Doses for commonly utilized antimicrobials for intrauterine administration (table reproduced courtesy of equine reproduction laboratory, Colorado State University).
\r\n\tSynthetic zeolites can be formed from different raw materials and among these many wastes represent some interesting sources due to their chemical and mineralogical composition. Today, a large number of different types of waste resulting from many human activities are produced in the world (e.g. industrial, municipal, agricultural waste) and most of them are deposed of in landfills thus determining a great environmental problem.
\r\n\r\n\tThis book intends to provide the reader with a comprehensive overview of the current state-of-the-art on the possibility to transform the different types of waste materials into useful products, zeolites, through conventional processes and innovative methods. The aim is to demonstrate that waste can be a problem or a resource depending on how it is managed.
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The scope of this chapter is to try to answer some of the most common questions an attending veterinarian may be asked to deal with, namely, shortening the vernal transition, dealing with postmating endometritis, and dealing with twin pregnancy, all of which can frustrate even the seasoned clinician. The aim of this chapter is to give the reader the background knowledge of why certain therapies may or may not work and to give the clinician workable solutions to some of the more common aspects of clinical reproductive work in the mare.
The mare is a seasonal, long-day, polyestrous animal, meaning that her reproductive status is intrinsically linked to photoperiod. In the Northern Hemisphere, the normal physiologic breeding season starts in spring (April) and continues through to autumn (September). This corresponds to increasing photoperiod (increasing daylight length). The light signals are received by the retina, processed by melanopsin [1], which, as a pigment, is located in retinal ganglion cells, themselves being photosensitive. This information reaches the suprachiasmatic nucleus via the retino-hypothalamic tract [2]. Melatonin produced in the pineal gland is suppressed during hours of darkness. This fall in melatonin as photoperiod increases during the spring stimulates the mare to, reproductively, enter the spring or vernal transition. The classical hypothalamic–pituitary-ovarian axis, known to many clinicians, is oversimplified.
In the last decade or so, numerous authors have examined the role of kisspeptin neurons in the relation of cyclicity in many animal models, including the mare. It appears that increasing photoperiod stimulates the main kisspeptin neuron population located in the arcuate nucleus of the hypothalamus [3]. Distinctly, the horse does not appear to have a secondary population of kisspeptin neurons in the preoptic area, unlike cattle and sheep [4]. A small population of these receptors are located within the ventromedial nucleus of the hypothalamus [5]. The kisspeptin neuron fibers are found throughout the septo-preoptic region, an area that the majority of gonadotrophin-releasing hormone (GnRH) neurons are located [6]. In 2007, Smith et al. were the first to note that kisspeptin neurons may be influenced by photoperiod [7]. They saw an increase in KISS1 mRNA in the arcuate nucleus in sheep in their physiologic breeding season. Our understanding of the role of kisspeptin in the mare and effects on her reproductive status is derived mainly from studies on sheep models; there have been limited studies in the mare.
In the sheep model, it appears that in artificially decreasing photoperiod, thereby eliciting a stimulatory effect in sheep (sheep are short-day breeders), there is a corresponding increase in the number of kisspeptin neurons [8]. Kisspeptin neurons appear to form numerous synapses with other neurons that produce dopamine [9], melanocyte-stimulating hormone [10], and GnRH [11], among others. The regulation of kisspeptin is still not fully understood, but it appears that it may consist of a combination of negative feedback via estrogen in the sheep model [12] and via dopamine. The dopamine neurons in the retrochiasmatic area of the hypothalamus exerts an inhibitory effect on GnRH secretion during anestrous but not during the physiologic breeding season [13]. There is an upregulation of dopamine receptors in the kisspeptin neurons during breeding season [13]. There appears to be a seasonal difference in the number of kisspeptin neurons in the population found in the arcuate nucleus of the hypothalamus, but no seasonal difference in the preoptic population. This has been confirmed in the mare [4]. This seasonality difference appears to be driven, or at least modulated, by photoperiod. However, from sheep models, we know kisspeptin does not express melatonin receptors [14], and it is proposed that any effect of melatonin on the functionality of kisspeptin may be indirect [3]. It has also been postulated there is an indirect effect of photoperiod that is modulated via the thyroid hormones [3]. Nearly all preoptic kisspeptin neurons express thyroid receptors [15]. It has been shown that the thyrotropes (the cells secreting these hormones) located in the pars tuberalis of the rostral adenohypophysis are melatonin responsive [16, 17]. It appears these cells display dramatic melatonin-dependent photoperiodic changes; under short photoperiod, there is low level expression, while under long photoperiod, there is high level expression [18, 19].
GnRH is a 10 amino acid peptide secreted by the hypothalamus. Its secretion, regulated by decreasing melatonin during increased photoperiod, is modulated via kisspeptin neurons mentioned above. Secretion of this peptide enters the hypothalamic-hypophyseal blood portal system, which bathes over the gonadotrophs located in the anterior pituitary, cells that synthesize and secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). During the vernal transition, there are ever-increasing circulating concentrations of FSH and LH. This increase is gradual, with LH in particular remaining low prior to the first ovulation. It is thought that the low circulating LH is due to the low storage of LH within the gonadotrophs [20]. Under the regulation described above, the increased GnRH stimulates FSH secretion and thus drives the growth of ovarian follicles. However during the vernal transition, mares undergo several follicular waves. Under these waves, follicles seemingly grow (although they rarely reach pre-ovulatory size), only to regress, and be replaced by another follicular wave. In a report by Watson et al. [21], only 31% of all FSH surges during this transition period lead to the production of a follicular wave. Only one a follicle under the influence of FSH, produces sufficient estrogen, will a follicle ovulate under the LH surge. Estrogen appears to be involved in numerous components of the mare reproductive cycle. It appears that estrogen has a negative and a positive feedback mechanism on kisspeptin within the arcuate nucleus [7, 22], while the fall in circulating estrogen levels leads to increased LH secretion at the level of the anterior pituitary. During the peri-ovulatory surge, declining FSH under the influence of increasing estrogen and inhibin production from the growing follicle, LH reaches maximum concentrations 1 day post ovulation. LH promotes the maturation and subsequent ovulation of the follicle.
Numerous issues can be seen related to this complex reproductive cycle. During the vernal transition, mares may be presented with multiple small follicles evident on the ovaries via transrectal ultrasonography. Follicles may grow and then regress. The unpredictable nature of the folliculogenesis and the exact duration of the vernal transition are not only frustrating for the owner but a headache for the attending clinician. It is imperative that the clinician has a thorough understanding of the mechanisms at play during this period. Having this knowledge will allow the veterinarian to potentially manipulate these mechanisms and the hormones involved and shorten this phase. Understanding the systems at play allows for proper management by the veterinarian and will increase the productivity of the mares under their control.
In the Northern Hemisphere, it has become standard industry practice to place mares under light regimes starting December 1 [23] in the breeding of thoroughbred racehorses. Nonetheless many breeders of other types of horses also utilize light manipulation to hasten time to first ovulation. A 200 watt incandescent light bulb in a 12 × 12 foot stall is sufficient to begin stimulating follicular activity. Typically light is added to the evening; mares are brought into their stalls from pasture before dusk and then exposed to artificial light until 23.00 hours. It is now known that light in the short wave spectrum (465–485 nm) is most effective at inhibiting melatonin production [24]. It is important to allow the mare to receive some hours of darkness and that exposing them constantly to light stimulation actually extends the anestrous period. On larger horse farms, the use of indoor schools, housing numerous barren, and/or maiden mares can be effective. However, in those large building, it is important to check the light intensity at all areas. A loose rule of thumb is that the light should cast no shadows and that you should be able to read a newspaper anywhere in the building. For those who want to be more scientific in their approach, a photometer can be utilized. Exposure to this light regimen should continue for at least 70 days. Within 60 days, most mares will show some follicular activity, with the majority expressing their first ovulation with 70 days of onset of light exposure. While exposure to artificial light does not eliminate the vernal transition, it simply moves it forward. In the natural physiologic breeding season, the mare will not display follicular activity until April, and many will not experience their first ovulation of the season until May. Moving the vernal transition forward several months allows the clinician to start breeding these mares in February and March.
There are disadvantages to this regime. The mares must be housed either in stalls or a large barn, which intensifies their maintenance. Stalls need to be cleaned out regularly, adding to staffing responsibilities. In addition mares housed in groups in barns allow for opportune risk for injury especially if they are fed together—the lowly mare has nowhere to run from her aggressive barn mate.
To counter the problems of intensified housing of mares under light, researchers in Ireland have come up with a novel way to provide the mare with enough stimulatory light to advance the physiologic breeding season, while in their pasture. These masks provide blue light to one eye. It was concluded by Murphy et al. [23] that one light stimulation to one eye is sufficient to stimulate onset of follicular activity, is as effective as stall or barn light regimes, but also has added benefits of being more economic, especially to the small-scale breeder, while increasing horse welfare. Horses can remain out in their pastures, which reduces stress on these animals. However, these are currently one-time use items (as in for one season) and cost a few hundred dollars per mask, and occasionally inquisitive mares may pull off the face mask of another. On larger studs where the infrastructure for housing numerous animals under artificial lights, and with adequate staffing, it appears that the traditional light regimes remain the favor. Despite this, there is a place of the use for such masks. Mares seem to lose interest in the mask of other horses within a few days (the likelihood of a mask being pulled off is highest at the start). Providing there is nothing in the pasture on which the mare could hook the mask on (access to tree branches or fence posts above rails), and given that it is securely fastened, the mask should remain in place. Those that have only a handful of broodmares may prefer this method, as it reduces labor costs involved with stalling the mare.
As described above, kisspeptin appears to regulate GnRH secretion. As of yet, no commercial kisspeptin product is available. A recent report by Australian researchers found that although kisspeptin administered to mares as a constant rate infusion elevated circulating LH levels, it did not lead to an LH surge and therefore did not evoke ovulations within their group of mares during the vernal transition [4]. It remains to be seen whether the use of kisspeptin may shorten time to first ovulation, by potentially driving follicle maturation, under influence of LH, without necessarily causing ovulation.
As shown, dopamine plays an essential role in the stimulation of the reproductive axis in the mare. Dopamine has an inhibitory effect on GnRH release. For completeness it appears that dopamine antagonist acts via the stimulation of prolactin. For both domperidone and sulpiride, the dose is 1 mg/kg given PO and IM, respectively. Both are administered once daily for 25 days. The reports on the efficacy of the use of these preparations to shorten time to first ovulation in the mare are conflicting. A recent study by Mari et al. [25], comparing the two products, found that sulpiride significantly shortened time to pregnancy establishment (61 days) compared with domperidone-treated mares (83 days). That group concluded sulpiride is effective in advancing the vernal transition, whereas domperidone is only effective in some mares.
As mentioned the long transitional phase exhibited by mares is characterized by numerous follicular waves, unpredictable follicle growth, and follicle regression. Many protocols have examined the use of progesterone (P4) to dampen down these unpredictable features of the transitional phase and to drive a follicle to become dominant and one that will ovulate. The physiological effect of exogenous progesterone supplementation is relatively simple. P4 exerts an inhibitory mechanism with regard to LH but has minimal effect on FSH secretion. As described earlier, LH is required for maturation and final ovulation of the dominant follicle. While the mare is exposed to exogenous P4, LH is blocked at the level of the anterior pituitary, while FSH continues to be secreted. Therefore the follicles continue to grow under influence of FSH. Once the exogenous source of P4 is removed, this sudden fall in circulating P4 stimulates the LH surge, leading to final maturation and ovulation of a dominant follicle. The typical regimen is a dietary supplementation with altrenogest (Regumate®) at 0.044 mg/kg PO for 10 days. Injectable P4 products are becoming more routinely available. In the USA compounded products such as progesterone in oil can be utilized. Controlled release of P4 from these compounds last between 7 and 10 days. Daily application of oral altrenogest can be time-consuming. There also is a risk of noncompliance, should a mare be difficult to catch, not to mention potential side effect for the operator. The use of these long-acting P4 BioRelease products have been shown to be effective [26]. It appears that the use of exogenous P4 has maximal benefits when the mare exhibits a follicle of at least 20 mm in diameter and when administered in deep anestrous has little effect [27, 28]. An injectable altrenogest marketed via BOVA has recently become available in the UK for the first time, although no studies on its efficacy are currently available.
Endometritis is a leading cause of subfertility in the mare [29] and is the third most reported condition seen in our equine patients [30]. Endometritis, simply, the inflammation of the lining of the uterus, has historically been attributed to bacterial colonization and infection of the uterus. However there are a subgroup of mares that will exhibit persistent mating-induced endometritis (PMIE), in the absence of bacterial isolation. Furthermore we will also examine in the chapter the role of biofilm formation and bacterial endometritis.
Post breeding, a normal, physiologic endometritis will be observed in all mares [31]. This normal, transient event, which peaks around 8 hours post insemination, occurs to eliminate excessive spermatozoa, seminal plasma, and contaminants from the uterus [32]. This physiologic response should be over by 48 hours post insemination [33]. The subgroup of mares that experience PMIE appear to have an altered inflammatory response to the presence of spermatozoa and seminal plasma within the uterus. These mares tend to be aged, have increased parity, may exhibit chronic inflammatory changes within the endometrium [34], and exhibit failure to clear intrauterine bacterial challenges [35]. Susceptibility rates among thoroughbred broodmares is 15% [36], and crucially the early embryonic death rate is three times higher in this group of mares [37]. A persistent inflammatory uterine environment 5 days post fertilization is incompatible with embryo survival [38].
It has long been proposed that mares are classified as either susceptible or resistant to PMIE. It has been shown that susceptible mares do have altered protein composition of their endometrial fluid [39] and these mares also exhibit higher levels of pro-inflammatory cytokines [40, 41]. It has also been shown that these mares with a delayed uterine clearance have contractile defects of the endometrium, possibly contributing to this delay in uterine fluid clearance [42]. It has been proposed that nitric oxide mediates smooth muscle relaxation [43]. It also important that mares that fall into this subgroup tend to have poor perineal conformation and a forward tilt to the uterus, such that it sits over the pelvic brim. It is therefore paramount to be able to identify these mares and initiate appropriate therapy.
Bacterial endometritis in the mare is primarily caused by four pathogenic species:
A list of commonly used intrauterine antibiotics and dosages can be found in Table 1 in the therapy section.
Product | Dosage | Notes | |
---|---|---|---|
Antifungals | Clotrimazole (100 mg/tablet) | 500 mg in 50 mls sterile saline | |
Fluconazole (200 mg/tablet) | 100–250 mg in 50 ml sterile water | Add 5 ml DMSO per 1 gram of fluconazole to aid in dissolving tablets | |
Antibacterials | Ampicillin (1 g vial) | 1–2 g in 50 ml sterile saline | Mainly effective against gram-positive bacteria |
Ceftiofur (1 g vial) | 1 g in 20 ml sterile saline | Broad-spectrum antibiotic | |
Ciprofloxacin (10 mg/ml) | 400–500 mg in 50 ml sterile saline | Mainly effective against gram-negative bacteria. Not first line; only utilize if strains are resistant to other antimicrobials | |
Gentamicin (100 mg/ml) | 1–2 g, buffer with 10 ml 8.4% sodium bicarbonate | Mainly effective against gram-negative bacteria | |
Penicillin (procaine) 300,000 units per ml | 15 ml, dilute to 50 ml in sterile saline | Mainly effective against gram-positive bacteria |
Doses for commonly utilized antimicrobials for intrauterine administration (table reproduced courtesy of equine reproduction laboratory, Colorado State University).
Around 5 percent of infectious endometritis are attributed to fungal organisms [48], of which
In any suspected fungal endometritis, it is imperative to send the sample swab to be tested for polymerase chain reaction (PCR). Fungal growth in routine laboratory cultures encompasses a long wait for results, whereas the turnaround for PCR is relatively quick.
Therapy for endometritis in the mare will vary depending on whether the attending veterinarian is dealing with a bacterial endometritis, fungal endometritis, or indeed PMIE. Nonetheless there are some therapies that will be necessary in all cases, and they are dealt with first.
It is imperative to correct any caudal reproductive tract anatomical anomalies, such as poor perineal conformation. Surgical correction, such as a vulvoplasty (also known as a Caslick procedure), should be performed on these mares prior to breeding. A temporary Caslick can aid in treatment during the few days intrauterine access is required. A permanent Caslick can then be placed after treatment has ceased or after breeding (and resolution of any post-breeding fluid). An alternative is to place a permanent Caslick and to administer the treatment via a speculum, giving access to the cervix. Fixing anatomical defects in this area will prevent recontamination of the caudal reproductive tract and helps to “pull” the uterus into a more caudal position, aiding the natural mechanical cleansing mechanism of the mare.
All mares that have excess fluid should undergo uterine lavages. In cases of infectious endometritis, these uterine lavages reduce the organism load, aid in removal of biofilms (see below for further treatments), and reduce particulate matter that may interfere with the antimicrobials used.
No attending veterinarian should underestimate the use of ecbolic when dealing with endometritis in the mare. The two commonly used preparations are oxytocin and prostaglandin F2α (PGF2α) in dealing with uterine fluid.
Oxytocin is by far the most commonly used of these two. Its ease of administration either given IM (intramuscular) or IV (intravenous) and its relatively short duration of approximately 30–45 minutes make it an essential product to have on standby when breeding mares. Side effects are minimal. However given its short duration of action, it does require multiple doses. Typically 1 ml either IV or IM of oxytocin given every 4 hours for 1 day, starting a minimum 4 hours post breeding, will be sufficient in treating most minor cases of uterine fluid retention.
The use of prostaglandins is not as straightforward as oxytocin. There are more side effects with the use of this preparation, and some are potentially quite serious. Prostaglandin is a known abortifacient. It is a good practice to always identify the mare in front of you for any reproductive treatment and, if in doubt, ultrasound the mare to confirm that she is indeed empty. Duration of action is approximately 4 hours. During this time, the mare may sweat, may act colicky, and may exhibit loose stools. It is recommended to monitor the mare during these 4 hours. Many clinicians are familiar with the use of PGF2α, as a luteolytic agent, and that is by far the most common use in equine reproduction. However, the veterinarian should not be afraid of its use when dealing with uterine fluid retention. Caution must be taken, however, when dosing PGF2α on the day of ovulation, as some studies have suggested that it can impact the formation of the corpus hemorrhagicum (which later becomes the CL, the source of progesterone required for maintenance of pregnancy). On the day of ovulation, it would steer the clinician away from use of prostaglandins, unless he or she is prepared to place that mare on an exogenous source of progesterone. The typical protocol initiated at my practice is that we would start with oxytocin for the first day and a half. If the mare has yet to respond satisfactorily to oxytocin therapy in that time, she is unlikely to respond. Throwing more oxytocin her way is futile. It is at this point we would consider the use of prostaglandin. In exceptional and severe cases, where there is significant fluid retention, it is not unknown to utilize both oxytocin and prostaglandin simultaneously on day 1.
Typically 3 days of intrauterine therapy is sufficient to see a positive outcome to therapy. It is bad practice to initiate intrauterine therapy for more than 3 days and predispose the bacterial inhabitants of the uterus to develop resistance to the antimicrobial utilized.
If the mare is presented with significant uterine fluid (in excess of 1 cm on ultrasonography), care must be taken to remove excessive uterine luminal fluid before commencement of the therapy. This is because we now know that certain antimicrobials may be affected by the fluid, but also there is a dilution factor to consider. Removal of fluid may include uterine lavages where 1–2 L of sterile fluid is distilled into the uterus and then allowed to flow back through the same giving set back into their original bags. Manual palpation of the uterus via the rectum at the same time the veterinarian is trying to remove the fluid may aid in evacuation of the uterine fluid. Ecbolics can be utilized concurrently, namely, oxytocin (see Table 2). For mares that present with minimal fluid, the use of ecbolics may be sufficient to remove the fluid. It is recommended to ultrasound the uterus prior to each intrauterine infusion.
Product | Dose and route of administration | Notes |
---|---|---|
Lutalyse® (dinoprost tromethamine) | 5–10 mg IM once | Naturally occurring prostaglandin F2α |
Estrumate® (cloprostenol) | 250 μg IM once | Synthetic prostaglandin F2α |
Oxytocin (20 units/ml) | 20 units IV or IM | q 6 hours |
Doses and routes of administration for the commonly utilized ecbolic agents (table reproduced courtesy of equine reproduction laboratory, Colorado State University).
Further to the treatments below (Table 1), it is indicated to lavage the uterus with dilute acetic acid or dilute povidone-iodine.
The use of exercise postmating, whether pasture turnout on the use of a horse walker, is widespread, yet the efficacy and examination in control studies are lacking. It is hypothesized that increases in intra-abdominal pressure from exercise transfer pressure to the uterus to aid in evacuating the contents and improve the lymphatic drainage [49]. Others have suggested that exercise can tone the hindquarters and leads to an improvement of perineal conformation [50]. Swift et al. [51] demonstrated that exercise was an effective management technique to aid in evacuation of uterine contents post breeding in mares. In their study, they note the lack of control studies on the efficacy of exercise alone as a treatment for uterine fluid retention post breeding in the mare.
The use of IV dexamethasone at a dose of 50 mg at time of treatment has become widespread following the classic studies by Bucca’s group in Ireland [52]. It has been shown that there is a negative correlation between elevated endometrial score at time of breeding and pregnancy rates [53]. Dexamethasone has been shown to modulate the inflammatory process, possessing anti-inflammatory effects (decreasing IgG) while showing a stimulatory effect on α1-antitrypsin and transthyretin, which both enhance the defense mechanisms of the uterus.
A recent and growing addition to the treatment of endometritis in the mare is acupuncture. It has been suggested that electroacupuncture stimulates afferent nerve fibers, leading to modulation of hormone release through ascending pathways to the hypothalamus as well as reflex activation of the autonomic efferent pathways to the uterus [54]. The first control study examining the use of electroacupuncture in the mare as a treatment modality for endometritis found mare resistance to treatment was a major limitation in the use of this treatment, and that given the multiple acupuncture points, as of yet, does not appear to be an effective mechanism when treating endometritis in the mare.
In an ideal world, we would swab the uterus, and if found to have an infection, we would “clean” her up and wait for the mare’s next cycle. However in the time-pressured breeding season, and in particular when dealing with valuable thoroughbred racehorses, time is seldom something the attending veterinarian has. This author has had great success breeding mares on dirty cycles, as long as there is at least 3 days prior to cover, to allow 3 days of intrauterine therapy. It is well established that the optimum time to swab the mare’s uterus is when there is presence of uterine edema; swabbing when there is no uterine edema raises the risk of a false-negative result. An assumption is that the mare is infection-free only to be found negative on her pregnancy scan. Moreover it was inappropriate for the attending clinician to swab the uterus of a mare in diestrus (i.e., that she has a CL present). For one, the cervix will be tightly closed, and you may damage the cervix while trying to force the culture instrument through. Additionally, as the cervix is tightly closed, if you have accidently tracked bacterial isolates from the external vulva, or indeed the vaginal vault into the uterus, thereby inoculating the uterus with an infectious agent, the infection will take hold as the mare will be unable to “cleanse” herself with a closed cervix.
We have all been there, as attending clinicians. We swab the mare, she cultures negative, there are no ultrasonic changes to make us think there may be an infection, and she returns negative on multiple cycles. There is a caveat here, that reproduction is a complex beast, and many, many things must fall into place for successful fertilization and subsequent embryonic development to take place. As the saying goes, it takes two to tango. However as this part of the chapter is dedicated to endometritis and often we do not have access to the stallion, it is fair for the clinician to start with the mare, and indeed her uterus, when beginning to evaluate why a mare may not become pregnant.
In the short breeding season, the author recommends that any mare that is negative on two cycles (i.e., she has been inseminated twice) should undergo a full reproductive examination that includes swabbing the uterus for culture. If there is any suspicion that the mare maybe dirty, but has a negative culture, then the clinician should explore other diagnostic routes. This would, namely, be low-volume lavage.
Nonetheless there are some mares that either routinely cultured negative but fail to conceive or conversely routinely cultured positive despite appropriate therapy based on sensitivities. In these cases, the attending clinician must consider the possibility of a biofilm. A biofilm as defined by Loncar et al. [55] is a community of bacteria that are attached to an interface or to one another, encased within an extrapolymeric matrix consisting of nucleic acids, lipids, proteins, and exopolysaccharides. These biofilm plaques are inherently resistance to both antimicrobial and innate immune defenses, which leads to a persistent, chronic infection, even in the face of prolonged antimicrobial therapy. The matrix reduces the penetration of antimicrobials. Gram-negative bacteria, such as
Twin or multiple pregnancies in the mare is the most common noninfectious cause of pregnancy loss. Twin pregnancies have been reported to account for up to 30% of abortions in the mare [56, 57]. When twin pregnancies are established, the pregnancy will continue as normal to approximately 6 months, when one or both fetuses will die due to insufficient placental supply. Typically mares carrying twins will abort around 5–9 months of gestation [58]. Only 14% of twin pregnancies resulted in foals surviving into their second week of postnatal life [56]. Mares producing live twins will inevitably require intense (and therefore expensive) neonatal care. The majority of twin pregnancies are dizygotic and arise from multiple ovulations which can be either synchronous or asynchronous in nature. Ginther [59] has proposed that there are familial lines higher than normal incidences of multiple ovulations and thereby there may be a genetic predisposition. Thoroughbreds show the highest incidence of multiple ovulations, while it is low in native breeds and yet to be reported in native Shetland ponies. Older mares also seem to have high incidences of multiple ovulations [60]; however lactating mares appear to have lower multiple ovulation rates, presumably due to the suckling effect on the hypothalamic–pituitary-ovary axis. Not only do mare normally abort twin pregnancies, they also show high incidence of dystocia, damage to the reproductive tract (including the cervix), retained placenta, and delayed uterine involution. These have ramifications on the future reproductive health of these mares. In one study only 38% of mares that had a twin pregnancy in the previous breeding season produced a viable foal the following year [61]. Given the significant risks associated with twin pregnancies, detection of these is paramount. The attending veterinarian should make detailed notes of the presence of large follicles on the ovary and, at ovulation detection, note all ovulations. However do not be fooled, if only one large follicle has ovulated and another large follicle remains. If this follicle should subsequently ovulate, there is a chance of the establishment of asynchronous twins. It is advised to examine the mare in stocks and have the mare adequately restrained. Checking for twins in the field, where a mare may be fractious and/or not restrained correctly, will lead the clinician to potentially rush through examination. There is a danger element to ultrasounding mares not in stocks. Occasionally owners will state that they do not wish to transport the mare to facilities that have the required setup. If this is the case, get the mare restrained as best as possible, and advise the owner that this is not optimal. No ultrasound examination is foolproof. Begin in a systematic manner. The author starts with the left horn, runs the ultrasound probe laterally until the left ovary is seen, and then returns to the bifurcation. This is repeated twice. The same is then done for the right horn. Finally the body of the uterus is examined twice. During the examination, it is paramount to retain the uterus within the center of the screen at all times. If you feel as though a section of the uterus has been missed, repeat. As can been seen, to do this in the field without stocks in a fractious mare can be difficult. Natural reduction of unilateral twins before day 40 is reported at 85% [62, 63].
Given the limitations of this chapter, only two techniques for dealing with twin pregnancies in the mare will be described. There are numerous other techniques described and the readers are encouraged to examine these. At approximately 16 days post ovulation, the embryo (in this case the embryos) become fixed. Up until this point, the embryos are highly mobile and move throughout the uterine lumen. Typically a twin check using transrectal ultrasound takes place before this day 16. Identification of the small embryo takes place. If the pregnancies are adjacent to one another, the probe is gently oscillated to move them apart. The smaller embryo is then moved to the tip of the uterine horn, while a downward pressure from the ultrasound probe on the selected embryo is performed. While keeping the embryo in focus on the ultrasound screen, rupture of the embryonic wall will be observed, and leakage of the embryonic fluid into the uterine lumen will also be observed. A quick check on the remaining embryo should also be performed, following this procedure. Adjunct therapy typically includes a single dose of flunixin meglumine (1 mg/kg IV) given prior to the elimination procedure. Typically these mares are placed on oral Regumate® (dose of 0.088 mg/kg SID PO), until a P4 sample is taken around the heartbeat ultrasound check (approximately day 25 post ovulation). Success rates of continued survival of the singleton pregnancy after a twin reduction around this time is in excess of 90% [64].
If you are presented with twin pregnancies beyond this stage, the clinician has a few options to choose from. After day 40, 63% of these pregnancies result in loss of both fetuses [65]. One of the authors preferred mechanism of twin reduction after day 40, which is cranio-cervical dislocation. Here the clinician is dislocating the first cervical vertebrae from the cranium along with disruption of the ligamentous attachments and severing the spinal cord via transrectal manipulation. This technique can be utilized between 60 and 110 days’ gestation. The mare is sedated and placed in stocks. Buscopan (2 cc IV) can facilitate manipulation of the fetuses. Flunixin meglumine (1 mg/kg IV) is administered prior. The small fetus is selected and identification of the head performed, via identification of the mandible. Stabilize the head between the thumb and the finger and move the head side to side. Place the thumb at the base of the cranium and apply pressure proximally and dorsally; this will result in dislocation, whereby a “pop” is felt. Adjunct therapy included altrenogest (Regumate® at dose 0.088 mg/kg SID PO). Fetal death should be confirmed in 1 week post procedure via transrectal ultrasonography. Viability of the remaining conceptus should be evaluated (viz., by continued growth and the presence of a fetal heartbeat). If both pregnancies continue to be viable, then further intervention will be necessary.
With a thorough understanding on the physiologic events in the spring/vernal transition, the clinician can aid in hastening time to first ovulation. Most mares, if not all, will show some transient uterine fluid accumulation post breeding. Having the skills to note which mares are likely candidates to have excessive fluid accumulation, or which mares have a uterine infection, will greatly improve pregnancy rates. Identification of mares that may develop twin pregnancies is a key skill of the equine theriogenologist, but transrectal ultrasonography has its limitations if the mare is examined in the field. Twin pregnancies are easily dealt with if identified prior to fixation.
The author declares no conflict of interest.
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\\n\\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\\n\\n3.2. CORRIGENDUM
\\n\\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\\n\\n4. FINAL REMARKS
\\n\\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\\n\\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\\n\\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
\\n\\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
\\n\\nPolicy last updated: 2017-09-11
\\n"}]'},components:[{type:"htmlEditorComponent",content:'IntechOpen’s Retraction and Correction Policy has been developed in accordance with the Committee on Publication Ethics (COPE) publication guidelines relating to scientific misconduct and research ethics:
\n\n1. RETRACTIONS
\n\nA Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\n\nA formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
\n\nPublishing of a Retraction Notice will adhere to the following guidelines:
\n\n1.2. REMOVALS AND CANCELLATIONS
\n\n2. STATEMENTS OF CONCERN
\n\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\n\nIntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\n\n3. CORRECTIONS
\n\nA Correction will be issued by the Academic Editor when:
\n\n3.1. ERRATUM
\n\nAn Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\n\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n3.2. CORRIGENDUM
\n\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n4. FINAL REMARKS
\n\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\n\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\n\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
\n\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
\n\nPolicy last updated: 2017-09-11
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Segmentation is a section of image processing for the separation or segregation of information from the required target region of the image. There are different techniques used for segmentation of pixels of interest from the image. Active contour is one of the active models in segmentation techniques, which makes use of the energy constraints and forces in the image for separation of region of interest. Active contour defines a separate boundary or curvature for the regions of target object for segmentation. The contour depends on various constraints based on which they are classified into different types such as gradient vector flow, balloon and geometric models. Active contour models are used in various image processing applications specifically in medical image processing. 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There are millions of imaging procedures done every week worldwide. Medical imaging is developing rapidly due to developments in image processing techniques including image recognition, analysis, and enhancement. Image processing increases the percentage and amount of detected tissues. This chapter presents the application of both simple and sophisticated image analysis techniques in the medical imaging field. This chapter also summarizes how to exemplify image interpretation challenges using different image processing algorithms such as k-means, ROI-based segmentation, and watershed techniques.",book:{id:"8125",slug:"medical-imaging-principles-and-applications",title:"Medical Imaging",fullTitle:"Medical Imaging - Principles and Applications"},signatures:"Yousif Mohamed Y. 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This provides a new idea for revealing the underlining mechanisms of neuropathic pain and improving the clinical treatment concepts. In this chapter, we summarized the recent studies of fMRI in neuropathic pain so that readers can better understand the research status and future research directions.",book:{id:"8125",slug:"medical-imaging-principles-and-applications",title:"Medical Imaging",fullTitle:"Medical Imaging - Principles and Applications"},signatures:"Zhi Dou and Liqiang Yang",authors:[{id:"302075",title:"Ph.D.",name:"Zhi",middleName:null,surname:"Dou",slug:"zhi-dou",fullName:"Zhi Dou"},{id:"310181",title:"Dr.",name:"Liqiang",middleName:null,surname:"Yang",slug:"liqiang-yang",fullName:"Liqiang Yang"}]},{id:"68142",doi:"10.5772/intechopen.88004",title:"Elastometry Indices of Unchanged Liver in Healthy Children",slug:"elastometry-indices-of-unchanged-liver-in-healthy-children",totalDownloads:681,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Two hundred healthy children aged 3–18 years were included in the study to determine liver stiffness indices by means of shear wave elastometry. The difference is significant when we compared shear wave velocity in children aged 3–6 years, on the one hand, and in children aged 7–18 years, on the other (p = 0.001). Liver stiffness indices in boys and girls were not different. As a result, liver stiffness indices in children in various age groups have been obtained, which can be recommended as normal ones for pediatric patients.",book:{id:"8691",slug:"ultrasound-elastography",title:"Ultrasound Elastography",fullTitle:"Ultrasound Elastography"},signatures:"Mikhail Pykov, Natalia Kuzmina, Nikolay Rostovtsev and Alexander Kinzersky",authors:null},{id:"68259",doi:"10.5772/intechopen.88183",title:"2D Shear Wave Elastography for Liver Fibrosis Evaluation",slug:"2d-shear-wave-elastography-for-liver-fibrosis-evaluation",totalDownloads:1218,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"2D shear wave elastography is a technique embedded in ultrasound machines which allows the interrogation of the tissue by acoustic radiation force impulses induced into the tissues by focused ultrasonic beams and captures the propagation of resulting shear waves in real time. Elasticity is displayed using a color-coded image superimposed on a B-mode image, and at the same time, a quantitative estimation of liver stiffness (LS) can be performed in a certain region of interest (ROI). The published data showed a real value of this method for liver stiffness estimation in patients with chronic hepatitis. It has the following advantages: it is integrated into standard ultrasound systems; it is a real-time elastographic method; and it is also feasible in patients with ascites and with large and adjustable size of the ROI that will be evaluated.",book:{id:"8691",slug:"ultrasound-elastography",title:"Ultrasound Elastography",fullTitle:"Ultrasound Elastography"},signatures:"Alina Popescu, Roxana Şirli and Ioan Sporea",authors:null}],mostDownloadedChaptersLast30Days:[{id:"67331",title:"Research in Medical Imaging Using Image Processing Techniques",slug:"research-in-medical-imaging-using-image-processing-techniques",totalDownloads:4379,totalCrossrefCites:5,totalDimensionsCites:9,abstract:"Medical imaging is the procedure used to attain images of the body parts for medical uses in order to identify or study diseases. There are millions of imaging procedures done every week worldwide. 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The features of some characteristic detector systems with the relative electronics and the data acquisition system (DAQ) are presented. Those detectors are related with the medical imaging sensor systems. The characteristics of the medical imaging process of the X-ray and nuclear imaging with SPECT, PET and the combination of PET-CT are presented. The computed X-ray tomography, called CT, and the nuclear medicine tomography are presented, implementing the most of the previous parts, as they are defined in PET and SPECT imaging plus the combination of PET with CT the PET-CT.",book:{id:"8125",slug:"medical-imaging-principles-and-applications",title:"Medical Imaging",fullTitle:"Medical Imaging - Principles and Applications"},signatures:"Evangelos Gazis",authors:[{id:"281707",title:"Prof.",name:"Evangelos",middleName:null,surname:"Gazis",slug:"evangelos-gazis",fullName:"Evangelos Gazis"}]},{id:"68830",title:"PET-CT Principles and Applications in Lung Cancer Management",slug:"pet-ct-principles-and-applications-in-lung-cancer-management",totalDownloads:1128,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Lung cancer is the most common malignant cancer throughout the world; the positron emission tomography/computed tomography (PET-CT) combines both the metabolism information from PET and anatomy details from CT, which is the state of the art. This manuscript introduced the PET-CT and applications in lung cancer diagnosing, staging, and treatment. Several aspects including clinical features, classification, grading and pathology of the lung cancer, principles of PET-CT, and evaluation of diagnosing and treatment had been covered. Detailed demonstration of each cancer subtype, staging criteria, and classification was described. The content will benefit the clinical doctors as well as radiologists.",book:{id:"8125",slug:"medical-imaging-principles-and-applications",title:"Medical Imaging",fullTitle:"Medical Imaging - Principles and Applications"},signatures:"Long Chen, Hua Sun and Yunchao Huang",authors:[{id:"278386",title:"Ph.D.",name:"Long",middleName:null,surname:"Chen",slug:"long-chen",fullName:"Long Chen"},{id:"280160",title:"Prof.",name:"Yunchao",middleName:null,surname:"Huang",slug:"yunchao-huang",fullName:"Yunchao Huang"},{id:"280161",title:"Prof.",name:"Hua",middleName:null,surname:"Sun",slug:"hua-sun",fullName:"Hua Sun"}]},{id:"64352",title:"Endoscopic Dacryocystorhinostomy",slug:"endoscopic-dacryocystorhinostomy-1",totalDownloads:5946,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Epiphora, or abnormal tearing, occurs because of the blockage in the lacrimal drainage system, which impairs normal tearing channeling into the nose. It is essential that with proper history and examination including syringing and probing, a correct diagnosis is made. Syringing and probing are performed only in congenital and acquired nasolacrimal duct obstruction (NLDO). Dacryocystorhinostomy (DCR) is a procedure performed for the treatment of tearing (epiphora) due to blockage of the nasolacrimal drainage system. Endoscopic dacryocystorhinostomy (E-DCR) using telescopes has gained a lot of momentum among otolaryngologists, since the outcomes are comparable to the external approach. Advances in surgical technique and a better understanding of the anatomy have resulted in improvements in outcomes. The anatomy of the lacrimal system will be discussed in detail including the surgical indications and techniques of DCR. 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Active contour is one of the active models in segmentation techniques, which makes use of the energy constraints and forces in the image for separation of region of interest. Active contour defines a separate boundary or curvature for the regions of target object for segmentation. The contour depends on various constraints based on which they are classified into different types such as gradient vector flow, balloon and geometric models. Active contour models are used in various image processing applications specifically in medical image processing. In medical imaging, active contours are used in segmentation of regions from different medical images such as brain CT images, MRI images of different organs, cardiac images and different images of regions in the human body. Active contours can also be used in motion tracking and stereo tracking. 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He previously worked as a post-doctoral fellow at the Ben-Gurion University of Negev, Israel; University of the Free State, South Africa; and Central University of Technology Bloemfontein, South Africa. He obtained his Ph.D. in Organic Chemistry from Nagaoka University of Technology, Japan. He has published more than seventy-four journal articles and attended several national and international conferences as speaker and chair. Dr. Kendrekar has received many international awards. He has several funded projects, namely, anti-malaria drug development, MRSA, and SARS-CoV-2 activity of curcumin and its formulations. He has filed four patents in collaboration with the University of Central Lancashire and Mayo Clinic Infectious Diseases. His present research includes organic synthesis, drug discovery and development, biochemistry, nanoscience, and nanotechnology.",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null},{id:"428125",title:"Dr.",name:"Vinayak",middleName:null,surname:"Adimule",slug:"vinayak-adimule",fullName:"Vinayak Adimule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428125/images/system/428125.jpg",biography:"Dr. Vinayak Adimule, MSc, Ph.D., is a professor and dean of R&D, Angadi Institute of Technology and Management, India. He has 15 years of research experience as a senior research scientist and associate research scientist in R&D organizations. He has published more than fifty research articles as well as several book chapters. He has two Indian patents and two international patents to his credit. Dr. Adimule has attended, chaired, and presented papers at national and international conferences. He is a guest editor for Topics in Catalysis and other journals. He is also an editorial board member, life member, and associate member for many international societies and research institutions. His research interests include nanoelectronics, material chemistry, artificial intelligence, sensors and actuators, bio-nanomaterials, and medicinal chemistry.",institutionString:"Angadi Institute of Technology and Management",institution:null},{id:"284317",title:"Prof.",name:"Kantharaju",middleName:null,surname:"Kamanna",slug:"kantharaju-kamanna",fullName:"Kantharaju Kamanna",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284317/images/21050_n.jpg",biography:"Prof. K. Kantharaju has received Bachelor of science (PCM), master of science (Organic Chemistry) and Doctor of Philosophy in Chemistry from Bangalore University. He worked as a Executive Research & Development @ Cadila Pharmaceuticals Ltd, Ahmedabad. He received DBT-postdoc fellow @ Molecular Biophysics Unit, Indian Institute of Science, Bangalore under the supervision of Prof. P. Balaram, later he moved to NIH-postdoc researcher at Drexel University College of Medicine, Philadelphia, USA, after his return from postdoc joined NITK-Surthakal as a Adhoc faculty at department of chemistry. Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. 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Reasoning in a sustainable way entails, first and foremost, managing the available resources efficiently and strategically, whether they are natural, financial, human or relational. In this way, value is generated by contributing to the growth, improvement and socio-economic development of the communities and of all the players that make up its value chain. In the coming decades, we will need to be able to transition from a society in which economic well-being and health are measured by the growth of production and material consumption, to a society in which we live better while consuming less. In this context, digitization has the potential to disrupt processes, with significant implications for the environment and sustainable development. There are numerous challenges associated with sustainability and digitization, the need to consider new business models capable of extracting value, data ownership and sharing and integration, as well as collaboration across the entire supply chain of a product. In order to generate value, effectively developing a complex system based on sustainability principles is a challenge that requires a deep commitment to both technological factors, such as data and platforms, and human dimensions, such as trust and collaboration. Regular study, research and implementation must be part of the road to sustainable solutions. Consequently, this topic will analyze growth models and techniques aimed at achieving intergenerational equity in terms of economic, social and environmental well-being. It will also cover various subjects, including risk assessment in the context of sustainable economy and a just society.
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