Extubation criteria for infants with severe BPD.
\r\n\tAbout 25 percent of all foods produced globally are lost due to microbial growth. L. monocytogenes is a microorganism ubiquitously present in the environment and affects animals and humans. L. monocytogenes can enter a factory and is able to survive in biofilms in the food processing environment. The use of adequate sanitation procedures is a prerequisite in risk prevention. Moreover, effective control measures for L. monocytogenes are very important to food operators.
\r\n\r\n\tThe safety and shelf life maximizing of food products to meet the demand of retailers and consumers is a challenge and a concern of food operators.
\r\n\r\n\tTo obtain food systems more sustainable, several developments are ongoing to ensure safe food products with an extended shelf life and a reduction of food loss and waste. The problem of antimicrobial resistance is also a great issue that must be taken into consideration.
\r\n\r\n\tThe implementation of natural antimicrobials, using food cultures, ferments, or bacteriophages, is one approach to control L. monocytogenes in food products that meet the consumer preference for clean label solutions.
\r\n\tThis book intends to provide the reader with a comprehensive overview of the current state-of-the-art about Listeria monocytogenes in terms of occurrence in humans, animals, and food-producing plants. Its control by more natural agents allows for more sustainable food systems and points future directions to transform challenges into opportunities.
Bronchopulmonary dysplasia (BPD) was first characterized by Northway and colleagues in 1967 as a chronic lung disease afflicting premature infants after neonatal intensive care unit (NICU) treatment that included administration of oxygen and mechanical ventilation [1]. Early descriptions of BPD noted profound airway inflammation, fibrosis, areas of emphysema, and a heterogeneous physiology. At that time BPD typically affected babies greater than 30 weeks of gestation at birth who weighed more than 1000 g, as few babies born earlier or smaller survived. As neonatal care has advanced, with widespread use of prenatal, antenatal, and postnatal treatments that have markedly improved survival, there has been a notable change in the epidemiology of BPD [2–4]. Such improvements in care include but are not limited to nearly universal administration of prenatal steroids to high risk infants, aggressive resuscitation practices, gentle forms of ventilation, improvements in parenteral and enteral nutrition, surfactant administration, and widespread use of nasal continuous positive airway pressure (nCPAP). The result of all these improvements in care has been marked increases in NICU survival of extremely low birth weight (ELBW) infants. While NICU survival has improved and BPD has become uncommon in infants greater than 30 weeks of gestation, rates of BPD have not changed for ELBW infants and thus the absolute number of infants diagnosed with BPD is likely increasing [5–7].
\nBPD is a phenotypically diverse disease with a variety of causes and consequences [8]. While previous definitions of BPD focused on a single diagnostic criteria (i.e., X-ray changes, a supplemental oxygen requirement at 28 days of age, or, more recently, a supplemental oxygen requirement at 36 weeks of corrected gestational age (CGA)) the most widely used current classifications divide BPD into mild, moderate, and severe based on the degree of support required at critical junctures. Mild BPD is defined as any supplemental oxygen requirement at 28 days of life, moderate BPD is defined as any supplemental oxygen requirement less than 0.3 FiO2 at 36 weeks, while severe BPD is defined as a supplemental oxygen requirement with a FiO2 greater than 0.3 and/or the need for positive pressure respiratory support at 36 weeks of CGA [9]. These changes in classification have been helpful in better defining BPD. However there remains a population of infants with the most severe forms of BPD who are not well characterized by the current classification and who represent the most difficult clinical cases typically cared for within neonatology (the severest of the severe). Such infants typically require chronic and extreme ventilator support with high peak inspiratory pressures (PIPs) and mean airway pressures (MAPs). They are often treated with high doses of neuroactive medications including narcotics, sedatives, and systemic corticosteroids. With a few notable exceptions [10], their neurodevelopmental outcomes are typically grim [11, 12]. The clinical management of patients with this degree of illness (informally known as “super-severe BPD”) will be the focus of this chapter.
\nTo understand the keys to clinical management of super-severe BPD as shown in the chest X-ray in Figure 1, it is critical to understand the underlying disease progression and physiology. ELBW infants are typically born at the intersection of the canalicular and saccular stages of lung embryogenesis whereas more mature infants in previous cohorts were born well after the saccular stage had commenced. This is a critical issue to understand modern, severe BPD because the stage of lung development during which lung damage occurs heavily influences both the pathological findings associated with the diagnosis and the clinical care required to manage infants with evolving BPD. Whereas older descriptions of BPD (referred to as “old BPD”) typically emphasized classic progressive stages including prominent fibroproliferative changes, recent descriptions (referred to as “new BPD”) have noted disruptions of distal lung growth [13, 14]. A key insight for the clinical management of the most severe forms of BPD, however, is the prominence of airway injury and dysfunction resulting from disruption of normal canalicular development.
\nA typical chest X-ray for a patient with severe BPD demonstrating areas of overinflation interspersed with areas of consolidation.
Most current lung-protective strategies in neonatology are directed towards surfactant deficiency, for which extremely preterm infants are at high risk early in their NICU course [15]. Surfactant deficiency is characterized by low lung compliance (CL, defined as change in volume for a given change in pressure or ΔV/ΔP expressed as ml/cmH2O) and normal lung resistance (RL, defined as change in pressure for a given flow rate of the gas or ΔP/flow expressed as cmH2O/ml/s). For infants in the early, acute stages of neonatal intensive care this is a very reasonable assumption, and the point of the lung protective strategy is to prevent BPD. However, this chapter discusses the mechanical ventilation of the patient with severe BPD, a relatively long time after admission to the NICU for initial respiratory care using appropriate lung protective strategies.
\nLet us consider how the lung fills and more importantly how the lung empties. The time needed to fill or empty is indicated by the product of CL and RL, termed the time constant (τ, measured in seconds). One time constant describes the time required to achieve 63% of maximal inhaled or exhaled volume, and 5 time constants are needed for 99% of maximal inhaled or exhaled volume. Since compliance is low and resistance is normal in early, acute lung disease afflicting extremely premature infants, the time required for full inflation or deflation of the lung is very short. Thus, in order to avoid overdistention and atelectasis and consequent injury, “gentle ventilation” emphasizes high-rate, low-tidal volume ventilation administered with short inspiratory times (Ti) with adequate positive end-expiratory pressure (PEEP)
While it may be safe to assume that early lung disease is associated with low compliance and normal resistance and can thus be adequately managed with a high-rate, low-tidal volume approach, are these assumptions valid in well-established BPD, particularly in the most severe forms? Severe BPD is often perceived to have reduced pulmonary compliance, however the predominant findings in established BPD are complex and measurement of pulmonary physiology in infants is technically difficult. The following is a summary of the current knowledge of pulmonary function in infants with the most severe forms of BPD.
\nWhile a variety of methods have been used to assess pulmonary function in infants during tidal breathing, it is critical to understand that each method has specific limitations and the results of such measurements must be understood within this context [16]. Measurements of CL, for instance, may be variable as they are typically determined over a limited tidal volume range and depend heavily on the lung volume at which they are obtained. Further, increased airway resistance can impact measurements of CL during tidal breathing depending on the respiratory rate. This is termed “frequency dependence” and can lead to reductions in measured compliance even in the absence of actual changes in true compliance. Other methods of assessing resistance and compliance present different problems; the single breath occlusion technique, for instance, assumes a linear, “one-compartment” model, however evidence strongly suggests that the curvilinearity of the passive expiratory flow-volume relationship in infants with severe BPD is much better described by a “two-compartment” model. Therefore, the one-compartment analysis available in ventilator software may substantially underestimate the time constant for the damaged portions of the lungs [17–19].
\nDespite the limitations described above, our own data combined with those of other advanced pulmonary centers describe a fairly consistent picture. In summary, infants with the most severe forms of BPD are overwhelmingly likely to have pulmonary function that is dominated by marked increases in resistance to airflow, as demonstrated by reductions in forced expiratory volume in the first 0.5 s (FEV 0.5) and in other forced expiratory flows (FEFs), with relatively normal compliance when normalized for the infant’s size [20–23]. This type of pulmonary function is, in many ways, similar to that found in asthma and severe bronchiolitis and is likely the result of injury to the developing airways predominant in ELBW infants.
\nVolume-time curve for one breath for typical patient with severe BPD showing the fast space and the slow space. In this example, the inspiratory time is 0.5 s and the rate is 17 breaths per minute. The fast compartment (black circles) has CL = 0.5 ml/cmH2O, RL = 0.2 cmH2O/(ml/s), and τ = 0.1 s, while the slow space (gray circles) has CL = 0.8 ml/cmH2O, RL = 0.75 cmH2O/(ml/s), and τ = 0.6 s. The open triangles are the total Vt and is the sum of the volumes in the fast space and slow space. In this example the total Vt is 31.4 ml, the Vt of the fast space is 11.9 ml, and the Vt of the slow space is 19.5 ml. Clearly demonstrated is that exhalation depends entirely on the slow space as the fast space has completely emptied by 1 s, while the slow space has only completely emptied by 3.5 s, the total time for 1 breath.
The injuries to the lungs of infants with severe BPD are not regionally uniform and thus the pulmonary function of the respiratory system is heterogeneous, with some portion of the lung functioning well and other portions that are severely affected. Because of this nonuniformity, the best way to describe this heterogeneity is a “two-compartment” model with two separate and distinct sets of pulmonary mechanics [17–19]. The healthy compartment (sometimes referred to as the fast compartment) has normal or near-normal compliance and resistance, and thus a near-normal time constant. Conversely the damaged compartment (sometimes referred to as the slow compartment) is often severely injured with extremely high resistance but normal or near-normal compliance (Figure 2). This creates a situation in which the optimal clinical strategies necessary to achieve adequate oxygenation and ventilation will be determined by the clinician’s assessment of the relative proportion of the lung that each compartment represents. Infants with relatively minimal disease, for instance, have lungs that are mostly composed of the fast compartment, while those with the most severe BPD are almost entirely slow compartment. Our own data suggest that on average 67% of the tidal volume is from the slow compartment in patients with severe BPD following bronchodilator treatment [17, 19]. This is a critical distinction as the most effective ventilatory strategy for patients with severe BPD must take into account the slow space, and the approach to ventilating the slow space is vastly different from the approach to ventilating the normal or fast space.
\nIn addition, infants with severe BPD have significant areas of ongoing ventilation/perfusion (V/Q) mismatch and other areas of tenuous V/Q matching which lead to ongoing hypoxia and occasional “blue spells” as the tenuous area becomes intermittently poorly ventilated.
\nPhysical examination findings in infants with evolving or established severe BPD are predictable but nonspecific as they represent typical findings of respiratory distress from any cause. Patients with severe BPD are typically tachypneic and will often have retractions, grunting, and nasal flaring. On auscultation wheezing and/or rales are common findings. In addition, infants with severe BPD will often be relatively hypoxic with substantial intermittent hypoxic spells that are unpredictable and often associated with movement, coughing, gagging, or bronchospasm [18]. Such infants may further appear stressed with varying degrees of hyper- or hypotonia depending on the scale of their respiratory insufficiency. On palpation, the abdomen is typically normal; however, the liver may be displaced by pulmonary hyperinflation into the abdomen and may be easily palpable.
\nRadiological findings in severe BPD are typically dependent on the progression of the disease. Infants in the early stages of BPD may have diffusely hazy lungs, with marked edema, and may be underinflated. As the disease evolves and becomes dominated by resistance, however, the typical chest X-ray will demonstrate hyperinflation, with relatively little direct correlation to ventilator pressures. This more likely results from breath-stacking due to prolonged expiratory time constants rather than the set ventilator pressures. Further, as the disease progresses the chest X-ray typically becomes much more heterogeneous with areas of patchy atelectasis intermixed with areas of hyperinflation (Figure 1).
\nLaboratory findings for infants with severe BPD are typically no different than for any infant with chronic respiratory insufficiency. Most notably, many such patients will have a chronic respiratory acidosis with an elevated pCO2 and consequently an elevated serum bicarbonate. They may have a compensatory metabolic alkalosis and if blood gases are obtained they may have a substantial base excess. In addition, infants with severe BPD are at extreme risk for growth failure and osteopenia of prematurity, and thus may have associated laboratory abnormalities including elevated alkaline phosphatase, low total protein, and low albumin levels.
\nThere are three critical components to successfully ventilating infants with BPD. The first is that the physician must come to terms with the fact that infants with severe BPD have significantly damaged lungs that are physiologically relatively static, in other words they have a chronic illness and not an acute illness. It is simply impossible for the lung function of such infants to change substantially over short periods of time (days to weeks) and it is therefore unreasonable to expect that the required respiratory support can be weaned relatively rapidly. Second, severe BPD is evolving in infants during periods of incredibly rapid neurodevelopment. Overall growth during the first few months of an extremely preterm infant’s life is geometric and represents their most rapid period of growth; consequently, missed opportunities for developmental gains may be irrecoverable. Thus it is imperative that the respiratory support provided such infants be adequate to support normal interactions with their parents, family, and environment, even if requiring mechanical ventilation. Finally, the modes of ventilation used in these patients must be optimized to address the pulmonary function present in the damaged part of the lung, which likely represents the majority of the lung. Strategies that are not aimed at the diseased compartment of the lung will by definition be focused on the little remaining healthy tissue which then must compensate by absorbing the entire ventilatory load.
\nSince pulmonary function in infants with severe BPD is dominated by increased resistance, the expiratory time constant is very long. In infants with the most severe forms of BPD, this time constant may be as long as 0.5–0.75 s [19]. Complete exhalation, by definition, requires 5 time constants and thus may require as long as four or five seconds (5 x 0.5 = 2.5 s; 5 x 0.75 = 3.5 s). Thus, the respiratory rate must be set to allow for 5 expiratory time constants in patients with severe BPD. For if too high a respiratory rate is set on the ventilator, then there will be inadequate time for exhalation, and the subsequent breath will begin with the lung already partially inflated (breath stacking). This cycle will occur with every breath; the damaged portion of the lung will rapidly become hyperinflated, and will not be able to contribute meaningfully to overall minute ventilation (MV). Therefore the primary goal of ventilation in infants with severe BPD is to allow adequate time, in absolute terms, for complete emptying. If we take an example assuming an inspiratory time of 0.5 s and an expiratory time constant of 0.6 s, the minimum inhalation/exhalation cycle length consistent with full exhalation is 3.5 s (inhalation = 0.5 s, exhalation = 3 s), and the maximum rate that can be used on the ventilator would be 60 seconds divided by 3.5 seconds per cycle, or 17 bpm (see Figure 2). Any respiratory rate greater than 17, in this example, will result in breath stacking, hyperinflation, and insufficient ventilation of the bulk of the lung. This will lead to V/Q mismatch and hypoxemia which will manifest as an increasing oxygen requirement.
\nCarbon dioxide removal however depends on MV. MV is equal to the rate times the tidal volume (MV = rate x Vt). If the MV is 200–300 ml/kg/min, and we need to limit the set rate on the ventilator to 17 bpm to avoid hyperinflation and hypoxemia, then the only variable that we can impact is Vt. The equation can be rearranged to determine the necessary Vt as follows: Vt = MV/rate, and substituting our MV and rate gives 200–300/17 which equals a Vt of 12–18 ml necessary to provide an adequate MV at a rate of 17. A lower Vt than this will, by definition, results in inadequate MV. Furthermore, keep in mind that increasing the rate will prevent adequate emptying, leading to hyperinflation which will make the lung less compliant and thereby lead to a decrease in Vt. Essentially then, the practitioner has no alternative that is consistent with both full emptying and adequate MV other than to utilize a low-rate, high-tidal volume ventilation strategy in the patient with severe BPD.
\nThe patient with severe BPD who is ventilated with a faster rate usually manifests air hunger demonstrated by tachypnea, retractions, and “fighting” the ventilator. These patients are often given sedatives and sometimes even paralyzed to facilitate ventilation. However in patients with severe BPD on mechanical ventilation, once a physiological slow-rate, high-tidal volume ventilation strategy is employed, the patient begins breathing more normally without air hunger. These patients usually do not require sedation and should be awake and active, such that they can interact with their environment and with therapies. Thus, this physiological ventilation strategy not only improves V/Q matching in the lung but also allows the patient to maximally benefit from neurodevelopmental therapy. Using this approach we have found that neurodevelopmental outcomes for patients with severe BPD are no longer grim, but rather are quite good [10, 24].
\nA small number of patients with severe BPD will not respond to this mechanical ventilation strategy. When a patient with severe BPD does not respond to slow-rate, high Vt ventilation, then the practitioner must consider rare but important causes of hypoxemia and V/Q mismatch. We recommend structure-function studies in these patients because a very small percentage of patients diagnosed with severe BPD will actually have a predominantly restrictive lung disease, and therefore will respond better to lower tidal volumes and/or PEEP. Also, there are some patients who will have tracheobronchomalacia as the predominant pathology. These patients will often benefit from relatively high PEEP to “stent” open airways on expiration. Another important cause of V/Q mismatch in this population, particularly those with severe degrees of hypoxia, is pulmonary hypertension [25]. Thus, we recommend an echocardiogram in patients who do not respond to the slow-rate, high Vt strategy with a decrease in FiO2, or in those patients who fail to subsequently wean on the mechanical ventilator. For patients with severe BPD it is prudent to follow echocardiograms while the patients are on mechanical ventilation, since they are at high risk of developing pulmonary hypertension [26].
\nOnce adequate MV is achieved in infants with severe BPD, it is imperative to avoid the usual acute care mentality of rapid weaning, as the underlying pathophysiology will change only with growth. In other words, once adequate MV and V/Q matching is established in the patient with severe BPD, the focus should change from weaning the ventilator to providing optimal nutrition [27]. Furthermore, the infant with severe BPD at this stage must be adequately supported at all times to allow proper neurodevelopment. In fact, attempts to wean support rapidly are highly unlikely to succeed and can impede neurodevelopmental progress putting the patient at higher risk for adverse neurodevelopmental outcomes. Our approach is to determine the most optimal ventilator settings as quickly as possible and then to delay attempts at weaning until the oxygen requirement has steadily declined to less than 40%. Optimal ventilator settings are those settings that allow for weaning of FiO2 and allow the patient to breath comfortably without evidence of air hunger. Even when these criteria are met, it is critical to assess each infant’s developmental response to therapy. If therapies are well tolerated and FiO2 is <40% then it is reasonable to try slowly weaning the ventilator. Although we are often successful extubating patients without any pressure weaning at all, if weaning is considered necessary then we recommend weaning Vt, either by decreasing PIP (for pressure-targeted ventilation) or decreasing set Vt (for volume-targeted ventilation). Each wean should be evaluated in terms of oxygen requirement and tolerance of therapies. If the wean does not result in an increase in oxygen need or a decreased tolerance of therapies then that wean was tolerated by the patient. If, on the other hand, the wean results in an increase in FiO2 or poor tolerance of therapies then that wean was not tolerated and the ventilator should be turned up again to the previous settings. Once extubation criteria are met (Table 1) and the patient is successfully extubated, infants with severe BPD will often need prolonged noninvasive positive pressure via nCPAP, which should only be weaned once the infant is thriving on relatively low amounts of supplemental oxygen (25–30%). Obviously, these patients will likely need supplemental oxygen therapy for a relatively long time. Although it is rare in our practice to discharge patients home on mechanical ventilation or positive pressure, the majority of our patients are, i.e. patients are discharged home on supplemental discharged home on supplemental oxygen.
\nNo airway anomalies | \n
Thriving with FiO2 ≤0.4 for at least 48 h | \n
No recent escalation in respiratory support | \n
Positive weight trend and good linear growth | \n
Full enteral feeds | \n
No surgery planned for at least 72 h | \n
No ROP examination on day of extubation | \n
No active infections | \n
All needed extubation medications ordered | \n
No recent extubation failures | \n
Team consensus that the patient is ready | \n
Extubation criteria for infants with severe BPD.
Infants with severe BPD are at extreme risk for morbidity and mortality. The vast majority of these infants, however, has fairly predictable pulmonary mechanics, characterized by high resistance. Once these pulmonary mechanics are understood, it is usually possible to adequately ventilate these babies using a physiological, low-rate, high-tidal volume approach aimed at supporting ongoing neurodevelopment. It is imperative to adequately support these patients for a relatively long time to allow for lung growth and neurodevelopment. The temptation to wean these patients rapidly, as we do for acutely ill patients, must be avoided to allow for optimal outcomes.
\nThe consumer’s interest in a healthier lifestyle has led to the development of foods that meet nutritional and health needs and that at the same time are attractive, tasty, and with good acceptance in the market. Products that support positive health effects or ingredients with these characteristics, claimed or proven, are called “emitted foods” [1].
The relationship between food and health is one of the keys to disease prevention and well-being promotion. As a result, industries have started to enrich foods with specific ingredients, differentiating them about the benefits offered to health compared to foods in their traditional forms [2, 3, 4].
In the present century, the scientific literature reports functional foods as allies in the treatment of obesity [5], prevention of cardiovascular diseases [1], plasma cholesterol balance [6], and cancer prevention [7]. Among functional foods, the literature reports prebiotics (added with non-digestible fibers), fortified (with vitamins, omega-3), altered (removing harmful components), and probiotics [8].
According to Resolution No. 19, of April 30, 1999, on the claim of functional property of food, it is that related to the metabolic or physiological role that the nutrient or non-nutrient has in the growth, development, maintenance, and other normal functions of the human organism [9]. Among the functional compounds most investigated by science, we have probiotics, which according to RDC n° 241, of July 26, 2018, are defined as live microorganisms that confer benefits to the individual’s health [10, 11].
The word probiotic has a Greek derivation in which it means “for the sake of life”, that term was first introduced by Lilly; Stillwel in 1965 to describe substances secreted by a microorganism, which stimulates the growth of another [12, 13, 14]. Fuller (1989) defined probiotics as a supplement composed of live microorganisms that benefit the host’s health through the balance of the intestinal microbiota. The term probiotic can be complemented as a pure culture or composed of living microorganisms that supplied to man or animals benefit the host by stimulating the properties existing in the natural microbiota [15].
Probiotics, after ingested, must be able to survive the stress conditions present in the gastrointestinal tract, such as gastric juice, the presence of bile salts, and digestive enzymes, and maintain their viability and metabolic activity in the intestine to exert beneficial effects on the hosts. As for the technological challenges for the industrial production of cells, they must remain stable and viable at satisfactory levels throughout the product’s validity period [16, 17, 18]. Based on this assumption, there is a recent and growing scientific interest in improving the stability, bioavailability, and shelf life of products with probiotic sources using nanotechnology as an enhancement technique, since nanostructured systems may be able to control stability, improve solubility, bioavailability, and controlling the release of bioactive compounds [19, 20, 21].
The reduction of materials to the nanoscale leads to new and exciting properties and the increase of the surface volume ratio, increasing its reactivity. This characteristic of nanoparticles has attracted commercial interest in the manufacture of nano-ingredients, supplements, and nutraceuticals. Several types of nanoparticles can be found in the literature, such as metallic, semiconductor, carbon-based, metallic, and polymeric oxides, which can be applied in various sectors, predominantly personal care, health care, and cosmetics. The benefits of nanotechnology in the food sector go through the entire food chain, starting from production to processing, transportation, security, storage, and delivery [22, 23]. Based on the above, we will cover in this chapter a review on the use of natural probiotics and nanomaterials, aiming to specify their advantages and methodologies of preparation and characterization.
Probiotics can be defined as food supplements that contain live microorganisms or microbial components that, when ingested in a certain number, have a beneficial effect on the health and well-being of the host [17].
Among these benefits include antimicrobial activity; control of pathogenic microorganisms [24]; lactose hydrolysis; modulation of constipation; antimutagenic and anticarcinogenic activity [25, 26]; reduction of blood cholesterol, improvement of patients with type 2 diabetes (insulin resistance) and obesity [27, 28, 29]; modulation of the immune system; improvement in inflammatory bowel disease; and suppression of
Probiotics can be incorporated into a wide variety of food products, mainly in dairy products, such as milk, ice cream, yogurt, and cheese. Its application has also grown in other types of foods, such as soy milk, mayonnaise, pates, meats, baby food, confectionery, sweets, cakes, and chewing gum [34, 35, 36, 37].
The selection of probiotic bacteria is based on the following criteria: gender, origin (which must be human), stability against stomach acid and bile salts, the ability to adhere to the intestinal mucosa, the ability to colonize, at least temporarily, the human gastrointestinal tract, the ability to produce antimicrobial compounds and metabolic activity in the intestine [38, 39, 40].
In order for the microorganism to be able to promote the aforementioned beneficial effects, a minimum intake of 108–109 colony-forming units (UFC) per day is recommended [41]. In addition, the minimum concentration of live bacteria should not be less than 10 CFU/g of food since many cells die during passage through the gastrointestinal tract (TGI) [1, 42].
Specific probiotic strains give the benefits transmitted to health, and not by specific species or genus. However, that each strain is related to a specific benefit. In this way, no strain will provide all of the proposed benefits. For example,
In a healthy adult intestine, the predominant microbiota is composed of health-promoting microorganisms (Table 1), mostly belonging to the genera
Lactobacilli | Bifidobacteria | Other bacteria | Fungus |
---|---|---|---|
Main microorganisms used for their probiotic properties, in the form of drugs or added to foods.
Strains that have been used in the prevention and treatment of allergic diseases [45].
Some individuals may experience little of the side effects related to the ingestion of probiotics due to the death of pathogens in the intestinal environment since they release toxic cellular products, a reaction called a “die-off reaction”. In such cases, the use of probiotics should be persisted in order to improve symptoms. There is a slight increase in gas production, abdominal discomfort, and even diarrhea, which resolves over time [12].
Three possible mechanisms of action are attributed to probiotics: the suppression of the number of viable cells through the production of compounds with antimicrobial activity, competition for nutrients, and competition for adhesion sites. The second of these mechanisms would be the alteration of microbial metabolism by increasing or decreasing enzyme activity. The third would be to stimulate the host’s immunity by increasing the levels of antibodies and increasing the activity of macrophages. The spectrum of activity of probiotics can be divided into nutritional, physiological, and antimicrobial effects [47, 48]. The direct modulation of the immune system may be secondary to the induction of anti-inflammatory cytokines or by the increase in the production of secretory IgA [45].
Despite the scientific evidence regarding the mechanisms of action of probiotics, there is still a lack in the literature on biochemical and molecular pathways that fully explain these effects, such as, for example, increasing the function of the intestinal barrier. Despite the scientific evidence regarding the mechanisms of action of probiotics, there is still a lack in the literature on biochemical and molecular pathways that fully explain these effects, such as, for example, increasing the function of the intestinal barrier [49].
Currently, the mechanisms of action of probiotics for anticarcinogenic effects have been studied. These are believed to occur through (1) inhibition of bacteria responsible for converting pre-carcinogenic substances (such as polycyclic aromatic hydrocarbons and nitrosamines) into carcinogens; (2) direct inhibition in the formation of tumor cells; and (3) the ability to bind and/or inactivate carcinogenic substances [25]. Several mechanisms of action have been suggested, including the stimulation of the host’s immune response (by increasing phagocytic activity, IgA synthesis, and the activation of T and B lymphocytes), the binding and degradation of compounds with carcinogenic potential, qualitative changes and/or quantitative in the intestinal microbiota involved in the production of carcinogens and promoters (ex: bile acid degradation), production of antitumor or antimutagenic compounds in the colon (such as butyrate), alteration of the metabolic activity of the intestinal microbiota, alteration of the physical- colon chemicals with decreased pH and effects on host physiology [33, 50].
The use of probiotics represents a promising and rapidly growing area for the development of functional foods. Probiotic cultures are successfully applied to different food matrices. However, the development of non-dairy products represents a challenge for the industry, as each food matrix has unique characteristics, and it is necessary to optimize and standardize each type of product [51].
In this context, nanomaterials have been widely studied as a technique to improve the stability of these microorganisms and functional foods, protecting them from unfavorable environments, improving the uptake, absorption, and bioavailability of nutrients for the body (Table 2) [19].
Documented effects on humans and/or animals | Possible immunomodulation mechanism | |
---|---|---|
Mucous barrier | Maintenance and repair of the intestinal barrier and intercellular junctions | Reduced permeability and decreased systemic absorption of allergens/antigens |
Enterocytes | Increased production of TGF-β and prostaglandin E2 responsible for promoting tolerance of antigen-presenting cells | Reduction of local inflammation and promotion of tolerance |
Receivers enterocytes (toll-like) | Anti-inflammatory effects of probiotics mediated by toll-like receptors 9 | Inhibition of allergic responses, type Th2: mechanism not yet clarified |
Cells presenting antigens (dendritic cells) | Increased activity of dendritic cells in the intestine | Promotion of tolerogenic effect by dendritic cells |
Auxiliary (or effector) T cells | Increased Th1-type response | Inhibition of Th2 response differentiation |
Regulatory T cells | Production of Il-10 and TGF-β associated with oral tolerance. Increased TGF-β (Th3) | TGF-β produced locally (including by enterocytes) promotes tolerogenic effect by dendritic cells, local IgA, and increased Treg activity |
B cells and antibodies | Colonization: enlarged lymphoid tissue | Promotion of a tolerogenic environment |
T cells | Increased Th1 differentiation | Secondary to the effects of T cells in the gastrointestinal tract |
B/IGA cells | Increased production of IgA in other tissues (respiratory tract) | Secondary to the effects of B cells in the tract gastrointestinal |
Technological advances aimed at developing imaging equipment and techniques for characterization make it possible to develop and characterize systems on a nanoscale through scanning electron microscopy and transmission electron microscopy. Nanotechnology in the food area is designed to encapsulate, carry, and release bioactive ingredients to incorporate and modify the food structure. In addition, they make it possible to study the structures in detail, make it possible to understand their properties and facilitate their handling to obtain new, high-quality and safe foods [52].
Nanotechnology involves the characterization, fabrication and/or manipulation of structures, devices, or materials that have at least a dimension of about 1–100 nm in length [53, 54] and has emerged as one of the most promising scientific areas of research. Numerous companies are currently specialized in the manufacture of new forms of materials (nanometric size) with typical applications in medical therapy, diagnostics, energy production, molecular computing, and structural materials [55]. This technology in food introduces new opportunities for innovation in the food industry with immense speed. Thus, some of the applications result in the presence of nanoparticles or nanostructured materials in the food. This innovation can be applied to the macroscale characteristics of foods, such as texture, taste, other sensory attributes, color intensity, processability, and stability during shelf life, leading to many new products. In addition, nanoencapsulation technology can also improve water solubility, thermal stability, and oral bioavailability of bioactive compounds [14, 56].
One of the biggest focuses of nanotechnology in the food industry is encapsulation systems and the controlled release of nutrients. The use of nanomaterials has shown improved properties for the encapsulation of probiotics. Due to their unique physical and chemical properties, nanostructured encapsulating materials show great promise of protecting microorganisms from acidic stomach conditions, increasing absorption and, therefore, allowing the successful release of probiotic cells trapped in the intestinal lumen with natural pH [57, 58].
The clinical efficacy of oral administration of probiotic bacteria is still diminished due to loss of viability during the gastrointestinal passage, resulting in poor intestinal distribution. Microencapsulation technology using nanomaterials is a successful strategy to solve this problem, maintaining the viability of probiotics, thus improving their effectiveness after oral administration [58]. In recent years, the production of probiotic and functional foods using nanotechnology represents one of the main current challenges [59].
The most basic nanomaterials used are nanoparticles. These can be presented in different forms, such as spherical nanoparticles (three nanometric dimensions); nanotubes and nanofibers (elongated structures with two dimensions on a nanoscale), and nanoplates (only have the nanometric thickness). Several examples of nanoparticles are cited in the literature, such as nano-clay, silver (Ag), titanium dioxide (TiO2), and zinc oxide (ZnO) nanoparticles [22].
Different types of nanoformulations can be used, which requires the adequate formulation and timely processing conditions. Among them, polymeric nanoparticles, nanocomposites, solid lipid nanoparticles (NLS), liposomes, and nanoemulsions are suitable for food applications [57, 60].
Nanoparticles (NPs) and nanostructured materials (NSMs) represent an active area of research with application in several domains. They are exciting nanoscale systems due to the ease with which they can be produced in different ways. NPs and NSMs arouse interest due to their adjustable physicochemical characteristics, such as melting point, wettability, electrical and thermal conductivity, catalytic activity, light absorption, and dispersion, resulting in improved performance compared to their mass counterparts [61]. NPs and nanosystems are broadly divided into several categories, depending on their morphology, size, and chemical properties [62]. Currently, some of the most studied nanostructured delivery systems are nanoemulsions, nanoliposomes, nanohydrogels, lipid nanoparticles, and coacervates with application in food (Figure 1) [63].
Types of nanoparticles. Inorganic nanoparticles, polymeric nanoparticles, solid lipid nanoparticles, nanosomes, nanocrystals or quantum dots, carbon nanotubes, and dendrimers.
Polymeric nanoparticles are formed by a polymeric matrix (nanospheres) or a reservoir system in which the main content is hydrophobic or oily surrounded by a polymeric wall (nanocapsule) [64]. They are among the delivery systems for bioactive compounds most accepted and approved by GRAS [65]. In addition, they gained considerable attention in nanomedicine due to the potential for surface modification, pharmacokinetic control, suitability for targeted delivery of therapies [66], mechanical properties [67], and design flexibility. More specifically, size, surface morphology, chemistry and charge, porosity and diffusivity of the drug, and encapsulation efficiency are properties that push polymeric nanoparticles to the forefront of nanomedicine applications [68] and may behave similarly when incorporated into food.
The chemical and biocompatibility properties of polymeric nanoparticles have been studied extensively in recent years and allow these nanometric delivery systems formed by natural or synthetic polymers to be helpful in the controlled release of natural bioactive compounds, hormones, genes, and anticancer drugs with greater effectiveness than micrometric systems such as microparticles [69]. Due to a high surface contact area occur an intense interaction between the matrix in which they are inserted and the nanoparticles [70].
Currently, the most used polymers for the formation of the nanometric system are poly (lactic acid) (PLA), poly (glycolic acid) (PGA), poly (lactic-co-glycolic acid) - (PLGA), and polycaprolactone (PCL). Nanoparticles and microparticles can be obtained through different techniques that can be classified into four categories. Category 1: a traditional method based on the formation of an emulsion consisting of single emulsion, double emulsion, and multiple emulsions, followed by evaporation of the solvent. Category 2: methods based on nanoprecipitation, the rapid expansion of supercritical fluid in liquid, salting, and dialysis. Category 3: direct composition methods, such as fusion technique, spray-drying, supercritical fluid. Category 4: new approaches, including microfluidic and mold/mold-based techniques [65, 69].
The main active substances used for encapsulation by the methods of obtaining nanoparticles are isolated substances. However, some authors, such as Nascimento et al. [71] and Azevedo et al. [65], developed polymeric nanoparticles of Brazilian red propolis extract contributing to the development of nanostructured technologies for natural products.
Nanoliposomes are defined as spherical lipid bilayer vesicles, resemble the lipid bilayer of cell membranes, and maintain nanometric or submicronic bands during storage and applications [72, 73, 74]. Its bilayer structure, formed by one-half of the lipid bilayer, contains a hydrophilic head and a lipophilic acyl chain. Thus, its amphipathic nature allows it to encapsulate hydrophilic and hydrophobic compounds individually or simultaneously due to its bifunctional physicochemical properties and, consequently, it presents interaction with a wide range and variety of molecules [75]. Nanosystems are drug-carrying structures with potential for application in the medical field and food industry. However, they have low robustness regarding physical and thermal stability and pH variations, being considered significant challenges for their intended commercialization [76].
The most common method used for the production of nanoliposomes is to obtain a double emulsion followed by a microfluidization process at room temperature after the previous removal of the solvent. It is possible to produce nanoliposomes using low-cost natural ingredients (for example, soy, egg yolk, sunflower, milk), optimizing the cost-effectiveness of the final product [72]. The literature reports several clinical trials using nanoliposomes, and studies reveal that they are excellent candidates for various distribution systems, such as anticancer, antifungal and antibiotic drugs, administration of genetic drugs, and administration of anesthetics and anti-inflammatory drugs [77]. Similarly, it will have application in the food area, allowing the incorporation and simultaneous release of two or more bioactive compounds with different solubilities, as is the case of medium-chain liposomes and vitamin C, enhancing food functionality [74].
Lipid nanoparticles are similar to nanoemulsions in which the oil phase was totally or partially solidified [56]. It is a colloidal carrier system that makes it possible to encapsulate, protect and distribute functional lipophilic components, such as bioactive lipids and drugs [70]. The size and structure of the lipid nanoparticles are similar to nanoemulsions, with a size that usually ranges from 50 to 1000 nm. The lipid nucleus in nanoemulsions is liquid, but the lipid nucleus is in a solid-state [78].
Solid lipid nanoparticles can be classified as solid lipid nanoparticles (SLNs) and nanostructured lipid transporters (NLCs). In general, homogenization techniques of cold or hot high pressure and double emulsions are currently being used more to produce SLNs and NLCs to encapsulate bioactive oils [79]. The composition of SLNs is usually lipids such as triglycerides (tristearin), partial glycerides (glyceryl monostearate), fatty acids (stearic acid), sterols (cholesterol), and waxes (cetyl palmitate) [70].
There is a great difficulty associated with lipophilic bioactive agents in food matrices in the food industry, one of the main problems for manufacturers in the development of nutraceutical and functional foods [80]. Thus, SLNs and NLCs aim to assist as a nanoparticle carrier of bioactive compounds with a lipophilic character. SLNs are nanometric lipid matrices between 50 nm and 1 mm in diameter, and these nanostructured systems are capable of effectively encapsulating active, sensitive molecules that must be protected from different environmental conditions, such as light, moisture, and oxidation. In addition, the solid matrix allows a controlled release and a high capacity to reach the target organ [79]. NLCs, whose matrix consists of a mixture of lipids with different physicochemical properties instead of just one type of lipid, were initially synthesized to avoid SLN problems with loading. They can form physical lipid mixtures through the mixture of solid and liquid lipids (oil), but without crystallization, presenting a more unstructured (entropic) matrix that allows the control of the molecular load [74, 79].
Nanohydrogels are defined as an infinite network of hydrophilic three-dimensional polymers swollen by water without losing their interconnected porous structure, expanding, and disintegrating [81, 82, 83]. For application in food, they must be composed of non-toxic, biodegradable, and biocompatible biopolymers to deliver bioactive compounds in / or through the mucosa of the gastrointestinal tract. Nanohydrogels are soft materials widely used by the food and nutraceutical industries [83].
Generally, hydrogels are formed by chemical or physical cross-linking polymers. They are basically formed by three integral parts: monomer, initiator, and crosslinker [84]. Different techniques can be adapted to obtain the nanohydrogels such as mass polymerization, solution, and suspension, taking into account that the impurities, including unreacted monomer, initiators, crosslinkers, and unwanted products generated, need to be removed after their preparation [81].
Nanohydrogels formed by biopolymeric proteins or polysaccharides are the best alternatives for application in food since they can offer improved functional properties compared to native proteins. The size, structure, load, permeability, porosity, and stability to environmental and solution conditions are essential and fundamental characteristics for nanohydrogels and depend in general on the physicochemical properties of the biopolymers chosen to obtain the gel. [85]. The proper adjustment of these variables allows the functional compounds to be loaded and then released from the polymeric matrix [86]. The choice of the type of polymeric matrix must be adequate considering that hydrophilic compounds can be released from a protein matrix by diffusion, while lipophilic compounds are released mainly by enzymatic degradation of the protein matrix in the GI tract [21, 81, 85].
The definition of nanoemulsion consists of an excellent dispersion composed of an oily phase (triglycerides or hydrocarbons) and an aqueous phase (water or water with some electrolyte or polyol), which appears as spherical drops with a diameter less than 100 nm [70]. The nanoemulsion droplets most often have a core of lipophilic material, which one or more non-polar components may form. The surrounding contents of the nucleus are formed by the material of opposite polarity [81].
There is a wide variety of methods for making stable nanoemulsion. The nanoemulsion preparation is divided according to the energy level adopted in the system as the high and low energy method [87]. The main methods used to obtain a nanoemulsion include high-pressure homogenizers and ultrasound generators representing the high energy method, including microfluidization [88]. Low-energy emulsification methods are cost-effective, in which nanoemulsions with tiny droplets are prepared using low amounts of energy, which stand out the methods of spontaneous emulsification, reverse phase technique, membrane emulsification method, and solvent displacement method [89].
Nanoemulsions offer a wide range of applications due to their composition flexibility in several fields, including food, beverage, and pharmaceutical industries for product storage and delivery. Currently, it can be used to encapsulate lipophilic components, such as vitamins, substances that impart flavors, colors, preservatives, nutraceuticals, and medicines. In addition, it can be applied to preserve food and bioactive compounds, increasing bioavailability and shelf life. Another essential application aimed at the food industry is the possibility of masking unpleasant odors and flavors and protecting bioactive molecules from oxidation and hydrolysis by the action of air and water, respectively [89].
Nanotechnology is a potential new technology in food, being one of the primary resources for development and innovation. Reducing the particle size of bioactive compounds can improve bioavailability, release control, delivery targeting, and solubility. The choice of the preparation technique for the nanostructured systems depends on the characteristics of the bioactive compound, such as hydrophilic or lipophilic, solubility, stability, and the desired properties for the product, such as particle size and bioavailability, among others. Thus, it is possible to verify some of the nanoencapsulation techniques that can be used in bioactive compounds, and many undesirable characteristics can be circumvented with nanotechnology.
This work was supported by grants of CNPq, CAPES, FAPEAL, and FAPEMIG.
The authors declare no conflict of interest.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. In the Engineering side, Digital Signal Processing, Computer Architecture, Electronics Devices, Digital Filtering and Engineering Management.\nApart from his Academic Interest and activities he loves sport especially, Cricket, Football, Snooker and Squash. He plays cricket for Esbjerg city in the second division team as an opener wicket keeper batsman. 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She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. 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He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"322007",title:"Dr.",name:"Maria Elizbeth",middleName:null,surname:"Alvarez-Sánchez",slug:"maria-elizbeth-alvarez-sanchez",fullName:"Maria Elizbeth Alvarez-Sánchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",country:{name:"Mexico"}}},{id:"337443",title:"Dr.",name:"Juan",middleName:null,surname:"A. 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Artificial insemination, for example, was the first technology applied on a large scale, initially in dairy cattle and afterward applied to other species. Nowadays, embryo production and transfer are used commercially along with other technologies to modulate epigenetic regulation. Gene editing is also emerging as an innovative tool. This topic will discuss the potential use of these techniques, novel strategies, and lines of research in progress in the fields mentioned above.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/28.jpg",hasOnlineFirst:!1,hasPublishedBooks:!0,annualVolume:11417,editor:{id:"177225",title:"Prof.",name:"Rosa Maria Lino Neto",middleName:null,surname:"Pereira",slug:"rosa-maria-lino-neto-pereira",fullName:"Rosa Maria Lino Neto Pereira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9wkQAC/Profile_Picture_1624519982291",biography:"Rosa Maria Lino Neto Pereira (DVM, MsC, PhD and) is currently a researcher at the Genetic Resources and Biotechnology Unit of the National Institute of Agrarian and Veterinarian Research (INIAV, Portugal). She is the head of the Reproduction and Embryology Laboratories and was lecturer of Reproduction and Reproductive Biotechnologies at Veterinary Medicine Faculty. She has over 25 years of experience working in reproductive biology and biotechnology areas with a special emphasis on embryo and gamete cryopreservation, for research and animal genetic resources conservation, leading research projects with several peer-reviewed papers. Rosa Pereira is member of the ERFP-FAO Ex situ Working Group and of the Management Commission of the Portuguese Animal Germplasm Bank.",institutionString:"The National Institute for Agricultural and Veterinary Research. 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