\r\n\tWith this goal in mind, together with the US Prof. John M. Ballato and the InechOpen publishing house since 2011 we have published in 2011, 2013, 2015 and 2017 4 books of our serial “Optoelectronics” and the book “Excitons”, edited in 2018 by Prof. Sergei L. Pyshkin. Publishing the new book “Luminescence” we are pleased to note the growing number of countries participating in this undertaking as well as for a long time fruitfully cooperating scientists from the United States and the Republic of Moldova.
\r\n\tSpecialists from all over the world have published in edited by us books their works in the field of research of the luminescent properties of various materials suitable for use in optoelectronic devices, the development of new structures and the results of their application in practice.
The technique of aortic root surgery has undergone many improvements during the past decades. These are a direct result of better understanding of the functional hemodynamics of the aortic root coupled with significant improvement in imaging. We present here a brief overview of pathology involving the aortic root with a special focus on the surgical aspects in these operative procedures. Our chapter includes tips on use of mechanical valve conduits, homograft, and stent-less valve prostheses as well as techniques implementing a valve-sparing approach.
Improved imaging and computer simulation has increased our understanding of the aortic root anatomy, structure and function. Aortic root had been described as the vascular tube supporting the aortic valve leaflets and connecting the left ventricular outflow tract inferiorly to the sinotubular junction superiorly [1]. Two thirds of the lower segment (aortic annulus) of the aortic root is attached to the interventricular septum while the remainder is attached to the fibrous part of the anterior mitral valve leaflet [2]. This tubular structure (Figure 1) encompasses the aortic valve leaflets, coronary ostia, commissures, interleaflet triangles and the sinuses [1]. All these components link together to act as a single unit. It is now clear, that this is much more than just a passive unit governed by pressure changes across the valve [3, 4]. The geometric relationship of the valve leaflets as well as individual lengths are important for it to work as a single efficient hemodynamic unit [5].
Opened aortic root section. Sinotubular junction is indicated by the open arrows, small arrows indicating the coronary ostia (left and right), broken lines indicating the fibrous skeleton between the aortic and mitral valves. L, R, and N mark the left, right and the non-coronary cusps, respectively [
The dilated portion of the aortic wall between the aortic annulus and sino-tubular junction is known as the sinus of Valsalva. These sinuses are named according to the relationship of the origin of the coronary ostia from the root that is left, right or non-coronary sinuses. The sinuses are labelled corresponding to their coronary ostia. One of the important roles provided by these sinuses is preventing obstruction of the coronary ostia during movement of the aortic valve leaflets against the aortic wall, so that coronary blood flow is maintained [5]. An important function is prevention of ostial obstruction during systole when the aortic valve is open [7]. Generation of Eddy currents during early systole prevents the aortic leaflets from touching the aortic wall [8].
The aortic valve leaflets which are inserted at their bases in a semilunar fashion to the aortic annulus. They allow uni-directional flow of blood from the left ventricle to the aorta. Aortic valve leaflets are variable in size and number, the non-coronary cusp being the largest compared to the left or right aortic valve cusps. The most common variation is the bicuspid aortic valve, which consists of a semi-lunar opening due to the presence of two leaflets, and the commonest deviation from the normal tri-leaflet pattern is the known congenital anomaly called bicuspid aortic valve [9]. The attachment of the curved aortic valve leaflets form the triangular space named as the interleaflet triangles, the apices of these triangles is known as the valve commissures which are at the level of the sinotubular junction [10]. Aortic valve competence depends on the overlap between these adjacent free margins of the leaflets.
The aortic valve annulus represents the ventriculo-aortic junction which is a complex structure and universally accepted term as aortic annulus [9]. The basic attachments of the aortic valve leaflets at the aortic annulus comprise muscular and fibrous parts [5]. The right aortic valve leaflet attaches to both the membranous and the interventricular septa, while the non-coronary leaflet attaches to the membranous septum and the fibrous skeleton of the anterior mitral valve leaflet, and the left aortic valve leaflet attaches to the fibrous skeleton of the anterior mitral valve leaflet and partly to the interventricular septum [9]. Connective tissue disorders that involve the fibrous skeleton of the aortic root lead to alteration in normal geometry. Damage begets further damage leading to significant valve distortion and subsequent clinical sequelae [9].
Connective tissue disorder is among the most common non-infective etiology of aortic root pathology. Marfan’s syndrome, Ehlers-Danlos syndrome and Loeys-Dietz syndrome predominantly involve the elastic aortic root [11, 12, 13]. Marfan’s syndrome is an autosomal dominant disorder characterized by mutation in the gene encoding for fibrillin-1. It leads to cystic medial necrosis and involves all connective tissue containing high percentages of elastin. Disease is multi-systemic; however aortic dissection remains an important cause of mortality [14]. The probability of aortic emergencies increases significantly when transverse aortic diameters is more than 45 mm [15].
Patients with vascular type of the Ehlers-Danlos syndrome are prone to aortic dissection rather than aneurysm, while patients with Loeys-Dietz syndrome are liable to have aortic aneurysm and dissection at younger age [11, 16, 17].
Bicuspid aortic valve (BAV) is present in 1–2% of the population; almost 40% also have thoracic aortic dilatation at the time of presentation [18].
While the inheritance of BAV is not clearly defined, gene sequence defects leading to aortopathy is more prevalent in this population [19]. Degenerative changes in the tunica media with reduced elastin increases risk of dissection these patients [20, 21].
Giant cell arteritis and Takayasu arteritis are rarer causes of aneurysmal dilatation/aortic dissection [22, 23]. While temporal artery involvement is the hallmark of giant cell arteritis, at least 0.15% also had aortic dissection in an autopsy series [22]. Takayasu arteritis on the other hand is an inflammatory disorder that leads to large vessel inflammation characterized by fibrosis and narrowing, which may lead to aneurysmal formation and possible rupture [23]. Corticosteroids are used for acute therapy and surgery is performed once active inflammation subsides [24, 25].
Cystic medial necrosis (CMN) is a pathological term that is characterized by the formation of cyst like lesions in the medial layer of the large arteries with accumulation of basophilic substances [26].
The American Association of Thoracic Surgeons present following guidelines regarding surgery for the ascending aorta [27]:
Surgical repair should be performed when aortic diameter (root or ascending aorta) is 55 mm or more.
Surgical repair should be performed when aortic diameter (root or ascending aorta) is 50 mm or more in the presence of certain risk factors such as: root phenotype bicuspid aortic valve, uncontrolled hypertension, history of aortic dissection or sudden death in the family, annual enlargement of 3 mm or more in the size of the aortic aneurysm, or predominantly aortic regurgitation.
Surgical repair should be performed when aortic diameter (root or ascending aorta) is 50 mm or more in patients with low operative risk being performed by experienced aortic surgical team in centers with well-established surgical outcomes
Surgical repair should be performed when aortic diameter (root or ascending aorta) is 45 mm or more in patients undergoing concomitant other cardiac surgery.
Patients with Marfan’s syndrome or Marfanoid habitus should be operated when their aortic root/ascending aorta is larger than 50 mm in maximal transverse diameter [28]. Gott and colleagues [27, 28] reported an improved 30-day survival in a series of 675 patients with Marfan’s syndrome who underwent elective compared to urgent or emergency replacement of the aortic root.
If patients have a family history of aortic dissection, demonstrate an annual increase of 3 mm or have significant aortic regurgitation, then aortic root surgery is warranted when diameters exceed 45 mm [29]. Hormonal changes during pregnancy significantly increase risk of aortic dissection. Hence, women of child-bearing age who are keen to have a family are recommended surgery prior to pregnancy. These guidelines are also applicable to patients with Ehlers-Danlos syndrome and Loeys-Dietz syndrome.
Sinus of Valsalva aneurysms are rare; reported in 0.09% of autopsy series [30]. This condition affects commonly the right coronary sinus to a lesser degree the non-coronary sinus; involvement of all three sinuses is reported but exceedingly uncommon [31]. While idiopathic in majority, endocarditis is a rare cause [32]. Surgery is indicated to prevent rupture [32]. Rupture is often into an adjacent heart chamber with high-out heat failure [33]. Surgery consists of patch closure of the involved sinus. Approach can be from the aorta as well as via the other heart chamber that the fistula opens [30].
Acute aortic dissection is a high-risk aortic catastrophe which occurs in 5–30/1,000,000 patient annually [37]. Almost 1/5th die before reaching the emergency [38]. The initiating factor is often uncontrolled hypertension. Patients may have an intra-mural hematoma prior to developing dissection.
Aortic dissection is classified according to the time after the start of symptoms, being acute if the time frame between the onset of symptoms and presentation is less than 14 days, and chronic if this period is more than 14 days [34]. Anatomical classification is based on the location and extension of the primary tear (Figure 2). Dr. DeBakey and colleagues [35] described a method of classification that differentiates the aortic segments involved into: Type I, when the dissections is involving all the aortic segments, while Type II, when the dissection is confined to the ascending aorta, while Type III, when the dissection process is affecting the descending thoracic aorta. A more functional classification was introduced by the Stanford University; type A if the dissection involves the ascending aorta, type B if it does not [37].
The anatomical classification of aortic dissection according to the location of the primary tear and the extent of the aortic segment involved are illustrated [
The devastating complications that may occur with aortic dissection including organ malperfusion syndromes, acute aortic regurgitation, pericardial tamponade and stroke [38]. Surgery is currently the gold standard for acute care of type A aortic dissection [38].
Bentall and de Bono described their technique of aortic root replacement with a synthetic tube graft and contained prosthetic valve [39]. The coronary ostia were implanted in an end to side fashion without coronary mobilization [39]. Bleeding and pseudo-aneurysms were important complications with their procedure [40]. The present method of coronary mobilization and anastomosis was introduced by Nicholas Kouchoukas [14].
Use of improved graft substitutes and local hemostatic agents have made this procedure safer [41]. Results are good in centers performing these procedures in high volume [40].
The Bentall procedure in younger patients is often performed with a mechanical valve conduit. Appropriate anti-coagulation is important to maintain event-free survival [42]. A recent meta-analysis of 7600 [42] patients who had a mechanical valve conduit reported reoperation rates of Bentall procedure using mechanical valve conduits that the annual linearized rate of occurrence of aortic root re-operation 0.45% (0.039–0.59%). Late mortality was 2.02% (1.77–2.31%) and for hemorrhage was 0.64% (0.47–0.87%) During a mean follow up of 6 years.
However, in older patients, or those who refuse/have contraindications for anti-coagulation, a biologic valve substitute can be used [43]. Gaudino and colleagues demonstrated in a propensity matched cohorts that included patients who underwent aortic root replacement utilizing mechanical valved conduit versus biological valved conduit versus valve sparing procedure that the type of procedure did not influence early or late outcome, however rate of aortic re-operation was 0, 2.4, 7.3% at 5 years for mechanical, biological valved conduits and valve sparing procedure, respectively [43].
Aortic root replacement with cryopreserved homograft tissue is often used for patients with an infected aortic root [44]. The structure of the homograft that includes the muscular part of the left ventricular outflow tract, the anterior mitral leaflet and the aorto-mitral continuity; these provide additional tissue to fill gaps created by aggressive debridement while treating endocarditis [44, 45]. Homograft provide excellent hemodynamics and do not need anti-coagulation. Reports demonstrate improved left ventricular mass regression and ejection fraction after homograft root replacement [46]. However, we would caution their use in young patients. Valve degeneration and subsequent need for re-operation is often inversely proportional to age at implant [44] (Figure 3).
The insertion of cryopreserved aortic homograft is indicated [
We feel that appropriate debridement rather than prosthesis selection determines outcome in patients with aortic root abscess. Jassar et al. reported similar rates of reinfection and reoperation in 134 patients who had aortic root replacement using either cryopreserved homograft, biological or mechanical valved conduits [47].
Stent-less valve conduit (Freestyle™ valve conduit, Medtronic Corporation, Minnesota, USA) are commercially easily available when compared to homograft tissue. Thus, in recent years, they are the prosthesis of choice for aortic root replacement in the elderly or those with an infective etiology [49]. Hemodynamics match those of homograft, especially in patients with a small aortic root [50]. The sinus structure of these valves mirrors the native aortic root; an additional benefit when compared to a stented valve conduit [49]. However, unlike stented bio-prostheses, the mechanism of failure of these valves is often leaflet tears [51]. These can occur suddenly leading to acute aortic regurgitation and left heart failure. LeMaire and colleagues demonstrated in 132 patients who had porcine bioroot replacement that there was no structural valve dysfunction in any case during the 5 year follow up period [52] (Figure 4).
The free style porcine bioprosthesis with re-implantation of the coronary buttons is demonstrated [
Here are the relevant steps that we use for our root replacement procedures. These steps remain the same irrespective of the type of prosthesis (mechanical valved-conduit or bioprosthesis):
We routinely cannulate the right axillary artery for arterial access in cardiopulmonary bypass in all patients with ascending aortic involvement with aneurysmal disease and certainly in all patients with aortic dissection. Our preferred method is direct cannulation of the axillary artery with a straight cannula (usually 18 or 20Fr); otherwise, an 8 mm vascular graft anastomosed in end-to-side manner to the vessel is used.
Upon median sternotomy, pericardium is opened and suspended. Ascending aorta is prepared depending on distal extend of aortic intervention. If feasible, ascending aorta is freed of attachments from the right PA posteriorly and main PA to on the left and taken with an umbilical tape which facilitates further manipulations of the ascending aorta. During this step, it is important to stay close to the aortic wall to avoid injury to the pulmonary artery. For primary aortic root replacement, it is almost always possible to identify and follow such connective tissue plane between the aorta and the pulmonary artery. For a redo operation, it is more difficult and carries some serious risks. We prefer to use cautery dissection rather than scissors or blunt dissection as we feel this technique reduces postoperative bleeding. Small arterial and venous branches are often present between the aorta and pulmonary artery, particularly as one proceeds with dissection more proximally. These are divided between clips. This initial dissection is preferably done prior to full heparinization.
Once the ascending aorta is mostly free of attachments and likely looped with an atraumatic tape, we give IV Heparin and cannulate aorta or the right axillary artery and right atrium for cardiopulmonary bypass. We always use retrograde cardioplegia delivered into the coronary sinus and use either a PA or an LV vent inserted via the right superior pulmonary vein.
Once aorta is cross-clamped and heart is arrested with a combination of antegrade and retrograde cardioplegia, the aorta is transected in mid portion. Clear identification of the ostium of the right coronary artery (RCA) is required, so that the initial cut through the ascending aorta is placed far enough away from the RCA ostium. It is also important to divide ascending aorta in a way that there is at least a couple of centimeters of the aortic wall above the ostium of the left main coronary artery (LMCA).
At this stage we place 4–0 silk stay sutures at the tips of the aortic valve commissures. Aortic valve is then excised, annulus is sized. When a Freestyle valve conduit is used, there is no need to have a cylinder-shaped sizer pass into the LV through the annulus as the prosthetic valve will be fixed in the supra annular position. As such, a larger prosthetic valve can be used. Sizing for a mechanical valve conduit has to be done according to the manufacturer recommendations as most of the mechanical valves are designed for an intra-annular position.
At this stage, additional dissection is carried out between the aortic root and pulmonary artery and RVOT. Unlike for a valve sparing aortic root replacement with root re-implantation, this dissection for a Bentall operation is limited to clearing the space for a safe fashioning of the coronary buttons, particularly, for the LMCA. There is no need to dissect deep between the aortic root and the RVOT to expose the aortic annulus from the outside.
Preparation of the coronary buttons is similar for any aortic root replacement operation. Normally, we start with the left coronary button. Here are the critical points and pitfalls:
Prior to cutting the button out of the corresponding sinus, we recommend marking up the “12 o’clock” point—the top of the button is marked with marker pen or a prolene stitch. This would allow for a precise orientation of the button when re-implanted into a sinus of the valve conduit. Tension or kinking or rotation of the re-implanted button may result in coronary ischemia and create a serious problem at the conclusion of the operation;
Once the top of the button is marked, we start with cutting the left coronary sinus from the top of the commissure between the left and non-coronary cusps down towards the annulus of the left sinus. Most of the time, the actual opening of the LMCA is kept in the middle of the button on all four aspects of it. In larger root aneurysms, there is occasionally too much tissue in the sinus, so attention should be paid to the size of the button 0.5–1.0 cm off of the edge of the ostium of the LMCA is usually enough for a safe button re-implantation;
The initial cut has to keep ~5–7 mm of the sinus tissue in place, so as we come down along the commissure, the tip of the scissors is turned away from the annulus and the cut is curved around the lower edge of the coronary artery ostium;
Next, we start the cut from the top of the commissure between the left and right sinuses. It is critical to fully understand the course of the LMCA to avoid injury to it in case of intramural passing in the aortic wall. Large coronary probe can be placed in the lumen to check the direction of the LMCA. The cut is then curved away from the annulus leaving the same 5–7 mm of the sinus tissue in place and completing a “button” by connecting with incision made from the other direction.
Great care has to be taken here as to not apply any excessive pulling on any portion of the button while making the cuts as this can lead to distortion and asymmetric fashioning of the button making safe re-implantation difficult;
Once the LMCA button is fashioned out, the connective tissue and fat between the lower edge of the button and rim of the sinus remnant and the annulus is divided with cautery to provide just enough mobility for the coronary button to facilitate re-implanting process;
Preparation of the RCA button follows the same general principles as described for the LMCA button—marking the top to maintain orientation, avoiding excessive pulling while fashioning the button, maintaining enough sinus tissue on the button itself as well as on the annulus.
After both buttons are prepared, inflow suture line is created. For a mechanical prosthesis, we use 2–0 pledgeted stitches with the pledgets placed in a suppraannular position. It is important to ensure that the pledgets are lined next to each other without much gap as this will ensure hemostasis. Some use a secondary continuous prolene layer to seal this anastomosis. With Freestyle bioprosthesis, we use simple 2–0 interrupted stitches. A pericardial strip is then gently placed between the loops prior to knotting. The pericardial strip acts as a gusset and also provides additional hemostasis to this layer.
Additional important point has to be made for cases when Freestyle conduit is used. Orientation of the valve is of critical importance prior to drawing inflow sutures through the valve. We recommend rotating the valve 120°clockwise from its natural orientation, so that a non-coronary sinus of the valve would now become a left coronary sinus into which LMCA is re-implanted. Such rotation will make left coronary sinus of the valve a new right sinus into which RCA button will be re-implanted. The right button of the Freestyle remains unused and has to be over sawn with 4–0 or 5–0 pledgeted sutures.
Once an opening in the new left sinus is made with coronary punch, the coronary button is anastomosed using 5–0 prolene. We use a technique of plicating the wall of the coronary button. A second layer is then used to ensure further hemostasis. Re-implantation of the right button is performed in a similar fashion. Once the aortic root is replaced and buttons re-implanted, we use local hemostatic glue to provide further sealing of needle holes.
Then depending upon the extent of aortic dilatation, the ascending aorta is replaced and attached to the proximal neo-root.
Once the patient is off cardiopulmonary bypass, the right axillary artery is carefully repaired between hemostatic clamps. A good Doppler signal is essential after repair.
It is important to ensure absolute hemostasis in the operating room prior to transferring the patient to the intensive care unit.
Sparing the patient’s native aortic valve while replacing the aortic root is an alternative option in selected patients [54]. This naturally avoids need for anti-coagulation [9]. After an initial pre-operative trans-esophageal echocardiogram, the valve leaflets should be examined prior to proceeding with valve-sparing approach. Leaflet quality is fundamental to event-free survival in these patients.
David and Feindel [9] recommend a technique of securing the aortic valve leaflets without the rigid synthetic graft. This technique prevents future annular dilatation. Dr. David et al. report excellent valve competence among 146 Marfan’s syndrome patients with valve-sparing aortic root replacement with their technique [55] (Figure 5).
The aortic re-implantation technique is illustrated (a). As demonstrated, the entire aortic annulus, aortic valve and a rim of aortic wall are all secured inside the synthetic graft, with re-implantation of the coronary buttons to the new graft (b). The distal part of the synthetic graft is anastomosed to the ascending aorta [
All preparatory steps for re-implantation procedure are similar as described above. Below are the critical steps unique for the re-implantation:
Once coronary buttons are prepared as described above, aortic annulus has to be dissected out so that on all sinuses the annulus can be exposed for precise placement of the sub-annular sutures. We use cautery at low settings to perform this dissection. The most difficult part of this step is to separate the root and the annulus from the RVOT. There is always a connective tissue plane between these structures which allows safe dissection down to the annulus;
Sizing of the annulus can be done by many previously described methods. We prefer to follow a simple rule that most of the male with BSA of ~2.0–2.2 m2 should have annulus of 23–25 mm, and so 3–5 mm larger diameter of the vascular graft would be chosen (most commonly, 28 or 30 mm). For a smaller female patient with a BSA of 1.8–2.0 m2 an annular diameter is 21–23 mm and accordingly 26–28 mm grafts are usually appropriate;
We prefer “Valsalva” grafts (Vascutek) which we trim on the inflow side leaving 2–3 mm (a couple of rings) of the grafts for the sub-annular sutures to be drawn through;
We then place sub-annular 2–0 ticron sutures with small pledgetes 2–3 mm below the annulus in the following order: the nadir of the non-coronary sinus; the left-to-non commissure; the nadir of the left coronary sinus; the nadir of the right coronary sinus; the right to-non commissure (avoiding membranous septum); extra sutures placed between the ones mentioned above can added in between the nadirs and the commissural sutures to a total of 6–9 sutures if needed;
Inflow edge of the Valsalva graft then marked to assure precise positioning of the sub annular sutures on the vascular graft;
Sub annular sutures are then drawn through the graft according to the markings;
In re-implantation procedure, instead of silk stay sutures at the tips of the commissures, we use 4–0 prolene with large needles. These stay sutures are brought inside of the graft at this stage, so that the graft is brought over, seated and fixed over the annulus by tying the sub-annular sutures;
Prolene sutures from the tips of the commissures are then drawn through the graft at the junction of the horizontal and vertical parts of the Valsalva graft;
Re-implantation of the aortic root is then started by suturing of the remnant of the coronary sinuses inside of the Valsalva graft. We routinely use double armed 4–0 or 5–0 Prolene and start the suture line just off the bottom of the sinus and proceeding towards the commissure between left and non-coronary sinuses bringing the stich to the top of the commissure on the outside. The other arm of the suture is then brought up the same way to the top of the left and right commissure;
Similar technique is then used to re-implant the right and finally the left coronary sinuses;
All three stay sutures are then tied and cut on top of the commissures followed by “working” sutures brought to the top of the corresponding commissures;
The valve is then checked for AI by filling the root with cold saline;
Coronary buttons are then re-implanted into corresponding sinuses as described above.
Yacoub developed his technique of creating three longitudinal neo-sinuses [56]. These are sutured to the aorta and then coronary buttons are re-implanted. This method does not protect against annular dilatation [9]. In this technique the synthetic graft is fashioned into three longitudinal neo sinuses, then after securing the valve commissures to the neo graft, the margins of the neo sinuses are anastomosed to the rim of the aortic wall. Coronary button re-implantation to the neo sinuses follows, and distal anastomosis of the neo graft to the ascending aorta completed the procedure (Figure 6).
The aortic remodeling technique is described. As shown, the aortic commissures are sewn to the graft, which is fashioned to form neo sinuses. Then the created tongues are sewn to the rim of the aortic wall. Coronary buttons re-implantation follows, then distal anastomosis between the graft and the ascending aorta is performed [
Aortic root operations reflect complex anatomic relations and physiologic interactions between the left ventricle and components of the aortic root—ventriculo-arterial junction (aortic annulus), sinuses of Valsalva, leaflets of the aortic valve, and sino-tubular junction. Whether a surgeon contemplates classic aortic root replacement with mechanical or tissue valve conduits or any of the valve sparing root reconstructions, close familiarity with the structure and function of the aortic root is necessary. Dreaded complications of such complex procedures (bleeding, most importantly) can be avoided by meticulous surgical technique in combination with intimate knowledge of the anatomical details of the aortic root and surrounding structures.
The views expressed are those of the authors and do not necessarily reflect the position or policy of the Department of Veteran Affairs or the United States Government.
The technique of aortic root surgery has undergone many improvements during the past decades. These are a direct result of better understanding of the functional hemodynamics of the aortic root coupled with significant improvement in imaging. We present here a brief overview of pathology involving the aortic root with a special focus on the surgical aspects in these operative procedures. Our chapter includes tips on use of mechanical valve conduits, homograft, and stent-less valve prostheses as well as techniques implementing a valve-sparing approach.
Improved imaging and computer simulation has increased our understanding of the aortic root anatomy, structure and function. Aortic root had been described as the vascular tube supporting the aortic valve leaflets and connecting the left ventricular outflow tract inferiorly to the sinotubular junction superiorly [1]. Two thirds of the lower segment (aortic annulus) of the aortic root is attached to the interventricular septum while the remainder is attached to the fibrous part of the anterior mitral valve leaflet [2]. This tubular structure (Figure 1) encompasses the aortic valve leaflets, coronary ostia, commissures, interleaflet triangles and the sinuses [1]. All these components link together to act as a single unit. It is now clear, that this is much more than just a passive unit governed by pressure changes across the valve [3, 4]. The geometric relationship of the valve leaflets as well as individual lengths are important for it to work as a single efficient hemodynamic unit [5].
Opened aortic root section. Sinotubular junction is indicated by the open arrows, small arrows indicating the coronary ostia (left and right), broken lines indicating the fibrous skeleton between the aortic and mitral valves. L, R, and N mark the left, right and the non-coronary cusps, respectively [
The dilated portion of the aortic wall between the aortic annulus and sino-tubular junction is known as the sinus of Valsalva. These sinuses are named according to the relationship of the origin of the coronary ostia from the root that is left, right or non-coronary sinuses. The sinuses are labelled corresponding to their coronary ostia. One of the important roles provided by these sinuses is preventing obstruction of the coronary ostia during movement of the aortic valve leaflets against the aortic wall, so that coronary blood flow is maintained [5]. An important function is prevention of ostial obstruction during systole when the aortic valve is open [7]. Generation of Eddy currents during early systole prevents the aortic leaflets from touching the aortic wall [8].
The aortic valve leaflets which are inserted at their bases in a semilunar fashion to the aortic annulus. They allow uni-directional flow of blood from the left ventricle to the aorta. Aortic valve leaflets are variable in size and number, the non-coronary cusp being the largest compared to the left or right aortic valve cusps. The most common variation is the bicuspid aortic valve, which consists of a semi-lunar opening due to the presence of two leaflets, and the commonest deviation from the normal tri-leaflet pattern is the known congenital anomaly called bicuspid aortic valve [9]. The attachment of the curved aortic valve leaflets form the triangular space named as the interleaflet triangles, the apices of these triangles is known as the valve commissures which are at the level of the sinotubular junction [10]. Aortic valve competence depends on the overlap between these adjacent free margins of the leaflets.
The aortic valve annulus represents the ventriculo-aortic junction which is a complex structure and universally accepted term as aortic annulus [9]. The basic attachments of the aortic valve leaflets at the aortic annulus comprise muscular and fibrous parts [5]. The right aortic valve leaflet attaches to both the membranous and the interventricular septa, while the non-coronary leaflet attaches to the membranous septum and the fibrous skeleton of the anterior mitral valve leaflet, and the left aortic valve leaflet attaches to the fibrous skeleton of the anterior mitral valve leaflet and partly to the interventricular septum [9]. Connective tissue disorders that involve the fibrous skeleton of the aortic root lead to alteration in normal geometry. Damage begets further damage leading to significant valve distortion and subsequent clinical sequelae [9].
Connective tissue disorder is among the most common non-infective etiology of aortic root pathology. Marfan’s syndrome, Ehlers-Danlos syndrome and Loeys-Dietz syndrome predominantly involve the elastic aortic root [11, 12, 13]. Marfan’s syndrome is an autosomal dominant disorder characterized by mutation in the gene encoding for fibrillin-1. It leads to cystic medial necrosis and involves all connective tissue containing high percentages of elastin. Disease is multi-systemic; however aortic dissection remains an important cause of mortality [14]. The probability of aortic emergencies increases significantly when transverse aortic diameters is more than 45 mm [15].
Patients with vascular type of the Ehlers-Danlos syndrome are prone to aortic dissection rather than aneurysm, while patients with Loeys-Dietz syndrome are liable to have aortic aneurysm and dissection at younger age [11, 16, 17].
Bicuspid aortic valve (BAV) is present in 1–2% of the population; almost 40% also have thoracic aortic dilatation at the time of presentation [18].
While the inheritance of BAV is not clearly defined, gene sequence defects leading to aortopathy is more prevalent in this population [19]. Degenerative changes in the tunica media with reduced elastin increases risk of dissection these patients [20, 21].
Giant cell arteritis and Takayasu arteritis are rarer causes of aneurysmal dilatation/aortic dissection [22, 23]. While temporal artery involvement is the hallmark of giant cell arteritis, at least 0.15% also had aortic dissection in an autopsy series [22]. Takayasu arteritis on the other hand is an inflammatory disorder that leads to large vessel inflammation characterized by fibrosis and narrowing, which may lead to aneurysmal formation and possible rupture [23]. Corticosteroids are used for acute therapy and surgery is performed once active inflammation subsides [24, 25].
Cystic medial necrosis (CMN) is a pathological term that is characterized by the formation of cyst like lesions in the medial layer of the large arteries with accumulation of basophilic substances [26].
The American Association of Thoracic Surgeons present following guidelines regarding surgery for the ascending aorta [27]:
Surgical repair should be performed when aortic diameter (root or ascending aorta) is 55 mm or more.
Surgical repair should be performed when aortic diameter (root or ascending aorta) is 50 mm or more in the presence of certain risk factors such as: root phenotype bicuspid aortic valve, uncontrolled hypertension, history of aortic dissection or sudden death in the family, annual enlargement of 3 mm or more in the size of the aortic aneurysm, or predominantly aortic regurgitation.
Surgical repair should be performed when aortic diameter (root or ascending aorta) is 50 mm or more in patients with low operative risk being performed by experienced aortic surgical team in centers with well-established surgical outcomes
Surgical repair should be performed when aortic diameter (root or ascending aorta) is 45 mm or more in patients undergoing concomitant other cardiac surgery.
Patients with Marfan’s syndrome or Marfanoid habitus should be operated when their aortic root/ascending aorta is larger than 50 mm in maximal transverse diameter [28]. Gott and colleagues [27, 28] reported an improved 30-day survival in a series of 675 patients with Marfan’s syndrome who underwent elective compared to urgent or emergency replacement of the aortic root.
If patients have a family history of aortic dissection, demonstrate an annual increase of 3 mm or have significant aortic regurgitation, then aortic root surgery is warranted when diameters exceed 45 mm [29]. Hormonal changes during pregnancy significantly increase risk of aortic dissection. Hence, women of child-bearing age who are keen to have a family are recommended surgery prior to pregnancy. These guidelines are also applicable to patients with Ehlers-Danlos syndrome and Loeys-Dietz syndrome.
Sinus of Valsalva aneurysms are rare; reported in 0.09% of autopsy series [30]. This condition affects commonly the right coronary sinus to a lesser degree the non-coronary sinus; involvement of all three sinuses is reported but exceedingly uncommon [31]. While idiopathic in majority, endocarditis is a rare cause [32]. Surgery is indicated to prevent rupture [32]. Rupture is often into an adjacent heart chamber with high-out heat failure [33]. Surgery consists of patch closure of the involved sinus. Approach can be from the aorta as well as via the other heart chamber that the fistula opens [30].
Acute aortic dissection is a high-risk aortic catastrophe which occurs in 5–30/1,000,000 patient annually [37]. Almost 1/5th die before reaching the emergency [38]. The initiating factor is often uncontrolled hypertension. Patients may have an intra-mural hematoma prior to developing dissection.
Aortic dissection is classified according to the time after the start of symptoms, being acute if the time frame between the onset of symptoms and presentation is less than 14 days, and chronic if this period is more than 14 days [34]. Anatomical classification is based on the location and extension of the primary tear (Figure 2). Dr. DeBakey and colleagues [35] described a method of classification that differentiates the aortic segments involved into: Type I, when the dissections is involving all the aortic segments, while Type II, when the dissection is confined to the ascending aorta, while Type III, when the dissection process is affecting the descending thoracic aorta. A more functional classification was introduced by the Stanford University; type A if the dissection involves the ascending aorta, type B if it does not [37].
The anatomical classification of aortic dissection according to the location of the primary tear and the extent of the aortic segment involved are illustrated [
The devastating complications that may occur with aortic dissection including organ malperfusion syndromes, acute aortic regurgitation, pericardial tamponade and stroke [38]. Surgery is currently the gold standard for acute care of type A aortic dissection [38].
Bentall and de Bono described their technique of aortic root replacement with a synthetic tube graft and contained prosthetic valve [39]. The coronary ostia were implanted in an end to side fashion without coronary mobilization [39]. Bleeding and pseudo-aneurysms were important complications with their procedure [40]. The present method of coronary mobilization and anastomosis was introduced by Nicholas Kouchoukas [14].
Use of improved graft substitutes and local hemostatic agents have made this procedure safer [41]. Results are good in centers performing these procedures in high volume [40].
The Bentall procedure in younger patients is often performed with a mechanical valve conduit. Appropriate anti-coagulation is important to maintain event-free survival [42]. A recent meta-analysis of 7600 [42] patients who had a mechanical valve conduit reported reoperation rates of Bentall procedure using mechanical valve conduits that the annual linearized rate of occurrence of aortic root re-operation 0.45% (0.039–0.59%). Late mortality was 2.02% (1.77–2.31%) and for hemorrhage was 0.64% (0.47–0.87%) During a mean follow up of 6 years.
However, in older patients, or those who refuse/have contraindications for anti-coagulation, a biologic valve substitute can be used [43]. Gaudino and colleagues demonstrated in a propensity matched cohorts that included patients who underwent aortic root replacement utilizing mechanical valved conduit versus biological valved conduit versus valve sparing procedure that the type of procedure did not influence early or late outcome, however rate of aortic re-operation was 0, 2.4, 7.3% at 5 years for mechanical, biological valved conduits and valve sparing procedure, respectively [43].
Aortic root replacement with cryopreserved homograft tissue is often used for patients with an infected aortic root [44]. The structure of the homograft that includes the muscular part of the left ventricular outflow tract, the anterior mitral leaflet and the aorto-mitral continuity; these provide additional tissue to fill gaps created by aggressive debridement while treating endocarditis [44, 45]. Homograft provide excellent hemodynamics and do not need anti-coagulation. Reports demonstrate improved left ventricular mass regression and ejection fraction after homograft root replacement [46]. However, we would caution their use in young patients. Valve degeneration and subsequent need for re-operation is often inversely proportional to age at implant [44] (Figure 3).
The insertion of cryopreserved aortic homograft is indicated [
We feel that appropriate debridement rather than prosthesis selection determines outcome in patients with aortic root abscess. Jassar et al. reported similar rates of reinfection and reoperation in 134 patients who had aortic root replacement using either cryopreserved homograft, biological or mechanical valved conduits [47].
Stent-less valve conduit (Freestyle™ valve conduit, Medtronic Corporation, Minnesota, USA) are commercially easily available when compared to homograft tissue. Thus, in recent years, they are the prosthesis of choice for aortic root replacement in the elderly or those with an infective etiology [49]. Hemodynamics match those of homograft, especially in patients with a small aortic root [50]. The sinus structure of these valves mirrors the native aortic root; an additional benefit when compared to a stented valve conduit [49]. However, unlike stented bio-prostheses, the mechanism of failure of these valves is often leaflet tears [51]. These can occur suddenly leading to acute aortic regurgitation and left heart failure. LeMaire and colleagues demonstrated in 132 patients who had porcine bioroot replacement that there was no structural valve dysfunction in any case during the 5 year follow up period [52] (Figure 4).
The free style porcine bioprosthesis with re-implantation of the coronary buttons is demonstrated [
Here are the relevant steps that we use for our root replacement procedures. These steps remain the same irrespective of the type of prosthesis (mechanical valved-conduit or bioprosthesis):
We routinely cannulate the right axillary artery for arterial access in cardiopulmonary bypass in all patients with ascending aortic involvement with aneurysmal disease and certainly in all patients with aortic dissection. Our preferred method is direct cannulation of the axillary artery with a straight cannula (usually 18 or 20Fr); otherwise, an 8 mm vascular graft anastomosed in end-to-side manner to the vessel is used.
Upon median sternotomy, pericardium is opened and suspended. Ascending aorta is prepared depending on distal extend of aortic intervention. If feasible, ascending aorta is freed of attachments from the right PA posteriorly and main PA to on the left and taken with an umbilical tape which facilitates further manipulations of the ascending aorta. During this step, it is important to stay close to the aortic wall to avoid injury to the pulmonary artery. For primary aortic root replacement, it is almost always possible to identify and follow such connective tissue plane between the aorta and the pulmonary artery. For a redo operation, it is more difficult and carries some serious risks. We prefer to use cautery dissection rather than scissors or blunt dissection as we feel this technique reduces postoperative bleeding. Small arterial and venous branches are often present between the aorta and pulmonary artery, particularly as one proceeds with dissection more proximally. These are divided between clips. This initial dissection is preferably done prior to full heparinization.
Once the ascending aorta is mostly free of attachments and likely looped with an atraumatic tape, we give IV Heparin and cannulate aorta or the right axillary artery and right atrium for cardiopulmonary bypass. We always use retrograde cardioplegia delivered into the coronary sinus and use either a PA or an LV vent inserted via the right superior pulmonary vein.
Once aorta is cross-clamped and heart is arrested with a combination of antegrade and retrograde cardioplegia, the aorta is transected in mid portion. Clear identification of the ostium of the right coronary artery (RCA) is required, so that the initial cut through the ascending aorta is placed far enough away from the RCA ostium. It is also important to divide ascending aorta in a way that there is at least a couple of centimeters of the aortic wall above the ostium of the left main coronary artery (LMCA).
At this stage we place 4–0 silk stay sutures at the tips of the aortic valve commissures. Aortic valve is then excised, annulus is sized. When a Freestyle valve conduit is used, there is no need to have a cylinder-shaped sizer pass into the LV through the annulus as the prosthetic valve will be fixed in the supra annular position. As such, a larger prosthetic valve can be used. Sizing for a mechanical valve conduit has to be done according to the manufacturer recommendations as most of the mechanical valves are designed for an intra-annular position.
At this stage, additional dissection is carried out between the aortic root and pulmonary artery and RVOT. Unlike for a valve sparing aortic root replacement with root re-implantation, this dissection for a Bentall operation is limited to clearing the space for a safe fashioning of the coronary buttons, particularly, for the LMCA. There is no need to dissect deep between the aortic root and the RVOT to expose the aortic annulus from the outside.
Preparation of the coronary buttons is similar for any aortic root replacement operation. Normally, we start with the left coronary button. Here are the critical points and pitfalls:
Prior to cutting the button out of the corresponding sinus, we recommend marking up the “12 o’clock” point—the top of the button is marked with marker pen or a prolene stitch. This would allow for a precise orientation of the button when re-implanted into a sinus of the valve conduit. Tension or kinking or rotation of the re-implanted button may result in coronary ischemia and create a serious problem at the conclusion of the operation;
Once the top of the button is marked, we start with cutting the left coronary sinus from the top of the commissure between the left and non-coronary cusps down towards the annulus of the left sinus. Most of the time, the actual opening of the LMCA is kept in the middle of the button on all four aspects of it. In larger root aneurysms, there is occasionally too much tissue in the sinus, so attention should be paid to the size of the button 0.5–1.0 cm off of the edge of the ostium of the LMCA is usually enough for a safe button re-implantation;
The initial cut has to keep ~5–7 mm of the sinus tissue in place, so as we come down along the commissure, the tip of the scissors is turned away from the annulus and the cut is curved around the lower edge of the coronary artery ostium;
Next, we start the cut from the top of the commissure between the left and right sinuses. It is critical to fully understand the course of the LMCA to avoid injury to it in case of intramural passing in the aortic wall. Large coronary probe can be placed in the lumen to check the direction of the LMCA. The cut is then curved away from the annulus leaving the same 5–7 mm of the sinus tissue in place and completing a “button” by connecting with incision made from the other direction.
Great care has to be taken here as to not apply any excessive pulling on any portion of the button while making the cuts as this can lead to distortion and asymmetric fashioning of the button making safe re-implantation difficult;
Once the LMCA button is fashioned out, the connective tissue and fat between the lower edge of the button and rim of the sinus remnant and the annulus is divided with cautery to provide just enough mobility for the coronary button to facilitate re-implanting process;
Preparation of the RCA button follows the same general principles as described for the LMCA button—marking the top to maintain orientation, avoiding excessive pulling while fashioning the button, maintaining enough sinus tissue on the button itself as well as on the annulus.
After both buttons are prepared, inflow suture line is created. For a mechanical prosthesis, we use 2–0 pledgeted stitches with the pledgets placed in a suppraannular position. It is important to ensure that the pledgets are lined next to each other without much gap as this will ensure hemostasis. Some use a secondary continuous prolene layer to seal this anastomosis. With Freestyle bioprosthesis, we use simple 2–0 interrupted stitches. A pericardial strip is then gently placed between the loops prior to knotting. The pericardial strip acts as a gusset and also provides additional hemostasis to this layer.
Additional important point has to be made for cases when Freestyle conduit is used. Orientation of the valve is of critical importance prior to drawing inflow sutures through the valve. We recommend rotating the valve 120°clockwise from its natural orientation, so that a non-coronary sinus of the valve would now become a left coronary sinus into which LMCA is re-implanted. Such rotation will make left coronary sinus of the valve a new right sinus into which RCA button will be re-implanted. The right button of the Freestyle remains unused and has to be over sawn with 4–0 or 5–0 pledgeted sutures.
Once an opening in the new left sinus is made with coronary punch, the coronary button is anastomosed using 5–0 prolene. We use a technique of plicating the wall of the coronary button. A second layer is then used to ensure further hemostasis. Re-implantation of the right button is performed in a similar fashion. Once the aortic root is replaced and buttons re-implanted, we use local hemostatic glue to provide further sealing of needle holes.
Then depending upon the extent of aortic dilatation, the ascending aorta is replaced and attached to the proximal neo-root.
Once the patient is off cardiopulmonary bypass, the right axillary artery is carefully repaired between hemostatic clamps. A good Doppler signal is essential after repair.
It is important to ensure absolute hemostasis in the operating room prior to transferring the patient to the intensive care unit.
Sparing the patient’s native aortic valve while replacing the aortic root is an alternative option in selected patients [54]. This naturally avoids need for anti-coagulation [9]. After an initial pre-operative trans-esophageal echocardiogram, the valve leaflets should be examined prior to proceeding with valve-sparing approach. Leaflet quality is fundamental to event-free survival in these patients.
David and Feindel [9] recommend a technique of securing the aortic valve leaflets without the rigid synthetic graft. This technique prevents future annular dilatation. Dr. David et al. report excellent valve competence among 146 Marfan’s syndrome patients with valve-sparing aortic root replacement with their technique [55] (Figure 5).
The aortic re-implantation technique is illustrated (a). As demonstrated, the entire aortic annulus, aortic valve and a rim of aortic wall are all secured inside the synthetic graft, with re-implantation of the coronary buttons to the new graft (b). The distal part of the synthetic graft is anastomosed to the ascending aorta [
All preparatory steps for re-implantation procedure are similar as described above. Below are the critical steps unique for the re-implantation:
Once coronary buttons are prepared as described above, aortic annulus has to be dissected out so that on all sinuses the annulus can be exposed for precise placement of the sub-annular sutures. We use cautery at low settings to perform this dissection. The most difficult part of this step is to separate the root and the annulus from the RVOT. There is always a connective tissue plane between these structures which allows safe dissection down to the annulus;
Sizing of the annulus can be done by many previously described methods. We prefer to follow a simple rule that most of the male with BSA of ~2.0–2.2 m2 should have annulus of 23–25 mm, and so 3–5 mm larger diameter of the vascular graft would be chosen (most commonly, 28 or 30 mm). For a smaller female patient with a BSA of 1.8–2.0 m2 an annular diameter is 21–23 mm and accordingly 26–28 mm grafts are usually appropriate;
We prefer “Valsalva” grafts (Vascutek) which we trim on the inflow side leaving 2–3 mm (a couple of rings) of the grafts for the sub-annular sutures to be drawn through;
We then place sub-annular 2–0 ticron sutures with small pledgetes 2–3 mm below the annulus in the following order: the nadir of the non-coronary sinus; the left-to-non commissure; the nadir of the left coronary sinus; the nadir of the right coronary sinus; the right to-non commissure (avoiding membranous septum); extra sutures placed between the ones mentioned above can added in between the nadirs and the commissural sutures to a total of 6–9 sutures if needed;
Inflow edge of the Valsalva graft then marked to assure precise positioning of the sub annular sutures on the vascular graft;
Sub annular sutures are then drawn through the graft according to the markings;
In re-implantation procedure, instead of silk stay sutures at the tips of the commissures, we use 4–0 prolene with large needles. These stay sutures are brought inside of the graft at this stage, so that the graft is brought over, seated and fixed over the annulus by tying the sub-annular sutures;
Prolene sutures from the tips of the commissures are then drawn through the graft at the junction of the horizontal and vertical parts of the Valsalva graft;
Re-implantation of the aortic root is then started by suturing of the remnant of the coronary sinuses inside of the Valsalva graft. We routinely use double armed 4–0 or 5–0 Prolene and start the suture line just off the bottom of the sinus and proceeding towards the commissure between left and non-coronary sinuses bringing the stich to the top of the commissure on the outside. The other arm of the suture is then brought up the same way to the top of the left and right commissure;
Similar technique is then used to re-implant the right and finally the left coronary sinuses;
All three stay sutures are then tied and cut on top of the commissures followed by “working” sutures brought to the top of the corresponding commissures;
The valve is then checked for AI by filling the root with cold saline;
Coronary buttons are then re-implanted into corresponding sinuses as described above.
Yacoub developed his technique of creating three longitudinal neo-sinuses [56]. These are sutured to the aorta and then coronary buttons are re-implanted. This method does not protect against annular dilatation [9]. In this technique the synthetic graft is fashioned into three longitudinal neo sinuses, then after securing the valve commissures to the neo graft, the margins of the neo sinuses are anastomosed to the rim of the aortic wall. Coronary button re-implantation to the neo sinuses follows, and distal anastomosis of the neo graft to the ascending aorta completed the procedure (Figure 6).
The aortic remodeling technique is described. As shown, the aortic commissures are sewn to the graft, which is fashioned to form neo sinuses. Then the created tongues are sewn to the rim of the aortic wall. Coronary buttons re-implantation follows, then distal anastomosis between the graft and the ascending aorta is performed [
Aortic root operations reflect complex anatomic relations and physiologic interactions between the left ventricle and components of the aortic root—ventriculo-arterial junction (aortic annulus), sinuses of Valsalva, leaflets of the aortic valve, and sino-tubular junction. Whether a surgeon contemplates classic aortic root replacement with mechanical or tissue valve conduits or any of the valve sparing root reconstructions, close familiarity with the structure and function of the aortic root is necessary. Dreaded complications of such complex procedures (bleeding, most importantly) can be avoided by meticulous surgical technique in combination with intimate knowledge of the anatomical details of the aortic root and surrounding structures.
The views expressed are those of the authors and do not necessarily reflect the position or policy of the Department of Veteran Affairs or the United States Government.
Edited by Jan Oxholm Gordeladze, ISBN 978-953-51-3020-8, Print ISBN 978-953-51-3019-2, 336 pages,
\nPublisher: IntechOpen
\nChapters published March 22, 2017 under CC BY 3.0 license
\nDOI: 10.5772/61430
\nEdited Volume
This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\\n\\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\\n\\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\\n\\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\\n\\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\\n\\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\\n\\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\\n\\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\\n\\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\\n\\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\\n\\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\\n\\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
\\n"}]'},components:[{type:"htmlEditorComponent",content:'This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\n\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\n\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\n\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\n\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\n\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\n\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\n\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
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\n\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\n\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\n\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
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As a reinforcement agent, calcium carbonate from avian eggshell waste was used, at 10 ph of micro particles, 125 μm. Admixtures were further processed in a single-screw extruder, using CO2 as physical blowing agent (PBA). Property investigations were performed by DSC, TGA, XRD, SEM, FTIR, and mechanical essays.",book:{id:"8352",slug:"use-of-gamma-radiation-techniques-in-peaceful-applications",title:"Use of Gamma Radiation Techniques in Peaceful Applications",fullTitle:"Use of Gamma Radiation Techniques in Peaceful Applications"},signatures:"Elizabeth C.L. Cardoso, Duclerc F. Parra, Sandra R. Scagliusi, Ricardo M. Sales, Fernando Caviquioli and Ademar B. 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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 is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. 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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}]},{type:"book",id:"7839",title:"Malaria",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7839.jpg",slug:"malaria",publishedDate:"December 11th 2019",editedByType:"Edited by",bookSignature:"Fyson H. Kasenga",hash:"91cde4582ead884cb0f355a19b67cd56",volumeInSeries:4,fullTitle:"Malaria",editors:[{id:"86725",title:"Dr.",name:"Fyson",middleName:"Hanania",surname:"Kasenga",slug:"fyson-kasenga",fullName:"Fyson Kasenga",profilePictureURL:"https://mts.intechopen.com/storage/users/86725/images/system/86725.jpg",biography:"Dr. Kasenga is a graduate of Tumaini University, Kilimanjaro Christian Medical College, Moshi, Tanzania and Umeå University, Sweden. He obtained a Master’s degree in Public Health and PhD in Public Health and Epidemiology. He has a background in Clinical Medicine and has taken courses at higher diploma levels in public health from University of Transkei, Republic of South Africa, and African Medical and Research Foundation (AMREF) in Nairobi, Kenya. Dr. Kasenga worked in different places in and outside Malawi, and has held various positions, such as Licensed Medical Officer, HIV/AIDS Programme Officer, HIV/AIDS resource person in the International Department of Diakonhjemet College, Oslo, Norway. He also managed an Integrated HIV/AIDS Prevention programme for over 5 years. He is currently working as a Director for the Health Ministries Department of Malawi Union of the Seventh Day Adventist Church. Dr. Kasenga has published over 5 articles on HIV/AIDS issues focusing on Prevention of Mother to Child Transmission of HIV (PMTCT), including a book chapter on HIV testing counseling (currently in press). Dr. Kasenga is married to Grace and blessed with three children, a son and two daughters: Happy, Lettice and Sungani.",institutionString:"Malawi Adventist University",institution:{name:"Malawi Adventist University",institutionURL:null,country:{name:"Malawi"}}}]}]},openForSubmissionBooks:{paginationCount:7,paginationItems:[{id:"11476",title:"Globalization and Sustainability - Recent Advances, New Perspectives and Emerging Issues",coverURL:"https://cdn.intechopen.com/books/images_new/11476.jpg",hash:"8d41fa5f3a5da07469bbc121594bfd3e",secondStepPassed:!0,currentStepOfPublishingProcess:4,submissionDeadline:"March 24th 2022",isOpenForSubmission:!0,editors:[{id:"335401",title:"Prof.",name:"Margherita",surname:"Mori",slug:"margherita-mori",fullName:"Margherita Mori"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11460",title:"Pluralistic Approaches for Conservation and Sustainability in Biodiversity",coverURL:"https://cdn.intechopen.com/books/images_new/11460.jpg",hash:"ab014f8ed1669757335225786833e9a9",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"April 22nd 2022",isOpenForSubmission:!0,editors:[{id:"101105",title:"Dr.",name:"Gopal",surname:"Shukla",slug:"gopal-shukla",fullName:"Gopal Shukla"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11475",title:"Food Security Challenges and Approaches",coverURL:"https://cdn.intechopen.com/books/images_new/11475.jpg",hash:"090302a30e461cee643ec49675c811ec",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"May 5th 2022",isOpenForSubmission:!0,editors:[{id:"292145",title:"Dr.",name:"Muhammad",surname:"Haseeb Ahmad",slug:"muhammad-haseeb-ahmad",fullName:"Muhammad Haseeb Ahmad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11450",title:"Environmental Impacts of COVID-19 Pandemic on the World",coverURL:"https://cdn.intechopen.com/books/images_new/11450.jpg",hash:"a58c7b02d07903004be70f744f2e1835",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"May 10th 2022",isOpenForSubmission:!0,editors:[{id:"63465",title:"Prof.",name:"Mohamed Nageeb",surname:"Rashed",slug:"mohamed-nageeb-rashed",fullName:"Mohamed Nageeb Rashed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11477",title:"Public Economics - 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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, Kuwait. His research interests include optimization, computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, and intelligent systems. Prof. Sarfraz has been a keynote/invited speaker at various platforms around the globe. He has advised/supervised more than 110 students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He has authored and/or edited around seventy books. Prof. Sarfraz is a member of various professional societies. He is a chair and member of international advisory committees and organizing committees of numerous international conferences. He is also an editor and editor in chief for 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:"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:null},{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:"Beijing University of Technology",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:"Lakhno Igor Victorovich 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.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of 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 a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), 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 DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. 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: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{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:"243698",title:"M.D.",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:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{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:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZkkQAG/Profile_Picture_2022-05-09T12:55:18.jpg",biography:null,institutionString:null,institution:null},{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:"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. 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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. 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