, LDL particle, and PCSK9 enter the lysosome. Once inside the lysosome, the LDL particle is degraded, whereas the LDL-R attached to PCSK9 fails to exit the lysosome, where it gets degraded and can no longer be recycled (Figure 1B) [10, 27, 28]. Using this intricate mechanism, PCSK9 would prevent overexpression of LDL-R and thus increase the intracellular cholesterol levels. On the other hand, in patients with elevated cholesterol levels, administering PCSK9 monoclonal antibodies would neutralize the PCSK9 molecules floating in the plasma, thus increasing LDL-R recycling and surface LDL-R (Figure 1C).
Under physiological conditions, PCSK9 expression is very low compared to LDL-R, thus allowing continuous recycling of the receptor (a). In the case of low intracellular levels of cholesterol, both LDL-R and PCSK9 are transcribed (b). In patients with elevated cholesterol levels, administering PCSK9 monoclonal antibodies would neutralize the PCSK9 molecules floating in the plasma, thus increasing LDL-R recycling and surface LDL-R (c).
To better understand the action of PCSK9 inhibitors, we can correlate it with the pharmacological action of HMG-CoA reductase inhibitors (statins). Cholesterol is mainly synthetized in the liver via the mevalonate pathway, with HMG-CoA reductase being the rate-limiting enzyme in the process. The decrease in the intracellular cholesterol in the liver is sensed by sterol regulatory element-binding protein 2 (SREBP2) which then increases the production of HMG-CoA reductase to promote the intracellular synthesis of cholesterol as well as increase LDL-R and PCSK9 levels. As a result, statins will (1) decrease intracellular cholesterol production, (2) increase LDL-R expression on the hepatocytes, and (3) increase PCSK9 levels. This can explain why addition of anti-PCSK9 monoclonal antibodies can accentuate the lipid-lowering effect of statins.
Currently, statins are the first-choice agents to reduce high blood cholesterol which is considered one of the main risk factors for cardiovascular disease (CVD). Cholesterol Treatment Trialists’ (CTT) Collaboration as well as other clinical trials showed that primary prevention with statins reduced all-cause mortality, reduced combined fatal and nonfatal stroke, reduced revascularization rate, and improved patient quality of life [29, 30]. Statin prescription is not associated with serious harm and is considered to be cost-effective [31]. That said, in the last decade, many patients have reported more and more severe side effects particularly with high-intensity statin therapy [32]. Additionally, certain patient populations (familial hypercholesterolemia) are at particular high risk for cardiovascular events. The risk can be attributed to the complexity of the underlying disease, and sole treatment with statins may be insufficient.
Multiple studies were performed to investigate the cardiovascular effect of the anti-PCSK9 monoclonal antibodies. The Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial, a randomized, double-blinded, placebo-controlled trial published in 2017, is currently considered one of the landmark studies in the efficacy of anti-PCSK9 monoclonal antibodies [36]. The aim of the study was to understand whether evolocumab (anti-PCSK9 monoclonal antibody) which lowers LDL-C levels by 69% can prevent cardiovascular events. This trial included 27,564 patients with atherosclerotic cardiovascular disease and LDL-C levels of ≥70 mg/dl while on maximally tolerated statin therapy. Patients were then randomly assigned to either evolocumab (140 mg every 2 weeks or 429 mg monthly) or placebo. The primary end point of the study was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The secondary end point was the composite of cardiovascular death, myocardial infarction, or stroke. The median duration of follow-up was 2.2 years. Inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL-C levels to a median of 30 mg/dl. Addition of evolocumab to statin therapy significantly reduces the risk of cardiovascular events, with a 15% reduction risk of primary composite and a 20% reduction risk of the secondary composite outcomes. Based on this study, PCSK9 inhibitor therapy should be considered for ASCVD risk reduction in patients with stable ASCVD, particularly in those with additional risk factors, on maximally tolerated statin therapy, with on-treatment LDL-C ≥70 mg/dl or non-HDL-C ≥100 mg/dl. In the same FOURIER trial, similar recommendations but with a lower level of evidence can also be applicable to patients with progressive ASCVD (additional diagnosis of MI or nonhemorrhagic stroke).
There is currently no universally accepted definition for statin intolerance. Previous studies have confirmed statin-related muscle side effects; however more needs to be done to accurately address the issue. That said, statin intolerance in individuals with a history of CVD is a challenge to a clinician. According to the latest National Lipid Association (NLA) recommendations, PCSK9 inhibitors may be considered to reduce LDL-C in selected very-high-risk patients who are classified as statin-intolerant, in the presence of additional LDL-C-lowering therapies [37]. The quality of evidence for such a recommendation is low.
Severe hypercholesterolemia is defined as LDL-C ≥190 mg/dl. The majority of these patients have polygenic hypercholesterolemia attributed to multiple, undefined genetic factors. Familial hypercholesterolemia (both heterozygous and homozygous) is due to defined mutations yet less commonly encountered. Regardless of the etiology, long-term risk for cardiovascular diseases in all these patients is very high. However, studies have shown that particularly patients with clinically defined FH have a greater risk for cardiovascular events despite being on maximum dose of statins. Studies in patients with heterozygous familial hypercholesterolemia who received PCSK9 inhibitors (either alirocumab or evolocumab) revealed significant additional LDL-C reduction.
Based on the current data, the National Lipid Association is recommending addition of PCSK9 inhibitors in patients with LDL-C ≥190 mg/dl with additional risk factors or genetic confirmation of FH on maximally tolerated statin ± ezetimibe.
In order to determine the effects of PCSK9 inhibitors (evolocumab) on progression of coronary atherosclerosis in statin-treated patients, the Global Assessment of Plaque Regression with a PCSK9 Antibody as Measured by Intravascular Ultrasound (GLAGOV) multicenter, double-blind, placebo-controlled, randomized clinical trial was conducted [38]. In this trial 968 patients with angiographic coronary disease were studied. These patients were randomized to receive monthly 420 mg evolocumab or placebo via subcutaneous injection for 76 weeks, in addition to moderate- or high-intensity statins. In this trial, the primary efficacy was the change in percent atheroma volume from baseline to week 78, measured by serial intravascular ultrasonography (IVUS) imaging. Secondary efficacy was measured in normalized total atheroma volume and patients demonstrating plaque regression. Interestingly, IVUS showed atherosclerosis regression during 18 months of therapy in patients treated with the combination of evolocumab and statins and absence of regression in patients treated with statin alone. Additionally, the evolocumab group showed a significant reduction in percent atheroma volume as well as total atheroma volume (−0.95%,
The most recent study to evaluate the effects of alirocumab on the occurrence of cardiovascular events in patients who have experienced an acute coronary syndrome (ODYSSEY OUTCOMES) suggested a reduction in mortality with alirocumab in patients after acute coronary syndrome [39].Based on the results from multiple trials, alirocumab reduced the risk of all-cause mortality: 6 fewer deaths per 1000 patients treated (RR, 0.82; 95% CI 0.72–0.95). No reduction in cardiovascular mortality was observed (RR, 0.87; 95% CI, 0.73–1.02) [40]. On the other hand, trials of evolocumab did not show a reduction in either all-cause or cardiovascular mortality (RR, 0.91; 95% CI, 0.57–1.44 and RR, 1.04; 95% CI, 0.88–1.24, respectively). Taken together, PCSK9 inhibitors did not reduce the risk of all-cause or cardiovascular mortality.
Both alirocumab and evolocumab reduced the risk of myocardial infarction, stroke, and coronary revascularization. Alirocumab, but not evolocumab, reduced stable angina hospitalization, and neither drug reduced heart failure.
Regarding the safety of anti-PCSK9 monoclonal antibodies (alirocumab and evolocumab), all phase 2 and 3 studies have demonstrated excellent safety profile [41]. The most commonly reported adverse effect has been injection site reaction [42]. As part of the safety analysis, fat-soluble vitamin concentrations (A, D, E, K) were measured. Compared to placebo, no change in the levels of any of these vitamins was reported. Additionally, no increase in neurocognitive events, new-onset or worsening diabetes, muscle-related events, or myalgia has been noted [43].
Bococizumab has been excluded from most of these studies as the drug is no longer available after the cessation of development by the manufacturer due to high rates of neutralizing antibody formation and subsequent loss of therapeutic efficacy (SPIRE trial) [44].
Since the early 1990s when statins were initially introduced, several large clinical trials have highlighted the benefits of their use with beneficial effects above and beyond lipid lowering [45]. Statins are currently the cornerstone of hyperlipidemia treatment. However, due to safety concerning high-dose therapy as well as residual risk of CVD especially in high-risk patients, additional lipid-modifying therapies have emerged in the last decades.
Ezetimibe reduces absorption of cholesterol from the brush border of the small intestine by targeting the Niemann-Pick C1-like 1 (NPC1L1) protein (Figure 2) [46, 47]. Genetic studies have shown that polymorphisms affecting NPC1L1 are associated with lower levels of LDL cholesterol and a lower risk of cardiovascular diseases [48]. A decrease in cholesterol absorption results in a decrease of total cholesterol, triglycerides, and LDL cholesterol and an increase in HDL cholesterol.
Ezetimibe reduces absorption of cholesterol from the brush border of the small intestine by targeting the Niemann-Pick C1-like 1 (NPC1L1) protein. In the liver, HMG-CoA reductase (statins) promotes the intracellular synthesis of cholesterol as well as increases LDL-R and PCKS9 levels. PCSK9 monoclonal antibodies would neutralize the PCSK9 molecules floating in the plasma, thus increasing LDL-R recycling and surface LDL-R in the liver.
It was FDA-approved in 2002 as an agent to treat people with hyperlipidemia. Ezetimibe given as monotherapy leads to an LDL reduction of approximately 20%. When added to statins, ezetimibe reduces LDL cholesterol levels by an additional 23–24% on average [49, 50]. The Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) was then conducted to understand if further lowering of the LDL-C levels by statin-ezetimibe dual therapy leads to clinical benefit [51]. In this trial they studied the effect of ezetimibe combined with simvastatin, as compared with that of simvastatin alone, in stable patients who had an acute coronary syndrome and whose LDL cholesterol values were within the guideline recommendations. The primary end points were death from cardiovascular disease, a major coronary event, or nonfatal stroke, assessed from the time of randomization until the first occurrence of one of the events. The combination of simvastatin and ezetimibe resulted in additional lowering of LDL-C levels as well as lower risk of cardiovascular event. A reduction of cholesterol levels of 12.8 mg per deciliter correlated with a proportionally 7.2% lower rate of major vascular events, providing further evidence for a relationship between lower lipid and improved outcomes.
Multiple statin trials including the CTT collaboration have shown clinical benefits when LDL cholesterol was lowered to progressively lower levels. It was on the basis of these trials that a LDL-C of <70 mg per deciliter has been recommended for patients with acute coronary syndrome. Data from the IMPROVE-IT trial support the previous finding and show a direct evidence between further lipid lowering and improved outcomes [51]. Additionally, this trial provides evidence, for the first time, that a non-statin lipid-lowering agent can reduce cardiovascular risk by lowering LDL-C and that statins are not the only beneficiary drugs in hyperlipidemia. The American College of Cardiology recommends consideration of ezetimibe therapy in addition to maximally tolerated statin therapy for both primary and secondary prevention in patients who have not achieved target reduction in their LDL-C by maximally tolerated statin therapy alone.
Ezetimibe is currently marketed as a monotherapy under the trade name of Zetia, as well as in combination with a statin such as Vytorin and Liptruzet. It has a half-life of 22 hours, and it can be administered at 10 mg daily. It can be taken at the same time as fenofibrates or statins, but it is recommended to take it at least 2 hours before or 4 hours after taking bile acid sequestrants.
Based on current studies, very few side effects to ezetimibe have been reported, most common being headache, runny nose, and sore throat [52]. Rhabdomyolysis has been reported only in combination with statin therapy and rarely with monotherapy. Due to its daily dosing and limited side effects, ezetimibe is considered a safer drug with no compliance issues. Contraindications to its use include hypersensitivity to possible ingredients of the formulation. It is not recommended in patients with moderate to severe hepatic impairment but can be administered in patients with renal impairment without any need for dose adjustment. Liver function tests need to be performed only if it is administered with a statin. It is worth mentioning that patients taking ezetimibe with cyclosporine are at an increased risk of ezetimibe toxicity as it can result in 2.3–12-fold increase in exposure [53]. In these cases, cyclosporine concentrations should be closely monitored.
When results from trials of ezetimibe (IMPROVE-IT) and PCSK9 inhibitors (FOURIER RCT) are compared in regard to secondary prevention of cardiovascular events in patients with ASCVD and type 2 diabetes, evolocumab (PCSK9 inhibitor) seems to be more effective [54]. Interestingly, as of December 2018, the annual cost of evolocumab is $6540 and $88 for ezetimibe. From a healthcare cost standpoint, ezetimibe has a significantly lower cost and may be considered a preferred add-on therapy for these patients. The difference in avoiding cardiovascular events between the two therapies is negligible compared with the significant difference in the drug costs. However, a randomized controlled trial (RCT) comparing evolocumab and ezetimibe would be necessary to evaluate and compare the effectiveness of these two drugs. Additionally, long-term effects of these novel drugs in reducing the cardiovascular events in patients with ASCVD and type 2 diabetes will be needed.
Dyslipidemia is a major risk factor for both fatal and nonfatal CVD. Lowering cholesterol levels particularly LDL-C, through lifestyle modifications as well as pharmacological interventions, is crucial for CVD risk reduction. Currently, statins are the cornerstone medication for treatment and primary prevention of hypercholesterolemia. Studies have shown that benefits from statins outweigh any possible adverse effects. However, as the intensity of statin therapy increases, intolerance to their use becomes more prominent. Additionally, high-risk patients on maximally tolerated statins may benefit from novel LDL-C-lowering therapies. Clinical trials have provided evidence that these novel drugs such as PCSK9 inhibitors or ezetimibe can successfully lower LDL-C in levels and contribute in lowering cardiovascular events in high-risk patients with elevated LDL-C on maximally tolerated statins. Both ezetimibe and PCSK9 inhibitors have demonstrated a modest absolute ASCVD risk reduction and good safety profiles. However, given cost considerations particularly for PCSK9 inhibitors, healthcare providers will need to carefully consider the subgroup of patients benefiting the most from their use.
The author declares no conflict of interest.
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Algal biorefineries must valorize the entire crop to grow profitable microalgae-based economies. With massive growth and demand for novel sustainable ingredients, farmed salmonid feed sectors are highly promising areas to focus on. Microalgae-based ingredients for salmonid feeds may have market advantages in terms of lower input costs, aerial foot-print, wastewater remediation benefits and carbon credits for industrial CO2 conversion. A handful of microalgae-based ingredients have been proposed as candidates to supply well-balanced nutrients and immunostimulatory compounds. However, technical gaps exist and need addressing before the industry could economically incorporate microalgae-based ingredients into commercial feeds. Current knowledge on comprehensive biochemical composition is incomplete, highly heterogeneous, and information on their nutritional value is scattered and/or inconsistent. The aim of this chapter is to consolidate relatively fragmented data on biochemical composition and nutritional value of microalgae-based ingredients focusing on farmed salmonid feeds. Presented are discussions on the potential for such ‘next-generation’ ingredients, opportunities/challenges for their use and a compendium of studies evaluating their performance in feeds for economically relevant farmed salmonids, including rainbow trout (Oncorhynchus mykiss), Arctic charr (Salvelinus alpinus) and Atlantic salmon (Salmo salar).",book:{id:"6541",slug:"microalgal-biotechnology",title:"Microalgal Biotechnology",fullTitle:"Microalgal Biotechnology"},signatures:"Sean Michael Tibbetts",authors:[{id:"228874",title:"Dr.",name:"Sean",middleName:null,surname:"Tibbetts",slug:"sean-tibbetts",fullName:"Sean Tibbetts"}]},{id:"59210",doi:"10.5772/intechopen.73791",title:"Spirulina Phycobiliproteins as Food Components and Complements",slug:"spirulina-phycobiliproteins-as-food-components-and-complements",totalDownloads:2615,totalCrossrefCites:15,totalDimensionsCites:26,abstract:"Spirulina has a documented history of use as a food for more than 1000 years, and has been in production as a dietary supplement for 40 years. Among many of Spirulina bioactive components, blue protein C-phycocyanin and its linear tetrapyrrole chromophore phycocyanobilin occupy a special place due to broad possibilities for application in various areas of food technology. The subject of this chapter is up-to-date food applications of these Spirulina components, with a focus on their use as food colorants, additives, nutriceuticals, and dietary supplements. Their other actual and future food application possibilities will also be briefly presented and discussed.",book:{id:"6541",slug:"microalgal-biotechnology",title:"Microalgal Biotechnology",fullTitle:"Microalgal Biotechnology"},signatures:"Dragana Stanic-Vucinic, Simeon Minic, Milan R. 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This interest has been partially due to the fact that some strains of microalgae and cyanobacteria have demonstrated the ability to produce a variety of bioactive products. Both, primary and secondary metabolism of these microorganisms has been demonstrated to play a key role in the production of special chemicals. Antioxidants, for instance, can be produced by some algal strains to protect photosynthetic cells from oxidative stress. Microalgae can produce a variety of polyunsaturated and monounsaturated fatty acids with clear health benefits for human nutrition. Potential products obtained from cyanobacteria and microalgae exhibiting interesting medical properties include polysaccharides, glycerol, glycoproteins, and antibiotics. From the aforementioned products, especially relevant has become the search of new antibiotics. The potential spread of bacterial resistance and the foreseen decrease on efficiency on antibiotics, has largely stimulated the research on novel antibiotics sources. Among these sources, cyanobacteria and microalgae have demonstrated a vast and just barely explored potential.",book:{id:"6541",slug:"microalgal-biotechnology",title:"Microalgal Biotechnology",fullTitle:"Microalgal Biotechnology"},signatures:"Elena Martínez-Francés and Carlos Escudero-Oñate",authors:[{id:"188725",title:"Dr.",name:"Carlos",middleName:null,surname:"Escudero-Oñate",slug:"carlos-escudero-onate",fullName:"Carlos Escudero-Oñate"},{id:"228683",title:"MSc.",name:"Elena",middleName:null,surname:"Martínez-Francés",slug:"elena-martinez-frances",fullName:"Elena Martínez-Francés"}]},{id:"59257",doi:"10.5772/intechopen.73702",title:"Bioeconomic Assessment of Microalgal Production",slug:"bioeconomic-assessment-of-microalgal-production",totalDownloads:1476,totalCrossrefCites:7,totalDimensionsCites:14,abstract:"Today, microalgae play an important role for the worldwide biofuel demand, together with the production of high value-added products used in pharmaceutical, nutraceutical and cosmetic industries. In 2014, the European Union adopted a strategy for developing the bioeconomy, by utilizing microalgae which represent an emerging biological resource of great importance for its potential applications in different fields. Huge potential of tiny microalgae could support a microalgae-based biorefinery and microalgae-based bioeconomy opening up vast opportunities in the global algae business. Nevertheless, in spite of having been studied for over 50 years now, there are still only just a few corporations that are cultivating algae on a large or commercial scale due to operational and capital cost. Techno-economic modeling is a powerful tool for guiding research priorities and assessing the economics, environmental impact and sustainability of microalgal productions. In this chapter, microalgal productions are assessed within bioeconomical aspects and case-studies on microalgal biorefinery are discussed.",book:{id:"6541",slug:"microalgal-biotechnology",title:"Microalgal Biotechnology",fullTitle:"Microalgal Biotechnology"},signatures:"Didem Özçimen, Benan İnan, Anıl Tevfik Koçer and Meyrem Vehapi",authors:[{id:"32444",title:"Dr.",name:"Didem",middleName:null,surname:"Özçimen",slug:"didem-ozcimen",fullName:"Didem Özçimen"},{id:"228422",title:"MSc.",name:"Benan",middleName:null,surname:"İnan",slug:"benan-inan",fullName:"Benan İnan"},{id:"240583",title:"MSc.",name:"Anıl Tevfik",middleName:null,surname:"Koçer",slug:"anil-tevfik-kocer",fullName:"Anıl Tevfik Koçer"},{id:"240584",title:"MSc.",name:"Meyrem",middleName:null,surname:"Vehapi",slug:"meyrem-vehapi",fullName:"Meyrem Vehapi"}]},{id:"57981",doi:"10.5772/intechopen.72175",title:"Application of Electrochemical Methods in Biosensing Technologies",slug:"application-of-electrochemical-methods-in-biosensing-technologies",totalDownloads:2102,totalCrossrefCites:7,totalDimensionsCites:14,abstract:"Introducing biochemical factor to electronic devices have created a new branch of science. Recent development in biosensing technology enabled progress in pathogens detection. Currently, wide range of biomarkers (enzymes, peptides, DNA, microorganisms, etc. )recognize various target analytes, starting from basic metabolism changes to serious infections caused by pathogens. Improved sensitivity, selectivity and response time of sensors have instantly replaced traditional techniques. Easy handling, low production costs and miniaturization have met therapeutics need. Biosensing technologies are very strong point in telemedicine in public healthcare. This chapter will focus on electrochemical techniques for pathogens detection and show trending applications in biosensing technologies.",book:{id:"6319",slug:"biosensing-technologies-for-the-detection-of-pathogens-a-prospective-way-for-rapid-analysis",title:"Biosensing Technologies for the Detection of Pathogens",fullTitle:"Biosensing Technologies for the Detection of Pathogens - A Prospective Way for Rapid Analysis"},signatures:"Karolina Dziąbowska, Elżbieta Czaczyk and Dawid Nidzworski",authors:[{id:"212390",title:"B.Sc.",name:"Karolina",middleName:null,surname:"Dziąbowska",slug:"karolina-dziabowska",fullName:"Karolina Dziąbowska"},{id:"212521",title:"Dr.",name:"Elżbieta",middleName:null,surname:"Czaczyk",slug:"elzbieta-czaczyk",fullName:"Elżbieta Czaczyk"},{id:"212524",title:"Dr.",name:"Dawid",middleName:null,surname:"Nidzworski",slug:"dawid-nidzworski",fullName:"Dawid Nidzworski"}]}],mostDownloadedChaptersLast30Days:[{id:"58097",title:"Detection and Control of Indoor Airborne Pathogenic Bacteria by Biosensors Based on Quorum Sensing Chemical Language: Bio-Tools, Connectivity Apps and Intelligent Buildings",slug:"detection-and-control-of-indoor-airborne-pathogenic-bacteria-by-biosensors-based-on-quorum-sensing-c",totalDownloads:1790,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Nowadays, lifestyles and climate change lead people to spend long periods in indoors spaces, where reduced ventilation and artificial light favor the concentration and spread of airborne pathogenic microorganisms. Current procedures for microbiological air evaluation are based on air sampling coupled to traditional microbiological culture-dependent methods such as biochemical tests and molecular rDNA 16S sequencing. These techniques generate an important delay in the application of prevention and control measures. This chapter presents whole cell-based biosensors that are able to detect quorum sensing signaling molecules produced by airborne pathogenic bacteria as a tool for indoor air monitoring. Furthermore, a general biosensor model is proposed. In this model, in vivo biosensors technology can be connected to online applications (Apps), being part of intelligent buildings, in order to reduce airborne pathogenic bacteria concentration and dissemination.",book:{id:"6319",slug:"biosensing-technologies-for-the-detection-of-pathogens-a-prospective-way-for-rapid-analysis",title:"Biosensing Technologies for the Detection of Pathogens",fullTitle:"Biosensing Technologies for the Detection of Pathogens - A Prospective Way for Rapid Analysis"},signatures:"Claudia Ibacache-Quiroga, Natalia Romo, Rodrigo Díaz-Viciedo and\nM. Alejandro Dinamarca",authors:[{id:"211459",title:"Prof.",name:"Alejandro",middleName:null,surname:"Dinamarca",slug:"alejandro-dinamarca",fullName:"Alejandro Dinamarca"},{id:"211467",title:"Ms.",name:"Natalia",middleName:null,surname:"Romo",slug:"natalia-romo",fullName:"Natalia Romo"},{id:"211474",title:"Dr.",name:"Claudia",middleName:null,surname:"Ibacache-Quiroga",slug:"claudia-ibacache-quiroga",fullName:"Claudia Ibacache-Quiroga"},{id:"230663",title:"Dr.",name:"Rodrigo",middleName:null,surname:"Díaz-Viciedo",slug:"rodrigo-diaz-viciedo",fullName:"Rodrigo Díaz-Viciedo"}]},{id:"65478",title:"The Oleaginous Red Yeast Rhodotorula/Rhodosporidium: A Factory for Industrial Bioproducts",slug:"the-oleaginous-red-yeast-em-rhodotorula-rhodosporidium-em-a-factory-for-industrial-bioproducts",totalDownloads:1290,totalCrossrefCites:5,totalDimensionsCites:9,abstract:"Rhodotorula genus, amended in 2015, is polyphyletic and contains Rhodotorula species that grow as single-cell yeast (monomorphic) and reproduce asexually via budding/fission (anamorphic); it also contains Rhodosporidium species that reproduce sexually (teleomorphic) and alternate between a yeast phase and dikaryotic filamentous phase (dimorphic). Several species of these “red yeast” produce industrial bioproducts, namely biofuel feedstocks, carotenoids, enzymes, and biosurfactants. This chapter highlights the biotechnology areas that Rhodotorula/Rhodosporidium contributes to and the future market value of those industries. The primary yeast species to be discussed include Rhodosporidium toruloides, Rhodotorula glutinis, Rhodosporidium diobovatum, Rhodosporidium kratochvilovae, Rhodotorula graminis, Rhodotorula babjevae, and Rhodotorula taiwanensis.",book:{id:"8107",slug:"yeasts-in-biotechnology",title:"Yeasts in Biotechnology",fullTitle:"Yeasts in Biotechnology"},signatures:"Mathew Lyman, Salustra Urbin, Cheryl Strout and Bonnee Rubinfeld",authors:[{id:"282320",title:"Dr.",name:"Mathew",middleName:null,surname:"Lyman",slug:"mathew-lyman",fullName:"Mathew Lyman"},{id:"290955",title:"Dr.",name:"Salustra",middleName:null,surname:"Urbin",slug:"salustra-urbin",fullName:"Salustra Urbin"},{id:"295704",title:"Dr.",name:"Cheryl",middleName:null,surname:"Strout",slug:"cheryl-strout",fullName:"Cheryl Strout"},{id:"295705",title:"Dr.",name:"Bonnee",middleName:null,surname:"Rubinfeld",slug:"bonnee-rubinfeld",fullName:"Bonnee Rubinfeld"}]},{id:"60275",title:"The Influence of Microalgae Addition as Co-Substrate in Anaerobic Digestion Processes",slug:"the-influence-of-microalgae-addition-as-co-substrate-in-anaerobic-digestion-processes",totalDownloads:1376,totalCrossrefCites:2,totalDimensionsCites:7,abstract:"Growth microalgae could be used as co-substrates in anaerobic digestion processes to produce biogas of a high-calorific value, which could be expended as heat or electricity in cogeneration engines. Lignocellulosic and high-carbon content wastes, due to their characteristics, hinder anaerobic digestion processes. The use of microalgae as a co-substrate with high-carbon content residues can adjust the C/N ratio and thereby obtain, in some cases, a higher biogas production and greater biodegradability of wastes during anaerobic digestion than without co-digestion options. In addition, microalgae and cyanobacteria are photosynthetic microorganisms that can produce oxygen and oxidize the organic matter and NH4+ contained in wastewaters. The growth of microalgae in industrial effluents and wastewaters can considerably reduce the organic matter contained in them and their pollutant load. This growth can take advantage of the nutrients that still remain in industrial effluents, avoiding the use of clean water for the growth of biomass. The chapter will focus on an overview of microalgae anaerobic co-digestion with different wastes and the benefits of this option.",book:{id:"6541",slug:"microalgal-biotechnology",title:"Microalgal Biotechnology",fullTitle:"Microalgal Biotechnology"},signatures:"Bárbara Rincón, María José Fernández-Rodríguez, David de la\nLama-Calvente and Rafael Borja",authors:[{id:"74541",title:"Dr.",name:"Barbara",middleName:null,surname:"Rincon",slug:"barbara-rincon",fullName:"Barbara Rincon"},{id:"89771",title:"Dr.",name:"Rafael",middleName:null,surname:"Borja",slug:"rafael-borja",fullName:"Rafael Borja"},{id:"246719",title:"MSc.",name:"María José",middleName:null,surname:"Fernández-Rodríguez",slug:"maria-jose-fernandez-rodriguez",fullName:"María José Fernández-Rodríguez"},{id:"246720",title:"MSc.",name:"David",middleName:null,surname:"De La Lama-Calvente",slug:"david-de-la-lama-calvente",fullName:"David De La Lama-Calvente"}]},{id:"64889",title:"Common Methods to Understand and Develop Indigenous Probiotics Yeast for Ruminant",slug:"common-methods-to-understand-and-develop-indigenous-probiotics-yeast-for-ruminant",totalDownloads:1397,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Probiotic yeast enhanced the ruminal gut microbial balance by producing intercellular effectors and important metabolites. The impact of yeast addition on animal health is influenced by different interlinked factors including animal genomics, its gut microbiota, and environment. Therefore, all factors should be considered regarding achieving the maximum outputs from animal probiotic yeast. In the situation of a high feeding cost, microbial feed supplements provide a suitable nutritional approach, which allows increased nutrient digestion rate and accordingly improves animal performance. Many yeast products are commercially available, but their efficiency as probiotic dietary addition in a particular breed is mostly questionable. Therefore, identification of ideal probiotic yeast strain is of great interest in this context. Innovative methods in relation to develop new probiotic are mainly focused on the exploring novel microbial strains from indigenous sources. It has been noted that for the identification of best probiotic strain for the host, a linkage between culture-independent and culture-dependent methods is a functional step. In this chapter, we will discuss the mode of action of probiotic yeast on animal lower gut microbiota and identification of ideal probiotic yeast by using advanced molecular methods.",book:{id:"8107",slug:"yeasts-in-biotechnology",title:"Yeasts in Biotechnology",fullTitle:"Yeasts in Biotechnology"},signatures:"Shakira Ghazanfar, Aayesha Riaz, Ghulam Muhammad Ali, Saima Naveed, Irum Arif, Sidra Irshad, Naeem Riaz and Khanzadi Nazneen Manzoor",authors:[{id:"202370",title:"Dr.",name:"Shakira",middleName:null,surname:"Ghazanfar",slug:"shakira-ghazanfar",fullName:"Shakira Ghazanfar"},{id:"286878",title:"Dr.",name:"Ghulam",middleName:null,surname:"Muhammad Ali",slug:"ghulam-muhammad-ali",fullName:"Ghulam Muhammad Ali"},{id:"286879",title:"Ms.",name:"Irum",middleName:null,surname:"Arif",slug:"irum-arif",fullName:"Irum Arif"},{id:"286880",title:"Ms.",name:"Sidra",middleName:null,surname:"Irshad",slug:"sidra-irshad",fullName:"Sidra Irshad"},{id:"286881",title:"Ms.",name:"Khanzadi",middleName:null,surname:"Nazneen Manzoor",slug:"khanzadi-nazneen-manzoor",fullName:"Khanzadi Nazneen Manzoor"},{id:"297912",title:"Dr.",name:"Naeem",middleName:null,surname:"Riaz",slug:"naeem-riaz",fullName:"Naeem Riaz"},{id:"304921",title:"Dr.",name:"Aayesha",middleName:null,surname:"Riaz",slug:"aayesha-riaz",fullName:"Aayesha Riaz"},{id:"304923",title:"Dr.",name:"Saima",middleName:null,surname:"Naveed",slug:"saima-naveed",fullName:"Saima Naveed"}]},{id:"58181",title:"FRET-Based Enzyme Activity Reporter: Practical Hints for Kinases as Indicators of Virulence",slug:"fret-based-enzyme-activity-reporter-practical-hints-for-kinases-as-indicators-of-virulence",totalDownloads:1450,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Modulation of protein kinases activity is often requested for pathogenicity or virulence. This chapter provides several hints for one who might be interested in using FRET-based kinase activity reporters. The archetypes of these reporters, which are now within the arsenal of biosensors, were devoted to the detection and characterization of the activity of the cAMP-Protein kinase A pathway. Based on the principle of this biosensor, other FRET-based kinase activity reporters emerged. Here, the choice of the kinase to be monitored, the artifacts that might be met, and the flexibility and amenability of the FRET-based kinase activity reporters both for high-throughput analysis and dissection of protein kinase functions are discussed.",book:{id:"6319",slug:"biosensing-technologies-for-the-detection-of-pathogens-a-prospective-way-for-rapid-analysis",title:"Biosensing Technologies for the Detection of Pathogens",fullTitle:"Biosensing Technologies for the Detection of Pathogens - A Prospective Way for Rapid Analysis"},signatures:"Corentin Spriet, Angelina Kasprowicz, Dave Trinel and Jean-\nFrançois Bodart",authors:[{id:"98539",title:"Prof.",name:"Jean-François",middleName:"Laurent",surname:"Bodart",slug:"jean-francois-bodart",fullName:"Jean-François Bodart"},{id:"226954",title:"Dr.",name:"Corentin",middleName:null,surname:"Spriet",slug:"corentin-spriet",fullName:"Corentin Spriet"},{id:"230593",title:"MSc.",name:"Angelina",middleName:null,surname:"Kasprowicz",slug:"angelina-kasprowicz",fullName:"Angelina Kasprowicz"},{id:"230594",title:"MSc.",name:"Dave",middleName:null,surname:"Trinel",slug:"dave-trinel",fullName:"Dave Trinel"}]}],onlineFirstChaptersFilter:{topicId:"893",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. These advances have helped foster better support for animal health, more humane animal production, and a better understanding of the physiology of endangered species to improve the assisted reproductive technologies or the pathogenesis of certain diseases, where animals can be used as models for human diseases (like cancer, degenerative diseases or fertility), and even as a guarantee of public health. Bridging Human, Animal, and Environmental health, the holistic and integrative “One Health” concept intimately associates the developments within those fields, projecting its advancements into practice. This book series aims to tackle various animal-related medicine and sciences fields, providing thematic volumes consisting of high-quality significant research directed to researchers and postgraduates. It aims to give us a glimpse into the new accomplishments in the Veterinary Medicine and Science field. 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After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"19",title:"Animal Science",coverUrl:"https://cdn.intechopen.com/series_topics/covers/19.jpg",isOpenForSubmission:!0,editor:{id:"259298",title:"Dr.",name:"Edward",middleName:null,surname:"Narayan",slug:"edward-narayan",fullName:"Edward Narayan",profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",biography:"Dr. Edward Narayan graduated with Ph.D. degree in Biology from the University of the South Pacific and pioneered non-invasive reproductive and stress endocrinology tools for amphibians - the novel development and validation of non-invasive enzyme immunoassays for the evaluation of reproductive hormonal cycle and stress hormone responses to environmental stressors. \nDr. Narayan leads the Stress Lab (Comparative Physiology and Endocrinology) at the University of Queensland. A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null},{id:"20",title:"Animal Nutrition",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",isOpenForSubmission:!0,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"28",title:"Animal Reproductive Biology and Technology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/28.jpg",isOpenForSubmission:!0,editor:{id:"177225",title:"Prof.",name:"Rosa Maria Lino Neto",middleName:null,surname:"Pereira",slug:"rosa-maria-lino-neto-pereira",fullName:"Rosa Maria Lino Neto Pereira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9wkQAC/Profile_Picture_1624519982291",biography:"Rosa Maria Lino Neto Pereira (DVM, MsC, PhD and) is currently a researcher at the Genetic Resources and Biotechnology Unit of the National Institute of Agrarian and Veterinarian Research (INIAV, Portugal). She is the head of the Reproduction and Embryology Laboratories and was lecturer of Reproduction and Reproductive Biotechnologies at Veterinary Medicine Faculty. She has over 25 years of experience working in reproductive biology and biotechnology areas with a special emphasis on embryo and gamete cryopreservation, for research and animal genetic resources conservation, leading research projects with several peer-reviewed papers. Rosa Pereira is member of the ERFP-FAO Ex situ Working Group and of the Management Commission of the Portuguese Animal Germplasm Bank.",institutionString:"The National Institute for Agricultural and Veterinary Research. Portugal",institution:null},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:19,paginationItems:[{id:"81793",title:"Canine parvovirus-2: An Emerging Threat to Young Pets",doi:"10.5772/intechopen.104846",signatures:"Mithilesh Singh, Rajendran Manikandan, Ujjwal Kumar De, Vishal Chander, Babul Rudra Paul, Saravanan Ramakrishnan and Darshini Maramreddy",slug:"canine-parvovirus-2-an-emerging-threat-to-young-pets",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"81271",title:"The Diversity of Parvovirus Telomeres",doi:"10.5772/intechopen.102684",signatures:"Marianne Laugel, Emilie Lecomte, Eduard Ayuso, Oumeya Adjali, Mathieu Mével and Magalie Penaud-Budloo",slug:"the-diversity-of-parvovirus-telomeres",totalDownloads:23,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg",subseries:{id:"19",title:"Animal Science"}}},{id:"79909",title:"Cryopreservation Methods and Frontiers in the Art of Freezing Life in Animal Models",doi:"10.5772/intechopen.101750",signatures:"Feda S. 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He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}},{id:"441116",title:"Dr.",name:"Jovanka M.",middleName:null,surname:"Voyich",slug:"jovanka-m.-voyich",fullName:"Jovanka M. Voyich",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Montana State University",country:{name:"United States of America"}}},{id:"330412",title:"Dr.",name:"Muhammad",middleName:null,surname:"Farhab",slug:"muhammad-farhab",fullName:"Muhammad Farhab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"349495",title:"Dr.",name:"Muhammad",middleName:null,surname:"Ijaz",slug:"muhammad-ijaz",fullName:"Muhammad Ijaz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}}]}},subseries:{item:{id:"23",type:"subseries",title:"Computational Neuroscience",keywords:"Single-Neuron Modeling, Sensory Processing, Motor Control, Memory and Synaptic Pasticity, Attention, Identification, Categorization, Discrimination, Learning, Development, Axonal Patterning and Guidance, Neural Architecture, Behaviours and Dynamics of Networks, Cognition and the Neuroscientific Basis of Consciousness",scope:"Computational neuroscience focuses on biologically realistic abstractions and models validated and solved through computational simulations to understand principles for the development, structure, physiology, and ability of the nervous system. 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