*1.1. Punishment Sensitivity*

The most applied measures to assess sensitivity to punishment (BIS) and reward (BAS) are the BISBAS scales [21] and the sensitivity to punishment and sensitivity to reward questionnaire (SPSRQ) [22], both based on the original RST theory. The BISBAS scales focus on the general disposition towards reward (e.g., "When I'm doing well, I love to keep at it.") and punishment, whereas the SPSRQ items often include specific situational triggers related to punishment and reward (e.g., "Do you often meet people that you find physically attractive?"). Patients with EDs (AN-R, AN-BP, or BN) typically report significantly higher scores on punishment sensitivity (BIS/SP) compared to healthy controls [8,23–29]. When comparing different ED subtypes, most studies did not find significant differences among AN-R, AN-BP, or BN patients [8,25,29,30]. Two studies [23,27] showed that AN-R patients scored significantly higher on sensitivity to punishment than AN-BP or ED-PB (AN-BP + BN) patients, whereas other studies found the opposite [24] or no significant differences [31].

Studies comparing patients with obesity to healthy controls on punishment sensitivity are rather scarce. Class I obese patients without BED scored significantly lower on punishment sensitivity compared to healthy controls [32], whereas Class I obese patients with BED did not significantly differ from healthy controls [33]. Class II obese patients with and without BED scored significantly higher on punishment sensitivity than healthy controls [32,34]. No study has compared patients with Class III obesity with and without BED to healthy controls with respect to punishment sensitivity. When comparing obese patients (Class II, III) with and without BED on punishment sensitivity, patients with and without BED did not differ from each other [6,34]; no studies were performed in Class I obese patients with and without BED.

Higher punishment sensitivity in patients with EDs, as compared to healthy controls, seems to be linked to their symptomatology. Patients with AN-R relate their self-worth to their weight [35] and are afraid of gaining weight; their strict dieting can be considered as a way to avoid anxiety for weight gain [7,8]. Several studies have demonstrated a positive association between sensitivity to punishment and restrained eating in both adolescents and young adults [20,36]. Patients with binge eating (AN-BP, BN) and obesity, on the contrary, often use food to comfort or soothe themselves and to escape from negative feelings [37]. Davis [38], for example, showed a positive association between sensitivity to punishment and the symptoms of binge eating. The compensatory behaviors of patients with AN-BP/BN can again be considered as a way to avoid weight gain [7,8].


Preface

**Chapter 7 117**

**Chapter 8 131**

Clinical Validation of a Whole Exome Sequencing Pipeline

Integrating Evolutionary Genetics to Medical Genomics:

*by Ugur Sezerman, Tugce Bozkurt and Fatma Sadife Isleyen*

Evolutionary Approaches to Investigate Disease-Causing Variants

*by Debra O. Prosser, Indu Raja, Kelly Kolkiewicz,*

*Antonio Milano and Donald Roy Love*

**II**

Understanding disease pathology and physiological pathways depends on research that examines how certain genes become abnormal. Disease processes with personal patterns can be elucidated through molecular medicine. The crux of the cure lies in precise detection and predisposition of the disease. Revealing molecular mechanisms helps create an effective personalized treatment and minimize side effects. Treatment risk and response to therapy prediction can be forecasted through early diagnosis, which improves prognosis reliability, and the effectiveness of therapies. Using this concept, monitoring health is a way to both make predictions and devise prevention. This book covers contemporary advances in molecular markers, disease-causing variants, retroelements, and the basis of distinct diseases.

> **Dr. Yusuf TUTAR** Professor, University of Health Sciences, Turkey

**1**

Section 1

Diseases

Section 1 Diseases

**3**

**Chapter 1**

**Abstract**

Diseases

Molecular Mechanisms of Distinct

*Adnan Batman, İrem Yalım Camci, Elif Kadioglu,*

*Ezgi Nurdan Yenilmez Tunoglu and Yusuf Tutar*

the most common disease of each class.

immunology and infectious diseases

with the molecular mechanisms.

**1.1 Chromosomal diseases**

*1.1.1 Down syndrome*

**1. Introduction**

*Kezban Uçar Çifçi, Berçem Yeman Kıyak, Servet Tunoglu,*

Molecular medicine describes molecular structures and mechanisms and this chapter focuses on molecular and genetics errors of diseases. Diseases can be classified into deficiency diseases, hereditary diseases, infectious diseases and physiological diseases and to get a glimpse of the mechanisms the chapter covers

**Keywords:** chromosomal diseases, cancer, neurodegenerative diseases, pulmonary

Distinct diseases have different etiology pattern and this chapter covers the chromosomal diseases, cancer, neurodegenerative diseases, pulmonary diseases, obesity-induced insulin resistance, lymphoblastic leukemia, viral immunology and infectious diseases. These communicable and non-communicable diseases negatively affect structure-function of the organism and specific symptoms are associated with these conditions. Pathogens or internal dysfunctions may lead these diseases. The chapter provides pathology of selected diseases from each class along

Down syndrome (DS) is the most common chromosomal genetic disorder. The disease is caused by the trisomy of human chromosome 21 (HSA21) and is also the most genetic mental disability [1]. The HSA21 mosaic can also lead to DS. Maternity age is an important aspect in the formation of an individual with DS [2]. The main cause of this disease is the absence of normal chromosome separation during meiosis and the production of gametes with two copies of chromosome copies instead of a single copy. As a result, DS individuals have trisomy 21 in some body cells, and a normal number of chromosomes in others. This is called mosaicism and is seen in approximately 4% of DS individuals. The term mosaicism was first reported in 1961

diseases, obesity-induced insulin resistance, lymphoblastic leukemia, viral


4.3.1. Water Treatment Technology and Regulations

While drinking water regulations have continued to evolve since 2006, they have had varied influence on the treatment of Delta source waters. The shift from chlorination as a primary disinfectant toward ozonation has continued since 2005. By 2020, about 85 percent of the combined treatment capacity of the participating agencies employed ozonation (Figure 2). In the current era, drinking water regulations have played a reduced role in driving MWQI program activities. However, that trend would likely reverse if new regulations were implemented. Examples of new DBPs being considered for regulation include four additional brominated HAAs and nitrosamines (such as N-nitrosodimethylamine or NDMA) [113]. In waters high in bromide, such as Delta waters, the five currently regulated HAAs may only represent around half of the concentration of the nine HAAs [114]. Certain pharmaceuticals discharged from wastewater treatment plants react with chloramines to form NDMA in drinking water [115]. The participating MWQI agencies that use ozone as the primary disinfectant use chloramines as the secondary disinfectant; thus, NDMA is produced at many of their water treatment plants.


**1. Introduction**

Shoulder arthroplasty is becoming an increasingly popular procedure performed for a variety of problems. It has been utilized with great success for advanced degenerative and traumatic conditions of the shoulder [1–5]. Because the shoulder joint is surrounded by vital structures including muscles, nerves, and blood vessels, great care must be taken to ensure safe but adequate exposure to the glenohumeral joint when performing shoulder arthroplasty. To date, the deltopectoral approach [6] and the anterosuperior lateral approach [7] are the two main approaches that have been well described in the literature for access to the glenohumeral joint for shoulder arthroplasty. Each approach offers distinct advantages and disadvantages with

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. © 2018 The Author(s). Licensee IntechOpen. 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.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons

regard to glenoid exposure as well as technical challenges for component implantation. The aim of this chapter is to describe these two different approaches to the glenohumeral joint, the indications for use, and the advantages of each.

tube should be positioned toward the nonoperative side. A pre-scrub with chlorhexidine, alcohol, and/or hydrogen peroxide may then be performed. Finally, a sterile skin preparation with chlorhexidine may be applied prior to final draping. The final draping should consist of down sheets to cover the head and lower extremities with split drapes or a specialized shoulder drape may be used to isolate the operative shoulder. The distal extremity can be placed in a stockinette and covered with a coban wrap, if preferred. An iodine-impregnated plastic drape or any other sterile adhesive dressing may be used to ensure that the edges of the drape adhere to the skin, ensuring a sterile field through the duration of the case. Prior to skin incision, it is important to administer appropriate antibiotics. Typically, this involves a second-generation cephalosporin such as cefazolin or, if the patient has an allergy to penicillin, clindamycin may be substituted. If preoperative testing indicates that the patient is colonized with methicillin-resistant *Staphylococcus aureus* (MRSA), studies show an increased risk of surgical-site infection [11]. In these situations, it is recommended either to decolonize the patient before the surgery or to give a one-time dose of vancomycin [12]. In addition to antibiotics, pre-incision intravenous administration of tranexamic acid has been shown in multiple studies to decrease intraoperative blood

Surgical Approaches in Shoulder Arthroplasty http://dx.doi.org/10.5772/intechopen.70363 65

The deltopectoral approach is an anterior approach to the shoulder that utilizes the plane between the deltoid and the pectoralis major muscles. It utilizes an internervous plane between the axillary nerve and the medial and lateral pectoral nerves. It is a robust approach to the shoulder as it has been used for fixation of proximal humerus fractures, reconstruction for shoulder instability, access to the glenohumeral joint in the setting of a septic shoulder, and others [15, 16]. When accessing the glenohumeral joint from the deltopectoral approach, the subscapularis tendon lies directly anterior to the joint capsule. It must be released to access the joint and there are a variety of methods for doing so which will be described in this chapter [17–19].

The surgeon should begin by palpating the bony landmarks around the shoulder, including the acromion, the clavicle, and the coracoid process. An 8–10-cm incision should be marked out, extending from the lateral margin of the coracoid process and extending down the deltopectoral groove toward the deltoid tuberosity. A scalpel should be used to carry the incision through the skin and the dermal layer. Electrocautery can then be used to address any bleeding in the subcutaneous layer. Dissection can continue through the subcutaneous tissue until the fascia overlying the deltoid and the pectoralis muscles is reached. At this point, careful dissection should be used to identify the interval between these muscles. The cephalic vein may be visualized running in the deltopectoral groove. If it is not evident, often times, a stripe of fat overlying the cephalic vein may be identified and used as a helpful marker for identifying the interval (**Figure 2**). The vein should be freed from the surrounding structures and retracted either medially or laterally, depending on surgeon preference. An anatomic study was performed on 40 cadaveric specimens with latex injection of the cephalic vein.

loss [13, 14]. At this point, skin incision is ready to be made.

**3. Deltopectoral approach**

**3.1. Superficial dissection**


**1. Introduction**

One of the challenges for coming decades in nutraceutical research is to find new potential resources that will provide an easy and low-cost approach to food necessities for the coming centuries. In this sense, jellyfish is a compartment in the marine food web (the greatest biome on earth) that often achieves high increases of biomass [1]. However, only recently has this wide group of organisms been starting to be seen from a more positive point of view [2], contrasting with the deleterious impact that it has on several economic human activities such as fisheries [3], clogging of power plants [4] and tourism [5]. This dark side of jellyfish blooms has been the only vision that has prevailed in the general human perception for many decades [6]. One example of the new positive point of view of the rapid increment of biomass in jellyfish is the cannonball, *Stomolophus meleagris*, in the Gulf of California, where a small Mexican community obtains benefits from switching for one month from fishing fish to fishing jellyfish, processes them, and sells them to the Asiatic market [7]. Another example of the explosive increment of jellyfish is the case of *Cotylorhiza tuberculata* in the Mar Menor lagoon in the

Mediterranean Sea, where during summer, fishermen are paid by regional authorities to catch jellyfish and bury them. Some summers they have caught more than five thousand tons of jellyfish [8,9].

The potential of jellyfish for human use is not only as a food resource [2,10–13], which is traditionally in Asian cuisine [14,15], but also recently as potential cosmeceutical and pharmacological applications [16]. Also, recently, jellyfish collagen has been studied for several biomedical applications [17], including antioxidant [18–20] and melanogenesis-inhibitory activity [18], skin photo-protection from Ultraviolet radiation [21,22], immunostimulatory effects [23,24], and antihypertensive effects [25].

The case we present here is unknown by the scientific community, and regards the potential use of the organic compounds and marine products from jellyfish. The jellyfish in the present work is *Rhizostoma luteum* Quoy and Gaimard, 1827 (Cnidaria: Scyphozoa: Rhizostomeae), which went scientifically unnoticed for more than 60 years until it was rediscovered and genetically characterized in 2012 [26]. Later, it was proved to be widely spread along the east coast of the Atlantic Ocean (from Portugal to South Africa) and in the Alboran Sea (Mediterranean Sea) and is much more frequent than previously thought, but was long misidentified for some of its congeners from the same geographical zones [27].

The purpose of the work is to describe the organic compounds for *Rhizostoma luteum* for the first time, with the hypothesis that it can be a candidate for the isolation and production of bioactive compounds in several fields of food, cosmetics, and biomedical industries. This hypothesis is based on three facts inherent to this jellyfish species: (1) it is from the family of the *Rhizostomaes*, which is the family of jellyfish preferable for consumption in Asiatic cuisine [28]; (2) The natural adult size of this jellyfish is very large, reaching more than 60 cm in umbrella size, weighing 13 kg and having 3 m tentacles [26,27,29], making one of the largest species of this family and therefore converting each individual into considerable amount of biomass; and (3) its life cycle has been recently described and closed entirely in captivity [29], which is a very difficult achievement since it is an open-ocean species. These three facts suggest that, in the case the potential use of *Rhizostoma luteum*, the exploitation of this species' biomass can be obtained both from the natural environment and from controlled culture in captivity. However, before using it, it is mandatory to characterize the different organic compounds and other properties inherent to this jellyfish.

The main aim of this work is the identification of the primary metabolites (fatty acids) with antioxidant activity of the jellyfish *Rhizostoma luteum*. This goal was achieved by combining the original data on biochemical composition, protein, and phenol contents with their antioxidant activity, and the analysis of lipid content (identifying each of the presented fatty acids). The results presented here suggest this jellyfish to be a promising sustainable source for the production of several natural products. *Rhizostoma luteum* appears all year around on the coasts of the east Atlantic Ocean and Alboran Sea [29], providing a highly unexploited biomass. Now a positive association of this giant jellyfish species and an isolation of its bioactive compounds can be established.

### **2. Results and Discussion**

### *2.1. Jellyfish Biomass Characterization*

Biometric and average biomass data of individuals of *Rhizostoma luteum* are shown in Table 1.

The specimens used are young medusae, with an age range from about 23–140 days (Table 1), with a proportionally increasing biomass with jellyfish age. The relation between fresh weight and diameter in *Rhizostoma luteum* has been described by [29], while the relationship between fresh weight (FW) and dry weight (DW) is documented for the first time for this species. The variability of the biometric measures, including the FW, the FW:diameter ratio and DW percentage values, is representative of the different growth stages of the jellyfish [30]. After lyophilization, the DW of *R. luteum* ranges from 3.9–31% of the FW, displaying a high variability in tissue consistency. The highest values correspond with the older jellyfish employed in this study.

FW, fresh weight; DW, dry weight; \* data are expressed as range and/or means standard deviation (5 < *n* < 61).

The first parameter that should be assessed for evaluation in its potential use as biomass is the total energy or gross energy value, which is directly related to DW. The DW of *R. luteum* is similar to the measured range of the FW of *Cotylorhiza tuberculata* (3.9–32.4%), which is higher than *Aurelia* sp. 1 (2.2–3%) and *Rhizostoma pulmo* (4.1–6.8%) [16]. These values provide important information for the potential exploitation of *R. luteum* jellyfish biomass. It has recently been documented using different techniques that jellyfish may practically represent the total diet of several organisms, such as leatherback sea turtles and several fish [31–34].

### *2.2. Jellyfish Carbon, Nitrogen and Sulfur Content*

The carbon, nitrogen and sulfur content of the jellyfish *Rhizostoma luteum* were 5.9 ± 0.3%, 1.6 ± 0.1% and 1.9 ± 0.2% of DW, respectively (mean ± standard deviation, *n* = 6 (Batch numbers: 3, 5–9)). The C:N molar ratio was 3.7 ± 0.1%. Similar values of carbon and nitrogen content have been reported in various of jellyfish such as *Aurelia aurita*, *Chrysaora fuscenses* and *Cyanea capillata* [35] and to the symbiotic jellyfish *Cassiopea xamachana* [36,37]. The C:N molar ratio of *R. luteum* is in the same range as overall medusae and ctenophores [38], and as the symbiotic adults of *Cotylorhiza tuberculata* [39] and *Cassiopea xamachana* [36,37].

### *2.3. Jellyfish Protein Content*

The total freeze-dried tissue of 8 different batches were subjected to phosphate-buffered saline (PBS) solvent extraction treatment. The whole tissues of *Rhizostoma luteum* contained proteins soluble in polar solvents, specifically in aqueous solution with a mean value of 13.7 ± 3.4 mg of proteins of per g of dry weight (mean ± standard deviation, *n* = 8 (Batch numbers: 1, 2, 4–7, 9, 10)). The values ranged between 8.4–18.7 mg of proteins/g of DW. Compared to other species, such as *Aurelia* sp. 1, *Cotylorhiza tuberculata* and *Rhizostoma pulmo*, with 22, 35 and 37 mg of proteins/g of DW, respectively [16], *R. luteum* contained less soluble protein but in the same order of magnitude. The content of protein in jellyfish is consistently the most abundant organic fraction [38] and has been studied in other rhizostomae jellyfish such as *Rhopilema asamushi* [40] and from *Cyanea nozakii* [41] for collagen isolation and characterization, which has been suggested for multipurpose uses in cosmetics and nutraceutical sectors [42].

### *2.4. Phenolic Compound Content in Jellyfish Aqueous Soluble Extract*

The total phenolic content of the jellyfish *Rhizostoma luteum* was 1964.9 ± 386.4 μg GAE (Gallic Acid Equivalent) per gram of DW in the PBS extract (mean ± standard deviation, *n* = 8 (Batch numbers: 1, 2, 4–7, 9, 10)). The values ranged between 1289.6–2597.1 μg GAE/g DW. The phenolic content in jellyfish is not well documented. Compared to *Aurelia* sp. 1 with 116 μg GAE/g DW in the PBS extract [16], *R. luteum* is in a position between *C. tuberculata* and *R. pulmo* reaching 1818 and 2079 μg GAE/g DW, respectively [16]. Also, phenolic compounds were detected in the podocyst and adults of *Chrysaora quinquecirrha* [43,44] and in *Cyanea capillata* and *C. tuberculata* [30,44].

The biostability and biochemical properties of collagen-based tissues may be enhanced by the polyphenols through modulation of mechanisms of collagen fiber cross-linking at different levels (molecular, inter-molecular and inter-microfibrillar) [45,46]. The high phenolic content of *R. luteum* (this study), *C. tuberculata* and *R. pulmo* [16], all of them large rhizostomae jellyfish, may be the reason for the robust and hardened mesoglea, compared to the flexible and soft *Aurelia* spp.

### *2.5. Antioxidant Activity in Jellyfish Aqueous Soluble Extract*

The total antioxidant activity of the jellyfish *Rhizostoma luteum* was 32,598 ± 9015 nmol of TE (Trolox Equivalent) per gram of DW in the PBS extract (means ± standard deviation, *n* = 8 (Batch numbers: 1, 2, 4–7, 9, 10)). The values ranged between 15,468–43,501 nmol of TE/g DW. These values of *R. luteum* are the highest values measured in a jellyfish so far, but in the same magnitude as other rhizostomae jellies such as *R. pulmo* and *C. tuberculata*, with antioxidant activity of 22,520 and 25,621 nmol of TE/g DW, respectively [16]. Meanwhile, *Aurelia* sp. 1 antioxidant activity was much lower, with measured values of 7651 nmol of TE/g DW [16].

The high values of *R. pulmo* and *C. tuberculata* compared to *Aurelia* sp. 1 were presumably attributed to the protein and phenols contents, although other unidentified compounds could be included [16]. Similarly, high values of antioxidant activity present in *R. luteum* in the present study could also be related to the protein and phenol content. The antioxidant activity referring to protein content, both in PBS extract, for *R. luteum* is 2379 nmol of TE/mg of proteins, showing evidence that this high antioxidant activity could be ascribed to the inherent protein properties of this jellyfish. Values of this ratio are double those reported by *R. pulmo* and *C. tuberculata* [16].


**4. Conclusions**

This paper has analyzed the main trends in global research on intelligent contracts, highlighting the main countries that have made a scientific effort in this area, in order of importance—the USA, China, the United Kingdom, Germany, and Italy—and scientific collaboration between these countries does not necessarily respond to obvious or expected trade relations. For example, in the case of Spain, the relationship is concentrated mainly with Canada, Iran and the United Kingdom. The publication of research, mainly in the form of communications in congresses, shows that intelligent contracts are emerging technologies and still in the initial study phase, unlike other more established technologies that do the same work in the form of articles or even books. In order of importance, the main subject areas found were computer science, engineering, mathematics, energy, social sciences, business, management, and accounting. In the absence of a greater degree of maturity and widespread use, smart contracts raise several legal issues that need to be addressed. Consequently, this paper demonstrates that the Social and Legal Sciences occupy the fifth position in the number of published papers, clearly indicating that the technological aspect of this issue needs to be given a legal character, as its implications and scope are of the utmost interest for the international scientific community. Therefore, further legal progress must be made on the reality of this new form of contracts, especially to support the two main lines towards which they have evolved—electronic money and energy costs.

Finally, the analysis of the themes of all these works, by means of the analysis of the keywords, have shown that there are 6 clearly differentiated clusters around which all these works can be grouped. Their temporal evolution shows a tendency towards two main lines of research—the electronic money (cryptocurrencies, or bitcoins) and the smart power grids and electricity market (electricity consumption, electric industry). Given the growing scientific interest shown by the growing number of publications, smart contracts can overcome the problems pointed out by many detractors, and they could be a driver of sustainability. For environmental sustainability applications, smart contracts should pay particular attention to small communities, since it has been observed that small communities are still poorly covered by this particular technology, in spite of often being stewards of natural resources.

**Author Contributions:** E.S.-M. and F.M.-A. have contributed in the same way to the writing of this manuscript, both authors have read and approved the final manuscript.

**Funding:** This research received no external funding.

**Acknowledgments:** The authors of this manuscript wish to thank the CIAIMBITAL research center for its support of this research.

**Conflicts of Interest:** The authors declare no conflict of interest.