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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An updated global climatology is presented, including the global occurrence of tropical cyclones and the terrestrial factors that may contribute to the variability and long-term trends in their occurrence. Research also examines long term trends in tropical cyclone occurrences and intensity as related to solar activity, while other research discusses the impact climate change may have on these storms. The dynamics and structure of tropical cyclones are studied, with traditional diagnostics employed to examine these as well as more modern approaches in examining their thermodynamics. \n\nThe book aptly demonstrates how new research into short-range forecasting of tropical cyclone tracks and intensities using satellite information has led to significant improvements. In looking at societal and ecological risks, and damage assessment, authors investigate the use of technology for anticipating, and later evaluating, the amount of damage that is done to human society, watersheds, and forests by land-falling storms. The economic and ecological vulnerability of coastal regions are also studied and are supported by case studies which examine the potential hazards related to the evacuation of populated areas, including medical facilities. These studies provide decision makers with a potential basis for developing improved evacuation techniques.",isbn:null,printIsbn:"978-953-307-238-8",pdfIsbn:"978-953-51-4907-1",doi:"10.5772/592",price:159,priceEur:175,priceUsd:205,slug:"recent-hurricane-research-climate-dynamics-and-societal-impacts",numberOfPages:632,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"603bbf36aa423b62f05802dabb4a4b6b",bookSignature:"Anthony Lupo",publishedDate:"April 19th 2011",coverURL:"https://cdn.intechopen.com/books/images_new/59.jpg",numberOfDownloads:87760,numberOfWosCitations:65,numberOfCrossrefCitations:43,numberOfCrossrefCitationsByBook:5,numberOfDimensionsCitations:93,numberOfDimensionsCitationsByBook:5,hasAltmetrics:0,numberOfTotalCitations:201,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 11th 2010",dateEndSecondStepPublish:"June 8th 2010",dateEndThirdStepPublish:"October 13th 2010",dateEndFourthStepPublish:"November 12th 2010",dateEndFifthStepPublish:"January 11th 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"18289",title:"Prof.",name:"Anthony",middleName:"Rocco",surname:"Lupo",slug:"anthony-lupo",fullName:"Anthony Lupo",profilePictureURL:"https://mts.intechopen.com/storage/users/18289/images/system/18289.png",biography:"Dr. Anthony R. Lupo is an Atmospheric Sciences Professor in the School of Natural Resources at the University of Missouri. He earned his BSc degree from the State University of New York at Oswego in 1988, and his M.S. and Ph.D. degrees from Purdue University in 1991 and 1995. His research is in large-scale atmospheric dynamics, climate dynamics, and climate change, and he has more than 130 peer-reviewed publications. Additionally, he edited the books; Recent Hurricane Research: Climate, Dynamics, and Societal Impacts (2011), and Recent Developments in Tropical Cyclone Dynamics, Prediction, and Detection (2016) with IntechOpen. He is a member of the American Meteorological Society, National Weather Association, Royal Meteorological Society (Fellow), American Geophysical Union, Sigma Xi, Gamma Sigma Delta, Phi Kappa Phi, and Missouri Academy of Science (Fellow). He was a Fulbright Scholar to Russia (summer 2004) at the Russian Academy of Sciences in Moscow. 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1. Introduction
It appears that for some time diastole was taken for granted and largely ignored. Systole was thought of as the only function that truly predicted cardiac risk. The fact that diastolic heart failure (DHF) was referred to at one point as “heart failure with normal ejection fraction (EF)” lends credence to this assumption. It has been proven since that cardiac relaxation is an active energy-dependent process that begins in late systole and extends into early or mid-diastole (Shah & Pai, 1992). The fact that diastolic dysfunction contributes to up to half of the cases of heart failure dispelled the myth that systolic function is the only factor to consider in cardiac risk assessments (Bhatia etal., 2006, Owan etal., 2006, Vasan etal., 1995). Cardiologists are ahead of surgeons in recognizing the importance of diastolic function in clinical practice. They have noticed that changes in diastolic filling pattern are of a prognostic value following myocardial infarction. Left ventricular remodeling following acute myocardial infarction (AMI) is a well known phenomenon occurring in the earliest post infarction phase and continuing for weeks or months. A restrictive transmitral filling pattern which is a marker of diastolic dysfunction provides significant information in these patients. A short initial deceleration time (DT) < 150 ms obtained as early as 1 day after AMI can identify patients who are likely to undergo LV remodeling in the following year (Otasević,2001). Remodeling is a precursor of heart failure and a strong predictor of mortality. Therefore, an early restrictive filling pattern as evidenced by a short DT identifies patients who are likely to develop progressive LV dilation and dysfunction. Persistence of a restrictive filling pattern is the most powerful independent predictor of severe dilation and late mortality (Temporelli etal,,2004, Whalley etal, 2006), The importance of diastolic dysfunction to the surgeon became apparent when it was established that it is a predictor of difficult weaning off cardiopulmonary bypass and mortality (Bernard etal, 2001, Salem etal, 2006). Finally, the impact of diastolic dysfunction affects the anesthesiologist as these patients may tolerate acute preload reduction with induction of anesthesia poorly leading to low cardiac output and hypotension. This patient population presents difficult anesthetic challenges and places these patients at high risk of perioperative morbidity and mortality (Couture etal, 2009\n\t\t\t\tSanders etal, 2009). In short, diastolic dysfunction has touched every facet of clinical practice. This chapter will predominantly focus on DHF (with normal EF) as distinct to the combined systolic and diastolic failure.
2. Clinical spectrum
Diastolic dysfunction can be defined as the inability of the left ventricle to adequately fill at low or normal atrial pressures unrelated to intrinsic valve disease or pericardial pathology. This dysfunction can result either from an impairment in LV compliance (passive mechanism) or from an alteration in LV relaxation (active process).
Since not all patients who undergo heart surgery have a normal EF, the classical definition of DHF of heart failure with normal EF does not always apply. It is therefore necessary not to overlook the status of the preoperative EF when assessing the DHF in the postoperative heart. With this understanding DHF in the postoperative state is better defined as a clinical syndrome of heart failure with a preserved left ventricular EF in the absence of major valve disease or pericardial pathology (Vasan & Levy, 2000\n\t\t\t\tVasan, 2003). It is associated with abnormalities of diastolic distensibility, filling, or relaxation of the left ventricle (Gaasch & Zile, 2004) clinically; DHF is usually accompanied by severe reduction of exercise capacity, neuroendocrine activation, and poor quality of life. Typically the ventricle has thick walls and a small cavity (increased left ventricular mass/volume ratio) (Kitzman etal, 2000). In contrast to systolic heart failure, DHF affects women more frequently. DHF can occur alone or in combination with systolic heart failure. In isolated DHF (characterized as a small stiff heart), the only abnormality in the pressure-volume relationship occurs during diastole, when there are increased diastolic pressures with a low end diastolic volume. In systolic heart failure, the abnormalities in the pressure-volume relationship during systole include decreased EF, stroke volume and stroke work. If there are in addition, changes in the diastolic portion of the pressure-volume relationship that leads to increased diastolic pressures, the implication then is that there is both systolic and diastolic cardiac failure (Zile &, Brutsaert, 2002; Deswal, 2005; Burkhoff etal. 2003).These concepts are depicted in Figure 1, using simplified pressure-volume loops, and showing the left ventricular end-diastolic pressure-volume curves. The normal left ventricle is shown with (LVEDP) < 16 mmHg. For DHF, the loop is smaller indicating reduced stroke volume, and shifted up and to the left, with LVEDP > 16 mmHg. It is important to note, that the end-diastolic volume in DHF is at the lower range of normal. In contrast, the end-diastolic volume in patients with systolic failure is increased.
3. Mechanics of diastole
Ventricular relaxation is an active energy-dependent process that begins in late systole and extends into early or mid-diastole (van Kraaij et al.2003). Relaxation can be defined as the time period during which the myocardium loses its ability to generate force and further shortening, and returns to an unstressed length and force (Zile &, Brutsaert, 2002) Diastole begins at the closure of the aortic valve and lasts until closure of the mitral valve
Figure 1.
Pressure–volume loop diagram indicating the position of the end-diastolic pressure–volume on curve for DHF; normal diastolic function (Normal); systolic failure (SF), and systolic and diastolic failure (S+DHF). A horizontal dashed line at >16 mmHg indicates division between normal and raised end-diastolic pressure. Adapted with permission from Elsevier Publishing (Alsaddique etal 2009]
(Kawaguchi et al, 2003). Broadly speaking, diastole can be looked at as two phases; isovolumetric relaxation corresponds to LV pressure decline at constant volume, that lasts from the closure of the aortic valve to opening of the mitral valve. The second phase is auxotonic relaxation corresponding to LV filling lasting until closure of the mitral valve. LV filling depends mainly on the pressure gradient between the LA and LV which is influenced by ventricular compliance, active relaxation, and augmented by atrial contraction towards end-diastole. Traditionally however, diastole is divided into four distinct phases: isovolumetric relaxation, early rapid ventricular filling, diastasis and atrial systole. The isovolumic relaxation time is a continuum of systole and is dependent on it. The early rapid ventricular filling phase is dependent on LV relaxation and compliance. Diastasis is dependent on both the heart rate and chamber compliance. The atrial contraction depends on the chamber compliance, left atrial (LA) function and the conduction system of the heart. At the cellular level, diastole begins when adenosine triphosphate hydrolyzes and actin-myosin cross bridges unlink, leading to sarcomeric relaxation. This is related to decreases in cytoplasmic Ca2 + and the subsequent dissociation of Ca2 + from troponin C. The majority of cytosolic Ca2 + is actively resequestered into the sarcoplasmic reticulum via the sarcoplasmic reticulum Ca2 +ATPase (SERCA2). The remaining cytosolic calcium is removed by the sarcolemmal sodium calcium exchanger and other mechanisms (Groban, 2005). Diastolic function depends on the passive elastic recoil properties of the LV as well as active relaxation. Impaired active myocardial relaxation causes a slow decline in the left ventricular intracavity pressure. The mitral valve opens later, as left atrial filling needs to increase in order to provide a positive gradient across the mitral valve. In severe cases, an increased left atrial pressure state is developed so as to exceed the (increased) left ventricular intracavity pressure (Aurigemma & Gaasch, 2004). An increase in passive chamber compliance can also produce the same pattern and result in elevated LVEDP, thereby necessitating an increased left atrial pressure to provide a driving gradient (Zile et al, 2004). The mechanisms that cause diastolic dysfunction are multifactorial (Kiss etal, 2004). However, they can be broadly categorized as intrinsic (that is affecting the ventricular muscle) or extrinsic (any process that can cause external compression of the left ventricle). A summary of these causes is shown in Table 1. Whilst many of these causes are not reversible in the short term, it is important for clinicians to understand potentially reversible causes so that they can be readily identified and treated. An example of extrinsic pathology is a distended abdomen caused by dilated stomach and bowels actively pushing on the diaphragm, compressing the heart and interfering with cardiac filling, thereby leading to or exacerbating the development of DHF. The major factors that affect diastolic function are ventricular relaxation and compliance. Other factors that influence diastolic function to a lesser degree include systolic function, left atrial pressure, the pericardium, and intrathoracic pressure (Wu &Yu, 2005). In diastolic dysfunction relaxation abnormalities appear early and the inability of the left ventricle to fill in early diastole significantly affect the rapid filling phase resulting in a compensatory increase in filling with atrial contraction. The other factor that determines LV filling is chamber compliance (distensibility of the ventricles), defined as the change in volume over the change in pressure (dV/dP). It can be derived using the relationship between changes in end diastolic pressure (EDP) and end diastolic volume (EDV) by using the formula:
When ventricular compliance begins to decrease the EDP rises, but the EDV remains unchanged. The increase in EDP reduces the pressure gradient across the mitral valve leading to reduced ventricular filling culminating in decreased cardiac output. Diastolic relaxation is more sensitive to ischemia than systolic contraction, and may lead to subtle relaxation abnormalities without systolic impairment (Garcia-Fernandez etal, 1999). In coronary artery disease, ventricular relaxation as reflected in the early diastolic filling rate may be impaired at rest.
4. Contributing factors
Primary diastolic failure is typically seen in patients with hypertensive or valvular heart disease as well as in hypertrophic or restrictive cardiomyopathy but can also occur in a variety of other clinical situations. The main risk factors for this form of heart failure are advancing age, hypertension, and diabetes mellitus (- Zile & Gaasch 2001). There is a high incidence of diastolic dysfunction among normotensive patients with diabetes mellitus (Boyer etal, 2004). Increased matrix collagen, interstitial fibrosis, myocardial microangiopathy, and myocytes hypertrophy are common findings in the diabetic heart that can lead to diastolic dysfunction. Tight glycemic control decreases the risk of heart failure in patients with diabetes (Iribarren etal, 2001; Liu etal, 2001).The defect in DHF is a combination of impaired ventricular relaxation and a decrease in passive ventricular distensibility (Aurigemma & Gaasch, 2004; Zile etal, 2004). The low cardiac output associated with DHF is due to inadequate ventricular filling, not impaired systolic contraction, and is an important point to remember when managing these patients. LV filling depends mainly on the pressure gradient between the LA and LV which is influenced by compliance, active relaxation, and at end diastole by atrial contraction (Appleton etal, 2000). There are number of predisposing factors that can contribute to DHF in the postoperative cardiac surgical patient. The mechanisms by which these factors exert their
Intrinsic causes
Cause
Comment
Delay in active relaxation
Any cause that interferes with myofilament cross-bridge detachment. Includes poor calcium sequestration, abnormal calcium sensitivity, myocardial ischemia, abnormal sodium/calcium exchanger or alteration in the myocyte calcium-handling proteins
Abnormal “cardiac spring”
During contraction, molecular springs such as Titan molecules are compressed, and during diastole contribute to chamber expansion via mechanical elastic recoil. Abnormalities of these molecules may cause diastolic heart failure. It also underlines the importance of systolic function in early diastolic recoil.
Myocardial fibrosis
Abnormalities of collagen, or other infiltrative processes (such as amyloid), may increase ventricular wall stiffness by a variety of mechanisms
Left ventricular hypertrophy
This is associated but not necessarily causative of diastolic dysfunction. Chronic increased load such as hypertension or aortic stenosis may also cause changes in collagen composition.
Acute myocardial ischemia
Active relaxation is highly energy dependent, and acute myocardial ischemia will lead to (reversible) diastolic dysfunction
Extrinsic causes
Right ventricle pressure or volume overload
The right ventricle physically compresses the left ventricle. In severe cases, the left ventricle becomes D-shaped rather than O-shaped. Any course of pressure or volume overload, including pulmonary hypertension will exacerbate left-sided diastolic dysfunction.
Pericardium
Pericardial fluid or restrictive pericardial disease will limit ventricular filling or physically compress the left ventricle.
Pleural fluid
A large pleural effusion may compress the heart
Hyper inflated lungs
Pressure from the lungs is transmitted via the pericardium to the heart. Severe lung hyperinflation mimics pericardial tamponade. High levels of PEEP are similar.
Distended abdomen
Fluid, fat, or gaseous distension can cause myocardial compression, particularly in the supine patient
Table 1.
Causes of diastolic dysfunction
effect are briefly explained. Atrial fibrillation is a common occurrence in the postoperative period. It causes loss of atrial contraction that results in impaired diastolic filling. Myocardial hypertrophy is another predisposing factor found in some of the valvular lesions and in hypertensive patients. Its presence interferes with the passive late phase of diastolic filling of the LV contributing to diastolic dysfunction. Myocardial ischemia in the postoperative cardiac surgical patient significantly slows active myocardial relaxation during early diastole. It may also lead to rhythm disturbances that will further aggravate LV diastolic dysfunction. Tachyarrhythmias impair LV filling by shortening the diastolic phase of the cardiac cycle resulting in impaired LV filling (- Zile & Brutsaert, 2002). The effect of positive pressure ventilation (to which virtually all of open heart surgery patients are subjected to postoperatively) on cardiac performance is complex involving changes in preload and afterload for both right and left ventricles. Positive pressure ventilation can lower ventricular filling, and may also reduce afterload, enhancing ventricular emptying during systole. The effect on cardiac output depends on whether the effect on preload or afterload predominates. If the patient is normovolemic and intrathoracic pressure are within normal the effect on afterload reduction predominates resulting in an increase in the cardiac output. The increase in stroke volume leads to increase in systolic blood pressure during lung inflation results in a phenomenon known as reverse pulsus paradoxus. The beneficial effects of positive pressure ventilation on cardiac output are reversed by hypovolemia leading to decreased cardiac output and hypotension (Pinsky, 2005\n\t\t\t\t2007)]. Pericardial constriction or tamponade causes increased resistance to diastolic filling and physiologically is “acute severe extrinsic diastolic failure” whereby the heart becomes physically compressed by the pericardial effusion. Renal insufficiency results in volume overload that leads to a slowing of myocardial relaxation potentially contributing to DHF (Tsuyuk etal, 2001). Chronic anemia is usually accompanied by an increase in cardiac mass due to volume overload. In the animal model, chronic anemia resulted in increased left ventricular end-diastolic pressure and decreased functional reserve which in turn can lead to diastolic dysfunction. It can also lead to tachycardia that it turn shortens diastole resulting in diastolic dysfunction. The anemia that is seen in the postoperative period due to excessive postoperative blood loss is transient, acute and is often rapidly corrected in these patients leading to very little if any effect on the diastolic function (Rakusan, etal 2001). Chronically uncontrolled hypertension is by far the most common predisposing factor in for DHF. It can lead to DHF through a number of ways; one of them is by causing LV hypertrophy that can results in a delayed LV relaxation with all its attendant effects on diastolic filling. The other mechanism is related to a reduced arterial compliance that can also contribute to diastolic dysfunction (Mottram etal, 2005). Hypertension that is seen at times in the postoperative period is usually transient is quickly managed and therefore does not pose the same risk of the more common form of hypertension. At times one may need to pace the heart in the post operative period; as most pacing wires placed at surgery are ventricular, pacing under these circumstances would affect diastolic filling bringing about diastolic dysfunction or could even trigger DHF in some instances. This is largely due to the loss of the atrial contribution to LV filling (Alsaddique, 2008). It is therefore better to keep this possibility in mind and make the extra effort of placing both atrial and ventricular wires for sequential pacing. There seems to be some evidence that Nitric Oxide (NO) metabolism plays a role in acute diastolic dysfunction following episodes of ischemia and reperfusion. It is thought that NO could have a beneficial role as pretreatment with cyclic guanosine monophosphate (cGMP) donors, or with NO donors protects myocytes from relaxation failure in animal models (Schlüter etal, 1994; Draper & Shah, 1997 ; du Toit etal, 1998).
5. Assessment of diastolic function
5.1. Echocardiography evaluation
Transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE) play a major role in the assessment of diastolic function. A combination of 2-dimensional echocardiography, pulsed wave Doppler, Color M-mode (CMM) and Tissue Doppler imaging (TDI) are used in combination to categorize the grade of diastolic dysfunciton.
2-D echocardiography is used to assess ventricular dimensions, LV mass, EF and LA size. Pulsed wave Poppler (PWD) measures the velocity of blood at the cursor position. The mitral inflow Doppler spectral display is composed of an E (early) wave for passive diastolic filling followed by an A (atrial) wave for atrial systole. Mitral blood flow is affected by LV relaxation, LV compliance, and the LA-LV pressure gradient. PWD is used to assess transmitral flow velocity recording and pulmonary vein flow velocity variables in the evaluation of diastolic dysfunction (Hunt etal, 2001; Vasan & Levy, 2000). The four useful variables from mitral flow are: peak early diastolic transmitral flow velocity (E), peak late diastolic transmitral flow velocity (A), early filling deceleration time (DT) and A wave duration [Adur] (Myśliński etal, 2002; Appleton etal, 1988). A normal E/A ratio is considered to be between 0.75 and 1.5. Early filling DT reflects LV compliance in early diastole. The normal DT is usually less than 200 milliseconds in young patients and may exceed 200 ms in patients over 60 years of age (Garcia etal, 1998). Pulmonary venous (PV) flow is composed of systolic and diastolic waves, and an atrial contraction reversal wave. The normal patterns is systolic predominance, but this is reversed when the LAP is elevated. In high LAP, the atrial reversal wave increased in duration such that it exceeds the mitral A wave duration. The major problem with the use of PV flow variables is the difficulty in obtaining adequate measurement when using TTE. The Doppler flow parameters are influenced by a variety of factors including altered loading conditions and heart rate, and not all patients “fit the pattern” (Appleton etal, 2001; Pirracchio etal, 2007). In the operative and critical care settings, the loading conditions and heart rates change frequently, and the patterns may alter without significant change in chamber compliance. Therefore, the results from these measurements may be inconsistent and accordingly inconclusive in the postoperative cardiac surgical patient. Color M-mode (CMM) Doppler flow propagation velocity (Vp) is an easily obtained diastolic index. It displays velocity information a long a line that extends from the mitral valve to the LV apex, providing superior temporal resolution (5 milliseconds), spatial resolution (1mm) and velocity resolution (5 cm/s). The commonly used variable for CMM Doppler is the Vp into the LV which is the velocity at which the blood travels from the mitral valve to the LV apex. In sinus rhythm CMM is characterized by 2 distinct waves, one corresponds to the E wave and the second one to the A wave.
Vp relates well to LV relaxation and is claimed to be relatively load independent. A Vp value of less than 45 cm / s is consistent with diastolic dysfunction in patients older than 30 years of age < 55 cm/s in patients less than 30 years of age (Onose etal, 1999; Dumesnil, etal, 1991). However, a major limitation of Vp is that it is heart rate dependent and in the perioperative setting, heart rate changes frequently.
Tissue Doppler imaging (TDI) is an ultrasound imaging modality that directly measures myocardial velocity during the cardiac cycle and allows wall movement to be directly analyzed (Vitarelli &, Gheorghiade, 1998; Dokainish, 2004). The myocardial portion commonly studied is above the mitral annulus at either the septal or lateral walls. Three wave forms are described, Peak systolic wave, early diastolic wave (Ea) and the end diastolic wave (aʹ) related to the atrial contraction. The Ea wave is relatively independent of loading state and is used to assess LV relaxation, a cut off of 8 cm /s for septal Ea or < 10 cm/s for lateral wall Ea measurement is now widely accepted as a sign of diastolic dysfunction (Sohn etal, 1997). It is easy to perform and available in the majority of patients even if the 2-D imaging is poor, and holds promise as a method to quantify change in diastolic function. When measuring TDI, Khouri and associates measure only early diastolic myocardial velocity (eʹ) at the lateral corner of the mitral annulus, because it has been noted that the lateral annular velocity is more reproducible than the septal annular velocity (Khouri etal, 2004). Figure 2 reveals Echocardiographic findings typical of DHF pattern. Transthoracic echocardiography (TTE) is not always possible in the postoperative situation, due to hemodynamic instability, mediastinal air, the close proximity to a fresh surgical wound, presence of drains and dressings, or due to the inability to position the patient in an optimum way. In addition, mechanical ventilation with high positive end-expiratory pressure, pacing wires, ECG leads further add to the obstacles for the desired examination window resulting in a poor image quality.
Figure 2.
Typical diastolic failure (small stiff heart) typically Grade 2 American Society of Echocardiography (ASE).This is a common pattern in the periopertive setting. Typically Cardiac Index (CI ) 1.8-2.2 l/min/m2 Pulmonary Artery Wedge Pressur( PCWP) > 15 mmHg
5.2. Use of Transesophageal Echocardiography (TEE)
TEE has a well established role in cardiac surgery as it has proved to be a valuable tool for intraoperative decisions particularly in valve surgery (Eltzschig etal, 2008). In addition, it has also proved to be useful in the field of intensive care for the assessment of hemodynamics and to track its variations after therapeutic interventions. Repeated measurements of left ventricular end-diastolic dimension are recommended in order to accurately track the hemodynamic changes, as a single determination is not felt to be reliable. TEE can adequately assess right ventricular function and left ventricular filling pressure using combined Doppler modalities (Vignon, 2005). The same parameters that are described for assessing diastolic function utilizing TTE can be achieved using TEE (Groban& Dolinski, 2005; Klein etal, 1999) though caution should be exercised as many of the Doppler parameters have not been extensively validated in sedated and ventilated patients.
5.3. Identifying a high left atrial pressure
A simple way to conceptualize diastolic failure is to recognize that if high left atrial pressure is present, then clinically important diastolic failure is present, as the body has had to adapt to a stiff ventricle by raising the LAP sufficient to provide an adequate transmitral driving gradient to fill the LV. Figure 3 High LAP can be diagnosed by invasive monitoring (such as a pulmonary artery catheter), or non-invasively with TTE or TEE. A simple pattern that can be easily recognized is that of a tense left atrium, evident by a fixed curve of the interatrial septum pointing from the left to the right atria. When the LAP is normal, the interatrial septum changes direction to point to the left atrium during mid-systole. Once a high LAP is detected, then echocardiography is focused on the chamber dimensions and EF to determine if it is DHF (small LV with normal EF), or systolic and diastolic failure (large heart with reduced EF).
Figure 3.
Flow chart to categorize diastolic dysfunction. Clinically important diastolic failure is associated with raised left atrial pressure. Diastolic dysfunction with normal left atrial pressure does not usually affect hemodynamic stability.The key is to identify high LAP and then identify if the LV volume is small to normal or dilated, in order to differentiate primary diastolic failure form systolic and diastolic failure.
5.4. Natriuretic peptides
B-type Natriuretic peptide (BNP) is a marker of systolic left ventricular dysfunction and heart failure. It however increases in subjects with diastolic dysfunction (mean 20.3+/-4.7 pg/ml vs. control 9.6+/-0.5 pg/ml, p<0.001). A normal BNP level virtually excluded the presence of diastolic dysfunction and concomitant left ventricular hypertrophy (LVH). Increased BNP concentrations in subjects with diastolic dysfunction are strongly related to LVH (Lukowicz etal, 2005).] In patients with normal systolic function, elevated BNP levels and diastolic filling abnormalities might help to reinforce the diagnosis diastolic dysfunction (Lubien etal, 2002; Krishnaswamy etal, 2001) A-type atrial, natriuretic peptide (ANP) is secreted from the atria in response to dilatation. Brain-type (B-type) natriuretic peptide (BNP) is a neurohormone that is released by the cardiac myocytes when left ventricular wall stress increases. After secretion the pro-hormone is cleaved to the biologically active hormone (BNP) and an inactive N-terminal fragment (N-BNP) Plasma levels of BNP increase in direct relation to increase in ventricular end-diastolic volume and end-diastolic pressure of both right and left side(Stewart, 2005). A rise in BNP produces vasodilatation and increase in renal sodium excretion (Maisel etal, 2002). Atrial natriuretic peptide and brain natriuretic peptide are known to be indices for heart failure. Postoperative ANP plateaus on the third postoperative day and decreases gradually down to the preoperative level by one month Postoperative BNP plateaus, showing very slow decrease and it never returning to the preoperative level (Song etal, 2004; Bail etal, 2004)]. This pattern of changes in the BNP and ANP levels after cardiac surgery makes it rather impractical to use them as markers for heart failure in the immediate postoperative setting of these patients.
5.5. Cardiac catheterization
The characteristic finding of DHF is an elevated left ventricular end diastolic pressure (LVEDP) over 16 mm Hg in the presence of a normal LV chamber size (van Heerebeek etal 2006; Kitzman etal, 2002) Vasan and Levy recommended cardiac catheterization as a prerequisite for making the diagnosis of a definite DHF (Vasan & Levy 2000). In the post-operative setting of a fresh open heart surgery cardiac, catheterization is probably not warranted and the diagnosis can be made by less invasive means.
5.6. Multidetector CT (MDCT) of the heart
Cardiac MDCT is most commonly performed for the purpose of noninvasive cardiac angiography. Image data are acquired continuously during a single breath-hold scan, typically 10 to 15 seconds in duration. Contrast is required for angiography and for endocardial border definition, with typical doses in the range of 60 to 80 mL per scan, quite comparable to a diagnostic cardiac catheterization. Patients with cardiomyopathies of all etiologies represent a large and growing population that stands to benefit from advanced imaging techniques (Sibley & Lima, 2008). Electron-beam computed tomography (EBCT) has been shown to be a reliable tool for the assessment of ventricular diastolic function and to detect constrictive filling pattern (Kloeters etal, 2008; Rumberger, 2000). These tools cannot be utilized in the assessment of the post operative heart for logistical reasons
5.7. Cardiac magnetic resonance
Cardiac magnetic resonance (CMR) is the latest addition to the diagnostic tools. The specific advantage of cardiac magnetic resonance (CMR) over echocardiography is the possibility to acquire images in any selected plane or along any selected axis. A routine CMR examination in the setting of heart failure will acquire short access images covering the entire heart from base to apex in addition, to the long access slices. It can also provide a range of LV filling parameters almost similar to those obtained by echocardiography (Rademakers & Bogaert, 2006; Hauser etal, 2004). CMR is considered as a valid alternative for echocardiography when an adequate echocardiographic assessment cannot be obtained. It is the diagnostic modality of choice for assessing small changes in LA or LV volumes and in LV mass (Rademakers, 2003). Clinical use of CMR is expanding and starting to address diastolic LV dysfunction. It is not of course practical to obtain CMR in the fresh postoperative cardiac surgical patient suspected to have DHF.
6. Diagnosis of DHF in postoperative heart
In an ICU environment, the diagnostic criteria are usually based on invasive hemodynamic measurements. As ventricular compliance begins to decrease, the end-diastolic pressure (EDP) rises but the end-diastolic volume (EDV) remains unchanged. The increase in EDP reduces the pressure gradient necessary for ventricular filling and this eventually leads to a lower EDV resulting in a decrease in cardiac output via the Frank-Starling mechanism. The usual method of assessing cardiac failure by the relationship between ventricular filling pressure and stroke volume does not distinguish between systolic and DHF. The end-diastolic pressure (EDP) is elevated in both types of heart failure. The end-diastolic volume (EDV) is increased in systolic heart failure and is decreased in DHF thus it is the parameter that will distinguish systolic from DHF (Aurigemma & Gaasch, 2004). The measurement that is most often utilized to distinguish between diastolic and systolic heart failure is the EF. The EF is normal or near normal in patients with DHF and is reduced in systolic heart failure.
Pulmonary artery catheter with a fast response thermistor can measure the EF of the right ventricle. These catheters are able to register the temperature (T) changes during each cardiac cycle. The change in temperature is due to dilution of the indicator fluid by venous blood that fills the ventricle during diastole. The amount of blood that fills the ventricle during diastole is equal to the stroke volume, the temperature differences between each plateau on the curve (T1 – T2) is the thermal equivalent of the stroke volume (SV) (Figure 4). Temperature T1 is the thermal marker for end-diastolic volume (EDV). The EF becomes equivalent to the ratio T1 – T2 / T1 or [SV/EDV] (Spinale etal, 1990,1991). Once the EF is measured the stroke volume can be calculated by dividing the cardiac output by heart rate. The EDV can be determined by rearranging the EF formula EDV = SV/ EF. The normal RV Right ventricular (RV) EF using thermodilution method is 0.45 to 0.50 which is about 10% lower than the EF measured by radionuclide imaging (Kay etal, 1983). The accepted normal for RVEDV is [80 to 140ml/m2] (Siniscalchi etal, 2005).
The chief points to help in the diagnosis of DHF in the postoperative heart are: (1) Hemodynamic evidence of heart failure (2) Mean pulmonary capillary wedge pressure >12 mmHg (Paulus etal, 2007) (3) Echocardiographic evidence of raised left atrial pressure (LAP) as evidenced by a distended LA with the interatrial septum displaying a fixed curvature towards the right atrium (Kusumoto etal 1993; Royse etal, 2004). (4) Echocardiographic evidence of a small LV in the absence of hypovolemia and valvular heart disease (5) Low EDV as determined by the pulmonary artery catheter (6) EF better or similar to the preoperative one. Table 2.
Increased PACWP EF Preop a Evidence of raised LAP a Small LV a Low EDV b Absence of significant pericardial effusion a a Revealed by echocardiography. b As determined by pulmonary artery catheter.
Table 2.
Features that would suggest DHF in a postoperative heart.PACWP: pulmonary artery capillary wedge pressure; CI: cardiac index; LAP: left atrial pressure; EF:; EDV: end diastolic volume. Adapted with permission from Elsevier Publishing (Alsaddique, 2008)
Indeed according to the European criteria, a normal cardiac index in the face of pulmonary edema suggests DHF (Paulus et al, 2007). Echocardiography is a useful tool to diagnose DHF. In the postoperative heart suspected to have DHF it is not always possible to get an adequate assessment. In addition, air trapped within the postoperative mediastinum creates poor acoustic windows through which ultrasounds waves cannot pass. An echocardiography study that would simply establish that the left ventricular function has not deteriorated compared to the preoperative one and rules out the presence of cardiac tamponade or significant pericardial effusion can usually be done and would probably suffice under the circumstances. If the hemodynamics allow, one can probably use TEE to diagnose of DHF, it remains however an invasive procedure that should only be carried out by an experienced operator. Published guidelines for performance of TEE should be followed (Nihoyannopoulos et al, 2007; Cheiltin et al, 2003; Benjamin et al, 1998). The information gained by TEE should be integrated with the rest of the hemodynamic parameters (pulmonary artery occlusion pressures or pulmonary artery end-diastolic pressures), LA dimensions, and conventional Doppler imaging of mitral inflow in conjunction with TDI of the lateral mitral annular wall.
Figure 4.
Thermodilution EF for the right ventricle. T\n\t\t\t\t\t\tB baseline blood temperature. T\n\t\t\t\t\t\t1, T\n\t\t\t\t\t\t2 and T\n\t\t\t\t\t\t3 are successive temperature plateaux. (Adapted with permission from Elsevier)
As it has been determined that objective measurement of LV diastolic function serves to confirm rather than establish the diagnosis of DHF. The diagnosis of DHF can be assumed without the measurement of the various parameters that reflect LV diastolic function in the presence of acute pulmonary edema associated with indirect signs of elevated left atrial pressure (Zile etal, 2001).
7. Perioperative management of DHF
Management begins by anticipating the problem before it actually happens. In the preoperative period, it is important to identify patients who may have or are at risk of DHF. Any prior history of DHF is important to identify and attention should be paid to patients who are likely to develop it in order to prevent any further deterioration of diastolic function in the post operative period. Chronically uncontrolled hypertension is a common cause of DHF it should be sought and aggressively treated prior to surgery to reduce the risk of perioperative heart failure (Kostis etal, 1997). Hypertension leads to DHF because of LV hypertrophy and decreased arterial compliance (Mottram etal, 2005). Diabetes mellitus, especially with poor glycemic control, is independently associated with abnormal LV relaxation, is similar in severity to that associated with systemic hypertension. The combination of diabetes and hypertension is associated with greater abnormality than patients with either condition alone. Aggressive control of diabetes, as well as of hypertension, should be considered an important component of the management in the pre operative period. Tight glycemic control decreases the risk of heart failure in patients with diabetes (Iribarren etal, 2001; Liu etal, 2001), It is helpful to avoid hypovolemia, tachycardia and tachyarrhythmias as they impair LV filling by shortening the diastolic phase of the cardiac cycle resulting in suboptimal LV filling (Zile & Brutsaert, 2002). Any reversible predisposing factors is to be corrected prior to surgery. Echocardiography is helpful in the preoperative assessment of patients especially those with compromised cardiac performance in order to identify the nature of heart failure. Risk factors for DHF include elderly patients, the female gender, hypertension, increased left ventricular mass, diabetes, obesity, and ischemic heart disease (Klapholz etal, 2004)
8. Intraoperative and postoperative management
The key to managing DHF is to maintain preoperative parameters as closely as possible. Managing DHF is analogous to walking on a tightrope. Any minor deviation from the “normal parameters tightrope” could lead to hypotension and low cardiac output, or pulmonary venous congestion. The second key principle is to maintain operating volume. As shown in Figure 1, the left ventricle with DHF operates at “just adequate” volume. If the volume is reduced, then a marked reduction in stroke volume will occur leading to low cardiac output and hypotension. It is also important to realize that it is difficult to achieve normal volume in DHF because of the relaxation abnormality. Although the left ventricular volume appears low, it is in the setting of an elevated left atrial pressure. Management of DHF is therefore a process of maintaining a delicate balance and avoiding the contributing and triggering factors that can lead to poor hemodynamic outcome. A summary of these contributing factors is shown in Figure 5. Reduced LV volume (such as blood loss or vasodilation) rapidly leads to hypotension. Tachycardia shortens the diastolic filling time, thereby reducing left ventricular volume and stroke volume (Zile & Brutsaert, 2002). High-dose inotropes initially may increase blood pressure, but as tachycardia ensues, it would cause progressive reduction in left ventricular volume producing a hyperdynamic empty ventricle. High levels of positive end expiratory pressure (PEEP), obesity, pericardial or pleural effusions cause extrinsic compression of the heart and worsen diastolic function. Conversely, excessive administration of fluid in an attempt to improve cardiac output may not produce an increase in stroke volume but will produce an increase in end-diastolic pressure. This may exacerbate pulmonary venous congestion. Excessive hypertension or vasoconstriction will reduce EF and increase left ventricular end-diastolic volume. This has the effect of shifting up the end-diastolic pressure-volume curve where a small increase in volume will produce a large increase in end-diastolic pressure, increasing the risk of pulmonary edema. Bradycardia increases diastolic filling time, and will lead to an increase in the peak LVEDP. DHF can lead to pulmonary hypertension due to elevated pressure transmitted back through the pulmonary veins (Owan etal, 2006). Hypercapnea and hypoxia are potent causes of pulmonary hypertension in the perioperative setting.
Figure 5.
Contributing factors to hemodynamic instability in patients with DHF. Deviation from normal parameters can lead to either hypotension/reduced cardiac output, or to pulmonary edema. (Adapted with permission from Elsevier)
9. Management strategies
A summary of clinical strategies is shown in Figure 6. The mainstay of treatment is to be realistic about hemodynamic goals, and to return the patient to normal preoperative parameters. Potential reversible causes (particularly extrinsic causes) should be identified and managed like pericardial tamponade and significant pericardial effusion as they cause resistance to LV filling leading to acute DHF. These conditions should therefore be suspected in the event of unexplained DHF in the postoperative patient. Echocardiography is the most effective clinical tool to diagnose and monitor DHF. It can even gives indications about the hemodynamic profile of the patient, a raised left atrial pressure can be identified by enlarged atria, and a fixed curvature of the interatrial septum bowing from left to right (Royse et al 2001). One has to assess the different hemodynamic parameters of the patient to find out the cause for the imbalance that led to failure. For example, in the setting of reduced volume, administration of fluids, avoidance of tachycardia and reducing high dose inotropes will improve left ventricular end-diastolic volume. Vasoconstrictors may be required to counteract the effect of vasodilation which is seen during and immediately after cardiac surgery, thereby returning systemic vascular resistance to normal. Mechanical ventilation may affect hemodynamic performance in DHF. The mechanism is complex involving changes in preload and afterload for both right and left ventricles. Positive pressure ventilation may reduce venous return thereby reducing preload; and it also may reduce afterload enhancing ventricular ejection. This may have a variable effect on cardiac output. If the patient is normovolemic and intrathoracic pressure is normal, then the effect on afterload reduction may increase cardiac output. The beneficial effects of positive pressure ventilation on cardiac output are reversed by hypovolemia leading to decreased cardiac output and hypotension. Mechanical ventilation is beneficial in order to avoid hypercapnea, and PEEP can help reduce pulmonary venous congestion (Pinsky 2005, 2007). The use of continuous positive airway pressure (CPAP) by a face mask in the spontaneously breathing patient is reported to be effective in the treatment of diastolic dysfunction and may therefore be a useful ventilatory support under these circumstances (Benjelid etal, 2005; Moritz etal, 2003; Bersten etal, 1991)
Figure 6.
Strategies to treat DHF in the perioperative setting. Treatment strategies are aimed to return to preoperative parameters. RV is right ventricle, PEEP is positive end-expiratory pressure; CPAP is continuous positive airway pressure. (Adapted with permission from Elsevier)
10. The contributing factors
Acute renal failure leads to volume overload and can trigger DHF (Tsuyuki etal 2001) Excessive fluid administration has the same effect and can be a contributing factor for post operative DHF. Atrial fibrillation (AF) leads to loss of effective atrial contraction, changes LV filling pattern and results in a slowing of myocardial relaxation thereby triggering DHF. Pharmacological or electrical cardioversion may be necessary to restore sinus rhythm or at least rate control. In the postoperative coronary artery bypass patient unexplained DHF should lead to the suspicion of acute graft malfunction, which could happen in the absence of any signs of ischemia. Postoperative myocardial ischemia is an important reversible cause of diastolic dysfunction in the postoperative period as ischemia significantly slows active myocardial relaxation during early diastole affecting thereby LV filling. Ischemia could also lead to rhythm disturbances that will further aggravate LV diastolic dysfunction. It is well known that tachycardia and dysrhythmias shorten diastole leading to impaired left ventricular filling. Restoration of sinus rhythm should always be a priority in management (Zile & Brutstaert, (Piaarcchio 2002). If pacing is required, then atrio-ventricular sequential pacing will enhance ventricular filling. Ventricular pacing alone leads to loss of the atrial contribution (Alsaddique, 2008) and right ventricular pacing may induce dyssynchronous contraction. Pain may induce tachycardia and hypertension with the potential of triggering DHF through these mechanisms.Sepsis can exacerbate DHF, as it affects both systolic and diastolic function of the heart. In case of DHF developing late in the postoperative period sepsis should be considered as one of the possibilities. The role of sepsis in causing diastolic failure was identified by using pressure-volume loops in anesthetized endotoxemic rabbits. Left ventricular diastolic properties were shown to be altered; with prolonged relaxation, decreased compliance leading to increased end-diastolic pressure. Diastolic dysfunction can contribute to the development of cardiogenic septic shock (Pirracchio etal, 2007). Other factors that can contribute to DHF include a large pleural effusion or any other process that causes extrinsic compression of the heart or that could potentially impair or delay ventricular filling could contribute to or trigger DHF. This includes pericardial tamponade which is in effect “acute extrinsic DHF”.
11. Additional management considerations
The incidence of pure DHF in the postoperative heart in not known. Many cases of failure that are thought of as systolic failure are in reality diastolic in nature. There is no consensus on management of diastolic failure in the postoperative heart or intensive care environment in general. Echocardiography can be used not only to diagnose but also to monitor therapy and the hemodynamic changes. These points deserve emphasis:
The management of DHF is based on the strategy of avoiding pulmonary congestion whilst maintaining adequate cardiac output, and correction of any predisposing factors. As the systolic function is maintained in diastolic failure positive inotropes have little role in the management. The exception is where there is “low normal” EF or evidence of RV dysfunction or RV strain in the setting of pulmonary hypertension. In these situations, low dose inotrope therapy may improve cardiac output and hemodynamic stability. High dose inotrope therapy will induce tachycardia, and shorten diastolic filling time, leading to progressive reduction in LV preload and deterioration in hemodynamics.
In diastolic failure ventricular filling is impaired, diuretic therapy leads to volume depletion that will further impair ventricular filling resulting in a more reduction of the cardiac output.
Vasodilation is the enemy of DHF. Though vasodilation facilitates ejection, the heart empties but is unable to adequately re-fill, leading to progressive reduction in preload and deterioration in hemodynamic conditions. Normalizing systemic vascular resistance with a vasoconstrictor helps to maintain hemodynamic stability and normotension.
Many patients with DHF also have pulmonary hypertension. Hypotension in this setting leads to compromise of RV blood flow and relative RV ischemia, thereby causing RV failure. The RV fails by dilating, which leads to further compression of the LV and worsening DHF. This can lead to a spiral of progressive hypotension. In these circumstances a vasoconstrictor to preserve blood pressure and maintain LV preload, and in addition low dose inotrope (such as dobutamine) to support RV function, can improve hemodynamic stability. If the situation remains refractory it is worth considering nitric oxide (NO) to selectively treat right ventricular pressure overload. There is to our knowledge no published work on the use NO in DHF but it remains as an option if all else fails (Granton & Moric, 2008; Natori etal, 2003).
12. Use of diuretics
Diuretics should be used with caution, as high filling pressure is required to maintain cardiac output. Diuresis may result in hypotension in patients with DHF because of the steep shape of the left ventricular end-diastolic pressure-volume relationship, where small changes in end-diastolic volume will lead to reduced stroke volume. The use of diuretics must be countered by increased vigilance of hemodynamic variables, as indiscriminate use can be counter-productive (Zile & Burstaert, 2002; Aurigemma & Gaasch 2004).
13. Antiarrhythmics
Intravenous digoxin is a commonly used therapy for the management atrial fibrillation and paroxysmal atrial tachycardia. Other therapeutic agents include calcium antagonists such as verapamil, beta-blockers such as esmololol sotolol for acute rhythm control, or amiodarone. The current evidence supports the use of amiodarone for AF occurring after cardiac surgery. Amiodarone also reduces perioperative ventricular tachyarrhythmias and strokes, and helps reduce duration of hospitalization (Bagshaw etal,2006; Saltman, 2003). Nevertheless digoxin continues to be valuable in long-term therapy of atrial flutter and fibrillation. More recently digoxin has been the subject of different studies to determine its effects on all forms of heart failure (HF). It has been shown that digoxin at serum concentration of 0.5-0.9 ng/mL reduces mortality and hospitalizations in all HF patients, including those with DHF. At higher serum levels, digoxin reduces HF hospitalization but has no effect on mortality or all-cause hospitalizations (Ahmed etal, 2006). The recommendation went further to suggest that the results of the DIG trial may provide support for the use of digoxin in patients who have heart failure with preserved EF, because a trend toward reduction in hospitalizations for heart failure was observed with digoxin in the ancillary trial (Ahmed, 2006)]. However the guidelines of the American College of Cardiology–American Heart Association Task Force for the management of heart failure and the Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology do not recommend the use of digoxin in patients who have heart failure with preserved EF (Hunt etal 2005; Swedberg etal, 2005).
13.1. Use of inotropes
Agressive use of positive inotropic agents have little role in the management of DHF, though low dose inotropes may improve stability in the setting of low-normal EF or where there is pulmonary hypertension as described earlier [such as a combination of 3-5mcg/kg/min dobutamine and norepinepherine 3-5 mcg/min] (Little & Brucks, 2005; Wu & Yu, 2005). This is a very common pattern in DHF in the perioperative setting and may be exaccerbated by poor cardioprotection (especially to the right heart), myocardial edema or reperfusion injury. Pharmacologically, the use of high dose inotropes leads to an increase in heart rate, which causes shortening of diastolic filling time leading to reduced ventricular volume and a gradual worsening of cardiac output. Therefore, in DHF it is probably wise to accept less than ideal hemodynamics provided adequate perfusion is maintained. It is therefore suggested that a cardiac index between 1.8 and 2.2 L.min.m-2 is acceptable. Aiming for higher levels of cardiac index may not be readily achieved, and the strategy used would necessitate higher doses of inotropes and volume, with potential for greater pulmonary venous congestion. The danger of increasing inotrope use is that if the patient deteriorates, the typical response is to increase the inotropic dose leading to further tachycardia and shortened diastolic filling, thereby further reducing stroke volume and worsening cardiac performance, effectively creating a vicious circle of deterioration. The art of managing these patients is to achieve the delicate balance between hypotension and pulmonary venous congestion by judicious use of vasopressors, low-dose inotropes and fluids, such that their baseline hemodynamic state is maintained until the recovery processes following surgery abate.
13.2. Role of Vasodilators
It is important to appreciate that vasodilators facilitate ventricular ejection, and in the setting of a stiff left ventricle, makes it difficult to re-fill. This is especially important if there is associated tachycardia, as this will further exacerbate the inability to adequately refill the ventricle. If vasodilators are used they could make the ventricle operates at a lower end-diastolic volume further contributing to the low cardiac output. Under these circumstances a vasoconstrictor may actually be helpful by reducing EF and increasing the end diastolic volume. Vasodilators (especially inodilators) are appropriate for secondary DHF (systolic and diastolic failure). It is important to remember, however, the goal of maintaining preoperative hemodynamics, which means that the level of vasodilation should not depart considerably from baseline. In practice, most patients will have a vasodilation state after surgery, and are already excessively dilated. Vasodilator use in this setting can be counterproductive. If using inodilators, then add norepinepherine to control excessive vasodilation, and return it towards normal.
13.3. Role of vasoconstrictors:
Vasoconstrictors should be considered as part of the management of DHF, if vasodilation is manifest in the postoperative course. Vasodilation is common both during and immediately after cardiac surgery, and is part of the sterile inflammatory response syndrome seen following cardiac surgery. Diastolic abnormality prevents adequate filling of the left ventricle so that the end-diastolic volume progressively declines. Low-dose vasoconstrictors are protective in this setting with the aim of normalizing but not increasing vascular resistance.
13.4. Other pharmacological agents.
The value of beta-blockers in the perioperative period has recently been questioned because of the POISE trial that has examined their effect on non-cardiac surgery patients (POISE study group, 2008). Nevertheless one could extrapolate that the same would probably happen in a cohort of cardiac surgery patients. Beta blockers offer cardiac protection in the shape of a reduction of myocardial infarction (Andersen etal, 2008; Everly etal, 2004). Conversely, the incidence of stroke and its resulting patient disability was increased in the treatment group leading to increased mortality (Sear etal, 2008). Caution should be exercised with aggressive use of perioperative beta blockade. Beta blockers in the postoperative heart are used for control of tachycardia in the presence of adequate volume. An ultra short acting agent given intravenously (e.g. esmolol or landiolol that have a very short half life can be helpful (Mitchell etal, 2002; Kirshenbaum etal 1985; Yoshida etal, 2008). They can also help in case of fast atrial fibrillation to achieve an initial rate control in the process of stabilizing the hemodynamics (Kobayashi etal, 2004). Verapamil, a calcium channel blocker, can also be used intravenously to control heart rate and to treat fast atrial fibrillation (Abernethy & Schwartz, 1999). Calcium channel blockers in general are effective in DHF caused by idiopathic hypertrophic cardiomyopathies (Setaro etal 1990), but they do not offer the same benefits to diastolic failure caused by other factors (Nishimura etal, 1993). There are no drugs specifically marketed for the treatment of diastolic dysfunction. Inodilators may improve diastolic function in systolic and DHF, or bi-ventricular failure, as they will maintain stroke volume at a lower left ventricular end-diastolic volume. This has the effect of the heart working at a lower end-diastolic pressure. Unloading of the right ventricle will reduce the effect of left ventricular compression via the interventricular septum.
Long-term (outpatient) treatment that addresses myocardial remodeling includes ACE-inhibitors and angiotensin receptor blockers, calcium channel blockers, careful use of diuretics such as spironolactone, carvidelol, control of hypertension and treatment of myocardial ischemia (Yip etal, 2008; Yamamoto etal, 2005;Bergstrom etal, 2004; Yoshhida etal, 2004) Future strategies are likely to address disorders of calcium handling, as well as modulating myocardial proteins and collagen subtypes (Kass etal, 2004)
13.5. Cardiac resynchronization therapy
Cardiac-resynchronization therapy (CRT) has been shown to improve the rate of survival, quality of life, exercise capacity, and functional status in patients with a prolonged QRS interval and moderate-to-severe heart failure that is resistant to optimal medical therapy. CRT is thought to improve the left ventricular EF and functional status by minimizing regional left ventricular delay caused by prolonged ventricular conduction, reducing mitral regurgitation and left ventricular reverse remodeling, and normalizing neurohormonal factors. Current guidelines support the use of CRT in patients with an EF of 35% or less, moderate or severe heart failure (New York Heart Association [NYHA] class III or IV), and a prolonged QRS interval [ 120 msec] (Abraham etal, 2002; (Leclercq etal, 2002). CRT did not improve peak oxygen consumption in patients with moderate-to-severe heart failure with narrow QRS intervals providing evidence these patients may not benefit from this form of therapy (Beshai etal, 2007). The effects on diastolic function have been the subject of recent studies by load-dependent pulsed-wave Doppler transmitral indices. A number of studies have shown that in heart failure patients receiving CRT, improvement in LV diastolic function is coupled to the improvement in LV systolic function (Waggoner etal, 2005). The specific value of CRT for the treatment of the DHF as distinct from systolic and diastolic failure has not however, been extensively investigated.
14. Summary
DHF is “ a small stiff heart” with high left atrial pressure, whereas systolic and diastolic failure is a dilated heart with reduced EF and a high left atrial pressure, and echocardiography is the best way to differentiate these two conditions.
The key operating principle in DHF is to maintain their preoperative haemodynamic state and maintain operating volume
The key operating principle of systolic and diastolic failure is to improve stroke volume at a lower operating volume
The cardiac index in DHF is not great - but is enough. Do not “shoot for the stars”.
Low dose inotropes and enough vasoconstrictors to normalise vascular resistance can improve hemodynamic stability
High dose inotropes are often counterproductive
Excessive vasodilation is the enemy of DHF.
\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/16135.pdf",chapterXML:"https://mts.intechopen.com/source/xml/16135.xml",downloadPdfUrl:"/chapter/pdf-download/16135",previewPdfUrl:"/chapter/pdf-preview/16135",totalDownloads:12164,totalViews:458,totalCrossrefCites:1,totalDimensionsCites:3,totalAltmetricsMentions:0,introChapter:null,impactScore:2,impactScorePercentile:78,impactScoreQuartile:4,hasAltmetrics:0,dateSubmitted:"November 11th 2010",dateReviewed:"March 15th 2011",datePrePublished:null,datePublished:"July 5th 2011",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/16135",risUrl:"/chapter/ris/16135",book:{id:"344",slug:"establishing-better-standards-of-care-in-doppler-echocardiography-computed-tomography-and-nuclear-cardiology"},signatures:"Juan Lacalzada, Amelia Duque, Alejandro de la Rosa, Antonio Barragan, María Manuela Izquierdo, Eduardo Arroyo, Ana Laynez and Ignacio Laynez",authors:[{id:"41600",title:"Dr",name:"Juan",middleName:null,surname:"Lacalzada",fullName:"Juan Lacalzada",slug:"juan-lacalzada",email:"jlacalzada@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"53439",title:"Dr.",name:"Antonio",middleName:null,surname:"Barragan",fullName:"Antonio Barragan",slug:"antonio-barragan",email:"ambarraganacea@yahoo.es",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"53440",title:"Dr.",name:"Amelia",middleName:null,surname:"Duque",fullName:"Amelia Duque",slug:"amelia-duque",email:"mameliaduque@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"53441",title:"Dr.",name:"Maria Manuela",middleName:null,surname:"Izquierdo",fullName:"Maria Manuela Izquierdo",slug:"maria-manuela-izquierdo",email:"mariela_izquierdo@hotmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"53442",title:"Dr.",name:"Eduardo",middleName:null,surname:"Arroyo",fullName:"Eduardo Arroyo",slug:"eduardo-arroyo",email:"earroyo@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"53443",title:"Dr.",name:"Alejandro",middleName:null,surname:"De La Rosa",fullName:"Alejandro De La Rosa",slug:"alejandro-de-la-rosa",email:"adelarosahdez@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"53444",title:"Dr.",name:"Ignacio",middleName:null,surname:"Laynez",fullName:"Ignacio Laynez",slug:"ignacio-laynez",email:"imlaynez@ull.es",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of La Laguna",institutionURL:null,country:{name:"Spain"}}},{id:"82907",title:"Dr.",name:"Ana",middleName:null,surname:"Laynez",fullName:"Ana Laynez",slug:"ana-laynez",email:"alaynez@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"MedStar Health",institutionURL:null,country:{name:"United States of America"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Clinical spectrum",level:"1"},{id:"sec_3",title:"3. Mechanics of diastole",level:"1"},{id:"sec_4",title:"4. Contributing factors",level:"1"},{id:"sec_5",title:"5. Assessment of diastolic function",level:"1"},{id:"sec_5_2",title:"5.1. Echocardiography evaluation",level:"2"},{id:"sec_6_2",title:"5.2. Use of Transesophageal Echocardiography (TEE)",level:"2"},{id:"sec_7_2",title:"5.3. Identifying a high left atrial pressure",level:"2"},{id:"sec_8_2",title:"5.4. Natriuretic peptides",level:"2"},{id:"sec_9_2",title:"5.5. Cardiac catheterization",level:"2"},{id:"sec_10_2",title:"5.6. Multidetector CT (MDCT) of the heart",level:"2"},{id:"sec_11_2",title:"5.7. Cardiac magnetic resonance",level:"2"},{id:"sec_13",title:"6. Diagnosis of DHF in postoperative heart",level:"1"},{id:"sec_14",title:"7. Perioperative management of DHF",level:"1"},{id:"sec_15",title:"8. Intraoperative and postoperative management ",level:"1"},{id:"sec_16",title:"9. Management strategies",level:"1"},{id:"sec_17",title:"10. The contributing factors",level:"1"},{id:"sec_18",title:"11. Additional management considerations",level:"1"},{id:"sec_19",title:"12. Use of diuretics",level:"1"},{id:"sec_20",title:"13. Antiarrhythmics",level:"1"},{id:"sec_20_2",title:"13.1. Use of inotropes",level:"2"},{id:"sec_21_2",title:"13.2. Role of Vasodilators",level:"2"},{id:"sec_22_2",title:"13.3. Role of vasoconstrictors:",level:"2"},{id:"sec_23_2",title:"13.4. Other pharmacological agents. ",level:"2"},{id:"sec_24_2",title:"13.5. Cardiac resynchronization therapy ",level:"2"},{id:"sec_26",title:"14. Summary ",level:"1"}],chapterReferences:[{id:"B1",body:'AbernethyD. R.SchwartzJ. B.\n\t\t\t\t\t1999 Calcium-antagonist drugs. N Engl J Med. 4;341\n\t\t\t\t\t19\n\t\t\t\t\t144757\n\t\t\t'},{id:"B2",body:'AbrahamW. T.FisherW. G.SmithA. L.DelurgioD. B.LeonA. R.LohE.KocovicD. Z.PackerM.ClavellA. L.HayesD. L.EllestadM.TruppR. 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Circulation. 2001;104\n\t\t\t\t\t77982\n\t\t\t'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Ahmed Alsaddique",address:null,affiliation:'
Professor of Cardiac Surgery King Fahad Cardiac Center,College of Medicine, King Saud University, Riyadh, Saudi Arabia
Professor of Anaesthesia and Pain Management UnitDepartment of Pharmacology, University of Melbourne, Australia
'}],corrections:null},book:{id:"344",type:"book",title:"Establishing Better Standards of Care in Doppler Echocardiography, Computed Tomography and Nuclear Cardiology",subtitle:null,fullTitle:"Establishing Better Standards of Care in Doppler Echocardiography, Computed Tomography and Nuclear Cardiology",slug:"establishing-better-standards-of-care-in-doppler-echocardiography-computed-tomography-and-nuclear-cardiology",publishedDate:"July 5th 2011",bookSignature:"Richard M. Fleming",coverURL:"https://cdn.intechopen.com/books/images_new/344.jpg",licenceType:"CC BY-NC-SA 3.0",editedByType:"Edited by",isbn:null,printIsbn:"978-953-307-366-8",pdfIsbn:"978-953-51-6435-7",reviewType:"peer-reviewed",numberOfWosCitations:10,isAvailableForWebshopOrdering:!0,editors:[{id:"47432",title:"Dr.",name:"Richard M.",middleName:null,surname:"Fleming",slug:"richard-m.-fleming",fullName:"Richard M. 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Gaze and Aleksandar Kibel",coverURL:"https://cdn.intechopen.com/books/images_new/9578.jpg",editedByType:"Edited by",editors:[{id:"71983",title:"Dr.",name:"David C.",surname:"Gaze",slug:"david-c.-gaze",fullName:"David C. Gaze"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],publishedBooksByAuthor:[]},onlineFirst:{chapter:{type:"chapter",id:"80159",title:"Proteolytic Enzymes Derived from a Macro Fungus and Their Industrial Application",doi:"10.5772/intechopen.102385",slug:"proteolytic-enzymes-derived-from-a-macro-fungus-and-their-industrial-application",body:'
1. Introduction
Enzymes are natural catalysts that evolve or require various biological processes and are utilized in various industrial applications. Scientists have recently focused on detecting new enzymes with various properties and best-suited commercial purposes [1, 2]. There are many advantages associated with industrial enzymes, such as reaction specificity, low energy needs, biodegradable sources such as plants, animals, and microbes used for enzymes production and isolation. Proteases are the best studied and utilized in a group of enzymes that have the best substrate specificity. Total enzymes are produced at the industrial level, of which one-third are hydrolyses, and 65% are proteases. Proteases are hydrolytic enzymes that catalyze the interruption of the polymerization of protein. It evolves in the metabolic processes of biological activities in almost all organisms [3, 4, 5, 6].
Different microbial sources have produced different proteases than plants and animals; microbial enzymes are more labor-intensive and best suitable for industrial applications [3, 7, 8]. Approximately two-thirds of commercial protease is produced from microbial origin in the world [6]. Microbial proteases production has advantages: short generation time, high growth rate, high yield, genetic modification is possible, cost-effective, and easy availability. These properties made microbial protease the best choice for biotechnological and industrial applications [9, 10].
Much research has been conducted to isolate and purify proteases from microbial sources and wieldy applied in industrial sectors [1, 11]. Bacteria are the most prominent microbes used for industrial-level protease production. Some groups of basidiomycetes also reported having proteases, and they provide the way for further study, fungal protease is neutral, acidic, or alkaline protease according to the species of fungi [12]. Fungi proteases have easy cell separation techniques, and a study revealed that micromycetes proteases have specific characteristics. Several fungal species include Aspergillus species, Fusarium graminarum, Chrysosporium keratinophilum, Penicillium chrysogenum, P.griseofulvin, Scedosporium apiosermum, and Trametes cingulata. Of all these species, Penicillium and Aspergillus are the most widely studied [12, 13, 14].
Basidiomycetes are important wood-degrading fungi in biological communities, and some genera of this group have been used as a food source. They are well studied for their extracellular enzymes production properties, such as xylanases, cellulases, and ligninolytic enzymes [15]. Proteases play essential roles in the biochemical process in fungi and the essential completion of the life cycle [16]. Mushrooms are the known Basidiomycetes in the fungi group. They have been used as food products for centuries as well as reported for their biological activity, among which, species of Pleurotus are globally known and valued as good food source and ease of cultivation. Mushroom bioactive compounds such as protein, vitamins. and enzymes, etc., are also examined for their biological activity such as antitumor, anti-inflammatory antidiabetic, antiviral, antioxidant, hypocholesterolemic, antitumor, immunomodulatory, and hepatoprotective actions [17, 18]. They are a good source of vitamins, protein, minerals, and very low fat content. They contain a variety of bioactive compounds, including protease, and there are more than 20 proteases that have been isolated [17, 19, 20].
Thus, the isolation of new proteases from different mushroom species is a novel area of research that needs much exploration. There is still much progress required for the study of proteases from edible mushrooms and has great future opportunities in the area of genome, proteome, and metabolome of mushroom proteases. Also, open new research relates to exploring downstream processing and economic aspects of mushroom proteases.
2. Classification of proteolytic enzymes or proteases
Proteolytic enzymes significantly participate in the metabolism of organisms such as plants, animals, bacteria, fungi, and viruses. Proteases are not explored and are essential in enzymology because of their substantial physiological significance and broad application in research activities [4]. Since proteolytic enzymes are requisite in providing nitrogen to xylotrophs under natural growth conditions (on living and dead wood), the absence of sufficient systematic information on secreted proteases of higher xylotrophic fungi is unnoticeable yet in biology. Research studies have been conducted to isolate and characterize proteolytic enzymes from the cultured mycelium and fruit bodies of basidiomycetes. Highly diverse types of structures and mechanisms of action, so proteases are not set aside with the rules of enzyme nomenclature [14]. So, the classification of these enzymes is often difficult. The enzyme that enters through the plasma membrane inside the cell is usually called an extracellular enzyme [6]. It must be classified into two categories according to their ability to cleave the peptide bonds as exopeptidases and cleave specific sites of peptide bonds as endopeptidases. They are industrially essential enzymes [21]. The diversity and specificity of these native enzymes are based on their broad characterization and isolation (Table 1). Based on active site present on proteases, they are classified as follows:
Exopeptidases are an enzyme that cleaves at the end site and requires free terminal groups close to the bond. It catalyzes the breakdown of specific peptide bonds after the carboxyl or amino terminals in the protein. Based on their efficiency in identifying the active site as either C or N terminal, they are further divided as carboxypeptidases or amino peptidases [36].
2.1.1 Aminopeptidases
Amino peptidases are the class of proteases enzymes that precisely cut at the N-terminal of the amino acid polypeptide chain, breaking it into dimer fragments or a single amino acid residue. After the recognition, they further remove the present methionine N-terminal of the polypeptide chain, which may differ in their expression. It is found in various microbial strains, including basidiomycetes fungi, molds, and bacteria, etc. Overall, amino peptidases work as intracellular enzymes; however, as per a report studied, amino peptidases that originated from Aspergillus oryzaea fungal species are extracellular enzymes [3, 4].
2.1.2 Carboxypeptidases
This enzyme performs its catalytic reaction on the C-terminal of the amino acid chain, breaking peptide bonds into monomers form. These are not predominantly recognized as endopeptidases because they leave few amino acid molecules at the target site of the protein. Instead, it can be employed to eliminate the additional tags at the carboxyl-terminal of the target protein. Among specific peptidases, metallocarboxy protease, type A carboxypeptidase, is known primarily for removing amino acid of the aromatic side chain while type B acts on essential amino acids [37].
2.2 Endopeptidases
Endopeptidases act at specific site of the peptide bond of the substrate [36]. It cleaves the internal peptide bonds of proteins influenced by the existing functional group present on the active site of the peptide chain. It is further classified as follows:
2.2.1 Serine proteases
These classes of proteases are broadly found in nature and present in cellular organisms. Along with all the identified proteolytic enzymes, a significant part is of serine proteases. It generally performs the cleavage action on the bond present in the central part of the amino acid chain. However, few Serine proteases act as exopeptidases by detaching the amino acids from the end terminal of the polypeptide chain. Its name derives from the Ser residue present in the peptide chain, which is nucleophilic and placed in the active site of the chain of amino acids. An intermediate substrate is formed by using the serine residues inform of acyl-enzyme at the C end terminal of the newly structured peptide bond [38].
2.2.2 Cysteine/thiol proteases
This enzyme contains cysteine residues at their active site present both in prokaryotes and eukaryotes microbes. It shows proteolytic activity at the 6–8 pH range with 50–70°C optimum temperature. Hydrogen cyanide is the key component that activates this enzyme, resulting in which SH group is formed in a polypeptide chain. Oxidizing agents can inhibit this kind of proteases and show sensitive action to the sulfhydryl agents, for example, p-CMB [39].
2.2.3 Metalloproteases
Metalloproteases are generally zinc-containing enzymes. In fungi or basidiomycetes, several metal ions such as calcium, cobalt, and zincare are involved in their reactivation. Zinc-containing enzymes and calcium are essential for proteineous activity and structural stability of protein at optimum pH 5–9. These are sensitive to an agent that causes chelation of metal, such as ethylen diamine tetracetic acid (EDTA), but are insensitive to cysteine inhibitors [40].
2.2.4 Aspartic proteases
It is a comparatively small class of endopeptidases that includes aspartic proteases. These proteases are composed of a pair of aspartates bilobed structures, including a leading catalytic site. It functions optimally on acidic pH and is present in nature. This enzyme is secreted by various microorganisms such as bacteria and fungus, as their virulence secretions. Also, it can perform the mutualistic function in the breakdown of proteins yielding nitrogen from urea. These kinds of proteases are primarily biased toward the hydrophobic amino acids nearer to the dipeptides bond. As compared with the other two endoproteases, it utilizes residues present in the active site showing nucleophilic attribute for proteolysis [41].
3. Proteolytic enzymes from mushroom species
As proteolytic enzymes are indispensable in supplying nitrogen to xylotrophs under natural growth conditions (on living and dead wood), the absence of sufficient systematic information on secreted proteases of higher xylotrophic fungi is not much explored [42]. The protein structure contains nitrogen, which is probably the reason for the secretion of extracellular proteolytic enzymes basidiomycetes or mushroom. The species belong to orders of basidial fungi, Polyporales, Boletales, and Agaricales, which are reported to secret proteolytic enzymes. Proteases secreted by mushrooms typically have a low molecular mass ranging from 26 to 50 kDa having isoelectric point’s up to 3.5–8.8. Acidic pH is usually optimal for these enzymes, ranging from 2.0 to 5.0. Proteinases isolated from Hypsizygis (H.) marmoreus, P. ostreatus, and F. velutipes are exceptional, as their optimal pH falls under the neutral range. Amino peptidases in the mushroom are usually intracellular enzymes; few reports have studied detecting extracellular aminopeptidases, such as Tramatellatrogii. Separately from endopeptidase activity, aminopeptidase, carboxypeptidase, and dipeptidyl aminopeptidase activities were revealed [43]. It is known that there is a high demand for industrial application of proteolytic enzymes with suitable specific properties and must be stable at various temperatures and pH. However, this chapter suggests that the studies of proteases from basidiomycete’s fungus or mushroom recommend that further detailed studies are required to explore proteases’ mechanisms and physiological effects.
4. Role of proteolytic enzymes in mushroom
Proteases perform complex physiological functions, including protein catabolism; blood clotting, cell growth and migration, morphogenesis, and development [4]. Mushrooms or basidiomycetes fungi are heterotrophic organisms. They can utilize both organic and inorganic nitrogen sources as nutrition. An under natural conditions, they usually secrete various extracellular enzymes to decompose natural organic materials such as ligninolytic enzymes. Protease from mushrooms involves endopeptidases, and exopeptidases act one after another as the former produces many free C and N terminal ends and latter act on the peptide fragments, thus forming the decomposed protein. This broad specificity is a significant property of the fungal secreted proteases and other proteolytic enzymes employed to break down proteins. An investigation reported on fungus T. rogii utilizes these enzymes to efficiently break down various peptides in the substrate [43]. Proteases secreted in mushrooms participate in the active regulation of other synthesized enzymes, resulting in regulating some physiological processes in mushrooms species such as P. ostreatus, P. chrysosporium, etc. The activity of ligninolytic enzymes is regulated via their specific activation or inactivation by the extracellular proteases secreted them [22] and perhaps has the ability to degrade the proteins controlling heat shock response, DNA repair pathway programmed cell death [4]. The metalloprotease plays a significant role in the fruiting body formation in P. ostreatus. Previous studies demonstrated that mRNA content is noticeably higher in the primordial stages of fruit body formation than in the vegetative mycelium stage [44]. So the extracellular occurrence of the fungal proteolytic enzymes may help the fungus grow on the host by utilizing its nutritional contents, may act as a pathogenic agent for the host. Under favorable conditions, P. pulmonarius grows only on dead decaying wood showing as ubtilisin-like proteolytic activity using proteases [45].
5. Methods used for proteolytic enzymes recovery and production
Enzymes recovery and production from mushrooms were directly influenced by the substrate type, composition, and recovery methods. Various research studies showed that solid-state and submerged fermentation mushrooms had been significantly used for enzyme production [46]. In solid-state cultivation, various agro wastes are utilized and produce fruiting bodies containing various metabolites primarily used for food sources. After harvesting, its by-products, spent mushroom substrate (SMS) that contains plenty of extracellular enzymes can be utilized as animal feeding and for enzymes recovery and production. It reported that laccase (EC 1.10.3.2) was the most prominent and common in Pleurotus sajor-caju [47], P. ostreatus, L. edodes, Flammulina velutipes and Hericium erinaceum [48], A. bisporus [49]. Another enzyme, lignin peroxidase productivity, was found to be the SMS of P. sajor-caju [47]. Researchers can significantly explore the production of lipases, pectinases, and phytases. Table 1 lists all the enzymes found in mushrooms and recovery methods. Convinced enzymes extraction and purification methods were widely applied, for example, dialysis, ultrafiltration, anion-exchange chromatography, and gel [50, 51, 52]. It is noteworthy that most of the investigations were carried out only for the fruiting body or mycelium of mushroom, not the SMS; therefore, it is an open possibility for the new finding for enzymes from SMS. Recently works were reported for enzyme recovery from SMS. Mayolo-Deloisa et al. [49] evaluated the use of aqueous two-phase systems to recover laccase from the residual compost of A. bisporus mushroom. They observed that valorizations of residual material give a 95% yield and have the potential for value-added products with commercial application [49]. Ko et al. [48] determined the production of amylase, cellulase, glucosidase, laccase, and xylanase from the SMS obtained from four edible mushrooms: P. ostreatus, L. edodes, F. velutipes and H. erinaceum, and evaluated its potential application using enzymes from SMS as industrial enzymes. It has been reported that a solvent such as water is used for enzymes recover from SMS with good activity; this fact is essential for an industrial application and related environmental concerns. However, the extraction of enzymes from submerged culture supernatant is more straightforward than from SMS because centrifugation is needed, and the obtained supernatant can be used as the crude enzyme. Some physical conditions are essential for optimizing scale-up, such as pH, temperature, extraction medium, incubation time, inoculums density, carbon and nitrogen source, and the impotent parameters for enzyme production.
6. Applications and future prospects
Novel investigation techniques revealed highly specific and selective protein modifications performed by proteases, including activating the zymogenic enzyme forms by limited proteolysis, forming hormones and other physiologically active peptides from precursor proteins, thrombus lysis, or the processing and transport of secreted proteins through the membrane (Figure 1). The vital role of proteolytic enzymes in metabolic and regulatory processes explains their occurrence in all living organisms [53].
Figure 1.
Application of edible mushroom as a potential source for enzymes production.
6.1 In the detergent industry
Proteases were used as a detergent centuries ago as the “Burnus” brand, along with sodium carbonate and pancreatic extract mixed in it [54]. Several industries, such as chemical, pharmaceutical, food processing, detergents, and leather processing, utilize the catalytic properties of proteases. Its application in the bioremediation of pollutants has also been reported. Several factors such as optimum substrate specificity, temperature, optimum pH, chemical stability, and catalytic activity may vary because of a diverse group and also can affect the production of proteases [21].
6.2 Cell-free enzyme preparation
Immense interest has been grown in proteases due to their thermal ability in a wide range of temperatures. It is also used as detergents in the cell separation process for the production of cell-free enzyme preparations. In these perspective, fungal enzymes have applications as these are extracellularly secreted [55, 56].
6.3 In the pharmaceutical and food industries
Some proteases are also found to produce due to the infection process caused by foreign invaders such as bacteria, fungus, and viruses. A variety of steps regulate the mechanism of proteolytic enzyme reactions, including substrate specificity, ATP-directed protein degradation, restricted access to the active site, highly specific protein modifications. It can activate zymogenic forms of enzymes by restricted proteolysis activity [57]. Including these protease enzymes that cause diseases to host cells has become a good option for developing therapeutic agents for the diseases such as cancer, hepatitis, malaria, and candidiasis. It has also been reported to demonstrate potent immunomodulatory activity [4].
6.4 Leather industry
The leather industry involves various steps to obtain processed leather, for example, soaking, liming, hair removal, bating, deliming, and degreasing. These steps are applied using poisonous chemicals such as salt, lime, solvents, and sodium sulfide, resulting in pollution. The exclusion of non-collagenous particles is required in leather processing, which decides the softness and durability of leather products [58, 59]. It can be controlled by applying enzymes such as proteases in the place of chemicals [60].
7. Conclusion
Most of the industrial proteases used are of microbial origin, especially of bacteria. These enzymes are preferentially selected because of their desired characteristics and lower cost. The bioengineering manufacture of microbial proteases is favored as they have short generation periods, high yield, ease of genetic desired modification, and diverse species available. Future opportunities are high in cutting-edge research from the pharmaceutical perspective of the protease gene. By the help via recombinant DNA technology, respective genes must have been cloned and sequenced to determine the function of enzymes that cause changes in the attributes of protease enzymes and enhance enzyme production for their commercial usage. In industries, proteases contribute to the high value-added products development, and the same way biological catalysts offer advantages over the use of chemical catalysts for numerous reasons, such as high catalytic activity, high specificity, and their availability in economically viable quantities.
Conversely, cost associated with the production of proteases from mushrooms or basidiomycetes is the major obstacle to their application in industries and pharmaceuticals. For that reason, further research studies should have been implemented to discover novel low-cost proteases from mushrooms and their application in commercial and industrial sectors. So, a great extent of the study of proteases from the mushroom requires further investigations.
Acknowledgments
The authors are thankful to the Junior Research Fellowship (DBT/JRF/BET-18/I/2018/AL/123), Department of Biotechnology, Biotech Consortium of India Limited, and Pt. Ravishankar Shukla University Research scholarship award (797/Fin/Sch./2021) for providing funding support. The authors are also are thankful to the Head, School of Studies in Biotechnology, Pt. Ravishankar Shukla University, Raipur.
Conflict of interest
The authors declare no conflict of interest.
\n',keywords:"proteolytic enzymes, Basidiomycetes, macro fungi, mushroom, industrial application",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/80159.pdf",chapterXML:"https://mts.intechopen.com/source/xml/80159.xml",downloadPdfUrl:"/chapter/pdf-download/80159",previewPdfUrl:"/chapter/pdf-preview/80159",totalDownloads:77,totalViews:0,totalCrossrefCites:0,dateSubmitted:"November 28th 2021",dateReviewed:"December 23rd 2021",datePrePublished:"February 7th 2022",datePublished:"June 15th 2022",dateFinished:"January 21st 2022",readingETA:"0",abstract:"Proteolytic enzymes are well known for catalyzing hydrolytic reactions. These enzymes fall under the group of large and complex, also known as proteases. Proteolytic enzymes mainly derived from microbial origin are favored because they have a short generation time, ease of genetic manipulation of microorganisms, and the availability of diverse species in nature. Macro fungi are significant and played an excellent role in degrading lignocellulosic compounds, such as mushrooms. They efficiently degrade cellulose and produce extracellular enzymes such as xylanases, cellulases, and ligninolytic enzymes. Furthermore, proteases play a significant role in fungi physiology, such as metalloproteinase, subtilases, aspartate, etc. Many worldwide researchers have reported the mycelial secretion of proteases from basidiomycetes. Thus, many protease extraction methods have been developed from the various categories of mushroom species, i.e., Pleurotusostreatus, Phanerochaetechrysosporium, Schizophyllum commune, Chondrostereumpurpureum, and Hypsizygusmarmoreus, etc. Furthermore, there is a high demand in the industry for specific proteolytic enzymatic activity. Numerous species of mushrooms have not been explored to date for the optimization and production of enzymes. Therefore, further detailed studies are required to expose the production mechanisms and application of proficient proteolytic enzymes from mushrooms. The present chapter will deliberately deal with proteolytic enzymes downstream processing and their various industrial applications.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/80159",risUrl:"/chapter/ris/80159",signatures:"Nagendra Kumar Chandrawanshi, Deepali Koreti, Anjali Kosre and Ashish Kumar",book:{id:"10841",type:"book",title:"Hydrolases",subtitle:null,fullTitle:"Hydrolases",slug:"hydrolases",publishedDate:"June 15th 2022",bookSignature:"Sajjad Haider, Adnan Haider and Angel Catalá",coverURL:"https://cdn.intechopen.com/books/images_new/10841.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-80355-163-0",printIsbn:"978-1-80355-162-3",pdfIsbn:"978-1-80355-164-7",isAvailableForWebshopOrdering:!0,editors:[{id:"110708",title:"Dr.",name:"Sajjad",middleName:null,surname:"Haider",slug:"sajjad-haider",fullName:"Sajjad Haider"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"216297",title:"Dr.",name:"Ashish",middleName:null,surname:"Kumar",fullName:"Ashish Kumar",slug:"ashish-kumar",email:"banjaraashish@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"436510",title:"Dr.",name:"Nagendra Kumar",middleName:null,surname:"Chandrawanshi",fullName:"Nagendra Kumar Chandrawanshi",slug:"nagendra-kumar-chandrawanshi",email:"nagenkumarchandra3@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"445110",title:"Ms.",name:"Anjali",middleName:null,surname:"Kosre",fullName:"Anjali Kosre",slug:"anjali-kosre",email:"akosre21@yahoo.in",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"447069",title:"Ms.",name:"Deepali",middleName:null,surname:"Koreti",fullName:"Deepali Koreti",slug:"deepali-koreti",email:"ranukoreti27@gmail.com",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. Classification of proteolytic enzymes or proteases",level:"1"},{id:"sec_2_2",title:"2.1 Exopeptidases",level:"2"},{id:"sec_2_3",title:"2.1.1 Aminopeptidases",level:"3"},{id:"sec_3_3",title:"2.1.2 Carboxypeptidases",level:"3"},{id:"sec_5_2",title:"2.2 Endopeptidases",level:"2"},{id:"sec_5_3",title:"2.2.1 Serine proteases",level:"3"},{id:"sec_6_3",title:"2.2.2 Cysteine/thiol proteases",level:"3"},{id:"sec_7_3",title:"2.2.3 Metalloproteases",level:"3"},{id:"sec_8_3",title:"2.2.4 Aspartic proteases",level:"3"},{id:"sec_11",title:"3. Proteolytic enzymes from mushroom species",level:"1"},{id:"sec_12",title:"4. Role of proteolytic enzymes in mushroom",level:"1"},{id:"sec_13",title:"5. Methods used for proteolytic enzymes recovery and production",level:"1"},{id:"sec_14",title:"6. Applications and future prospects",level:"1"},{id:"sec_14_2",title:"6.1 In the detergent industry",level:"2"},{id:"sec_15_2",title:"6.2 Cell-free enzyme preparation",level:"2"},{id:"sec_16_2",title:"6.3 In the pharmaceutical and food industries",level:"2"},{id:"sec_17_2",title:"6.4 Leather industry",level:"2"},{id:"sec_19",title:"7. Conclusion",level:"1"},{id:"sec_20",title:"Acknowledgments",level:"1"},{id:"sec_23",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Inacio DF, Ferreira RO, CA VA, Brugnari T, Castoldi R, Peralta RM, et al. Proteases of wood rot fungi with emphasis on the genus Pleurotus. BioMed Research International. 2015;2015:1-10'},{id:"B2",body:'Daroit DJ, Correa APF, Brandelli A. Production of keratinolytic proteases through bioconversion of feather meal by the Amazonian bacterium Bacillus sp. P45. International Biodeterioration and Biodegradation. 2011;65:45-51'},{id:"B3",body:'Rao CS, Sathish T, Ravichandra P, Prakasham R. 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Food Technology and Biotechnology. 2006;44(2):211-220'},{id:"B56",body:'Shaba AM, Baba J. Screening of Pleurotus ostreatus and Gleophylumsepiarium strains for extracellular protease enzyme production. Bayero Journal of Pure and Applied Sciences. 2014;5(1):187-190'},{id:"B57",body:'Vandeputte-Rutten L, Gros P. Novel proteases: Common themes and surprising features. Current Opinion in Structural Biology. 2002;12(6):704-708'},{id:"B58",body:'Khan F. New microbial proteases in leather and detergent industries. Recent Innovations in Chemical Engineering. 2013;1:1-6'},{id:"B59",body:'Wahab WAA, Ahmed SA. Response surface methodology for production, characterization and application of solvent, salt and alkali-tolerant alkaline protease from isolated fungal strain aspergillus Niger WA. International Journal of Biological Macromolecules. 2017;115:447-458'},{id:"B60",body:'Sharma M, Gat Y, Arya S. A review on microbial alkaline protease: An essential tool for various industrial approaches. 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Open Access publication costs can often be designated directly in the grants or in specific budgets allocated for that purpose. Many of the most important funding organisations encourage, and even request, that the projects they fund are made available at no cost to the wider public. IntechOpen strives to maintain excellent relationships with these funders and ensures compliance with mandates.
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Please be aware that you must be a member, or grantee, of the institutions/funders listed in order to apply for their Open Access publication funds.
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\n\n
In order to help Authors identify appropriate funding agencies and institutions, we have created a list, based on extensive research on various OA resources (including ROARMAP and SHERPA/JULIET) of organizations that have funds available. Before consulting our list we encourage you to petition your own institution or organization for Open Access funds or check the specifications of your grant with your funder to ascertain if publication costs are included. Where you are in receipt of a grant you should clarify:
\n\n
\n\t
Does your institution already have a budget for covering Open Access publication costs?
\n\t
Does your grant list Open Access publication fees as legitimate direct/indirect costs?
\n
\n\n
If you are associated with any of the institutions in our list below, you can apply to receive OA publication funds by following the instructions provided in the links. Please consult the Open Access policies or grant Terms and Conditions of any institution with which you are linked to explore ways to cover your publication costs (also accessible by clicking on the link in their title).
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Please note that this list is not a definitive one and is updated regularly. To suggest possible modifications or the inclusion of your institution/funder, please contact us at funders@intechopen.com
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Increasing concerns about pollution levels in the oceans and coastal regions have led to multiple approaches for measuring and mitigating marine pollution, in order to achieve sustainable marine water quality. Satellite remote sensing, covering large and remote areas, is considered useful for detecting and monitoring marine pollution. Recent developments in sensor technologies have transformed remote sensing into an effective means of monitoring marine areas. Different remote sensing platforms and sensors have their own capabilities for mapping and monitoring water pollution of different types, characteristics, and concentrations. This chapter will discuss and elaborate the merits and limitations of these remote sensing techniques for mapping oil pollutants, suspended solid concentrations, algal blooms, and floating plastic waste in marine waters.",book:{id:"7547",slug:"monitoring-of-marine-pollution",title:"Monitoring of Marine Pollution",fullTitle:"Monitoring of Marine Pollution"},signatures:"Sidrah Hafeez, Man Sing Wong, Sawaid Abbas, Coco Y. T. 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Increasing concerns about pollution levels in the oceans and coastal regions have led to multiple approaches for measuring and mitigating marine pollution, in order to achieve sustainable marine water quality. Satellite remote sensing, covering large and remote areas, is considered useful for detecting and monitoring marine pollution. Recent developments in sensor technologies have transformed remote sensing into an effective means of monitoring marine areas. Different remote sensing platforms and sensors have their own capabilities for mapping and monitoring water pollution of different types, characteristics, and concentrations. This chapter will discuss and elaborate the merits and limitations of these remote sensing techniques for mapping oil pollutants, suspended solid concentrations, algal blooms, and floating plastic waste in marine waters.",book:{id:"7547",slug:"monitoring-of-marine-pollution",title:"Monitoring of Marine Pollution",fullTitle:"Monitoring of Marine Pollution"},signatures:"Sidrah Hafeez, Man Sing Wong, Sawaid Abbas, Coco Y. T. 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In this chapter, a broad overview of recent empirical statistical and machine learning techniques for modelling PM10 is presented. This includes the instrumentation used to measure particulate matter, data preprocessing, the selection of explanatory variables and modelling methods. Key features of some PM10 prediction models developed in the last 10 years are described, and current work modelling and predicting PM10 trends in New Zealand—a remote country of islands in the South Pacific Ocean—are examined. In conclusion, the issues and challenges faced when modelling PM10 are discussed and suggestions for future avenues of investigation, which could improve the precision of PM10 prediction and estimation models are presented.",book:{id:"5356",slug:"air-quality-measurement-and-modeling",title:"Air Quality",fullTitle:"Air Quality - Measurement and Modeling"},signatures:"Jacqueline Whalley and Sara Zandi",authors:[{id:"188593",title:"Associate Prof.",name:"Jacqueline",middleName:null,surname:"Whalley",slug:"jacqueline-whalley",fullName:"Jacqueline Whalley"},{id:"188594",title:"Ms.",name:"Sara",middleName:null,surname:"Zandi",slug:"sara-zandi",fullName:"Sara Zandi"}]},{id:"72766",title:"Industrial Air Emission Pollution: Potential Sources and Sustainable Mitigation",slug:"industrial-air-emission-pollution-potential-sources-and-sustainable-mitigation",totalDownloads:970,totalCrossrefCites:4,totalDimensionsCites:6,abstract:"Air of cities especially in the developing parts of the world is turning into a serious environmental interest. The air pollution is because of a complex interaction of dispersion and emission of toxic pollutants from manufactories. Air pollution caused due to the introduction of dust particles, gases, and smoke into the atmosphere exceeds the air quality levels. Air pollutants are the precursor of photochemical smog and acid rain that causes the asthmatic problems leading into serious illness of lung cancer, depletes the stratospheric ozone, and contributes in global warming. In the present industrial economy era, air pollution is an unavoidable product that cannot be completely removed but stern actions can reduce it. Pollution can be reduced through collective as well as individual contributions. There are multiple sources of air pollution, which are industries, fossil fuels, agro waste, and vehicular emissions. Industrial processes upgradation, energy efficiency, agricultural waste burning control, and fuel conversion are important aspects to reducing pollutants which create the industrial air pollution. Mitigations are necessary to reduce the threat of air pollution using the various applicable technologies like CO2 sequestering, industrial energy efficiency, improving the combustion processes of the vehicular engines, and reducing the gas production from agriculture cultivations.",book:{id:"10178",slug:"environmental-emissions",title:"Environmental Emissions",fullTitle:"Environmental Emissions"},signatures:"Rabia Munsif, Muhammad Zubair, Ayesha Aziz and Muhammad Nadeem Zafar",authors:[{id:"251787",title:"Dr.",name:"Muhammad",middleName:null,surname:"Zubair",slug:"muhammad-zubair",fullName:"Muhammad Zubair"},{id:"318519",title:"Ms.",name:"Rabia",middleName:"Jathol",surname:"Munsif",slug:"rabia-munsif",fullName:"Rabia Munsif"},{id:"320637",title:"Ms.",name:"Ayesha",middleName:null,surname:"Aziz",slug:"ayesha-aziz",fullName:"Ayesha Aziz"},{id:"320675",title:"Dr.",name:"Muhammad Nadeem",middleName:null,surname:"Zafar",slug:"muhammad-nadeem-zafar",fullName:"Muhammad Nadeem Zafar"}]},{id:"48090",title:"Biological Contamination of Air in Indoor Spaces",slug:"biological-contamination-of-air-in-indoor-spaces",totalDownloads:2778,totalCrossrefCites:6,totalDimensionsCites:9,abstract:null,book:{id:"4572",slug:"current-air-quality-issues",title:"Current Air Quality Issues",fullTitle:"Current Air Quality Issues"},signatures:"Anca Maria Moldoveanu",authors:[{id:"25924",title:"Prof.",name:"Anca",middleName:"Maria",surname:"Moldoveanu",slug:"anca-moldoveanu",fullName:"Anca Moldoveanu"}]},{id:"64537",title:"Degradation Pathways of Persistent Organic Pollutants (POPs) in the Environment",slug:"degradation-pathways-of-persistent-organic-pollutants-pops-in-the-environment",totalDownloads:2103,totalCrossrefCites:8,totalDimensionsCites:20,abstract:"Persistent organic pollutants (POPs) are resistant to most of the known environmental degradation processes. Because of their persistence, POPs bioaccumulate in animal tissues and biomagnify along food chains and food webs with potential adverse impacts on human and wildlife health and the environment. Although POPs are resistant to most of the environmental degradation processes, there are some environmental processes mostly microbial degradation that can degrade POPs to other forms that are not necessarily simpler and less toxic. The Stockholm Convention on Persistent Organic Pollutants adopted in 2001 was meant to restrict the production and use of these toxic chemicals in the environment.",book:{id:"7224",slug:"persistent-organic-pollutants",title:"Persistent Organic Pollutants",fullTitle:"Persistent Organic Pollutants"},signatures:"James T. Zacharia",authors:[{id:"28551",title:"Dr.",name:"James T.",middleName:null,surname:"Zacharia",slug:"james-t.-zacharia",fullName:"James T. 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Rodriguez-Morales",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},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"3",title:"Bacterial Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/3.jpg",isOpenForSubmission:!0,editor:{id:"205604",title:"Dr.",name:"Tomas",middleName:null,surname:"Jarzembowski",slug:"tomas-jarzembowski",fullName:"Tomas Jarzembowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKriQAG/Profile_Picture_2022-06-16T11:01:31.jpg",biography:"Tomasz Jarzembowski was born in 1968 in Gdansk, Poland. He obtained his Ph.D. degree in 2000 from the Medical University of Gdańsk (UG). After specialization in clinical microbiology in 2003, he started studying biofilm formation and antibiotic resistance at the single-cell level. In 2015, he obtained his D.Sc. degree. 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He is also a reviewer and a member of editorial boards of a number of international journals.",institutionString:"Medical University of Gdańsk, Poland",institution:null},editorTwo:{id:"484980",title:"Dr.",name:"Katarzyna",middleName:null,surname:"Garbacz",slug:"katarzyna-garbacz",fullName:"Katarzyna Garbacz",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003St8TAQAZ/Profile_Picture_2022-07-07T09:45:16.jpg",biography:"Katarzyna Maria Garbacz, MD, is an Associate Professor at the Medical University of Gdańsk, Poland and she is head of the Department of Oral Microbiology of the Medical University of Gdańsk. She has published more than 50 scientific publications in peer-reviewed journals. She has been a project leader funded by the National Science Centre of Poland. Prof. Garbacz is a microbiologist working on applied and fundamental questions in microbial epidemiology and pathogenesis. Her research interest is in antibiotic resistance, host-pathogen interaction, and therapeutics development for staphylococcal pathogens, mainly Staphylococcus aureus, which causes hospital-acquired infections. Currently, her research is mostly focused on the study of oral pathogens, particularly Staphylococcus spp.",institutionString:"Medical University of Gdańsk, Poland",institution:null},editorThree:null},{id:"4",title:"Fungal Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",isOpenForSubmission:!0,editor:{id:"174134",title:"Dr.",name:"Yuping",middleName:null,surname:"Ran",slug:"yuping-ran",fullName:"Yuping Ran",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9d6QAC/Profile_Picture_1630330675373",biography:"Dr. Yuping Ran, Professor, Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China. Completed the Course Medical Mycology, the Centraalbureau voor Schimmelcultures (CBS), Fungal Biodiversity Centre, Netherlands (2006). International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. Board Member and Chair of Mycology Group of Chinese Society of Dermatology.",institutionString:null,institution:{name:"Sichuan University",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null},{id:"5",title:"Parasitic Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",isOpenForSubmission:!0,editor:{id:"67907",title:"Dr.",name:"Amidou",middleName:null,surname:"Samie",slug:"amidou-samie",fullName:"Amidou Samie",profilePictureURL:"https://mts.intechopen.com/storage/users/67907/images/system/67907.jpg",biography:"Dr. Amidou Samie is an Associate Professor of Microbiology at the University of Venda, in South Africa, where he graduated for his PhD in May 2008. He joined the Department of Microbiology the same year and has been giving lectures on topics covering parasitology, immunology, molecular biology and industrial microbiology. 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Saxena",hash:"d92a4085627bab25ddc7942fbf44cf05",volumeInSeries:2,fullTitle:"Current Perspectives in Human Papillomavirus",editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:250,paginationItems:[{id:"274452",title:"Dr.",name:"Yousif",middleName:"Mohamed",surname:"Abdallah",slug:"yousif-abdallah",fullName:"Yousif Abdallah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274452/images/8324_n.jpg",biography:"I certainly enjoyed my experience in Radiotherapy and Nuclear Medicine, particularly it has been in different institutions and hospitals with different Medical Cultures and allocated resources. Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"243698",title:"Dr.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:null,institution:null},{id:"7227",title:"Dr.",name:"Hiroaki",middleName:null,surname:"Matsui",slug:"hiroaki-matsui",fullName:"Hiroaki Matsui",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Tokyo",country:{name:"Japan"}}},{id:"312999",title:"Dr.",name:"Bernard O.",middleName:null,surname:"Asimeng",slug:"bernard-o.-asimeng",fullName:"Bernard O. Asimeng",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}}]}},subseries:{item:{id:"9",type:"subseries",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. 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Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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