Simulation configurations for two-level exclusive cache.
\r\n\t- BMD measurement technology
\r\n\t- Osteoporosis and fracture risk
\r\n\t- Bone growth and remodeling
\r\n\t
\r\n\tThe submission is also open to any other original study related to these research topics.
The computer has three major parts, namely, processor, memory and input–output. The modern computer is based on Von Neumann architecture of stored program concept. Any application/program is fetched into main memory and executed. The program has instructions. Any instruction is fetched into the processor (CPU) and executed based on pipeline concepts. The instructions act on data. Any program has 80% of its instructions in loops. Repeated access of data gives the concept of locality of reference. If any data is accessed repeatedly it has temporal locality. Data that are in vicinity of access are said to have spatial locality. Taking advantage of locality of reference, the concept of caches was introduced in computers. The data/instruction from main memory is fetched into cache before accessed by the CPU. This improves the performance. The memory hierarchy thus runs from registers, caches, main memory, secondary memory, tertiary memory, etc. The performance of memory system is measured as average memory access time (AMAT). Various cache levels are prevalent in modern processors.
\nA processor cache is denoted by the tuple (C, k, L) where C is the capacity, k the associativity and L the line size. Based on the various values of k, three types of caches are known. These are direct mapped cache with k = 1, set associative cache with k > 1, fully associative cache with one set and n blocks. An address a is mapped to set given by a mod S, with tag value a div S for S sets. If a line is present in cache, it is cache hit, else it is cache miss. Cache misses are of three kinds: cold, capacity and conflict. A cache miss for first occurrence is called cold miss. The difference between misses in cache and fully associative cache of same capacity is the capacity miss. If a line maps to occupied set or way, it is called conflict miss. A computer system usually has many cache levels. A line can reside in cache level and higher cache levels in inclusive caches. A line resides in only one cache level in exclusive caches. Usually processors have caches dedicated to instructions and data separately. These are called instruction cache and data cache, respectively. Certain systems have same cache for both instruction and data. These are called unified caches. A system with caches of two or more kinds (direct mapped, set associative, fully associative) is called multilateral or hybrid cache. As the address mapping may vary with each cache level, the average memory access time (AMAT) is used to measure the cache performance.
\nAs the number of computer components active increases, the energy consumed also increases. The power consumed by cache depends on number of active components. The energy is given as E = power × time. The energy is given by the formula E = \n
The performance of CPU caches is measured by execution time for various applications. Benchmarks are used to measure the CPU performance. The SPEC2000 benchmarks are one of standard benchmarks. The integer benchmark suites of SPEC2K are given as follows:
\nName | \nDescription | \n
---|---|
256.bzip2 | \nCompression | \n
181.mcf | \nCombinatorial optimization | \n
197.parser | \nWord processing | \n
300.twolf | \nPlace and route simulator | \n
255.vortex | \nObject-oriented database | \n
175.vpr | \nFPGA circuit placement and routing | \n
The memory performance is improved by adding caches. The inclusive, exclusive and two-type data cache models are presented in this chapter. The proposed models are simulated using SPEC2000 benchmarks. The benchmarks are run using Simplescalar Toolkit for simulations.
\nConsider cache system of n cache levels, main memory. Let the cache levels are \n
Inclusive cache of n levels.
Let the levels be \n
The first three terms in Eq. (1) are the access time of level one, level two and level three cache hits. The last term is the miss penalty. This expression can be extended to any number of cache levels.
\nEnergy consumed in cache depends on number of active components. The individual lines can be selectively switched on in caches using certain software techniques or hardware circuits. The total power consumed can be reduced through this technique. Consider w-way set associative cache of S sets. Let the power consumed per line be p watts. The total power consumed is wpS. Consider a circuit which enables lines if occupied. This is shown in Figure 2. If the power consumed by the circuit is q watts, the number of occupied lines is y, the total power consumed is q + yp. An improvement in power consumption is observed if q + yp < wpS.
\nSequential circuit in cache way to save power consumption. For details, refer [
Power saving using software techniques involves mapping lines to fixed ways by address mapping techniques [4].
\nExclusive caches have a line in one cache level only. There is no containment property of the inclusive caches. Let the cache levels be \n
Exclusive cache of n levels.
Consider cache with two cache levels. The placement, replacement algorithm as proposed by Jouppi and Wilton [5] is given as follows:
Check if line is present in level one. If present, access the line and stop.
Check if line is present in level two. If present, swap with level one cache line, access and stop.
If line is not present in cache, put the line in level one cache evicting the victim in first level cache to second level cache.
The number of sets in both levels has to be equal in the abovementioned design. Let \n
The first term in Eq. (2) is level one hit time. The second term is level two hit time. The factor of 2 in this expression is because of swapping of the lines. The third term is the miss penalty.
\nAnother logic to realize exclusive caches is proposed by Subha [6]. Consider two-level cache system. The placement, replacement logic is given as follows:
Initialize all lines to be in level zero.
If the line is present in level one or level two cache (cache hit), let the line be in logical level one and stop.
Check if level one cache line is free. If so, place the line in level one cache, consider it as logical level one cache and stop.
Check if level two cache line is free. If so, place the line in level two cache; consider it as logical level one cache and stop.
Check the status of physical level one and physical level two caches. If physical level one cache has status of logical level two and vice-versa, place the block in level one cache and change its status to logical level one, change the status of physical level two cache to logical level two cache and stop. Else, place the block in physical level two, treat physical level one as logical level two, physical level two as logical level one and stop. [Put in logical level two, flip the level indices].
The abovementioned model does not require the two cache levels to have equal sets. There is a path between main memory and level two. Let \n
where \n
The simulations of exclusive cache proposed in [6] using SPEC2K benchmarks are presented in the following section. Table 1 gives the configurations and Table 2 gives the AMAT.
\nSimulation configurations for two-level exclusive cache.
AMAT values of two-level exclusive caches.
The AMAT is depicted in Figure 4.
\nAMAT comparisons of two-level exclusive caches.
The power consumed by exclusive depends on the number of active cache lines. One method to reduce the number of active lines is to have separate cache called tag cache [7]. The tag cache contains the tag values of all cache levels. The address mapping proceeds as follows in the tag cache.
Compute the following
Set1 = a mod \n
Tag1 = a div \n
Set2 = a mod \n
Tag2 = a div \n
Check in tag cache for the matching of Tag1. If match is found, the line is present in level one cache as it is level one hit condition. Access the line in level one cache and stop. If there is level one cache miss, check for level two cache hit by inspecting match of Tag2. If there is level two cache hit, access the line in level two cache and stop.
This step is for cache miss condition. Place the least recently used line in Set2 of level two in main memory. Transfer the least recently used line of Set1 in level one cache in the evicted level two line. Place the line with address a in level one cache. Update the entries in the tag cache.
Stop
In the abovementioned algorithm, a level one cache line or higher level cache line is enabled only on cache hit or cache miss in all levels. This saves the energy consumed by the cache system. The cache is exclusive in nature and the exclusive algorithm proposed by Jouppi and Wilton [5] is used. The proposed model has scalability. The architecture is shown in Figure 5.
\nExclusive tag cache architecture [
Let trace be R references. Let \n
The tag cache access time is the first term in Eq. (5). The hit time accesses to level one and level two caches are given by second and third terms, respectively. The time taken to fill vacant way in level one cache is given by the fourth term. This involves accessing tag cache in level one, fetching the line to level one cache and updating the tag cache entry. The time taken to fill vacant second level cache line is given by the fifth term. This includes accessing the tag cache to check for match in level one cache and level two cache and placing the line in level two cache, updating the tag cache entry. The time taken to replace existing line is given by the sixth term. This involves checking for tag match in level one cache, level two cache, replacing the level one cache line and updating the tag cache entries. As the tag cache contains the tags in consecutive locations, it may be the case that the tag entries in level one and level two are in two different cache blocks.
\nThe energy consumed in exclusive tag cache is calculated in the following section. Let us assume that the cache operates in two modes: high-power mode and low-power mode. On accessing cache way, its corresponding set is placed in high-power mode from low-power mode. Let \n
The first term in Eq. (6) is the energy consumed when the cache is not accessed. The second term is the energy consumed in level one hits. This is equal to enabling the line in tag cache and accessing the ways in the level one cache for the set. The third term gives the energy consumed for level two cache hits. The fourth term is the energy consumed for filling a vacant level one cache line. The fifth term is the energy consumed to fill a vacant level two cache line. The sixth term is the energy consumed to replace an existing line in level one cache on a conflict miss. Consider a traditional exclusive cache with the same algorithm given in Section 3. The energy consumed for R references is calculated as follows. Let \n
A saving in energy consumption is observed as given by Eq. (8).
\nThe simulations for the above proposed tag cache model of exclusive cache is presented in the following section [7]. The simulation parameters are given in Table 3. The energy consumed in low-power mode is 5 J and high-power mode is 15 J. The AMAT was calculated using C routines. Figure 6 gives the AMAT and Figure 7 gives the energy consumed. As seen from Figure 6, the AMAT performance is comparable with traditional exclusive cache. The energy is saved by 23% as seen from Figure 7 when compared with traditional exclusive cache.
\nSimulation parameters for Exclusive Tag cache model.
AMAT comparison for tag cache model of exclusive caches.
Energy comparison of tag cache model of exclusive caches.
A hardware method [8] to improve the power consumption is to enable level one and level two cache lines based on the contents of the tag cache. This is depicted in Figure 8.
\nProposed hardware for power saving in exclusive tag cache architecture of two levels [
The simulations for the model presented in [8] are presented in the following section. The simulation parameters are shown in Table 4. The power consumed is shown in Table 5. The AMAT is shown in Figure 9. The t is traditional model and p is the proposed model. There is 49% improvement in power consumption with no change in AMAT for this model compared with the exclusive model proposed in tag cache model of exclusive cache (t in this discussion) as proposed in [7].
\nSimulation parameters of sequential circuit for exclusive caches.
Power consumed in sequential circuit of exclusive cache.
AMAT comparison of sequential circuit model for exclusive caches.
The caches discussed so far in this chapter are inclusive and exclusive. A two-level data cache model [9] which selectively makes the cache ways in various levels as inclusive or exclusive is presented in the following section. This model makes the cache ways inclusive based on access. A two-level data cache is chosen for discussion. Initially, both cache levels are exclusive. The first occurrence of address places the data in one of cache levels making the occupied way exclusive. Preference is given to place the data in level one in this case. On consecutive access to data in level one cache, cache way is made inclusive with level two cache. During this process, data in level two cache may be replaced. The least recently used algorithm (LRU) is used for data replacement in level two cache. If the data have temporal access in level two cache, the way is made exclusive. On a cold miss with both the levels occupied, the block is placed in level one cache making it exclusive. As the number of ways to place the data increases, the performance increases in terms of the average memory access time (AMAT). Figure 10 shows this architecture.
\nTwo-type data cache model [
The algorithm for two-type data cache model is given in the following section.
\nAlgorithm for two-type data cache: Given two-level data cache, this algorithm places the line in the cache system. Input is the address. An index array is maintained per cache for each way. It is zero to indicate inclusive and one to indicate exclusive.
A level one hit occurs if the address is found in level one. The block is made inclusive by placing a copy of it in level two cache. The index array entry is set to 00 to indicate this in both the levels. The block is accessed and the process stops.
A level one miss and level two hit occurs if the address is not found in level one but is found in level two cache. The block is made exclusive in this case. This is indicated by setting index array entry of block to 11. The block is accessed and the process stops.
A cache miss occurs if the block is not present in level one and level two cache. If level one cache is vacant, it is placed in level one cache. Else, if level two cache way is vacant, it is placed in level two cache. The block is made exclusive. The block is accessed and process stops. If the level one set is full, the block replaces an existing block based on least recently used algorithm. The corresponding index array entry is made exclusive by setting it to 11. The mapping process stops. Table 6 gives the algorithm.
Two-type data cache algorithm.
Let R, \n
where \n
In Eq. (9) the first term gives inclusive cache type hits, the second term indicates first time level one hits. The third term indicates the level two hits. The fourth term indicates placing a block in vacant level two way/set. The fifth term indicates either placing a block in free level one cache set/way or replacing a level one cache set/way on cache full scenario. It is assumed that exchange of a block from level one to memory can be done in parallel. The term 2 k is to update the index arrays of both the cache levels. The first term gives the hit time in level one cache. The second term gives the hit time in level two cache. This involves accessing level one and level two caches. The third term gives the time to service the misses. This involves accessing level one and level two caches, determining if it is missed in both levels, accessing main memory and fetching the block into level one. The level one block is written to the memory before the new block is fetched. Simultaneously, the requested block is sent to the processor.
\nDenote the inclusive cache as \n
The AMAT for inclusive cache is given by Eq. (10).
\nThe first term is the level one hit time. The level two hit time is given by second term. This involves accessing level one, level two and transferring data from level one to memory and data from level two to level one cache. The miss time is given by third term. This involves accessing level one, level two to determine it is a miss in both levels, write from level one to memory and level two to memory the existing blocks. The new block from main memory is fetched into level two cache and from there to level one cache. Simultaneously, it is given for processing. An improvement in performance is observed as given by Eq. (11).
\nThe AMAT for the exclusive system is given by Eq. (12).
\nThe first term in Eq. (12) is the level one hit time. The second term is for level two cache hits. This needs access of level one cache, level two cache and exchange the contents. On a miss in both the levels, the contents of level two are updated in the main memory, level one cache block is sent to level two and new block is fetched from main memory to level one cache. Simultaneously, the requested block is sent to the processor. The terms in Eq. (9) and Eq. (12) differ due to the architectural differences. A performance improvement in the proposed model over exclusive cache is seen as given by Eq. (13).
\nIn all the models, it is assumed that the cache block when fetched into the cache is simultaneously sent to the processor.
\nThe proposed two-type data cache model is simulated using SPEC2000 benchmarks. The proposed model is compared with inclusive, exclusive caches described in this chapter. The simulation parameters are given as follows (Tables 7 and 8):
\nSimulation parameters of proposed two-type data cache and inclusive cache.
Simulation parameters for exclusive cache in two-type data cache.
The AMAT values are given in the graph in Figure 11. It is compared with inclusive and exclusive caches.
\nAMAT comparison with inclusive cache.
As observed from Figure 11, improvement in AMAT in proposed system compared with inclusive cache is seen. There is a decrease in AMAT by 3% compared with exclusive caches. The proposed model has better performance for systems where elements of set are accessed more than two times after a sequence of other cold misses mapped to the same set such that the number of total misses is a multiple of number of elements of level one cache.
\nThe AMAT values are shown in Table 9.
\nAMAT values for two-type data cache simulations.
The author thanks Santa Clara University, Santa Clara, CA, USA for providing SPEC2000 benchmarks.
\nApproximately 25 to 30% of the world’s human population is infected by toxoplasma [1]. Ocular toxoplasmosis is one of the most common cause of posterior uveitis caused by an intracellular parasite, toxoplasma gondii [2, 3].
1952, Helenor Campbell Wilder (later Helenor Campbell Wilder Foerster) confirmed the growing suspicion that toxoplasma gondii was a cause of uveitis in otherwise healthy adults by identifying the presence of both trophozoites and brachyzoites in enucleated eyes, that suffered severe intraocular inflammation [4].
Retinitis is the most common manifestation of ocular toxoplasmosis with vitritis. Factors that may influence visual prognosis include severity of the inflammation, size of the lesion and site of the inflammation. Also, progression to complications such as a neovascularization, vitreomacular traction, retinal detachment, glaucoma and cataract renders worse visual prognosis. Multimodal imaging can assist in meticulously evaluating and studying the extent of intraocular damage imposed by toxoplasma inflammation. Laboratory testing of intraocular fluid has been widely studied and employed, including PCR testing and detection of intraocular antibodies using Goldmann-Witmer coefficient (GWC), to enable more precise diagnosis Ocular toxoplasmosis has a self-limiting nature, treatment can help rapid control of inflammation specially if the retinitis involves the posterior pole. Treatment includes different combinations of antimicrobials; none have can prevent recurrences, but some combinations have shown more effective reduction in the size of the retinal lesion in comparison to other combinations or no treatment [5].
Toxoplasma exists in 3 infectious forms including sporozoites, which are contained within oocysts, tachyzoites and bradyzoites, which reside in tissue cysts. Oocysts are produced only in cat intestines and become infectious when defecated by cats. Tachyzoites are the fastest replicating form and responsible for systemic dissemination and active tissue infection in intermediate hosts. Tachyzoites can enter almost any type of host cell and multiply until the host cell is filled with parasites. Lysis of the host cell results in tachyzoite release followed by reentry into a new host cell. As a result of this cycle, multifocal tissue necrosis may occur. The host usually limits this phase of infection, then the parasite enters the dormant form, named bradyzoites, and gets isolated in tissue cysts. Cysts may contain hundreds of bradyzoites. These cysts usually cause no host reaction and may remain dormant throughout the life of the host [6].
The infection may be acquired or congenital by vertical transmission to the fetus. However, reports have supported the view that acquired infections might be a more important cause of ocular diseases than congenital [7, 8, 9].
Acquired infection occurs by consumption of raw meat containing cysts or ingestion of water or food contaminated by oocytes [9, 10]. Once the active parasite has invaded the body, it will spread via the blood stream, and due to a high affinity for cerebro- and retinovascular endothelial cells, can become established within the retina [10]. Following invasion of the parasite into the eye, the tachyzoite remains latent in the cyst under the control of the immune response of host [11, 12, 13]. In event of trigger of cyst rupture, the tachyzoite is converted to bradyzoite, and the inflammatory response is activated [5, 14].
Congenital- transplacental transmission occurs in 40–70%, while acquired ocular involvement was reported in 1–21% [15]. However, each entity has significantly different clinical manifestation. A study conduct in southern Brazil reported lower prevalence of ocular toxoplasmosis in children been 5.1% below the age of 13 and 21.3% above the age of 13, concluding that ocular toxoplasmosis is a sequela of postnatal rather than congenital infection [7].
Ocular lesions are the most frequent manifestations of congenital toxoplasmosis [16, 17]. Vertical transmission of toxoplasmosis occurs during primary infection in pregnant women, and generally the maternal disease goes unnoticed. When pregnant women become infected in the first trimester, the frequency of fetal infection goes up to 15–20%, in the second up to 25%, and in the third up to 65–70%. The most compromised fetuses are those who are infected earlier [1, 18, 19].
Besides retinochoroiditis, other ocular manifestations of congenital toxoplasmosis are described, such as microphthalmia, optic nerve atrophy, and abnormalities of the iris, cataract, and strabismus [17, 20, 21, 22, 23, 24].
However, typical presentation in the retina is an atrophic hyperpigmented scarred macular lesion that is described as ‘wagon-wheel’ lesion caused by congenital toxoplasmosis. It shows a central area composed of glial and pigmented material connected by pigmented strands to a peripheral ring of pigment at the edge of the lesion Figure 1. A study designed to detect ocular involvement in infants with congenital toxoplasma reported that ocular involvement occurred in 70.4% of the cases, with mean age of active lesion at 1.4 months. Bilateral involvement occurred in 15.7% of the patients, mainly involving the papillomacular bundle in 76.3%. The retinochoroiditis lesions were active in 15.7% of the eyes and had healed in 84.3% [25].
Colored image (left) and fundus fluorescein angiography (right) of atrophic pigmented congenital toxoplasma ‘wagon wheel’ macular scar.
It is worth mentioning that new lesions continue to appear well after the age of 5 years, likely with severe visual impairments. Therefore, screening of women for toxoplasmosis before pregnancy is advisable [26].
A significant reduction in prevalence and severity of the disease has been attributed to prenatal and neonatal treatment maintained throughout the first year of life [27, 28, 29].
Acquired ocular toxoplasmosis commonly manifests in the second through fourth decades [10, 30]. Approximately 10% of otherwise healthy individuals who contract the infection report nonspecific symptoms, such as fatigue, fever and myalgias. Cervical lymphadenopathy [31].
Though floaters with altered vision may be the most common symptom of toxoplasma retinitis, however, clinical presentation ranges a wide spectrum.
Anterior uveitis is a common finding, with mutton-fat keratic precipitates, fibrin, cells and flare, iris nodules and posterior synechiae [32]. Raised intraocular pressure has been reported in (30%–38%) of the cases [33, 34].
This usually manifests as active focal necrotizing retinitis, at the edge of an old, pigmented scar with overlying vitritis Figure 2. Bosch-Driessen et al. reported 72% of the patients had pre-existing retinochoroidal scars, indicating prior subclinical disease. The pigmented scar has been described to harbor the cysts that remain dormant until the cyst ruptures with release of organisms into the surrounding retina inducing adjacent retinitis [10].
Colored image of a supranasal peripapillary pigmented scar (yellow arrow) with adjacent area of active retinitis (white arrow).
Toxoplasma retinitis may occasionally manifest without an adjacent scar Figure 3. It is known that tissue cysts can exist in normal-appearing retina. The retina may be infected at the time of an initial systemic infection, but without clinically apparent lesions at the time [32].
Colored image of superior macular toxoplasma retinitis lesion (white arrow) without adjacent scar.
The focus of retinitis is of necrotizing nature and usually involves the full thickness of the retina, although occasional limited involvement of either inner or outer retina occurs, as described by Friedmann and Knox. Depending upon the thickness of involved retina, the overlying vitreous and underlying choroid are variably involved [30].
Large, full-thickness lesions tend to incite more severe vitritis, producing the classic ‘headlight in the fog’ sign. Optical coherence tomography (OCT) of active lesions can detect the level of retinal involvement, severity of choroiditis, as well as monitoring the regression of the lesion with treatment Figures 4 and 5. On regression of the retinitis, a pigmented scar that is smaller than the actual size of the retinitis forms.
OCT line scan through full thickness retinitis seen between the two white arrows with compete loss of architecture of inner retinal layers, with a small deep retinal infiltrate (orange arrow) and adjacent mild subretinal fluid. Dense localized overlying vitreous infiltration overlying the area of retinitis.
OCT line scan through active toxoplasma retinitis seen between the white arrows in the photo on the left with underlying choroidal involvement exhibiting a hyporeflective elevated appearance. Healed lesion in the photo on the right between yellow arrows shows resolved retinitis with thinned retina, decreased thickness of the choroid with increased choroidal transmission.
Punctate outer retinal toxoplasma (PORT) was first described in 1985 by Doft and Gass [35]. They elucidated the outer variation of punctate toxoplasmosis that primarily affects the outer retinal layers of the macular area. This entity usually presents in younger, immunocompetent patients [35, 36]. These can be either a single or several deep retinal infiltrates that may extend as far as the inner plexiform layer (IPL). The underlying retinal pigment epithelium is interrupted with variable involvements of the Bruch’s membrane and choroid. These lesions have been detected in the same eye with typical retinal toxoplasma lesions as in Figures 6 and 7 or in eyes with no previous toxoplasma lesions [37]. PORT lesions resolve slowly, leaving an atrophic chorioretinal scar and frequently recur in adjacent areas of the macula [38].
Autofluorescence showing foveal hypoautofluorescent toxoplasma lesion with an active edge, and two nasal PORT lesions (white arrow).
Inflammatory vascular involvement in acute toxoplasma retinochoroiditis constitutes an invariable clinical sign of the disease and was reported in (100%) of cases in a previous study [39].
During the acute phase of toxoplasmic retinochoroiditis, perivasculitis with arterial involvement in the form of multiple small periarterial plaques, previously described as Kyreiles plaques [40], may occur, whereas that of the vein may show scattered infiltration of the wall, sheathing, or both Figure 8. Obstruction of a branch of the central retinal artery and vein as well as choroidal vascular occlusion have also been reported to occur [41, 42, 43, 44, 45].
Small Kyreilles plaques along the retinal artery (white arrow) adjacent to patch of toxoplasma retinitis with perivenular infiltrates (yellow arrow).
The pathogenesis of vasculitis, was previously explained to be, is secondary to a reaction between local antigens and circulating antibody, and the beads seen along the vessels represent cuffs of mononuclear cells [46, 47].
Inflammation of the retinal vessels can occur in close proximity to the area of retinitis. The intensity of the vascular involvement was reported to be more prominent were the vessel traverses the active lesion. Vasculitis may also present away from the actual focus of inflammation Figure 9 and involve vessels in all four quadrants [39].
Fundus fluorescein angiography (FFA) in the left image, exhibiting superior old hypofluorescent scar with adjacent active retinitis (white arrow) and supranasal active satellite lesion (yellow arrow). Perivenular leakage in the image on the right is evident supratemporally and infratemporally (white arrow) away from the actual foci of active retinitis.
Occasionally, vascular occlusion may occur when thick focal retinitis engulfs the course of retinal vessels, leaving a permanent area of retinal ischemia [43] Figure 10. Retinal vascular occlusion has been reported to be 5% [39].
Supratemporal thick toxoplasma retinitis along the supratemporal vessels (white arrow in the left side image) with occluded vessels distal to the lesion (yellow arrow). FFA performed after healing of the retinitis (right image), demonstrating an atrophic patch at previous site of retinitis (orange arrow) with occluded supratemporal vessels and a large area of retinal ischemia (red arrows).
Optic nerve involvement may be due to parasitic invasion or reactive inflammation [48, 49, 50, 51]. Eckert et al., reported optic nerve changes in 5% of the cases. In 35% of the cases, retinitis was juxtapapillary Figure 11. In pure papillitis, the parasite affects the optic disc directly, causing a swollen papilla with sheathing of the peripapillary veins and there may be no concurrent active retinochoroiditis lesion [50]. Optic nerve involvement may induce severe visual field defects as well as loss of color vision [6]. Neuroretinitis has also been described as a unique presentation of ocular toxoplasmosis [51, 52].
Multicolored images (left side photo of superior peripapillary lesion (yellow arrow). OCT line scans through superior peripapillary lesion exhibiting almost full thickness retinitis with overlying localized dense vitritis (yellow arrow) in right side photo.
Macular oedema has been reported in 12% of toxoplasma cases [10]. Subretinal fluid accumulation (SRF) of variable severity, adjacent to area of retinochoroiditis involving the macula, has been described Figure 12. This was explained by. Khairallah, as the disrupted outer blood retinal barrier, secondary to the adjacent inflammatory process. Ultimately the fluid regresses as the retinitis heals [53].
Full thickness retinitis in OCT line scan indicated by the white arrow with adjacent foveal SRF.
Cystoid macular oedema (CME) may occur in active ocular toxoplasmosis with different phenotypes. Ouyang et al. reported that 7.5% of the cases presented with CME, while 2.5% presented with a huge outer retinal cyst (HORC). Interestingly, the same study reported that 3.5% of the cases showed cystoid degeneration in the inner retina next to the retinal vessels without other any retinal/choroidal abnormality in the macula [54].
HORC was described to be intraretinal cyst with a membranous structure bordering the outer border of that cyst Figure 13. Ouyang et al., hypothesized that this structure represents the tissue between ELM and the inner boundary of the RPE (i.e., photoreceptor layer), which further suggests that the lesion represents an intraretinal rather than a subretinal fluid accumulation. With regression of the fluid, the membranous structure resumes its anatomical location in the macular layer architecture [55].
Toxoplasma lesions healing starts to be appreciated as the vitritis regresses and the toxoplasma lesion starts to show more defined borders, because cicatrization occurs from the periphery towards the center, with variable pigmentary hyperplasia [32].
OCT is a sensitivity tool that has been used to study toxoplasma lesions in the active and healed stage [55, 56]. In the acute stage, retinal necrosis is detected by OCT as hypereflective disorganized thickening of the neurosensory retina. Underlying RPE clumping and disruption of the ELM and photoreceptors is seen. Choroidal inflammation may occasionally occur, and is detected by OCT appearing, hyporeflectivite thickening and, confined underneath area of retinitis. Overlying toxoplasma retinitis lesions, hyperreflective vitreous aggregates settling over inflamed retinal surface has also been reported [55].
As the retinitis starts to heal, the OCT scans show the hyperreflective area of retinitis, within the neurosensory retina starts to decrease in thickness with regressing of any adjacent SRF or CME. The RPE clumping starts to be more obvious and may show localized heaping which is likely the commencement of the pigmentary scar. As the hyperreflectivity of the retinitis recedes, degenerative cystoid spaces occasionally develop that resolves as healing reaches a final stage. The posterior hyaloid starts to get thicker, may exerts vitroemacular traction, which occasionally may spontaneously be released, with the separation of the posterior hyaloid from the macular surface Figure 14.
OCT scan through the fovea demonstrating toxoplasma necrotizing retinitis evolving from the active stage into an atrophic healed scar tissue. A: Full thickness retinitis. B: The retinitis has resolved remarkably with evolution of small deep residual area foveally with overlying appearance of the thick posterior hyaloid. C: Decreased size of the residual deep hyperreflective material with adjacent degenerative cystoid spaces and vitreofovel tangential traction. D: As healing progresses, the posterior hyaloid detaches completely with release of the vitreofoveal traction. E: Complete resolution of the retinitis with atrophic appearance of the inner layers, resolved degenerative cyst and disrupted outer foveal layers.
Occasionally, when retinitis is severe and recalcitrant to treatment, upon eventually evolving into the healing stage, the retinal layers exhibit severe, disorganization, thinning, with a fibrotic appearance, that may be laminated and splitted. Severe vitreomacular traction in such cases, can progress to retinal detachment Figure 15.
55-year-old female patient with neglected toxoplasma retinitis a and B: Colored and OCT images respectively, exhibit large active retinitis involving all the macular area, with overlying dense vitritis. C and D multicolored and OCT images respectively, demonstrate photos after complete healing of the retinitis. D shows OCT image denoting complete disruption of the inner macular layers been replaced with laminated and split fibrosed tissue with focal area of traction parafoveally.
Reported complications of ocular toxoplasmosis include isolated retinal tear (6%), retinal detachment, which is usually rhegmatogenous and/or tractional (6%), pre-retinal membrane (7%), choroidal neovascularization (<1%), vitreous hemorrhage (2%), optic atrophy (4%) and cataract (5%–13%) [10, 57].
Atypical manifestations include exceptionally large, multifocal, bilateral, diffuse retinal involvement or panophthalmitis. Elderly, AIDS, immunocompromised individual, or even rarely younger, immunocompetent patients as well [58] are likely to have specific defects in immune response that render them more at risk for atypical forms of toxoplasmosis [59]. This extensive toxoplasma retinitis presents similarly to necrotizing herpetic retinopathies, with large confluent full thickness areas of retinitis involving the peripheral retina and posterior pole. The thick, more densely yellow-white appearance of the lesion borders with a distinct, smooth contoured edge; and lack of hemorrhage, may distinguish these lesions from viral retinitis [60].
Following an episode of toxoplasmic retinochoroiditis, the risk of recurrence is reportedly higher during the first year than during subsequent years: 29–32% of recurrences occur within 1 year, and 53–57% within 2 years [10, 32, 61].
Reasons for recurrences are not usually identified. They may arise from senescent changes in tissue cysts, with an accompanying release of parasites or antigens or as a result of trauma, hormonal fluctuations or even, transient immune responses of humoral or cellular nature [62]. Patients who are relatively young at the first presentation are at increased risk of recurrence compared to older patients who have been independently confirmed [63]. A larger retinal parasite load in younger patients is one explanation that Holland et al. offered for this observation [64]. In AIDS patients, recurrence is the rule in the absence of long-term antiparasitic therapy [65].
Pregnancy and cataract surgery have both been associated with an increased risk of reactivation [62, 66]. Bosch-Driessen and associates [10], reported that 9% of women with ocular toxoplasmosis developed recurrences during pregnancy. It has been hypothesized that this relationship is attributable to hormonal or immunological changes that occur during pregnancy [67].
There is substantial variation in the severity of intraocular toxoplasma inflammation, attributable to multiple host- and disease-related factors.
Individuals less than 60 years showed significantly higher incidence of having lesions less than1 disc area (DA) as compared to those above the age of 60, showing lesions more than 1DA in size with P = 0.02. The same study reported that larger lesions were associated with more severe vitreous humor inflammation [57]. Patients with AIDS develop extensive disease and frequently reactivate, if treatment is discontinued [68].
Diagnosis of ocular toxoplasmosis starts at the point where the classic retinal manifestation is highly suggestive of the disease. However, in many instances the clinical findings cannot be sufficient to confirm a diagnosis, especially in the atypical form of presentation and thus laboratory investigations are necessary.
Ocular disease in the context of the presence of serum IgG and IgM antibodies against Toxoplasma gondii measured by screening tests such as the enzyme-linked immunosorbent assay (ELISA) or CLIA (Chemiluminescence immune assay) is compatible with acute or recent infection with toxoplasma supporting the diagnosis [69], yet can never be confirmatory, unless a definitive test like the dye test (Sabin-Feldman), IFAT (indirect fluorescent antibody test), immunoblot, and ISAGA (immunoglobulin-M immunosorbent agglutination assay) is performed. Nonetheless, these methods are performed only by specialized laboratories, they are complex and costly [70].
If retinitis develops within a year of an acquired systemic infection, anti-toxoplasma IgM should be detectable, but the variable rate of decline of this Ig isotype also limits the usefulness of such testing. The only exception is during pregnancy, when maternal IgM may herald acute infection of both the mother and foetus triggering urgent consultation with the obstetrician and neonatologist [71].
Since seropositivity is prevalent in most communities, the positive predictive value of IgG is low, and a positive IgG cannot be interpreted as indicative of active toxoplasmic infection. However, a rise in titer of specific IgG antibodies over a 3-week period has been used as an indicator of recent infection [72].
In immunosuppressed subjects, positive serological tests indicate infection, however, negative tests do not exclude previous or concurrent infections [73].
Levels of antibodies in aqueous humor and their relationship to serum antibodies may help in establishing the diagnosis of ocular toxoplasmosis [74, 75]. The Goldmann-Witmer coefficient (GWC) has been proposed as a valuable index of intraocular antibody production in active toxoplasmic retinochoroiditis in the immunocompetent subject [76].
(GWC) is calculated as the proportion of specific immunoglobulin (Ig)G in ocular fluid versus serum samples. It is determined as follows (anti-Toxoplasma IgG in aqueous humor/total IgG in aqueous humor)/(anti-Toxoplasma IgG in serum/total IgG in serum). Although a ratio over one should indicate intraocular antibody production, this also occurs in healthy controls, and therefore a ratio of at least three is often preferred for certain diagnosis [77].
The polymerase chain reaction (PCR) is an in-vitro method for exponentially replicating nucleic acids. PCR allows the detection and analysis of infinitesimal quantities of DNA. PCR of intraocular fluid has been extensively used to diagnosis infectious uveitis [78].
PCR testing of ocular sample can be useful in presumed toxoplasmosis in patients older than 50, in cases with inflammation (Tyndall ≥1/2+, panuveitis), area of retinochoroiditis>3 DA, and when ocular sampling performed within 1 week of presentation after onset of symptoms and up to 4 months [79, 80].
GWC testing is of better sensitivity than real time PCR, and is the preferred diagnostic procedure in ocular toxoplasmosis, especially if the testing is carried out in younger patients with quiet eyes and with smaller sized chorioretinal lesions [79].
Real time PCR confirmed the clinical diagnosis of toxoplasmosis in 62.5% of the cases, while the GWC confirmed in 87.5% [79]. Other studies reported that for 25 patients who suffered from ocular toxoplasmosis, the GWC was positive in 90%, while PCR testing was positive in just 36% [80]. Also, Labalette et al., noted the aqueous PCR was positive in 60% when lesions were larger than three-disc areas, but in only 25% when lesions were smaller. Overall, GWC was more likely positive than PCR (i.e., 89% vs. 44%) in this group [81]. Also, the rates of positive PCR are high in aqueous humor, obtained from HIV-infected or elderly subjects presenting toxoplasma retinitis [82].
No drug has been proven to cure infection [5], therefore, the aim of antibiotic treatment is to reduce the duration and severity of symptoms of acute intraocular inflammation, the risk of permanent visual impairment (by reducing the size of the eventual retinochoroidal scar), and the risk of recurrent episodes [83].
In immunocompetent individuals, toxoplasma retinochoroiditis typically resolves over a period of 1 to 2 months [84].
Previous reports indicated that toxoplasma treatment was employed if dense vitritis developed, retinitis is located close to the optic nerve, papillomacular area, or close proximity of lesions to major retinal vessels or if decreased vision occurs [5]. However, Holland reported the results of a survey from1991 to 2001, where members of the AUS showed a shift in management over 10 years, were in favor of treatment of both mild and severe disease [85].
Treatment of active ocular toxoplasmosis in immunocompromised individuals regardless of the severity is the recommended practice with less debate [85].
Several antimicrobial drug combinations are used to treat ocular toxoplasmosis.
Classic therapy is a combination of pyrimethamine 25 mg–50 mg daily orally with folinic acid 5 mg every other day and sulfadiazine 1 g four times daily orally with systemic corticosteroid [84]. Pyrimethamine side effects include gastrointestinal and dermatological manifestations as well as hematological adverse events, including leukopenia and thrombocytopenia, that mandate monitoring of the blood picture regularly throughout the treatment course. 26% of the patients on this regimen were reported to discontinue treatment due to complications from the drugs [5].
The alternate treatment regimen is trimethoprim-sulfamethoxazole 160 mg–800 mg twice daily orally with systemic corticosteroid, which is a well-tolerated combination although sulfonamide-related reactions may occur. The common side effects include mild gastrointestinal symptoms and mild maculopapular rash. However, this regimen is relatively well tolerated with side effects requiring discontinuation in 4% of patients [5].
Both pyrimethamine and sulfadiazine, as well as trimethoprim-sulfamethoxazole, have a similar mechanism of action, inhibiting tetrahydrofolate synthesis, thereby impacting nucleic acid synthesis of toxoplasma gondii. No reported difference in treatment results was reported when the classic or alternate treatment was used, however, treatment with classic therapy showed a greater reduction in the size of the retinal lesion than patients receiving other treatments or no treatment [5]. Other reports comparing these two regiments showed different results and concluded that drug efficacies in terms of reduction in retinal lesion size and improvement in visual acuity were similar. Reduction in the size of the lesion was comparable between the two treatment groups been 59% for trimethoprim-sulfamethoxazole and 61% for classic therapy, and there was no significant difference in post-treatment visual acuity. Therefore, trimethoprim/sulfamethoxazole seems to be an acceptable alternative for the treatment of ocular toxoplasmosis [86, 87].
Clindamycin 300 mg orally four times daily [84], is often added to triple therapy, which is then referred to as ‘quadruple therapy’. Animal studies showed that clindamycin reduced numbers of tissue cysts [86]. However, experience has shown that it does not prevent recurrent disease in human beings [88]. Pseudomembranous colitis is a well-recognized potential complication of clindamycin, as well as diarrhea. Clindamycin continues to be the most popular supplemental agent for treatment of patients with severe or persistent disease.
Opremcak and associates reported a series of 16 patients who were treated for toxoplasmic retinochoroiditis with trimethoprim (160 mg)/sulfamethoxazole (800 mg). Four were treated with trimethoprim/sulfamethoxazole alone, four were treated with trimethoprim/sulfamethoxazole and clindamycin, and eight were treated with trimethoprim/ sulfamethoxazole, clindamycin and oral prednisone. They concluded that trimethoprim/sulfamethoxazole accelerated the rate of resolution of toxoplasmic retinochoroiditis and improved the visual outcomes of their patients, although the study was uncontrolled [89].
Atovaquone 750 mg three/four times daily orally or azithromycin 250 mg daily orally are two antiparasitic agents used for treatment of toxoplasma. However, these agents do not appear to prevent recurrent toxoplasmic retinochoroiditis in the human host convincing activity against encysted parasites in experiment systems [90, 91]. Atovaquone was well tolerated but reactivation was reported by Winterhalter et al., in 44% of the cases within an interval averaging 39 months. [92]. Azithromycin in treatment of ocular toxoplasmosis has shown regression of the retinitis within 1 month in 64% of the patients, however, 27% experienced recurrence within the first year of follow-up, thus debating the effectiveness in decreasing recurrences [91]. The effective potency of this drug with no reported side effects that needed stopping the drug while used in treatment of ocular toxoplasma has been reported [92].
Recent research suggests that there is widespread variation for se of steroids in clinical practice for treating ocular toxoplasmosis. In a cross-sectional survey of uveitis specialists, 17% used oral corticosteroids in the treatment of ocular toxoplasmosis in immunocompetent patients, regardless of clinical findings. The other clinicians used corticosteroids for specific indications, such as severe vitreous inflammatory reaction (71%), decreased vision (59%), proximity of the lesions to the fovea or optic disc (35%), and for large lesions (5%) [93].
Oral corticosteroids are used during the active phase to reduce the retinal inflammation and thus further collateral tissue damage and also to prevent blood-retinal barrier breakdown. Furthermore, it can also reduce toxoplasma scarring. Steroids are usually started from 1 to 3 days after starting antiparasitic agent and continued for approximately 1 month. Indications for stopping therapy earlier include substantial improvement in the lesion appearance (“hardening” of lesion margins), substantial reduction of inflammatory reactions, marked improvement in vision, and adverse drug effects. Occasionally, antiparasitic agents are continued at least 2 days after stopping corticosteroids [84]. Oral corticosteroids are not used in immunocompromised individuals to treat ocular toxoplasma, thereby reducing the risk of further suppression of host defenses. Clinical series have shown that the signs of ocular toxoplasmosis, including inflammatory signs, can respond rapidly to antiparasitic therapy alone in immunocompromised patients [68, 94, 95].
Trimethoprim and sulfamethoxazole may be used in the prevention of recurrent attacks of ocular toxoplasmosis. Silveira et al. found that trimethoprim-sulfamethoxazole (160 mg–800 mg), taken orally every 3 days for 20 months, significantly reduced the risk of recurrent toxoplasmic retinochoroiditis from 23.8% in untreated control subjects to 6.6% [96].
The investigators suggested a role for such preventive treatment in patients with a history of frequent and severe recurrences or with toxoplasmic scars adjacent to the fovea where any reactivation can result in profound vision loss.
The rationale behind prophylactic treatment is the fact that recurrence rates decrease with duration of infection, even without treatment. If the frequency of recurrences decreases over time, it may be useful immediately after acquired infections to suppress recurrences during the period of greatest risk [96].
Recurrences of toxoplasmic retinochoroiditis may occur following LASIK and phacoemulsification with posterior chamber intraocular lens implantation [64, 97]. It is therefore recommended that prophylactic treatment be given to patients 2 days prior to surgery and to be continued for a period of 1 week.
Intravitreal clindamycin (1 mg) and dexamethasone (400 μg) have been used, injections can be repeated at 2-week intervals, based on a 5.6-day half-life of intravitreal clindamycin.
Soheilian et al. reported the results of treating patients with ocular toxoplasmosis involving or threatening macula or optic nerve, or adjacent to a large vessel and/or associated with severe vitritis with intravitreal treatment versus oral treatment using pyrimethamine and sulfadiazine plus prednisolone [98].
The mean number of injections in the intravitreal clindamycin was 1.6. Mean reduction in lesion size, increase in visual acuity and decrease in vitreous inflammation were not significantly different between groups, however, significantly reduction in size of lesions in IgM-positive patients who received classic treatment versus those who received intravitreal treatment was reported. This can be explained by the fact that a patient with acquired toxoplasmosis confronts a systemic infection that is treated better with systemic therapy.
The authors stressed that intravitreal clindamycin is a better alternative for pregnant and pediatric patients. Furthermore, the results of this study cannot be generalized to immunocompromised patients, monocular cases, and eyes with lesions inside the fovea (500 um). However, acquired toxoplasmosis confront systemic infection and, therefore, may benefit from systemic therapyas well, rather than just intravitreal injections [99].
Bosch-Driessen and associates, reported that seven (9%) of 82 women with ocular toxoplasmosis developed recurrences during pregnancy [10]. Some reported, recurrent toxoplasma retinochoroiditis in a pregnant woman poses minimal risk to the fetus, and treatment is not indicated for the sole purpose of preventing vertical transmission [100]. However, other studies stressed that infection by toxoplasma will need treatment using spiramycin 1 g orally every 8 hours if a seronegative pregnant patient gets infected up to 18 weeks into the pregnancy or within the 6 months prior to pregnancy [71]. Intravitreal clindamycin can be a reasonable choice of treatment in pregnant mothers.
Vitreoretinal surgery may be indicated in cases of persistent vitreous opacities, tractional or rhegmatogenous retinal detachment. In the setting of severe refractory vitritis precluding fundus examination, pars plana vitrectomy may be used for both diagnostic and therapeutic purposes [85].
Retinal detachment was reported in 11.4% of the cases. 75% underwent pars plana vitrectomy and 25% underwent laser retinopexy. 50% presented with recurrent RD requiring scleral buckle. At final follow-up, all patients who underwent surgical repair had attached retinas; with severe vision loss of 20/200 or worse [101].
Cataract surgery with intraocular lens implantation is often indicated in cases of significant lens opacification, after resolution of inflammation.
Ocular toxoplasmosis presents in a myriad of manifestations in the eye with variable complications and can be vision depleting. Multimodal imaging is useful in carefully monitoring treatment response, detecting, regression or progression of toxoplasma lesions and also show complications such as vitreomacular traction, CNVs or even subtle SRF, that cannot be clinically detected early. Molecular biological advances have improved the ability for diagnosis. Though current treatment modalities are effective in healing active disease yet does not effectively prevent recurrence. Further studies could be dedicated to developing antimicrobials that can help eradicate the disease.
Al Watany Eye Hospital Cairo Egypt, the hospital I have worked at and learnt a lot over the years. The hospital is very supportive of research work and all the images included in this chapter were either captured in the hospital or were in the patient’s electronic medical record. Retinal imaging team WEH dedicated hard work.
I have no financial disclosures or conflict of interest.
‘Special thanks to my dear Mother
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
\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
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One of the most suitable examples of nanoparticles used for this purpose are quantum dots, a type of colloidal fluorescent semiconducting nanocrystalline material that has the possibility, due to its unique optical and electronic properties, to be used in numerous technological applications such as biosensing, in vivo imaging techniques, photovoltaics, nanomedicine, molecular pathology, and drug delivery. Thus, there are almost endless possibilities for quantum dots materials. In spite of the fast advance in the search of quantum dots with better nanomaterial performance, environmentally benign and sustainable production is still lacking. Although the use of these materials is developing promptly, there is increasing concern that these materials might pose potential risks to human health. Herein, we discuss principal properties of quantum dots, including their functional architecture and toxicity, and review the main studies about “green” quantum dots synthesis to be aligned with green nanotechnology approach for nontoxic, cleaner, safer, and more responsible processes. The organometallic colloidal synthesis and the aqueous colloidal synthesis, as well as their drawbacks and benefits, are conferred. Recent advances in technological and biological quantum dots–based applications are also discussed in this chapter.",book:{id:"5170",slug:"green-nanotechnology-overview-and-further-prospects",title:"Green Nanotechnology",fullTitle:"Green Nanotechnology - Overview and Further Prospects"},signatures:"Carlos A. Martínez Bonilla and Vladimir V. Kouznetsov",authors:[{id:"105180",title:"Prof.",name:"Vladimir V.",middleName:"V.",surname:"Kouznetsov",slug:"vladimir-v.-kouznetsov",fullName:"Vladimir V. 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In this sense, new materials such as nanocomposites may overcome these issues taking advantage of the peculiar properties of materials at nanoscale. Research on novel nanotechnologies must bring advances in order to contrast and prevent water scarcity and pollution. In order to be effective, these nanotechnologies should run at low operational cost, even in places unequipped by strong infrastructures and in concert with conventional cheap methodologies.",book:{id:"5170",slug:"green-nanotechnology-overview-and-further-prospects",title:"Green Nanotechnology",fullTitle:"Green Nanotechnology - Overview and Further Prospects"},signatures:"Giuseppe Cacciato, Massimo Zimbone, Francesco Ruffino and Maria\nGrazia Grimaldi",authors:[{id:"178880",title:"Ph.D.",name:"Francesco",middleName:null,surname:"Ruffino",slug:"francesco-ruffino",fullName:"Francesco Ruffino"},{id:"180334",title:"Dr.",name:"Giuseppe",middleName:null,surname:"Cacciato",slug:"giuseppe-cacciato",fullName:"Giuseppe Cacciato"},{id:"180335",title:"Dr.",name:"Massimo",middleName:null,surname:"Zimbone",slug:"massimo-zimbone",fullName:"Massimo Zimbone"},{id:"180336",title:"Prof.",name:"Maria Grazia",middleName:null,surname:"Grimaldi",slug:"maria-grazia-grimaldi",fullName:"Maria Grazia Grimaldi"}]},{id:"50705",doi:"10.5772/63314",title:"Metal Nanoparticles as Emerging Green Catalysts",slug:"metal-nanoparticles-as-emerging-green-catalysts",totalDownloads:3246,totalCrossrefCites:2,totalDimensionsCites:8,abstract:"Green nanotechnology is defined as the technology applied for building clean technology by which one can reduce the potential risks of environment and also improve human health conditions. It is linked with the implementation of products of nanotechnology and its process of manufacturing. Green nanotechnology synthesizes new nanoproducts with improved properties in such a way that they can substitute some of the existing low‐quality products. The main motive of developing new nanoproducts is to enhance sustainability and also to make them more environment friendly. In particular, nanoscale materials (e.g., nanoparticles) can be defined as those having characteristic length scale lying within the nanometric range, that is, in the range between one and several hundreds of nanometers. Within this length scale, the properties of matter are sufficiently different from individual atoms/molecules or from bulk materials. The primary objective of this chapter is to provide comprehensive overview about metal nanoparticles (MNPs) and its application as emerging green catalysts. This chapter contains six sections in total. Section 1 starts with a general introduction, recent progress, and brief summary of the application of MNPs as green catalyst. Section 2 reviews the preparation and characterization of supported metal nanoparticles for a wide range of catalytic applications. Section 3 presents the catalytic properties of supported metal nanoparticles. Section 4 describes briefly some of the most commonly reported supported MNPs in different green catalytic applications. Section 5 concentrates on our own results that related to the application of supported MNPs in catalysis. In this section, the oxidation of benzyl alcohol to benzaldehyde, the production of adipic acid from cyclohexane, the photodegradation of dyes using green route will be discussed. Finally, Section 6 describes the summary of main points and also presents an outlook of the application of MNPs in green chemistry.",book:{id:"5170",slug:"green-nanotechnology-overview-and-further-prospects",title:"Green Nanotechnology",fullTitle:"Green Nanotechnology - Overview and Further Prospects"},signatures:"Ahmad Alshammari, V. Narayana Kalevaru and Andreas Martin",authors:[{id:"178547",title:"Dr.",name:"Ahmad",middleName:null,surname:"Alshammari",slug:"ahmad-alshammari",fullName:"Ahmad Alshammari"},{id:"180753",title:"Dr.",name:"V. Narayana",middleName:null,surname:"Kalevaru",slug:"v.-narayana-kalevaru",fullName:"V. 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This chapter focuses on the many ways that allow to tailor and organize TiO2 crystallites at the nanometre scale to make the most of this amazing material in the field of photovoltaics and gas sensing.",book:{id:"5170",slug:"green-nanotechnology-overview-and-further-prospects",title:"Green Nanotechnology",fullTitle:"Green Nanotechnology - Overview and Further Prospects"},signatures:"André Decroly, Arnaud Krumpmann, Marc Debliquy and Driss\nLahem",authors:[{id:"108357",title:"Dr.",name:"Marc",middleName:null,surname:"Debliquy",slug:"marc-debliquy",fullName:"Marc Debliquy"},{id:"156323",title:"Dr.",name:"Driss",middleName:null,surname:"Lahem",slug:"driss-lahem",fullName:"Driss Lahem"},{id:"179585",title:"Associate Prof.",name:"André",middleName:null,surname:"Decroly",slug:"andre-decroly",fullName:"André Decroly"},{id:"179653",title:"MSc.",name:"Arnaud",middleName:null,surname:"Krumpmann",slug:"arnaud-krumpmann",fullName:"Arnaud Krumpmann"}]},{id:"50087",doi:"10.5772/62240",title:"Friccohesity and Tentropy: New Models of Molecular Sciences",slug:"friccohesity-and-tentropy-new-models-of-molecular-sciences",totalDownloads:1697,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Understanding and developing new molecules in chemical sciences have been great thrust areas of research, not only to develop new synthetic methods or reaction mechanisms of new and greener experimental conditions but also to know what are the new molecule science and what are the new models which can track their new role in chemical processes and also their applications in allied interdisciplinary sciences. The SAR (structure-activity relationship) and STAR (structure-thermodynamics activity relationship) have been the most intimate theories in understanding and finding unique applications of the new molecules. Initially, simple molecules are the focus; however, proteins, hemoglobin, starch, and certain metallic complexes are also in the focus but as natural chemicals; but for past few decades, a lot of focus has been on synthesizing new complex molecules to make them suitable for varieties of applications such as solar, catalysts, biosensors, and others. Hence, it has been essential for focusing on structural sciences of the chemical substances. Dendrimers have been the invention of 1990s in the areas of biocomplexes, biomaterials which are hot thrust areas in molecular interaction engineering to focus on intramolecular potential for industrial applications. Thus, the molecule’s internal structure signifies the various scientific components for playing or making their best use in materials sciences, semiconductor, spintronics, photonics, electronics, etc. Therefore, the molecule’s interacting response with other molecules becomes cohesive or kinetic in nature or whether it induces structuredness or weakens the binding forces and allows more and more kinetic movement or the motion is noted or defined by friccohesity as it is expressed as frictional and cohesive forces. Thus, the friccohesity is a dual forces theory which deals with frictional and cohesive forces together and determined with Survismeter using Mansingh equation molecules [1–3].",book:{id:"5170",slug:"green-nanotechnology-overview-and-further-prospects",title:"Green Nanotechnology",fullTitle:"Green Nanotechnology - Overview and Further Prospects"},signatures:"Man Singh",authors:[{id:"24553",title:"Prof.",name:"Man",middleName:null,surname:"Singh",slug:"man-singh",fullName:"Man Singh"}]}],mostDownloadedChaptersLast30Days:[{id:"50106",title:"“Green” Quantum Dots: Basics, Green Synthesis, and Nanotechnological Applications",slug:"-green-quantum-dots-basics-green-synthesis-and-nanotechnological-applications",totalDownloads:3775,totalCrossrefCites:9,totalDimensionsCites:19,abstract:"Nanotechnological development of new materials involves the discovery or design of materials at small length scales with controlled physical and chemical properties than can be tuned or modified in function of their applications. 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Herein, we discuss principal properties of quantum dots, including their functional architecture and toxicity, and review the main studies about “green” quantum dots synthesis to be aligned with green nanotechnology approach for nontoxic, cleaner, safer, and more responsible processes. The organometallic colloidal synthesis and the aqueous colloidal synthesis, as well as their drawbacks and benefits, are conferred. Recent advances in technological and biological quantum dots–based applications are also discussed in this chapter.",book:{id:"5170",slug:"green-nanotechnology-overview-and-further-prospects",title:"Green Nanotechnology",fullTitle:"Green Nanotechnology - Overview and Further Prospects"},signatures:"Carlos A. Martínez Bonilla and Vladimir V. Kouznetsov",authors:[{id:"105180",title:"Prof.",name:"Vladimir V.",middleName:"V.",surname:"Kouznetsov",slug:"vladimir-v.-kouznetsov",fullName:"Vladimir V. Kouznetsov"},{id:"179817",title:"M.Sc.",name:"Carlos A.",middleName:"Andrés",surname:"Martínez Bonilla",slug:"carlos-a.-martinez-bonilla",fullName:"Carlos A. Martínez Bonilla"}]},{id:"50705",title:"Metal Nanoparticles as Emerging Green Catalysts",slug:"metal-nanoparticles-as-emerging-green-catalysts",totalDownloads:3247,totalCrossrefCites:2,totalDimensionsCites:8,abstract:"Green nanotechnology is defined as the technology applied for building clean technology by which one can reduce the potential risks of environment and also improve human health conditions. It is linked with the implementation of products of nanotechnology and its process of manufacturing. Green nanotechnology synthesizes new nanoproducts with improved properties in such a way that they can substitute some of the existing low‐quality products. The main motive of developing new nanoproducts is to enhance sustainability and also to make them more environment friendly. In particular, nanoscale materials (e.g., nanoparticles) can be defined as those having characteristic length scale lying within the nanometric range, that is, in the range between one and several hundreds of nanometers. Within this length scale, the properties of matter are sufficiently different from individual atoms/molecules or from bulk materials. The primary objective of this chapter is to provide comprehensive overview about metal nanoparticles (MNPs) and its application as emerging green catalysts. This chapter contains six sections in total. Section 1 starts with a general introduction, recent progress, and brief summary of the application of MNPs as green catalyst. Section 2 reviews the preparation and characterization of supported metal nanoparticles for a wide range of catalytic applications. Section 3 presents the catalytic properties of supported metal nanoparticles. Section 4 describes briefly some of the most commonly reported supported MNPs in different green catalytic applications. Section 5 concentrates on our own results that related to the application of supported MNPs in catalysis. In this section, the oxidation of benzyl alcohol to benzaldehyde, the production of adipic acid from cyclohexane, the photodegradation of dyes using green route will be discussed. Finally, Section 6 describes the summary of main points and also presents an outlook of the application of MNPs in green chemistry.",book:{id:"5170",slug:"green-nanotechnology-overview-and-further-prospects",title:"Green Nanotechnology",fullTitle:"Green Nanotechnology - Overview and Further Prospects"},signatures:"Ahmad Alshammari, V. Narayana Kalevaru and Andreas Martin",authors:[{id:"178547",title:"Dr.",name:"Ahmad",middleName:null,surname:"Alshammari",slug:"ahmad-alshammari",fullName:"Ahmad Alshammari"},{id:"180753",title:"Dr.",name:"V. Narayana",middleName:null,surname:"Kalevaru",slug:"v.-narayana-kalevaru",fullName:"V. Narayana Kalevaru"},{id:"180804",title:"Dr.",name:"Andreas",middleName:null,surname:"Martin",slug:"andreas-martin",fullName:"Andreas Martin"}]},{id:"49331",title:"Metal Complexes Immobilized on Magnetic Nanoparticles",slug:"metal-complexes-immobilized-on-magnetic-nanoparticles",totalDownloads:2096,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"The reusability of valuable catalysts in organic reaction without change in properties is known as an important feature in the evolution of green processes. The imobilization of metal catalysts on magnetic nanoparticles makes them recoverable and can be used as building blocks for the fabrication of various functional systems, which are applied in several fields such as catalysis, environmental remediation magnetic resonance imaging, data storage, and biotechnology. Applying magnetic nanoparticles in organic reaction as a scaffold for the immobilization of metal complexes is reviewed as well as the improvement of the methods of production and applying catalysts with magnetic properties in organic reaction.",book:{id:"5170",slug:"green-nanotechnology-overview-and-further-prospects",title:"Green Nanotechnology",fullTitle:"Green Nanotechnology - Overview and Further Prospects"},signatures:"Seyed Mohsen Sadeghzadeh and Mehdi Mogharabi",authors:[{id:"175879",title:"Dr.",name:"Seyed Mohsen",middleName:null,surname:"Sadeghzadeh",slug:"seyed-mohsen-sadeghzadeh",fullName:"Seyed Mohsen Sadeghzadeh"},{id:"191799",title:"Dr.",name:"Mehdi",middleName:null,surname:"Mogharabi",slug:"mehdi-mogharabi",fullName:"Mehdi Mogharabi"}]},{id:"50132",title:"Recent Highlights in Green Oxidative Chemical Processes Applied to Steroid Chemistry",slug:"recent-highlights-in-green-oxidative-chemical-processes-applied-to-steroid-chemistry",totalDownloads:2379,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Steroids and their oxidation products are widely distributed in living organisms and are important intermediates for the synthesis of many biologically active molecules. Due to their pharmacological and synthetic relevance, several oxidative chemical processes for the functionalization of the steroid nucleus have been developed. Green chemistry principles have been incorporated in some oxidative transformations of steroids, allowing significant advances in synthetic chemistry applied to these compounds. This chapter presents a selection of relevant applications of pharmaceutical green chemistry to steroid’s oxidative processes. Special emphasis is given to catalytic processes encompassing heterogeneous nanocatalysts, whose application in this context is increasing over the past years. This chapter is organized according to the reaction type that includes alcohol oxidation, epoxidation of alkenes, and allylic oxidation of alkenes to enones, among other relevant oxidative transformations. Biocatalytic oxidative methods applied to steroid synthesis are not included in this review.",book:{id:"5170",slug:"green-nanotechnology-overview-and-further-prospects",title:"Green Nanotechnology",fullTitle:"Green Nanotechnology - Overview and Further Prospects"},signatures:"Samuel M. Silvestre, M. Manuel C. Silva and Jorge A. R. Salvador",authors:[{id:"69976",title:"Prof.",name:"Jorge António Ribeiro",middleName:null,surname:"Salvador",slug:"jorge-antonio-ribeiro-salvador",fullName:"Jorge António Ribeiro Salvador"},{id:"157541",title:"Prof.",name:"Samuel",middleName:null,surname:"Silvestre",slug:"samuel-silvestre",fullName:"Samuel Silvestre"},{id:"185027",title:"Prof.",name:"Maria Manuel Cruz",middleName:null,surname:"Silva",slug:"maria-manuel-cruz-silva",fullName:"Maria Manuel Cruz Silva"}]},{id:"50074",title:"Nanostructured TiO2 Layers for Photovoltaic and Gas Sensing Applications",slug:"nanostructured-tio2-layers-for-photovoltaic-and-gas-sensing-applications",totalDownloads:2105,totalCrossrefCites:3,totalDimensionsCites:6,abstract:"Titanium dioxide (TiO2) has been an important material for decades, combining numerous attractive properties in terms of economy (low price, large availability) or ecology (non-toxic), as well as broad physical and chemical possibilities. In the last few years, the development of nanotechnologies offered new opportunities, not only in an academic perspective but also with a view to many applications with particular reference to the environment. This chapter focuses on the many ways that allow to tailor and organize TiO2 crystallites at the nanometre scale to make the most of this amazing material in the field of photovoltaics and gas sensing.",book:{id:"5170",slug:"green-nanotechnology-overview-and-further-prospects",title:"Green Nanotechnology",fullTitle:"Green Nanotechnology - Overview and Further Prospects"},signatures:"André Decroly, Arnaud Krumpmann, Marc Debliquy and Driss\nLahem",authors:[{id:"108357",title:"Dr.",name:"Marc",middleName:null,surname:"Debliquy",slug:"marc-debliquy",fullName:"Marc Debliquy"},{id:"156323",title:"Dr.",name:"Driss",middleName:null,surname:"Lahem",slug:"driss-lahem",fullName:"Driss Lahem"},{id:"179585",title:"Associate Prof.",name:"André",middleName:null,surname:"Decroly",slug:"andre-decroly",fullName:"André Decroly"},{id:"179653",title:"MSc.",name:"Arnaud",middleName:null,surname:"Krumpmann",slug:"arnaud-krumpmann",fullName:"Arnaud Krumpmann"}]}],onlineFirstChaptersFilter:{topicId:"851",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261",scope:"Modern physiology requires a comprehensive understanding of the integration of tissues and organs throughout the mammalian body, including the cooperation between structure and function at the cellular and molecular levels governed by gene and protein expression. While a daunting task, learning is facilitated by identifying common and effective signaling pathways mediated by a variety of factors employed by nature to preserve and sustain homeostatic life. \r\nAs a leading example, the cellular interaction between intracellular concentration of Ca+2 increases, and changes in plasma membrane potential is integral for coordinating blood flow, governing the exocytosis of neurotransmitters, and modulating gene expression and cell effector secretory functions. Furthermore, in this manner, understanding the systemic interaction between the cardiovascular and nervous systems has become more important than ever as human populations' life prolongation, aging and mechanisms of cellular oxidative signaling are utilised for sustaining life. \r\nAltogether, physiological research enables our identification of distinct and precise points of transition from health to the development of multimorbidity throughout the inevitable aging disorders (e.g., diabetes, hypertension, chronic kidney disease, heart failure, peptic ulcer, inflammatory bowel disease, age-related macular degeneration, cancer). With consideration of all organ systems (e.g., brain, heart, lung, gut, skeletal and smooth muscle, liver, pancreas, kidney, eye) and the interactions thereof, this Physiology Series will address the goals of resolving (1) Aging physiology and chronic disease progression (2) Examination of key cellular pathways as they relate to calcium, oxidative stress, and electrical signaling, and (3) how changes in plasma membrane produced by lipid peroxidation products can affect aging physiology, covering new research in the area of cell, human, plant and animal physiology.",coverUrl:"https://cdn.intechopen.com/series/covers/10.jpg",latestPublicationDate:"May 14th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:11,editor:{id:"35854",title:"Prof.",name:"Tomasz",middleName:null,surname:"Brzozowski",slug:"tomasz-brzozowski",fullName:"Tomasz Brzozowski",profilePictureURL:"https://mts.intechopen.com/storage/users/35854/images/system/35854.jpg",biography:"Prof. Dr. Thomas Brzozowski works as a professor of Human Physiology and is currently Chairman at the Department of Physiology and is V-Dean of the Medical Faculty at Jagiellonian University Medical College, Cracow, Poland. His primary area of interest is physiology and pathophysiology of the gastrointestinal (GI) tract, with the major focus on the mechanism of GI mucosal defense, protection, and ulcer healing. He was a postdoctoral NIH fellow at the University of California and the Gastroenterology VA Medical Center, Irvine, Long Beach, CA, USA, and at the Gastroenterology Clinics Erlangen-Nuremberg and Munster in Germany. He has published 290 original articles in some of the most prestigious scientific journals and seven book chapters on the pathophysiology of the GI tract, gastroprotection, ulcer healing, drug therapy of peptic ulcers, hormonal regulation of the gut, and inflammatory bowel disease.",institutionString:null,institution:{name:"Jagiellonian University",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:49,paginationItems:[{id:"80495",title:"Iron in Cell Metabolism and Disease",doi:"10.5772/intechopen.101908",signatures:"Eeka Prabhakar",slug:"iron-in-cell-metabolism-and-disease",totalDownloads:2,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Iron Metabolism - Iron a Double‐Edged Sword",coverURL:"https://cdn.intechopen.com/books/images_new/10842.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81799",title:"Cross Talk of Purinergic and Immune Signaling: Implication in Inflammatory and Pathogenic Diseases",doi:"10.5772/intechopen.104978",signatures:"Richa Rai",slug:"cross-talk-of-purinergic-and-immune-signaling-implication-in-inflammatory-and-pathogenic-diseases",totalDownloads:8,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81764",title:"Involvement of the Purinergic System in Cell Death in Models of Retinopathies",doi:"10.5772/intechopen.103935",signatures:"Douglas Penaforte Cruz, Marinna Garcia Repossi and Lucianne Fragel Madeira",slug:"involvement-of-the-purinergic-system-in-cell-death-in-models-of-retinopathies",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81756",title:"Alteration of Cytokines Level and Oxidative Stress Parameters in COVID-19",doi:"10.5772/intechopen.104950",signatures:"Marija Petrusevska, Emilija Atanasovska, Dragica Zendelovska, Aleksandar Eftimov and Katerina Spasovska",slug:"alteration-of-cytokines-level-and-oxidative-stress-parameters-in-covid-19",totalDownloads:9,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Chemokines Updates",coverURL:"https://cdn.intechopen.com/books/images_new/11672.jpg",subseries:{id:"18",title:"Proteomics"}}}]},overviewPagePublishedBooks:{paginationCount:27,paginationItems:[{type:"book",id:"7006",title:"Biochemistry and Health Benefits of Fatty Acids",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7006.jpg",slug:"biochemistry-and-health-benefits-of-fatty-acids",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Viduranga Waisundara",hash:"c93a00abd68b5eba67e5e719f67fd20b",volumeInSeries:1,fullTitle:"Biochemistry and Health Benefits of Fatty Acids",editors:[{id:"194281",title:"Dr.",name:"Viduranga Y.",middleName:null,surname:"Waisundara",slug:"viduranga-y.-waisundara",fullName:"Viduranga Y. Waisundara",profilePictureURL:"https://mts.intechopen.com/storage/users/194281/images/system/194281.jpg",biography:"Dr. Viduranga Waisundara obtained her Ph.D. in Food Science and Technology from the Department of Chemistry, National University of Singapore, in 2010. She was a lecturer at Temasek Polytechnic, Singapore from July 2009 to March 2013. She relocated to her motherland of Sri Lanka and spearheaded the Functional Food Product Development Project at the National Institute of Fundamental Studies from April 2013 to October 2016. She was a senior lecturer on a temporary basis at the Department of Food Technology, Faculty of Technology, Rajarata University of Sri Lanka. She is currently Deputy Principal of the Australian College of Business and Technology – Kandy Campus, Sri Lanka. She is also the Global Harmonization Initiative (GHI) Ambassador to Sri Lanka.",institutionString:"Australian College of Business & Technology",institution:null}]},{type:"book",id:"6820",title:"Keratin",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6820.jpg",slug:"keratin",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Miroslav Blumenberg",hash:"6def75cd4b6b5324a02b6dc0359896d0",volumeInSeries:2,fullTitle:"Keratin",editors:[{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. 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Later, he completed his postdoctoral research at the Center of Molecular Biosciences, University of the Ryukyus, Japan, as a recipient of the Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship. He was also the recipient of the Australian Government Endeavour Research Fellowship for postdoctoral research as an adjunct senior researcher at the University of Tasmania, Australia. Dr. Hasanuzzaman’s current work is focused on the physiological and molecular mechanisms of environmental stress tolerance. Dr. Hasanuzzaman has published more than 150 articles in peer-reviewed journals. He has edited ten books and written more than forty book chapters on important aspects of plant physiology, plant stress tolerance, and crop production. According to Scopus, Dr. Hasanuzzaman’s publications have received more than 10,500 citations with an h-index of 53. He has been named a Highly Cited Researcher by Clarivate. He is an editor and reviewer for more than fifty peer-reviewed international journals and was a recipient of the “Publons Peer Review Award” in 2017, 2018, and 2019. He has been honored by different authorities for his outstanding performance in various fields like research and education, and he has received the World Academy of Science Young Scientist Award (2014) and the University Grants Commission (UGC) Award 2018. He is a fellow of the Bangladesh Academy of Sciences (BAS) and the Royal Society of Biology.",institutionString:"Sher-e-Bangla Agricultural University",institution:{name:"Sher-e-Bangla Agricultural University",country:{name:"Bangladesh"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",biography:"Kusal K. Das is a Distinguished Chair Professor of Physiology, Shri B. M. Patil Medical College and Director, Centre for Advanced Medical Research (CAMR), BLDE (Deemed to be University), Vijayapur, Karnataka, India. Dr. Das did his M.S. and Ph.D. in Human Physiology from the University of Calcutta, Kolkata. His area of research is focused on understanding of molecular mechanisms of heavy metal activated low oxygen sensing pathways in vascular pathophysiology. He has invented a new method of estimation of serum vitamin E. His expertise in critical experimental protocols on vascular functions in experimental animals was well documented by his quality of publications. He was a Visiting Professor of Medicine at University of Leeds, United Kingdom (2014-2016) and Tulane University, New Orleans, USA (2017). For his immense contribution in medical research Ministry of Science and Technology, Government of India conferred him 'G.P. Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. degree in chemistry in 2000 and Ph.D. degree in physical chemistry in 2007 from the University of Khartoum, Sudan. He moved to School of Chemistry, Faculty of Science, University of Sydney, Australia in 2009 and joined Dr. Ron Clarke as a postdoctoral fellow where he worked on the interaction of ATP with the phosphoenzyme of the Na+/K+-ATPase and dual mechanisms of allosteric acceleration of the Na+/K+-ATPase by ATP; then he went back to Department of Chemistry, University of Khartoum as an assistant professor, and in 2014 he was promoted as an associate professor. In 2011, he joined the staff of Department of Chemistry at Taif University, Saudi Arabia, where he is currently an assistant professor. His research interests include the following: P-Type ATPase enzyme kinetics and mechanisms, kinetics and mechanisms of redox reactions, autocatalytic reactions, computational enzyme kinetics, allosteric acceleration of P-type ATPases by ATP, exploring of allosteric sites of ATPases, and interaction of ATP with ATPases located in cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. His Works are realted to the Green chemistry field, biolubricants, biodiesel, transesterification reactions for biodiesel production and the manipulation of oils for therapeutic purposes.",institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",country:{name:"Argentina"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",biography:"Francisco Javier Martín-Romero (Javier) is a Professor of Biochemistry and Molecular Biology at the University of Extremadura, Spain. He is also a group leader at the Biomarkers Institute of Molecular Pathology. Javier received his Ph.D. in 1998 in Biochemistry and Biophysics. At the National Cancer Institute (National Institute of Health, Bethesda, MD) he worked as a research associate on the molecular biology of selenium and its role in health and disease. After postdoctoral collaborations with Carlos Gutierrez-Merino (University of Extremadura, Spain) and Dario Alessi (University of Dundee, UK), he established his own laboratory in 2008. The interest of Javier's lab is the study of cell signaling with a special focus on Ca2+ signaling, and how Ca2+ transport modulates the cytoskeleton, migration, differentiation, cell death, etc. He is especially interested in the study of Ca2+ channels, and the role of STIM1 in the initiation of pathological events.",institutionString:null,institution:{name:"University of Extremadura",country:{name:"Spain"}}},{id:"217323",title:"Prof.",name:"Guang-Jer",middleName:null,surname:"Wu",slug:"guang-jer-wu",fullName:"Guang-Jer Wu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217323/images/8027_n.jpg",biography:null,institutionString:null,institution:null},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/148546/images/4640_n.jpg",biography:null,institutionString:null,institution:null},{id:"272889",title:"Dr.",name:"Narendra",middleName:null,surname:"Maddu",slug:"narendra-maddu",fullName:"Narendra Maddu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272889/images/10758_n.jpg",biography:null,institutionString:null,institution:null},{id:"242491",title:"Prof.",name:"Angelica",middleName:null,surname:"Rueda",slug:"angelica-rueda",fullName:"Angelica Rueda",position:"Investigador Cinvestav 3B",profilePictureURL:"https://mts.intechopen.com/storage/users/242491/images/6765_n.jpg",biography:null,institutionString:null,institution:null},{id:"88631",title:"Dr.",name:"Ivan",middleName:null,surname:"Petyaev",slug:"ivan-petyaev",fullName:"Ivan Petyaev",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Lycotec (United Kingdom)",country:{name:"United Kingdom"}}},{id:"423869",title:"Ms.",name:"Smita",middleName:null,surname:"Rai",slug:"smita-rai",fullName:"Smita Rai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424024",title:"Prof.",name:"Swati",middleName:null,surname:"Sharma",slug:"swati-sharma",fullName:"Swati Sharma",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"439112",title:"MSc.",name:"Touseef",middleName:null,surname:"Fatima",slug:"touseef-fatima",fullName:"Touseef Fatima",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424836",title:"Dr.",name:"Orsolya",middleName:null,surname:"Borsai",slug:"orsolya-borsai",fullName:"Orsolya Borsai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",country:{name:"Romania"}}},{id:"422262",title:"Ph.D.",name:"Paola Andrea",middleName:null,surname:"Palmeros-Suárez",slug:"paola-andrea-palmeros-suarez",fullName:"Paola Andrea Palmeros-Suárez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Guadalajara",country:{name:"Mexico"}}}]}},subseries:{item:{id:"12",type:"subseries",title:"Human Physiology",keywords:"Anatomy, Cells, Organs, Systems, Homeostasis, Functions",scope:"Human physiology is the scientific exploration of the various functions (physical, biochemical, and mechanical properties) of humans, their organs, and their constituent cells. The endocrine and nervous systems play important roles in maintaining homeostasis in the human body. Integration, which is the biological basis of physiology, is achieved through communication between the many overlapping functions of the human body's systems, which takes place through electrical and chemical means. Much of the basis of our knowledge of human physiology has been provided by animal experiments. Because of the close relationship between structure and function, studies in human physiology and anatomy seek to understand the mechanisms that help the human body function. 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