**4.1 Photostimulation**

Photostimulation is carried out using a special device combined with an electroencephalograph, which makes it possible to produce rhythmic light flashes at a given frequency.

The color of the flash may be white or red, depending on the design of the device. The light source can be a gas discharge lamp or high-power LEDs. *Practical Recommendations for Conducting an EEG Study in a Neurophysiological Laboratory DOI: http://dx.doi.org/10.5772/intechopen.108879*

#### **4.2 Contraindications for the test**

Pregnancy is a relative contraindication to a photostimulation test, as there is a risk of adverse effects on the fetus in the event of an epileptic seizure.

**Important!**

**When using a photostimulator with a gas discharge lamp as a light source, never test with open eyes, due to the risk of eye damage from the powerful light flux of the gas discharge lamp!!!**

#### **4.3 Hyperventilation**

During hyperventilation, the subject takes a deep breath (trying to fill the lungs as best as possible and exhale through slightly closed lips).

#### **4.4 Contraindications for the test**

Relative contraindications to the hyperventilation test: History of indications of cardiac arrhythmias Intracranial tumors of subtentorial localization Myocardial infarction Diabetes mellitus in the stage of decompensation Acute intoxications Chronic obstructive pulmonary disease Frequent series of generalized and secondary generalized seizures

#### **4.5 Absolute contraindications**

Trauma to the upper respiratory tract Paroxysmal ventricular arrhythmias Acute period of myocardial infarction Pneumothorax

In addition to the contraindications listed above, the hyperventilation test should not be continued if true epileptiform activity is clearly presented in the record, since the main goal of the test has been achieved, and its continuation may lead to the development of a clinical seizure, or in an unfavorable case, status epilepticus.

#### **Important!**

When performing the test, frequent, shallow, and ineffective breathing should be avoided, since in this case, the state of hyperoxia is not achieved and the test becomes ineffective.

#### **Important!**

The main task of a routine examination is to ESTABLISH A DIRECT RELATION-SHIP between the development of a functional disorder and the type of functional load imposed, which is confirmed by the development of pathological activity in the EEG recording!!!

In the absence of a direct connection between the development of a functional disorder and a provoking factor, it is concluded that further examination is necessary using long-term EEG recording technologies.


**Appendix B**

To ensure that a physically sensible optimum is obtained, the initial search space must be generated properly. The procedure below shows how ISLA generates the initial search space, but this does not guarantee a global optimum value as with nonlinear optimization problems. Nonetheless, the results generated by ISLA for energy-only microgrid systems were consistent with those from HOMER Pro®.

The sizes of solar PV, diesel, and the desalination unit are rated based on their maximum power [kW] or flowrate [m3/h] generation, thus, the optimum value must be based on the peak demand. A crude approximation of the peak electrical demand *Ppk* is calculated as shown in Equation (A10). The constant 10 kW/(m3/h) was arbitrarily chosen such that it is near the electrical energy intensities EIel of the desalination units in this study.

$$P\_{pk} = \max\left\{ P\_{ld}(t) + \frac{10\text{ kW}}{\text{m}^3/\text{h}} \dot{V}\_{ld}(t) \right\},\tag{A10}$$

The initial search spaces of solar PV {*SPV*}0, diesel {*Sds*}0, and the desalination unit {*Sde*}0 are shown in Equations (A11)–(A13). Constants are multiplied to *Ppk* due to the possibility of the optimum size deviating from the crudely approximated peak demand. The diesel generator has a small associated constant because its optimum size must be near the peak demand. Smaller sizes may be technically infeasible, while larger sizes will incur high capital cost. Solar PV has a larger associated constant because it has power peaks during the day that are much larger than the peak demand.

$$\{S\_{PV}\}\_0 = \begin{bmatrix} \ 0 \ \ \ \ \ \ \ \end{bmatrix} \tag{A11}$$

$$
\langle \mathbb{S}\_{ds} \rangle\_0 = \left[ \begin{array}{cc} 0, & \text{3P}\_{pk} \end{array} \right]\_{\prime} \tag{A12}
$$

$$\{S\_{d\varepsilon}\}\_0 = \left[ \begin{array}{cc} 0, & \frac{2P\_{pk}}{\mathbb{E}\mathbb{I}\_{\rm el}} \end{array} \right], \tag{A13}$$

The Li-ion BESS and water storage undergo daily cycles of influx and efflux; thus, it is unlikely to have a Li-ion BESS or water storage that drains in less than a day. Their search spaces are therefore based on daily consumption. A crude approximation of the daily power consumption *Edy* is given by Equation (A14). Compared to Equation (A10), a smaller constant of 5 kW/(m3/h) was chosen because the average daily power consumption is less sensitive to sharp peaks in the actual demand profile.

$$E\_{dy} = \frac{1}{365} \left[ \sum\_{i=0}^{8759} P\_{ld}(t) \Delta t + \frac{5 \text{ kW}}{\text{m}^3/\text{h}} \cdot \sum\_{i=0}^{8759} \dot{V}\_{ld}(t) \Delta t \right] . \tag{A14}$$

The initial search spaces of Li-ion BESS {*SLi*}0 and water storage {*Stank*}0 are shown in Equations (A15) and (A16). Constants are multiplied to *Edy* due to the possibility of the optimum size deviating from the crudely approximated daily energy consumption. These constants are smaller, however, because caution against sharp peaks in the actual demand profile is unnecessary.

$$\{S\_{Li}\}\_0 = \begin{bmatrix} & 0, & 2E\_{dy} \end{bmatrix} \tag{A15}$$

$$\{S\_{tank}\}\_0 = \begin{bmatrix} 0 \ \ \ \ \ \frac{2E\_{d\mathbf{y}}}{\mathbb{E}\mathbb{I}\_{\text{el}}} \ \end{bmatrix} \tag{A16}$$


Preface

Entrepreneurship is an evolving and expanding multidisciplinary field of study. Research on entrepreneurship is being conducted from various perspectives and realities of markets and participants. Some of the principal areas of entrepreneurship research are technopreneurship, immigrant entrepreneurship, social entrepreneurship, women entrepreneurship, entrepreneurship in emerging markets, and start-up ventures.

This book is a collection of reviewed and relevant research chapters concerning developments within the field of entrepreneurship. It includes scholarly contributions by various authors and is edited by a group of experts in business, management, and economics.

The book includes the following chapters:

Chapter 1: "New Perspectives for Technological Entrepreneurship in the Age of Change: Between Success and Resilience"

Chapter 2: "Innovation and Entrepreneurship to Address the UN Sustainable Development Goals"

Chapter 3: "Entrepreneurship in Emerging Economies: The Role of Innovation and Institutions"

Chapter 4: "Project Coordinator Competence and the Success of International Development (ID) Projects: Standard Models Tested in Practice"

Chapter 5: "Entrepreneurship and Factors Affecting Entrepreneurial Decisions"

Chapter 6: "Start-up Business Investment: The Case of Mongolia"

Chapter 7: "Ultra-Micro Business Algorithm: Village Economic Metabolism in the Coastal Area"

Chapter 8: "Women Entrepreneurship Psychology in Managing Micro, Small, and Medium Enterprises (MSMEs): A Case Study in Indonesia"

Chapter 9: "Women Entrepreneurs as Vloggers: Turkish Beauty YouTubers in the Context of Simulative Labor"

Chapter 10: "Role of Mentoring for Women Entrepreneurs"

Chapter 11: "A Review of the Impact of Covid-19 Pandemic on Women Entrepreneurs"

Chapter 12: "Role of the Family in Fostering Student's Entrepreneurial Intention"

Chapter 13: "Entrepreneurial Intention, Life Satisfaction, and Impulsivity in University Students"

Chapter 14: "Digital Entrepreneurship in Vocational High School Student Level"

The target audience comprises scholars and specialists in the field.


**4. Experimental tests**

To achieve successful results, the experimental tests must reproduce the operation conditions as close as possible to the application for thermal management of thermoelectric cooling. Then, to evaluate the thermal performance of the analyzed passive heat transfer devices, an experimental apparatus and some experimental procedures were used.

## **4.1. Experimental apparatus**

The essential experimental apparatus for the experimental tests, shown in **Figure 13**, is composed of a data logger (*Agilent*™ 34970A with 20 channels), a power supply unit (*Keysight* ™ U8002A), a laptop (*Dell*™), an uninterruptible power supply (*NHS*™), a universal support, and a fan (*Ultrar*™).

For the evaluation of the temperature of the different heat transfer passive devices, K-type thermocouples *Omega Engineering*™ are used. They should be fixed on the outer surface of devices by a thermosensitive adhesive strip *Kapton*™. They should be distributed in the length of the heat pipes and thermosyphon. Thus, there are three thermocouples in the evaporator (*Tevap*,1, *Tevap*,2, and *Tevap*,3), one thermocouple in the adiabatic section (*Tadiab*) e four thermocouples in the condenser (*Tcond*,1, *Tcond*,2, *Tcond*,3, and *Tcond*,4) in passive devices (heat pipes and thermosyphon), as shown in **Figure 14**. For the rod, two thermocouples were fixed in the evaporator

**Figure 13.** Experimental apparatus.

**Figure 12.** Structure sintered copper powder. (a) General view and (b) microscale image.

**Figure 11.** Microgrooves made by wire-EDM. (a) Scheme of microgroove profile and (b) microscale image.

in length, an adiabatic region of 20 mm in length, and a condenser of 100 mm in length. The working fluid used is distilled water with filling ratios related to the evaporator volume based on the best performance of each capillary structure. **Table 1** shows the main characteristics of

The mesh heat pipe used one layer of phosphor bronze screen mesh #100 (**Figure 10a**) as capillary structure. A microscale image of screen mesh #100 is shown in **Figure 10b**. The image was obtained by backscattered electron detector (BSD) for scanning electron microscope (SEM).

The grooved heat pipe shown schematically in **Figure 11a** had 32 microgrooves made by the wire electrical discharge machining (wire-EDM). **Figure 11b** presents the axial microgrooves details with an average diameter of 220 μm by a micro-scale image. The image was obtained by backscattered electron detector (BSD) for scanning electron microscope (SEM). More

the heat transfer passive devices analyzed in this research.

362 Bringing Thermoelectricity into Reality

details about this heat pipe can be found in [24, 28].

More information about this mesh heat pipe can be found in [23].

**5. Data reduction**

culated by:

Defined by:

denser length.

where *Di*

length can be defined by:

**5.2. Uncertainties analysis**

**5.1. Thermal parameters**

*Rth* = \_\_\_

the evaporator and the condenser, respectively.

*keff* = *q Leff* \_\_\_\_\_\_\_\_\_\_

*Leff* = *Levap* \_\_\_\_

The heat transfer cross-sectional area can be defined by:

is the inner diameter of the heat transfer passive device.

*AC* = (*πDi*

The thermal performance of the heat pipes and the thermosyphon was analyzed and compared by the operating temperatures (*Top*), the global thermal resistance (*Rth*), and the effective thermal conductivity (*keff*). The analyzed operating temperature is the temperature of the adiabatic region. The global thermal resistance, *Rth*, of a heat pipe and a thermosyphon can be defined as the difficulty of the passive device to transport the heat power and can be cal-

Heat Pipe and Thermosyphon for Thermal Management of Thermoelectric Cooling

Δ*T*

*q* = (*Tevap* − *T* \_\_\_\_\_\_\_\_\_ cond)

where, *q* is the heat transfer capability of the device, *Tevap* and *Tcond* are the mean temperature of

The effective thermal conductivity, *keff*, is the property of a certain material to conduct heat.

where, *Leff* is the effective length and *AC* is the heat transfer cross-sectional area. The effective

2 + *Ladiab* +

2 ) \_\_\_\_\_

where, *Levap* is the evaporator length, *Ladiab* is the adiabatic section length, and *Lcond* is the con-

In general, the experimental uncertainties are associated to the K-type thermocouples, the data logger, and the power supply unit. The experimental measurement uncertainties were analyzed using the uncertainty combination method described in [29] considering the combination of uncertainties of correlated quantities. They are shown in the obtained

*L* \_\_\_\_ *cond*

*AC* Δ*T* = *q L* \_\_\_\_\_\_\_\_\_\_\_ *eff*

*q* (1)

http://dx.doi.org/10.5772/intechopen.76289

365

*AC*(*Tevap* − *T*cond) (2)

2 (3)

4 (4)

**Figure 14.** Thermocouple positions in heat pipes.

(*Tevap*,1 and *Tevap*,2), one thermocouple in the adiabatic section (*Tadiab*) and three thermocouples in the condenser (*Tcond*,1, *Tcond*,2, and *Tcond*,3).

As is already known, for the correct operation of the heat pipe and thermosyphon, a heating system is needed in the evaporator and a cooling system in the condenser. The evaporator can be power dissipation in any kind of resistor (strip, cartridge) or a heat source, as the TEC hot side. The cooling system can consist of forced convection by air, water, or coolant, in most of the cases. The adiabatic section may have variable dimensions (in some cases, it is absent) and should be insulated from the external environment.

Thus, in this research, the heating system of the evaporator is conducted by power dissipation from the passage of an electric current in a nickel-chromium alloy power strip resistor *Omega Engineering*™ with 0.1 mm of thickness and 3.5 mm of width. To ensure that the generated heat by Joule effect is transmitted to the evaporator, an aeronautic thermal insulation and a layer of polyethylene are installed in this region. A fiberglass tape is used in adiabatic section as heat insulation between the support and the passive device. The cooling system using air forced convection consisted of a fan in the condenser region.

#### **4.2. Experimental procedure**

To ensure the best results and the repeatability of experimental tests, the environment temperature was maintained at 20°C ± 0.5°C. A thermal conditioning system *Carrier™* was used for this purpose. A detailed check of the equipment and the heat pipe or thermosyphon (fixing thermocouples, thermal insulation, resistor connection, among others) must be made before each experimental test. The heat pipe or thermosyphon was carefully fixed to the universal support bracket in the adiabatic region in the desired position. The cooling system was turned on in the condenser region and set at a speed of 5 m/s controlled by a potentiometer with a combined error of ±0.2 m/s. The data acquisition system was turned on, collecting the temperatures measured by the K-type thermocouples. The temperatures should be verified according to the environment temperature, and if these were stable and approximately 20°C, finally, the heating system can be turned on and adjusted to the dissipation power desired. The initial load was 5 W and, after approximately 15 min, the thermocouples showed stationary values. If it happened, the thermal load has been increased by 5 W. The load increment was made until the maximum temperature of the device reached the critical temperature (150°C), where the melting of the materials could happen. Data were acquired every 5 s, recorded on the desktop by the software *Agilent™ Benchlink Data Logger 3*.


**1.1 Global production of sheep's milk**

The constant population growth and the increase in the demand for dairy products and their derivatives have generated a continuous increase in the world per capita consumption of milk, which reached 111.3 kg in 2015, and an increase of 12.5% is estimated by 2025 [1]. However, there are significant regional disparities among developing countries, where fresh dairy products remain, by a large margin, the most consumed, unlike in developed countries where consumer preferences

**Figure 1.**

*Per capita consumption of processed and fresh dairy products. OECD-FAO, 2016 (adapted from [2]).*

incline toward processed products (butter, cheese, skimmed milk powder and whole milk powder) (**Figure 1**) [2].

The world production of milk of all species has followed an upward trend in recent decades, reaching in 2015 approximately 818 million t [1]. The highest percentage of dairy production is derived from the dairy industry (82.6%), followed by buffaloes (13.9%), goats (1.9%), sheep (1.3%), and finally, camels, which contribute only 0.3% of the total [2] (**Figure 2**).

The dairy industry is markedly regionalized and is associated with a long tradition of production and consumption of dairy products, mainly cheeses. The world production of fresh sheep's milk registered in 2016 by FAO estimates 10,366,980 t. This is mainly produced in the Asian region (44.6%), which houses the two main producing countries: China (1,361,360 t) and Turkey (929,432 t). In the European continent (32.7%), Greece (711,577 t) and Romania (631,419 t) stand out, ranking as the third and fifth largest producers of sheep's milk, respectively. The African

**Figure 2.**  *World milk production by species. FAO 2016 [2].*

*Production, Processing, Commercialization and Analysis of Costumer Preferences of Sheep… DOI: http://dx.doi.org/10.5772/intechopen.83806*

**Figure 3.**  *Geographical distribution of sheep's milk production. FAO 2016 [3].*

continent produces almost a quarter of the international sheep milk inventory (21.8%), with subsistence production systems; countries such as Syria (651,867 t), Mali (529,373 t) and Sudan (403,008 t) are among the top 10 producing countries worldwide. The American continent has a relatively minimal participation in the world production of sheep's milk (0.9%); only the following countries provide official productivity data: Mexico (57,589 t), Bolivia (29,617 t) and Ecuador (3617 t) (**Figure 3**) [3].

 Sheep's milk production in the North American countries is not significant; it is estimated that Mexico, the United States and Canada have approximately 200 production units dedicated exclusively to the production of milk, with less than 10,000 sheep each [3, 4]. Data from associations of producers estimate that in 2010, there were 20 production units with the potential to milk sheep with an approximate inventory of 6000 animals distributed in the states of Coahuila, Guanajuato, State of Mexico, Puebla, Querétaro and Veracruz (**Table 1**). In 2009, Querétaro was the state that presented the highest production, with 30,000 liters. Likewise, in this state, the first association of dairy sheep called "Producers of Milk and Derivatives of Sheep S.A. of C.V." united 13 producers and integrated the collective brand "Del Rebaño" [5].

 In Chile, the sheep cheese market, unlike that for goat cheeses, is very underdeveloped, given the low national consumption tradition and the low consumer culture regarding this product. However, in the country, there are foreign colonies of immigrants from Mediterranean countries that have favored the expansion of these products. In 1995, the first exploratory imports of sheep's milk cheese were carried out, with a volume of 1.25 t, and a positive evolution was observed, which was manifested the following year with an increase to 3.88 t. In 1998, the total national supply in the sheep cheese market reached 7.2 t, of which two were of national origin and the rest imported mainly from Spain and France. Currently, the national demand is less than 6 t per year, a figure that represents a volume of milk of less than 40,000 liters. The national production of sheep's milk associated with its industrialization and cheese making is estimated between 20,500

### **Table 1.**

*Some units of sheep milk production in Mexico [8, 16].*

 and 22,000 liters per year, equivalent to between 3 and 4 t of cheese [6]. In 2014, the *El PASO* location assessed five regions that produce most of the country's cheeses: Los Ríos (49,394 t), Los Lagos (30,939 t), La Araucanía (6202 t), Biobío (906) and Metropolitana de Santiago (273 t) [7].

In Chile, two sheep dairy breeds have been introduced: Milchschaf and Latxa, which have been fostered through the crossing of dairy males with sheep from Chilean cattle ranchers, with the aim of reducing the initial investment costs. The dairy breed of the male or the genetic improvement program that is chosen will basically depend on three aspects: forage potential, adaptation of the dairy breed that is being introduced to the area, and the reproductive and productive characteristics of each one [8]. Within the dairy production and ovine cheese industry, a highlight is the initiative developed by the University of Magallanes in the city of Puerto Natales (Chilean Patagonia) that produces the southernmost cheese of Chile [9].

### **1.2 Sheep's milk: physicochemical characteristics and nutritional properties**

 Recent studies have determined that the chemical composition of milk varies depending on the feeding of the sheep, modifying the percentages of fat, protein, lactose and the fatty acid profile of the milk depending on the ratio of forage to concentrate in the diet or of the supplementation with protected fat. The results show that diets with the highest forage content (>40% DM) have a significantly lower milk yield (0.8 g/kg), but with a higher fat content (0.32 g) and concentration of conjugated linoleic acid (CLA) (2.28 mg/kg). The addition of protected fat in the rumen in the diets has a positive effect on the concentration of fat (0.22 g/100 g) and CLA (3.98 mg/g) in milk, but the protein concentration is reduced (*P* < 0.001). On the other hand, diets with a higher proportion of concentrate (>40% DM) affect the biodegradation processes and the synthesis of CLA (**Table 2**) [10].

The particular characteristics in the chemical composition of sheep's milk, mainly in relation to its high levels of total solids and protein, make it especially suitable for transformation into yogurt and cheese. About 95% of sheep's milk is converted into dairy products, which also acquire a regional connotation of origin and quality [11, 12]. For this reason, when we refer to the quality of sheep's milk, we must concentrate mainly on its ability to be transformed into high-quality dairy products, generate high yields of these products per liter of milk and ensure the safety of these foods [11]. In this way, three types of "quality" can be distinguished when analyzing products of animal origin: hygienic and sanitary quality, dietetic and nutritional quality and gustatory and gastronomic quality [12].

The unique characteristics of sheep's milk have been discussed in extensive reviews of literature [11–15], in which the quality of sheep's milk is evaluated in terms of its technological and coagulation properties. High concentrations of

*Production, Processing, Commercialization and Analysis of Costumer Preferences of Sheep… DOI: http://dx.doi.org/10.5772/intechopen.83806*

1 *mg/g of methylated fatty acids; F, forage based rations; C, concentrate based ration; S, protected fat supplemented rations; U, unsupplemented fat protected rations.*

### **Table 2.**

*Descriptive statistics of data used in forage:concentrate ratio and protected fat supplementation meta-analysis [10].*

protein, fat and total solids in milk are associated with high yields in the production of dairy products; therefore, the aforementioned studies conclude that sheep's milk has higher yields compared to goat's milk and cow's milk because of its superior chemical composition (**Table 3**) [13].

Milk proteins include caseins and whey proteins; caseins are a family of phosphoproteins synthesized in the mammary gland in response to lactogenic hormones [17], which represent the highest protein share of sheep's milk (76–83%) [18]. The heterogeneity of the caseins is determined mainly by the presence of genetic variants; four genetic variants of caseins are recognized: αs1-CN, αs2-CN, β-CN and κ-CN. Sheep's milk has higher concentrations of the four casein variants compared to sheep and goat milk [17]. Whey proteins represent 17–22% of the total protein content; 75% of whey proteins are albumins (α-lactoalbumin and β-lactoglobulin), with a high content of the AA phenotype of β-lactoglobulin, which has been shown to provide greater efficiency in the manufacture of sheep cheese [19, 20].

In recent decades, there has been an increase in interest in foods with specific nutritional properties. The nutritional advantages of sheep's milk over other species does not derive from its content of protein, minerals or vitamins; the superiority as a functional food lies in its lipid content, more specifically in its fatty acid profile; ovine products have received direct attention due to the possibility of being enriched with fatty acids' potential benefits to health, especially vaccenic acid (VA, C18: 1 t11), c9, t11CLA, also

*NNP, non-protein nitrogen. 1 Retinol. 2 Tocopherol. 3 Thiamine. 4 Riboflavin. 5 Niacin. 6 Pantothenic acid. 7 Pyridoxine. 8 Biotin. 9 Folic acid. 10Cobalamin.*

### **Table 3.**

*Comparison of the chemical composition of different species (adapted from [13, 18, 22]).*

called rumenic acid, and α-linolenic acid (ALA, C18: 3, n3). Sheep's milk, compared to cow's milk, contains three to four times the amount of VA and CLA c9T11 [15].

The milk of small ruminants and their derivatives are the largest source of CLA in human food [21]. The content of CLA in ruminant milk decreases in the following order: sheep > cow > goat, with contents 1.08, 1.01 and 0.65%, respectively [22]. However, the particular management conditions of sheep herds determine seasonal oscillations in CLA concentrations due to the variability in the availability and quality of forage [23].

*Production, Processing, Commercialization and Analysis of Costumer Preferences of Sheep… DOI: http://dx.doi.org/10.5772/intechopen.83806*


**2. Air pollution**

Air pollution can be composed by a cocktail of different substances that in large amounts can be harmful to the ecosystem. The industrial revolution marks the beginning of an accelerated global urbanization process. As a result, large urbanized areas suffer from, amongst other problems, a high concentration of air pollutants. The most evident form of air pollution is a dark layer of gas – also known as smog – present above big cities. Nevertheless, there are different kinds of air pollution that are not as visible. Sources include natural processes, such as volcano emissions, and also industrialized sources found in urban centres linked to human activities. The latter includes power plants, factories, burning of fossil fuel and transportation.

© 2014 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

#### **2.1. Classification of air pollutants**

Air pollutants can be found in different forms and sizes. They can be solid particles, liquid molecules or gases. According to the way they are generated these pollutants can be consid‐ ered as primary (directly produced) or secondary (formed by the interaction of primary pollutants). Some pollutants can be both produced directly as well as formed by the reaction of other pollutants. In addition, there are indoor and outdoor pollutants, all of which can be detrimental to human health. Although indoor pollution is generally low, its levels can be augmented by the use of several chemical products (e.g. cleaning products, paints), heaters, stoves and indoor smoking. Fortunately, various countries have already adopted policies that ban smoking in closed public spaces. Description and classification of the main pollutants resulting from human activity are listed in table 1 below.

**3. General health consequences of exposure to air pollution**

consequences of air pollution exposure [5, 11, 12].

economic issue to countries affected [14].

stroke [20, 22-24].

The analyses of recent epidemiological studies, conducted in various urban centres, have provided coherent evidence that elevated levels of air pollution are associated with an increased risk of respiratory diseases, chronic obstructive lung diseases (COPD), cancers, cerebrovascular-strokes, cardiovascular diseases and mortality. These occur due to the nature of the pollutants and via their impacts on the respiratory and cardiovascular systems [1-7]. Air pollution does not only affect individuals that are directly exposed to it, but it also has a deleterious effect on foetal development and preterm birth. Various studies have shown that decreases in neonate birth weight are associated with exposure to air pollu‐ tion [8-10]. Children are also very susceptible to the harmful effects of pollution expo‐ sure. This is reflected by an increase in the number of young children admitted to hospitals for acute lower respiratory infection: pneumonia and bronchiolitis. These respiratory infections are the largest causes of mortality among young children worldwide, especially in developing countries. Within these countries a low socioeconomic status potentiates the

Lung Inflammation, Oxidative Stress and Air Pollution

http://dx.doi.org/10.5772/58252

3

These adverse effects on health, caused by air pollution, have been shown to occur in both developed and developing countries. However, its health-related burden falls most heavily on developing countries [3, 6, 13-15]. According to the World Health Organisation [16], air pollution is responsible for over 800, 000 premature deaths each year, with more than 6 million years of life lost annually. Asia alone would account for approximately two thirds of these numbers [2]. It goes without saying that this air pollution disease-burden is a great

The World Health Organisation, together with governments of various countries, have proposed guidelines for maximum concentrations of the different pollutants (see table 2). Nevertheless, this does not always translate into national policies and various cities are unable to maintain pollution levels within the suggested guidelines. The implementation of anti-pollution measures is not always straight forward. At times, for example, it means there is a need to change energy sources and invest in green technology. As a conse‐ quence, some countries are more reluctant than other to execute such measures [3, 17].

In relation to indoor air pollutants, on March 2004, the Republic of Ireland became the first country to completely ban smoking from workplaces. More and more countries gradually adopted this public-space smoking ban. Nowadays, most countries in the world have some kind of law pertaining to the issue. There is a growing body of evidence on the positive health outcomes and the economic benefits related to the adoption of smoke-free laws. Improvements in lung function, airway and systemic inflammation, and adverse respiratory symptoms were observed in individuals working in bars [18, 19]. Hospital admissions of children and adults presenting asthma and other pulmonary illnesses also decreased as a result of reduced exposure to environmental tobacco smoke [20-22]. Smoking bans also positively impacted individuals with heart diseases which include myocardial infarction, unstable angina and

**Table 1.** Main primary pollutants resulting from human activity

## **3. General health consequences of exposure to air pollution**

**2.1. Classification of air pollutants**

2 Lung Inflammation

resulting from human activity are listed in table 1 below.

• Strong pungent smell

• Brownish-red colour • Strong smell

**Air Pollutant Characteristics Source**

• No colour

• No smell

• No colour • Strong smell

particles

• No colour • Strong smell

and liquids

• Strong smell

**Table 1.** Main primary pollutants resulting from human activity

• Gases emitted from solids

Ozone (O3)

or Tropospheric O3 or ground level O3

Volatile Organic Compounds (VOCs)

Air pollutants can be found in different forms and sizes. They can be solid particles, liquid molecules or gases. According to the way they are generated these pollutants can be consid‐ ered as primary (directly produced) or secondary (formed by the interaction of primary pollutants). Some pollutants can be both produced directly as well as formed by the reaction of other pollutants. In addition, there are indoor and outdoor pollutants, all of which can be detrimental to human health. Although indoor pollution is generally low, its levels can be augmented by the use of several chemical products (e.g. cleaning products, paints), heaters, stoves and indoor smoking. Fortunately, various countries have already adopted policies that ban smoking in closed public spaces. Description and classification of the main pollutants

Ammonia (NH3) • Gas Produced industrially. Mostly used as fertiliser to agricultural crops (over

Carbon monoxide (CO) • Gas A major source of this poisonous gas is vehicular exhaust. It is also a

Nitrogen dioxides (NO2) • Gas Released by internal combustion engines and power-plants. Indoor

• No colour product of incomplete combustion of carbon-containing fuels.

the formation of O3 pollution.

Particulate Matter (PM) • Solid or liquid This pollutant can vary in size, form and composition being made up by a

Sulfur oxides (SOx) • Gas Amongst the highly reactive gases of this group is the sulphur dioxide

are precursors of O3.

• Gas This highly oxidant pollutant is formed by the reaction of nitrogen oxides

in large urban areas but also in rural areas.

circulation and affect other organs.

80%). Also used, for example, in the fermentation and textile industry, as cleaning product, and as antimicrobial agent for food products.

sources of this pollutant include gas and kerosene heaters. It is also released by electric discharge during storms. NO2 is also a precursor for

and volatile organic compounds in the presence of sunlight. As it is easily transported by the wind it can be found in high concentrations not only

mixture of extremely small particles (metals, soil, dust) and liquid droplets (acids, organic compounds). The smaller the PM size the deeper it can penetrate into the lungs and might even be able to pass to the systemic

(SO2) that is produced by the burning of fuels such as petrol, diesel, and coal. It is naturally released into the atmosphere by activated volcanoes.

VOCs are mainly indoor pollutants because they can be released by a variety of materials and products which are used in the households and offices such as paints, disinfectant, air-fresheners and photocopy machines. VOCs are also released by fuels. As mentioned previously they The analyses of recent epidemiological studies, conducted in various urban centres, have provided coherent evidence that elevated levels of air pollution are associated with an increased risk of respiratory diseases, chronic obstructive lung diseases (COPD), cancers, cerebrovascular-strokes, cardiovascular diseases and mortality. These occur due to the nature of the pollutants and via their impacts on the respiratory and cardiovascular systems [1-7]. Air pollution does not only affect individuals that are directly exposed to it, but it also has a deleterious effect on foetal development and preterm birth. Various studies have shown that decreases in neonate birth weight are associated with exposure to air pollu‐ tion [8-10]. Children are also very susceptible to the harmful effects of pollution expo‐ sure. This is reflected by an increase in the number of young children admitted to hospitals for acute lower respiratory infection: pneumonia and bronchiolitis. These respiratory infections are the largest causes of mortality among young children worldwide, especially in developing countries. Within these countries a low socioeconomic status potentiates the consequences of air pollution exposure [5, 11, 12].

These adverse effects on health, caused by air pollution, have been shown to occur in both developed and developing countries. However, its health-related burden falls most heavily on developing countries [3, 6, 13-15]. According to the World Health Organisation [16], air pollution is responsible for over 800, 000 premature deaths each year, with more than 6 million years of life lost annually. Asia alone would account for approximately two thirds of these numbers [2]. It goes without saying that this air pollution disease-burden is a great economic issue to countries affected [14].

The World Health Organisation, together with governments of various countries, have proposed guidelines for maximum concentrations of the different pollutants (see table 2). Nevertheless, this does not always translate into national policies and various cities are unable to maintain pollution levels within the suggested guidelines. The implementation of anti-pollution measures is not always straight forward. At times, for example, it means there is a need to change energy sources and invest in green technology. As a conse‐ quence, some countries are more reluctant than other to execute such measures [3, 17].

In relation to indoor air pollutants, on March 2004, the Republic of Ireland became the first country to completely ban smoking from workplaces. More and more countries gradually adopted this public-space smoking ban. Nowadays, most countries in the world have some kind of law pertaining to the issue. There is a growing body of evidence on the positive health outcomes and the economic benefits related to the adoption of smoke-free laws. Improvements in lung function, airway and systemic inflammation, and adverse respiratory symptoms were observed in individuals working in bars [18, 19]. Hospital admissions of children and adults presenting asthma and other pulmonary illnesses also decreased as a result of reduced exposure to environmental tobacco smoke [20-22]. Smoking bans also positively impacted individuals with heart diseases which include myocardial infarction, unstable angina and stroke [20, 22-24].

On the other hand, free radicals and reactive species are essential to our well-being. This happens because these molecules are necessary for a variety of reactions to occur. For example, they are used by the immune system to attack and kill pathogens in a process called respiratory burst. They are also used for gene stimulation, cell signalling, vasoregulation and inflamma‐

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Antioxidants are often reducing agents capable of being promptly oxidized by free radicals and reactive species, eliminating their pro-oxidant nature before they react with cell compo‐ nents. There is a wide range of antioxidants in body fluids, tissues and organs. They are present both intracellular and extracellular, working synergistically in a network to balance the free radicals and reactive species. Therefore, the action of one antioxidant may depend on the

Antioxidants are both synthesized *in vivo* and absorbed through the diet and they can be divided into two groups: enzymatic and non-enzymatic. Enzymatic antioxidants include superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT). Each of these enzymes is responsible for the reduction of different pro-oxidants and they are located in different cellular compartments. Glutathione, vitamin C, vitamin E, carotenoids, and uric acid are some examples of non-enzymatic antioxidants. Similarly to the enzymatic antioxidant, these are present in different cellular compartments and elicit distinct antioxidant properties which maximize their effectiveness [29]. Antioxidants can also be classified according to their soluble nature: hydrophilic (water soluble) or lipophilic (lipid soluble). It is this characteristic

tory processes [31, 32].

**Figure 1.** Redox balance

**4.2. Antioxidants**

correct function of other antioxidants in the system.

that allows them to be present in different parts of the cells.

**Table 2.** Updated WHO air guideline values

#### **4. Oxidative stress and air pollution**

The mechanism responsible for the adverse effect of oxidant pollutants – ozone, PM – in the lungs, which might possibly also lead to a systemic outcome, would be its direct and indirect oxidative reaction with molecules and cells present in the airways [25, 26]. This might result in oxidative stress in the airway tissues [27]. But what is oxidative stress?

#### **4.1. Oxidative stress**

Oxidative stress can be defined as damage that might occur in cell components, such as membranes, RNAs and DNA, as a result from an imbalance in the body's ability to neutralize certain molecules or to repair the resulting damage. Free radicals and reactive species (reactive oxygen species and reactive nitrogen species) are molecules that easily react with other molecules to become more stable. This is an oxidation reaction, because there is transfer of electrons from a substance to the free radicals/reactive species (oxidaizing agents). When in our organism these reactions occur with cell components, which could have detrimental effects such as cell function impairment and cell death. Nevertheless, the body has an elaborate antioxidant defence system that neutralizes the reactive species and free radicals so as to maintain a redox homeostasis. This balance, however, can be disturbed if the concentration of pro-oxidants (reactive species and free radicals) overwhelms the available antioxidants or if the antioxidants are depleted due to disease or poor diet. This associated with reduced repairing process, can result in oxidative stress, and impaired cellular function may occur. In humans, oxidative stress has been shown to be the cause and consequence of various diseases (Fig 1). These include, but are not limited to, cancers, atherosclerosis, Alzheimer's disease, Parkinson's disease, dementia, heart diseases and pulmonary disorders [28-30].

On the other hand, free radicals and reactive species are essential to our well-being. This happens because these molecules are necessary for a variety of reactions to occur. For example, they are used by the immune system to attack and kill pathogens in a process called respiratory burst. They are also used for gene stimulation, cell signalling, vasoregulation and inflamma‐ tory processes [31, 32].

**Figure 1.** Redox balance

**4. Oxidative stress and air pollution**

**Table 2.** Updated WHO air guideline values

PM2.5 1year 10

PM10 1year 20

O3 8 h, daily maximum 100 NO2 1year 40

SO2 24 h 20

**4.1. Oxidative stress**

Source: (WHO 2012)

4 Lung Inflammation

The mechanism responsible for the adverse effect of oxidant pollutants – ozone, PM – in the lungs, which might possibly also lead to a systemic outcome, would be its direct and indirect oxidative reaction with molecules and cells present in the airways [25, 26]. This might result

**Pollutant Averaging time Air quality guideline values (ug/m3)**

24 h (99th percentile) 25

24 h (99th percentile) 50

1 h 200

10 min 500

Oxidative stress can be defined as damage that might occur in cell components, such as membranes, RNAs and DNA, as a result from an imbalance in the body's ability to neutralize certain molecules or to repair the resulting damage. Free radicals and reactive species (reactive oxygen species and reactive nitrogen species) are molecules that easily react with other molecules to become more stable. This is an oxidation reaction, because there is transfer of electrons from a substance to the free radicals/reactive species (oxidaizing agents). When in our organism these reactions occur with cell components, which could have detrimental effects such as cell function impairment and cell death. Nevertheless, the body has an elaborate antioxidant defence system that neutralizes the reactive species and free radicals so as to maintain a redox homeostasis. This balance, however, can be disturbed if the concentration of pro-oxidants (reactive species and free radicals) overwhelms the available antioxidants or if the antioxidants are depleted due to disease or poor diet. This associated with reduced repairing process, can result in oxidative stress, and impaired cellular function may occur. In humans, oxidative stress has been shown to be the cause and consequence of various diseases (Fig 1). These include, but are not limited to, cancers, atherosclerosis, Alzheimer's disease,

in oxidative stress in the airway tissues [27]. But what is oxidative stress?

Parkinson's disease, dementia, heart diseases and pulmonary disorders [28-30].

#### **4.2. Antioxidants**

Antioxidants are often reducing agents capable of being promptly oxidized by free radicals and reactive species, eliminating their pro-oxidant nature before they react with cell compo‐ nents. There is a wide range of antioxidants in body fluids, tissues and organs. They are present both intracellular and extracellular, working synergistically in a network to balance the free radicals and reactive species. Therefore, the action of one antioxidant may depend on the correct function of other antioxidants in the system.

Antioxidants are both synthesized *in vivo* and absorbed through the diet and they can be divided into two groups: enzymatic and non-enzymatic. Enzymatic antioxidants include superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT). Each of these enzymes is responsible for the reduction of different pro-oxidants and they are located in different cellular compartments. Glutathione, vitamin C, vitamin E, carotenoids, and uric acid are some examples of non-enzymatic antioxidants. Similarly to the enzymatic antioxidant, these are present in different cellular compartments and elicit distinct antioxidant properties which maximize their effectiveness [29]. Antioxidants can also be classified according to their soluble nature: hydrophilic (water soluble) or lipophilic (lipid soluble). It is this characteristic that allows them to be present in different parts of the cells.

Numerous studies have investigated the effects by which O3 affects the human lungs. Never‐ theless, the mechanisms responsible for such adverse effects, such as an increase in the airway inflammation and impairment in lung function, are only partly understood. It is known that when O3, or indeed any gas, is inhaled, it first comes into contact with the RTLF. Indeed, ozone is not able to infiltrate further than the RTLF and the membranes of cells from the lung-air interface, yet it is still known to cause damage beyond the lungs. Once O3 comes into contact with the RTLF, it induces oxidative stress by two different mechanisms. The first would be by reacting directly with the constituents of the RTLF and the underlying epithelium [26]. It has been suggested that antioxidants present in the RTLF, such as glutathione, uric acid and ascorbic acid have an important role in neutralizing part of the radical generation, hence reducing the ozone induced oxidative stress [35]. Studies analysing the effect of ozone inhalation and airway antioxidant consumption have indeed shown significant alterations in

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The second mechanism by which ozone can increase the oxidation process is indirectly because, even though O3 does not react directly with the epithelial cells, these cells do react in response to the oxidation products produced in the RTLF. As a consequence they release a variety of pro-inflammatory mediators and more reactive species [25, 26]. These processes combined could overwhelm the local and systemic antioxidant network leading to an increase in the oxidative process, the intensity of which varies depending on the O3 inhaled dose and also on the antioxidants present in the lining fluid. If the oxidative stress is sufficient, the activation of an inflammatory response occurs and is characterized by the intense arrival and activation of neutrophils. These neutrophils produce further ROS through the respiratory burst process. Hence, the overproduction of ROS might result in oxidative stress in the airway tissues. The hypothesis is that the antioxidants present in the epithelial lining fluid of the lungs would neutralize the excess production of free radicals and ROS, consequently reducing lung injury induced by air pollution [27, 35]. This will be discussed in the following sections.

Airway inflammation and any other inflamed tissue can be characterized by an increase in inflammatory cells, such as neutrophils and macrophages, as well as inflammatory mediators: interleukin-6 (IL-6), interleukin-8 (IL-8), and prostaglandins. An increase in neutrophil numbers and percentage is a good indicator of the beginning of an inflammatory response because these cells account for 50-60% of the total white blood cells in the circulation and are the first cell type to migrate to sites of injury and inflammation. When a tissue is inflamed, an increase in the expression of adhesion molecules of the selectin family (E-and P-selectin molecules) occurs in the local endothelium. This process is mediated by cytokines and other inflammatory mediators. Neutrophils present in the blood recognise the site of inflammation because of these adhesion molecules which bind to the other molecules (mucin-like celladhesion molecules, CAM) on the neutrophil surface. This step is referred to as rolling: the first step to the attachment of neutrophils onto the endothelium. In order for them to adhere firmly and be able to migrate through the endothelial to the inflamed site, the neutrophils are

airway antioxidants, such as uric acid, ascorbic acid and GSH [36-38].

**5. Lung inflammation and air pollution**

**Table 3.** Important antioxidants

Most antioxidants undergo redox cycling. This means that once oxidized they can be reduced to their former state and act again as an antioxidant. Nevertheless, this redox cycling allows the antioxidant to act as pro-oxidant promoting free radical formation. This would happen if there is an unbalance in the antioxidant network system. Vitamin C and vitamin E are examples of antioxidants with this characteristic, while melatonin is considered a terminal antioxidant because it cannot be recycled.

**Figure 2.** Redox cycling of vitamin E (vit E) by vitamin C (Vit. C)

#### **4.3. Lung oxidative stress**

Oxidant air pollutants such as ozone, particulate matter and nitrogen dioxide have been shown to induce lung inflammation through stimulation of the oxidative stress process. Little is known, however, about their effects as oxidant compounds in the lungs or about the role and the effectiveness of the antioxidants present in the respiratory tract lining fluid (RTLF) in scavenging and protecting against their harmful effects. A great variety of antioxidants can be found in human RTLF. Their concentration and distribution throughout the airways, however, is not homogeneous, with high levels of GSH in the alveolar epithelial regions and uric acid predominating in the upper airways [33, 34].

Numerous studies have investigated the effects by which O3 affects the human lungs. Never‐ theless, the mechanisms responsible for such adverse effects, such as an increase in the airway inflammation and impairment in lung function, are only partly understood. It is known that when O3, or indeed any gas, is inhaled, it first comes into contact with the RTLF. Indeed, ozone is not able to infiltrate further than the RTLF and the membranes of cells from the lung-air interface, yet it is still known to cause damage beyond the lungs. Once O3 comes into contact with the RTLF, it induces oxidative stress by two different mechanisms. The first would be by reacting directly with the constituents of the RTLF and the underlying epithelium [26]. It has been suggested that antioxidants present in the RTLF, such as glutathione, uric acid and ascorbic acid have an important role in neutralizing part of the radical generation, hence reducing the ozone induced oxidative stress [35]. Studies analysing the effect of ozone inhalation and airway antioxidant consumption have indeed shown significant alterations in airway antioxidants, such as uric acid, ascorbic acid and GSH [36-38].

The second mechanism by which ozone can increase the oxidation process is indirectly because, even though O3 does not react directly with the epithelial cells, these cells do react in response to the oxidation products produced in the RTLF. As a consequence they release a variety of pro-inflammatory mediators and more reactive species [25, 26]. These processes combined could overwhelm the local and systemic antioxidant network leading to an increase in the oxidative process, the intensity of which varies depending on the O3 inhaled dose and also on the antioxidants present in the lining fluid. If the oxidative stress is sufficient, the activation of an inflammatory response occurs and is characterized by the intense arrival and activation of neutrophils. These neutrophils produce further ROS through the respiratory burst process. Hence, the overproduction of ROS might result in oxidative stress in the airway tissues. The hypothesis is that the antioxidants present in the epithelial lining fluid of the lungs would neutralize the excess production of free radicals and ROS, consequently reducing lung injury induced by air pollution [27, 35]. This will be discussed in the following sections.


**4. MPD strictures**

In cases of stenosis in the MPD, possible malignancy should be ruled out using high-quality pancreatic CT or magnetic resonance cholangiopancreatography (MRCP). Brush cytology should be performed, and biopsy should be performed if necessary. A dominant MPD stricture is characterized by upstream MPD dilatation of ≥6 mm, prevention of contrast medium outflow alongside a 6-Fr catheter inserted upstream from the stricture, and abdominal pain during continuous infusion of a nasopancreatic catheter inserted upstream from the stricture with 1 L saline for 12–24 h. Technical success was defined as stent insertion across the dominant MPD stricture. This management aims to decompress the MPD, improves pain, dilates the stricture, and allows stone clearance after ESWL. A prospective non-randomized study on patients with dominant strictures reported less pain in the temporary pancreatic stenting group during a 5-year follow-up (15% vs. 50%) [27]. These strictures

### *Endoscopic Management of Chronic Pancreatitis DOI: http://dx.doi.org/10.5772/intechopen.107321*

are generally single in >80% of the patients. Temporary single pancreatic stents provide 9–50% resolution and 67.5% pain relief [28, 29].

A refractory stricture was defined as symptomatic persistent dominant strictures or relapse after 1 year of single pancreatic stenting. Refractory strictures can be treated with multiple side-by-side stents, self-expanding metallic stents (SEMSs), or surgery. Temporary insertion of multiple side-by-side stents provided high stricture resolution and pain relief of 89.5% and 77.1%, respectively, during a 9.5-year follow-up [30]. SEMS insertion also achieved high pain improvement in 37–88% of all patients in a follow-up of 3–4 years [31]. Unlike SEMS, uncovered and partially covered stents are not suggested for migration risk.

Pancreatic sphincterotomy is mainly suggested if biliary drainage is necessary to facilitate MPD cannulation. Sphincterotomy is not mandatory for pancreatic stenting. Pancreatic stenting is performed mostly after ESWL if there is a pancreatic stone. The technical success of a single pancreatic stent is approximately 92%. In 18 series of 811 patients, the mean stenting duration was 10.6 months [32].

Multiple side-by-side pancreatic stents are another treatment option for refractory cases. Different stent designs are used: straight, winged, and s-shaped, with side holes. Stents with large side holes are suggested to have a low occlusion risk. The stent diameter is also critical. Patients with CP with ≤8.5-Fr pancreatic stents are 3.2 times more often hospitalized with abdominal pain than patients with CP with a 10-Fr pancreatic stent [33, 34].

The "on-demand" stent exchange strategy is based on clinical and laboratory evaluation at 6-month intervals, such as secretin-enhanced (S)-MRCP, abdominal ultrasound, abdominal radiography, and blood/urinary lipase analysis. However, this policy, in four series of 288 patients, reported a 5.2% rate of pancreatic sepsis [35]. Nevertheless, 12 series of 521 patients in whom the pancreatic stent was changed every 3 months regularly reported no septic complications [36].

Mild pancreatitis and worsening pancreatic pain are the most common shortterm complications after plastic stenting, followed by sepsis, cholangitis, and post-sphincterotomy bleeding. During follow-up, proximal and distal stent migration was reported in 2.7% and 3.6% of the cases, respectively. Stent-induced ductal lesions were observed in 18% of the cases, and the mortality rate was 0.4% (7/1620). Complications after SEMS insertion include migration (15–46%), de novo strictures (16–27%), severe pain (7–20%), and stent removal (15%).

EUS-guided access and drainage is another treatment modality for patients with symptomatic MPD obstruction and failed transpapillary drainage. After puncturing the MPD through the gastric or duodenal wall, transpapillary drainage can be facilitated with a guidewire (rendezvous technique)**,** transmural drainage with a plastic stent**,** or a fully covered SEMS (FCSEMS) can be used to achieve successful pain relief. This is one of the most challenging EUS-guided therapies. Failed EUS-guided access and drainage occur in 10% of cases, and complications such as severe pancreatitis, perforation, bleeding, and hematoma can occur [37]. This procedure is suggested only in tertiary centers after multidisciplinary discussion.


**5.1 VCE**

*Digestive System - Recent Advances*

**3. Clinical presentation**

**4. Clinical evaluation**

• Drug history: NSAIDs.

Lynch syndrome).

suggest Peutz-Jeghers syndrome.

mid-GI bleeding:

Rarely, polyposis syndromes involving the small bowel may present with mid-GI bleeding. These include familial adenomatous polyposis, Peutz-Jeghers syndrome, and generalized juvenile polyposis. Over the age of 40, the most common causes of mid-GI bleeding include angioectasia, nonsteroidal anti-inflammatory drug (NSAID)-induced ulcers, Dieulafoy's lesion, and small bowel tumors. On rare occasions, other small bowel lesions can cause gastrointestinal bleeding. These include small intestinal diverticuli, small intestinal varices, hereditary hemorrhagic telangiectasia, Kaposi sarcoma, intestinal tuberculosis, blue rubber bleb nevus syndrome, hematobilia, hemosuccus entericus, aortoenteric fistula, infectious enteritis, radiation enteritis, ulcerative jejunoileitis due to celiac disease, cryptogenic multifocal ulcerous stenosing enteritis [12], amyloidosis, Behcet's disease, pseudoxanthoma elasticum, and Ehlers-Danlos syndrome [13]. The incidence of small bowel neuroendocrine tumors (SBNET) has been increasing over the last few decades, and they are now considered as the most common primary malignancy of small bowel. Adenocarcinomas are generally seen in the proximal small bowel, whereas SBNET and lymphoma are commonly located in the distal small bowel. Sarcomas (GIST and non-GIST mesenchymal tumors: leiomyosarcoma, liposarcoma, fibrosarcoma, Kaposi's sarcoma, angiosarcoma) are evenly located throughout the small bowel.

Patients with mid-GI bleeding generally present with melena, occult gastrointestinal bleeding (anemia with heme-positive stool), or iron deficiency anemia. Sometimes, they may present with hematochezia as well when there is brisk mid-gut bleeding. Hematemesis is rare but can happen if bleeding occurs proximal to the ligament of Treitz. Patients can have abdominal pain, constipation, diarrhea, or constitutional symptoms like fever, anorexia, or weight loss depending on the underlying etiology. Symptoms (fatigue, shortness of breath, dysphagia due to esophageal web) and signs (pallor of conjunctiva, atrophic glossitis, and koilonychia) can be present depending on the severity and chronicity of iron deficiency anemia [14]. Patients may give history of receiving multiple blood transfusions acutely, subacutely, or chronically despite having multiple endoscopies, colonoscopies, and imaging studies.

A thorough history and physical examination are essential in the evaluation of mid-GI bleeding. Besides the symptoms and signs mentioned above, there are certain clinical clues which may direct us to suspect the underlying etiology of

• Personal history: aortic stenosis (suspecting Heyde syndrome), cancer, melanoma, lymphoma, immunosuppressive state including human immunodeficiency virus (HIV) infection, celiac disease, radiation, polyposis syndrome.

• Family history: early colorectal cancer or endometrial cancer (suspecting

• Hyperpigmentation around the mouth and on the lips, fingers, or toes may

**24**

VCE has revolutionized the visualization of the entire mucosa of the small bowel. It was approved by the US Food and Drug Administration (FDA) in 2001. The video capsule (size: 13 × 27.9 mm) takes 2 pictures per second with a total of approximately 57,600 color pictures wirelessly over a period of 8 hours [19]. It can detect subtle mucosal changes which cannot be detected by imaging studies. VCE is very useful not only in patients with chronic or intermittent mid-GI bleeding but also in acute overt mid-GI bleeding. VCE should be done as soon as possible after the bleeding episode ideally within 14 days in the case of chronic or recurrent overt mid-GI bleeding and within 24–72 hours of acute overt mid-GI bleeding for maximal diagnostic yield [20]. The European Society of Gastrointestinal Endoscopy (ESGE) recommends that patients should take 2 L of polyethylene glycol (PEG) and simethicone (80–200 mg) prior to VCE. Prokinetic drugs (metoclopramide or domperidone) should be given if the video capsule stays in the stomach for more than 30–60 minutes as shown by real-time VCE viewer [21, 22]. Ideally video capsule should be placed endoscopically into the small bowel by using a capsule endoscope delivery device in patients with dysphagia or abnormal gastrointestinal anatomy or delayed gastric emptying where there will be increased risk of incomplete VCE study [23]. It is safe to perform VCE in patients with cardiac pacemaker, automatic implantable cardioverter-defibrillator (AICD), and left ventricular assist device [24].


Contents

**Chapter 7 127** Neurotoxin Decontamination *by Dongmei Ye and Susan Rempe*

Preface

This book, *Acetylcholine – Recent Advances and New Perspectives*, comes more than 100 years after the discovery of acetylcholine as a neurotransmitter in 1921 by Otto Loewi. Since then, the study of this neurotransmitter has been a magnificent chronicle in terms of its chemistry, biochemistry, function in the central and peripheral nervous system, and its relevance for neurological disorders and diseases. To this day, the study of acetylcholine and its receptors astounds us with novel features and exciting news. This book focuses on the role of this neurotransmitter in the physiology of individual neurons as well as in neural circuits and specific brain regions. It illustrates acetylcholine in all its dimensions, from historical perspectives to technological advances, as well as the use of novel tools in health and disease, in various animal models and organisms related to this critical neurotransmitter. Targeted at students and researchers in biological, chemical, medical and history disciplines, this book provides an overview of the work that is being done on this key signaling molecule of the nervous system and brain and highlights any gaps and areas that would benefit from further exploration.

The book is organized into two sections. Section 1, "Acetylcholine, Receptors and Diseases", includes five chapters. Section 2 "Acetylcholine Esterase, Neurotoxin",

Chapter 1, "Introductory Chapter: The Neurotransmitter Acetylcholine – A Young Centenarian" by Thomas Heinbockel, outlines the events leading to the discovery of acetylcholine as a neurotransmitter and the role that Otto Loewi and Henry Dale

In Chapter 2, "Avian Muscarinic Receptors: An Update", Presannan Usha Aswathy, Suresh Narayanan Nair, Basavapura Mahadevappa Sanjay and Sanis Juliet take the reader to the world of birds. The authors review the distribution of avian muscarinic receptor subtypes, the characterization of muscarinic acetylcholine receptors in various organs and organ systems, and the sequence similarity of muscarinic acetylcholine

Chapter 3, "Central Nicotinic and Muscarinic Receptors in Health and Disease" by Yousef Tizabi, Bruk Getachew, Vassiliy Tsytsarev, Antonei B. Csoka, Robert L. Copeland and Thomas Heinbockel, provides a detailed account of the interaction of nicotinic and muscarinic acetylcholine receptors. Following a brief description of acetylcholine actions and its central circuitry, the authors give an update on muscarinic and nicotinic acetylcholine receptors and how their interaction may impact neuropsychiatric and neurodegenerative diseases. Finally, the authors touch upon potential novel therapeutic interventions based on these interactions, particularly in

Chapter 4, "Modes of Acetylcholine Signaling in the Prefrontal Cortex: Implications for Cholinergic Dysfunction and Disorders" by Matthew Fecik and Lisa M. Savage, reviews

receptor subtypes between various birds and animals.

relation to Alzheimer and Parkinson disease.

includes two chapters.

played in its discovery.


**3. Phytochemical components and pharmacological potential of Jimson weed**

The phenolic compounds (metabolites) present are linked to the biological functions assigned to the genus Datura. Plants create these chemicals in both their primary and secondary metabolism [5]. Plants' primary metabolites play a direct role in their growth, development, and reproduction, whereas secondary metabolites play *Pharmacological, Biopesticide, and Post-Harvest Loss Management Application of Jimsonweed… DOI: http://dx.doi.org/10.5772/intechopen.102789*

an ecological role [6]. Different classes of phenolic compounds, such as terpenoids, flavonoids [7], steroids [8, 9], lectins [10, 11], glycosides, fatty acids, saponins [12], tannins [13], phenolic compounds [14], withanolides [15], and various volatile terpenes [16, 17], have been identified in *Datura* species.

#### **3.1 Phenolic compounds**

In methanolic and hydroalcoholic extracts, the existence of distinct classes of phenolic compounds in the genus Datura has been demonstrated. Flavonoids, tannins, and glycosidic phenolic substances are found in *D. metel* and *D. stramonium* [12].

In diverse solvent fractions such as ethyl acetate, butanol, hexane, chloroform, and methanol, Hossain et al. [14] investigated the existence of phenolic compounds in *D. metel*. Gallic acid, vanilic acid, quercetin, and ferulic acid were identified as the primary phenolic components in the methanolic extracts of *D. metel* roots and leaves [18].

On the other hand, LC-ESI-MS/MS analysis of the methanolic extract of *D. innoxia* aerial organs revealed the presence of 20 distinct phenolic compounds, with (−)-epicatechin, (+)-catechin, hyperoside, and p-coumaric acid being the most abundant metabolites detected [19].

#### *3.1.1 Withanolides*

Withanolides are steroidal lactones that have been identified from various Solanaceae genera [20]. Biological actions such as anti-inflammatory, antioxidant, anticancer, insecticide, antifood, and immunosuppressive characteristics have been found for these substances [20]. Within the genus *Datura (daturalactones)*, various withanolides have been identified and described, distinguishing themselves by having an epoxy in the lactone ring [21]. Five with anolides were discovered in the aerial portions (flowers, leaves, and stems) of *D. quercifolia Kunth* that have modest cytotoxic and prooxidant effects, as well as acetylcholinesterase inhibitory activity [22].

*D. metel* leaves have yielded a number of previously unknown withanolides, two of which exhibit anti-inflammatory properties [23]. In addition, 13 others with anolides were isolated from *D. metel* flowers and showed immunosuppressive properties against splenocyte proliferation in mice, as well as activity *in vitro* against human gastric adenocarcinoma cell proliferation (SGC-7901), human hepatoma (HepG2), and human breast cancer cell proliferation (HepG2) (MCF-7) [24].

#### *3.1.2 Terpenes*

Datura produces volatile substances that protect plants from herbivore harm by having varying quantities and types of glandular and non-glandular trichomes [25]. *D. wrightii* contains 17 volatile chemicals, the majority of which are sesquiterpenes (**Figure 2**), such as limonene, linalool, (E)-3,8-dimethyl-1,4,7-nonatriene (DMNT), and (E)—ocymene, with (E)—caryophyllene being the most common [25].

#### *3.1.3 Lectins*

*D. stramonium* and other Solanaceae have been found to contain lectins, a category of carbohydrate-specific binding proteins [26]. The biological role of lectins is controversial, albeit due to their toxicity in both mammals and insects, a defensive role for plants has been hypothesized [27].

#### **Figure 2.**

*Structure of some isolated volatile compounds (terpenes) in the genus Datura in response to insect damage.*

The chitin-binding lectin *D. stramonium* agglutinin (DSA) has been isolated and purified from *D. stramonium* seeds [28]. In diabetic patients, the use of *D. stramonium* agglutinin in lectin microarrays has been used to identify kidney diseases. The amount of nacetyl-D-glucosamine (GlcNAc) coupled to (−1,4)-linked N-acetyl-Dglucosamine identified by lectin *D. stramonium* agglutinin (DSA) was significantly higher in individuals with diabetic nephropathy, according to the results of lectin microarrays [29].

#### *3.1.4 Alkaloids*

*Datura* has a diverse phytochemical makeup of tropane-type alkaloids, which are the plant's most potent chemicals [30, 31].

Tropane alkaloids, in particular, are a collection of roughly 200 alkaloids with a tropane ring (N-methyl-8-azabicyclo in their chemical structure, with L-ornithine as the major precursor) [32]. Atropine (hyoscyamine) and scopolamine (hyoscine) are the most prevalent alkaloids in the genus *Datura* [33].

The alkaloid fraction of *D. ceratocaula* revealed 36 compounds with a distinctive mass fragmentation spectrum, with atropine being the most abundant alkaloid in seed and scopolamine being the most abundant alkaloid in flowers [34]. Atropine and scopolamine were found in similar abundances in *D. ferox*, with 0.32 g of scopolamine per 100 g of dry plant material [35].

Scopolamine and atropine were the major alkaloids, with quantities changing based on the region of the plant [36]. The most abundant alkaloids in *D. quercifolia* are tropinone, tropine, pseudotropine, atropine, and scopolamine [37].

In the species *D. stramonium*, at least 67 tropane alkaloids (**Table 1**) have been found in various sections of the plant. Tropine, 3-tigloyloxy-6-propionyloxy-7-hydroxytropane, and 3,6-ditigloyloxy-7-hydroxytropane [38] have been identified as the most prevalent, alongside atropine and scopolamine. Okwu and Igara [39], on the other hand, discovered one steroidal alkaloid in *D. metel* that had antibacterial activity.

#### **3.2 The biological functions of the Datura**

#### *3.2.1 Insecticide action*

Different writers have looked at the insecticidal and repellant properties of *Datura* species. In contact and spray application experiments, leaf extracts of *D. metel* (acetone, water, and petroleum ether) have been shown to exhibit insecticidal and insect repellent activity against a variety of insect species. In organic extracts of *Pharmacological, Biopesticide, and Post-Harvest Loss Management Application of Jimsonweed… DOI: http://dx.doi.org/10.5772/intechopen.102789*

#### **Table 1.**

*Most abundant tropane alkaloids identified in the genus Datura [33, 37, 38].*

*D. metel*, EC50 values of 12,000 ppm for grasshoppers and 11,600 ppm for red ants were found [31]. In the case of *D. stramonium*, pesticide activity has been assessed in non-polar extracts in adult individuals and larvae of various insects, both by contact and by food [27].

The larvicidal efficacy of *D. stramonium* aqueous root extract was tested on two mosquito species and found to be between 50 and 100 percent larval mortality at 100 percent concentration of the extracts 24 hours after treatment [40]. Different quantities of an aqueous extract of *D. stramonium* leaves and seeds were shown to be effective against flea beetles, a common maize pest [41].

The toxic effect of acetone extracts from *Datura inoxia* was evaluated against *Tribolium castaneum*, *Trogoderma granarium*, and *Sitophilus granarius*, where the plant extracts were observed in addition to the inhibition of enzymes acetylcholinesterase, carboxylesterase, acid phosphatases, and alkaline phosphatases (ALP) in toxicity test survivors [41].

#### *3.2.2 Herbicidal*

In aqueous and methanolic extracts, *D. metel* has shown possible herbicidal efficacy against "noxious weed parthenium," with the root showing superior effects to the stems, with both extracts reducing weed germination as well as stem development in individuals of a few weeks [1]. Similarly, germination inhibition was seen in methanolic and hexane root extracts of *D. metel* when it was tested for herbicide action against Phalaris minor.

Sakadzo et al. [42] found that an aqueous extract of *D. stramonium* inhibited root development, plumule length, and dry matter amount in *Amaranthus hybridus* and Tegetes minuta, with herbicidal effects both pre- and post-emergence.

#### *3.2.3 Acaricide activity*

The methanolic extracts of *D. stramonium* leaves and seeds showed acaricidal effects, with 98 percent mortality of adult Tetranychus urticae Koch (spider mites) in the leaf extract and 25 percent mortality in the seed extract, with a direct relationship between concentration and mortality rate for the leaf extracts but not for the seed extracts [7].

In adult mite immersion trials, an ethanolic extract from *Datura stramonium* leaves caused 20% mortality against *Rhipicephalus microplus* (Asian blue tick) [43]. *In vitro* experiments showed that the methanolic extract of *D. stramonium* inhibited the oviposition of Rhipicephalus (Boophilus) microplus by 77% [44].

#### *3.2.4 Antifungal activity*

Three members of the genus, *D. discolor, D. metel, and D. stramonium*, were tested for antifungal activity. Ethanolic and methanolic extracts from D. discolor stems and leaves were combined with culture medium to prevent the growth of Aspergillus flavus, Aspergillus niger, Penicillium chrysogenum, Penicillium expansum, Fusarium moniliforme, and Fusarium poae [12].

Rhizoctonia solani was inhibited by aqueous and methanolic extracts of *D. metel* leaves. D. metel's methanolic extract was up to 35 percent more toxic than the other 15 species investigated, preventing mycelial growth and being used in agriculture (herbicide, acaricide, insecticide) and medicine (antibacterial, cytotoxic, or antioxidant) production of sclerotium [15].

Furthermore, extracts of all parts of *D. metel* in various solvents (hexane, chloroform, acetone, and methanol) showed antifungal activity against three Aspergillus species: *A. fumigatus*, *A. niger*, and *A. flavus*, with the chloroform fraction having the lowest inhibitory concentration (MIC) of 625.0 g/mL [45].

The growth inhibition of five fungal species: *A. flavus*, *A. niger*, Alternaria solani, Fusarium solani, and Helianthus sporium used to assess the antifungal efficacy of methanol extracts from the leaves, seeds, stems, and roots of *D. inoxia* [46].

The antifungal activity of *D. stramonium* extracts on *Candida albicans* was stronger in aqueous extracts (74 percent), while methanol and chloroform extracts had good inhibitory activities (69 percent and 65 percent, respectively) [47].


*2.5. Evaluation of the Clinical Tolerance to the Biscuits Labelled without Milk and Egg*

Within one month of inclusion in the study, the selected patients underwent SPT and OFC with milk and egg –free biscuits "Magretti" [Galbusera S.p.A., Cosio Valtellino (SO), Italy] from 12 different lots. Such biscuits are labelled as "not containing milk and egg". However, the label indicates "it cannot be excluded that any traces of these allergens are present, in any case less than 5 mg/kg" (Table 1).

Based on the age of patients, seven or eight incremental doses of food were administered at 20-min intervals under clinical supervision. The first six doubling doses, starting from 0.25 g up to 8.00 g, were the same for all study participants. The seventh and eighth doses differed in different age groups (Table S1). A sample of the biscuits used for the OFC and SPT was stored for proteomic evaluation. A symptoms-based clinical score assessing the degree of gastro-intestinal, respiratory, cardiovascular and dermatological reactions was applied to monitor the acute allergic reactions. The procedure was interrupted when clear-cut objective symptoms were present, or after any severe, persistent (over 40 min) subjective symptom, according to our stopping rules [17].

**Table 1.** Magretti biscuit composition.


**Lemon Grass (***Cymbopogon citratus***)**

**Lemon Grass (***Cymbopogon citratus***)**

#### Miss Phool Shahzadi Miss Phool Shahzadi Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.69518

#### **Abstract**

Lemon grass is, also called fever grass, a perennial plant with thin, long leaves that is indigenous to many Asian countries. Lemon grass contains citral, which is an essential oil, having medicinal and other useful significance. In the present work, essential oil 3,7-dimethyl-2,6-octadienal (citral) is hydrodistilled from lemon grass in the laboratory, 3,7-dimethyl-2,6-octadienal acetals (citral acetals) are synthesized from citral along with para-toluene sulfonic acid as a catalyst, which are used in perfumery, flavor, for fortifying lemon oil and has strong antimicrobial qualities. Infrared spectroscopy (IR) and gas chromatography (GC) were conducted for verification of chemical constitution present in essential oil and acetals of lemon grass. Nutritionally, lemon grass is a good source of vitamins A and C, folic acid, magnesium, zinc, copper, iron, potassium, calcium and manganese. Lemon grass oil (citral) is hydrodistilled and IR and GC are conducted to verify its constituents.

DOI: 10.5772/intechopen.69518

**Keywords:** lemon grass, essential oil, citral, ionons, vitamin E


**5.2 CO2 combustion: subsequent improvements**

subsequent studies will focus on alternative methodologies to achieve higher carbon dioxide combustions. There are several methods that can be considered such

**Figure 13.** *Oxide formation after the motor experiment.*

as (i) magnesium additive mass fraction increase in paraffin wax (up to 80%), (ii) aft injection methodologies to increase adiabatic flame temperature, (iii) Potassium nitrate addition into the fuel grain, and (iv) angled or swirl injection methods. All these methods are currently being used by hybrid propulsion community to improve internal ballistics during the combustions.


**4. Antenna design and testing**

#### **4.1 Antenna design**

While designing an antenna one should follow the following characterization of implantable antenna:

Following commercial tools are used for designing an implantable antenna such as computer simulation tool (CST) Microwave Studio, High-Frequency Structure Simulator (HFSS), Advanced Designed System (ADS), and XFDTD. In [55] for analyzing electromagnetic characteristics of the implantable antenna inside head and body, Finite-difference-time-domain (FDTD) and Spherical dyadic Green's function (DGF), etc. functions are applied. In [83] Antenna simulated using FDTD overall efficiency improved and suitable design obtained in minimal time with help of a genetic algorithm.

In general, a one-layer skin model is widely used for implantable antenna design. Although, 2/3 muscle model and three-layer tissue (skin, fat, muscle) mode are also typically for antenna designing. These three models make simulation efficient and measurement easier as this model is made from different materials to active accurate permittivity and conductivity.

In [26] implantable antenna designed with FDTD method including 2/3 muscle model. In [28, 33] antenna simulated in HFSS and CST respectively and a singlelayer skin model is used. To design an implantable antenna in a realistic environment then it must evaluate within accurate human body models such as the human Voxel model shown in **Figure 3**. For neural recording systems and wireless

*Microwave Antennas Suggested for Biomedical Implantation DOI: http://dx.doi.org/10.5772/intechopen.101060*

> **Table 5.**

*Volume occupied by MICS, ISM and medradio band implantable antenna and its miniaturized techniques: A literature.*

**Figure 3.** *Front and side view of CST human voxel mode used for simulation testing of various antenna.*

endoscope systems, an accurate human model is required. For different biomedical applications, the implant's position and depth could be a different and single layer or three-layer modeling used according to application. In **Figure 4** one-layer tissue model is shown.


*E. Coli* Infections - Importance of Early Diagnosis and Efficient Treatment

*Edited by Luis Rodrigo*

Published in London, United Kingdom

## *Supporting open minds since 2005*

E. Coli Infections - Importance of Early Diagnosis and Efficient Treatment http://dx.doi.org/10.5772/intechopen.80139 Edited by Luis Rodrigo

#### Contributors

Marit Nilsen-Hamilton, Soma Banerjee, Baoping Zhang, Paul Onkundi Nyangaresi, Liang Shen, Yanhong Liu, Peng Ji, Xunde Li, Saloua Helali, Adnane Abdelghani, Luis Ángel Fernández, Massiel Cepeda-Molero, Stephanie Schüller, Gad Frankel, Hussein O.M. Al-Dahmoshi, Noor Salman Al-Khafaji, Ukun Soedjanaatmadja, Iman P. Maksum, Safri Ishmayana, Ahmad Nabiel, Mario Galindo-Méndez, Ashok Palaniappan, Sangeetha Muthamilselvan, Nivedita Jaishankar, Akshay Kumar, Nimisha Shiwalkar, Ana Francesca Vommaro Leite, Lais Sanches Maekewa, Silas Jose Braz Filho, Purnadeo Narpaul Persaud, Roopvir Kaur, Asim Kichloo, Juber Dastagir Shaikh, Mohammed H.O. Al-Allak

#### © The Editor(s) and the Author(s) 2020

The rights of the editor(s) and the author(s) have been asserted in accordance with the Copyright, Designs and Patents Act 1988. All rights to the book as a whole are reserved by INTECHOPEN LIMITED. The book as a whole (compilation) cannot be reproduced, distributed or used for commercial or non-commercial purposes without INTECHOPEN LIMITED's written permission. Enquiries concerning the use of the book should be directed to INTECHOPEN LIMITED rights and permissions department (permissions@intechopen.com).

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Individual chapters of this publication are distributed under the terms of the Creative Commons Attribution 3.0 Unported License which permits commercial use, distribution and reproduction of the individual chapters, provided the original author(s) and source publication are appropriately acknowledged. If so indicated, certain images may not be included under the Creative Commons license. In such cases users will need to obtain permission from the license holder to reproduce the material. More details and guidelines concerning content reuse and adaptation can be found at http://www.intechopen.com/copyright-policy.html.

#### Notice

Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book.

First published in London, United Kingdom, 2020 by IntechOpen IntechOpen is the global imprint of INTECHOPEN LIMITED, registered in England and Wales, registration number: 11086078, 5 Princes Gate Court, London, SW7 2QJ, United Kingdom Printed in Croatia

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E. Coli Infections - Importance of Early Diagnosis and Efficient Treatment Edited by Luis Rodrigo p. cm. Print ISBN 978-1-83962-523-7 Online ISBN 978-1-83962-524-4 eBook (PDF) ISBN 978-1-83962-525-1


**3. Vestibular system**

The vestibular system is a complex network that includes small sensory organs of the inner ear (utricle, saccule, and semicircular canals) and connections to the brainstem, cerebellum, cerebral cortex, ocular system, and postural muscles [4, 5].

The vestibular system is distinctive from other systems because it becomes immediately multisensory and multimodal [4]. For example, the vestibular system intercorrelates with the somatosensory system through the vestibulospinal reflex that is responsible for postural control and with the visual system controlling the vestibulo-ocular reflex (VOR), that maintains visual stability during head movements.

These linked group of systems allows the brain to differentiate active from passive head movements and provide information regarding head movements and positions to maintain visual and balance control. Furthermore, visual and somatosensory systems interact with the vestibular system throughout the central vestibular pathways and are essential for gaze and postural control. This interaction *Concussion and Balance in Sports DOI: http://dx.doi.org/10.5772/intechopen.97024*

of multisensory and multimodal pathways is important for higher level of function such as self-motion perception and spatial orientation [2, 4–6].

Usually, individuals who present impairments related to the vestibulo-ocular reflex complain about dizziness and visual instability, this is due the organization and neurophysiology of the vestibular system [4].

Inversely, vestibulo-spinal dysfunction (correlated to the vestibulo-spinal reflex - VSR) normally present as consequences imbalance. Since these reflexes do not share the same neuronal circuitry, it is possible to have damages one without affecting the other [4, 6].

## **4. Sport-related concussion**

Traumatic Brain Injury (TBI) occurs in subjects of all age groups and is a significant public health issue [7].

The Post-Concussive Syndrome (PCS) defines the set of symptoms and signs present frequently in a persistent mild TBI [8]. The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) presents the clinical criteria for PCS [9]. The symptoms include headache, fatigue, vision changes, disturbances in balance, confusion, dizziness, insomnia, neuropsychiatric symptoms, and difficulty with concentration [7–9].

Disturbances in balance and dizziness are described in literature by 23–81% [8, 10–13] of concussed athletes [and is correlated with a 6.4-times higher risk to have another concussion if not treated, comparing to any other on-field symptom [11, 14]. Currently, several studies have presented that imbalance and dizziness are usual after a TBI have a correlation with the time to recovery (protracted recovery superior to 21 days), causing a delay comparing to the ones who did not present those symptoms [10–14].

Cohort studies and analysis had shown that women are at greater risk for persistent PCS. Besides, they are more likely to present headache, irritability, fatigue, and concentration problems post-concussion. Increases in age are also associated with a higher risk of PCS [15].

#### **5. Assessment**

The assessment of an injured player is facilitated by the presence of a certified athletic trainer, team physician, or other health care provider at the location where the injury occurred. It is important to mention that balance symptoms may not become apparent for several hours after injury bringing an additional obstacle to identification. Thus, the follow up for SRC is crucial to assess any balance dysfunction and treatment during the patient's recovery. Hence, vestibular and balance evaluations must be included in the concussion assessment battery and when available, objective tests may be used [16].

The assessments strategies present in this chapter were noted in scientific literature to be used as part of the concussion evaluation as well as a preseason baseline. The same tools for assessment are applied and can benefit other individuals with vestibular and ocular/oculomotor disorders as well [16–18].

Among the recommended assessments are physical examinations, clinical interviews, symptom reports, and neurocognitive and balance tests. For that reason, is recommended to use the Symptom Checklist. It is a self-report graded symptom checklist validated for concussion assessment. One example is the Sport Concussion Assessment Tool 5 (SCAT-5). The SCAT-5 contain 22 items and corresponding 0 to 6 points where higher numbers indicate greater symptom severity [19].

Below, it is described some assessments that can be applied in case of vestibular impairments after concussions:

Balance Error Scoring System (BESS) Sensory Organization Test (SOT) Head Shake-Sensory Organization Test (HS-SOT) Concussion Balance Test (COBALT) Vestibulo-Ocular Reflex and Vestibular/Ocular Motor Screen (VOMS) Dynamic Visual Acuity Test (DVAT) Head Impulse Test (HIT) Post-Concussion Symptom Scale (PCSS) Dizziness Handicap Inventory (DHI) Dix-Hallpike Maneuver


2.2.2. Olive Mill Wastewater Extract

The OMW was collected in the crop season 2020/2021 from Ottobratica olive cultivar and produced according to a three-phase centrifugation process. The phenolic extract was obtained following the method previously reported by [28], with some modifications. Briefly, two liters of OMW were acidified to pH 2 with hydrochloric acid and washed three times with hexane (1:1, *v*/*v*) to remove the lipid fraction. The obtained mixture was vigorously shaken and centrifuged at 1550× *g* rpm for 3 min at 10 ◦C. The extraction procedure was carried out in separate funnels and repeated three times using ethyl acetate (1:4, *v*/*v*) as a solvent. The organic phase was then separated and filtered through a Buchner apparatus. The ethyl acetate was evaporated under vacuum in a rotary evaporator (Laborota400, Heidolph Instrument, Schwabach, Germany) at 25 ◦C. Finally, the obtained residue was dissolved in water to a final volume of 100 mL, further filtered by using a PTFE syringe filter (0.45 μm pore-size) and stored at 4 ◦C before analysis. To ensure that both hexane and ethyl acetate were removed (or were present in trace amounts) from the obtained extract, a headspace analysis using GC Thermo Trace 1310 apparatus (Waltham, MA, USA) equipped with a Single Quadrupole Mass Spectrometer ISQ LT system and a fused-silica capillary column (Thermo Scientific, Waltham, MA, USA) was carried out. It was found that the concentration of both the solvents used was below the limit of detection of the instrument.

### 2.2.3. Total Polyphenol Content and Antioxidant Activity of OL and OMW Extracts

The total polyphenol content of both OL and OMW extracts (hereinafter referred to as OLE and OMWE) was measured using the Folin-Ciocalteau reagent in a spectrophotometer (mod. Cary 3500, Agilent, Cernusco, Milan, Italy) set at 750 nm [29]. Briefly, after a proper dilution, an aliquot of 0.5 mL of extract were mixed with 0.5 mL of Folin-Ciocalteau reagent, 10 mL of sodium carbonate (7.5%) and adjusted to 25 mL with distilled water. The mixture was incubated in the dark for 1 h at room temperature before readings. Calibration curves were made using gallic acid and the results (mean of three replicates) were expressed as mg of gallic acid equivalents (GAE) per g of extract.

The free radical scavenging activity of both extracts was determined using a discoloration curve of the stable radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). After proper dilution, an aliquot of 0.3 mL of extract was added to 2.7 mL of 0.0634 μmol mL−1 DPPH methanol solution for 1 h at 515 nm and 22 ◦C. Results (mean of three replicates) are expressed as decrease in absorbance (%) per mg of extract when 0.17 μmol of DPPH are available to react.

The determination of the phenolic compounds and antioxidant activity was carried out simultaneously in both the extracts and the breadstick samples only a few days after the extraction process (specifically, no more than 15 days later).

#### *2.3. Preparation of GF Breadsticks*

GF control breadsticks were prepared using a conventional GF formulation consisting of 50% rice flour and 50% corn starch as the basic recipe. The other ingredients used, which were added as % on flour basis, were: 55% water (26 ◦C), 10% sunflower oil, 4% compressed yeast, 3% sugar, 1.8% salt, 1.5% guar gum, and 1.5% *Psyllium* fiber. For the preparation of the enriched GF samples, OLE and OMWE were singly added to the basic formulation (on flour basis) a two different level of supplementation: low (500 mg kg−1) and high (1000 mg kg−1). Breadstick sample codes were defined according to the type of extract and the level of supplementation used, as follows: Control (no extract addition), Leaf50 (low addition of OLE), Leaf100 (high addition of OLE), WasteW50 (low addition of OMWE) and WasteW100 (high addition of OMWE). For each formulation, GF breadsticks were prepared by firstly suspending extracts, yeast, salt and sugar in aliquots of warm water. Then, these dissolved ingredients and the sunflower oil were slowly added to the pre-mixed dry ingredients and kneaded using a mixer (KitchenAid Professional, Model 5KSM7990, St. Joseph, MI, USA) equipped with a dough hook at speed 1 for 5 min followed by other 8 min at speed 2. After mixing, the obtained doughs (three for each sample) were proofed in a climate chamber for 30 min (33 ◦C–90% RH), manually shaped into 28 g weighted and 30 cm length sticks, placed on rectangular baked pans, and proofed once again for 30 min (33 ◦C–90% RH). Finally, the GF breadsticks were baked in an electric oven (Europa, Malo, VI, Italy) following a two-step baking process: they were firstly baked at 180 ◦C for 13 min, allowed to cool at room temperature for 30 min and then baked once again for other 22 min at 160 ◦C. After baking, breadstick samples were cooled for 1 h, before the analysis.

### *2.4. Breadsticks Measurements*

#### 2.4.1. Moisture Content and Water Activity

The moisture content of the GF breadstick samples was determined using a moisture analyzer (Model Kern-DAB 100-3, KERN & SOHN GmbH, Balingen, Germany) equipped with a halogen quartz glass heater (400 W) and set with a standard heating profile at 105 ◦C. The results were expressed in % as the average of five repetitions.

Water activity was measured on ground and homogenized samples with an electronic hygrometer (model Aw-Win, Rotronic, Bassersdorf, Switzerland) equipped with a Karl-Fast probe previously calibrated in the range of 0.1–0.95 with solutions of lithium chloride (LiCl) of known activity. A total of five repetitions for each sample were made.


**1. Introduction**

328 Chronic Kidney Disease

Cruz J, Restrepo C A. Accidental implantation of hemodialysis catheter in persistent left

For many years, radical nephrectomy (RN) has been the gold standard treatment for renal tumours. However, at present the available evidence supports elective nephron-sparing surgery (NSS) as the standard surgical treatment for renal cortical tumours ≤4 cm (clinical stage T1a). Furthermore, an increasing body of evidence demonstrates that even a minor loss of renal function can increase cardiovascular morbidity and consequently reduce life expectancy (Go et al., 2004). Thus, surgeons have the responsibility to preserve as much renal parenchyma as possible.

International guidelines at present recommend NSS for small renal tumours up to 4 cm. However, the role of NSS for larger renal tumours (stage T1b: 4.1 – 7 cm, stage T2: >7 cm) remains controversial. During the last couple of years, data has emerged which demonstrates that NSS can be safely performed with acceptable complication rates compared to RN (Van Poppel et al., 2010). The advantage of NSS lies in avoiding the development of end-stage renal disease and the need for haemodialysis, while maintaining quality of life (Lesage et al., 2007).

The size of the tumour is no longer considered to be a limiting factor for NSS and some now advocate NSS whenever possible and feasible (Becker et al., 2009).