**2.5 da Vinci SP**

da Vinci SP (Intuitive Surgical) is a single port surgical system [10–13]. A camera and three 6-mm instruments are bundled inside a 25-mm cannula. Thus, they can be inserted into the patient body from single incision. Each instrument has seven degrees of freedom, including "elbow" and "shoulder". The camera also has multi-bending neck, so that the camera head movement is independent of instruments, and operator can look down the devices. Although initial position of

**97**

**Figure 5.**

*Intelligent Information-Guided Robotic Surgery DOI: http://dx.doi.org/10.5772/intechopen.82191*

**2.6 SPORT surgical system**

**2.7 Endoscope holding robot**

joystick.

the instruments inside the cannula is straight, the "elbow" and "shoulder" make triangulation possible inside the body. It has cleared FDA for urologic procedures. The other applications which the company is aiming at are rectum [11], laryngeal

SPORT surgical system (TITAN Medical, Canada) is also a single port surgical system. It has two articulating instruments and a camera, in a cannula (**Figure 5**). It

In the history of the surgical robot, AESOP (Computer Motion, Inc., US) [15],

an endoscope holding robot, was one of the pioneers, which was launched in 1994. Although AESOP discontinued, there are some new camera holding robots. Their purpose is mainly to solve the issue of human resources in hospital. Viky (EndoControl, France) [16] is a compact camera holder which can be mounted on the operation bed (**Figure 6**). Freehand (Freehand 2010 Ltd., UK) [17] is also mounted on bed. SoloAssist (AKTORmed, Germany) [18], MTG-H100 (Hiwin Technologies Corp, Taiwan), and EMARO (Riverfield Inc., Japan) stands on the floor. Various control methods are employed, such as voice, head movement, and

*SPORT surgical system. Reprinted by permission from Springer Nature: Springer Nature [14].*

is under development, and the company expects its FDA clearance in 2019.

[12, 13] (through natural orifice), and other abdominal procedures.

**Figure 4.** *MiroSurge system. Reprinted by permission from Springer Nature: Springer Nature [8].*

*Intelligent Information-Guided Robotic Surgery DOI: http://dx.doi.org/10.5772/intechopen.82191*

the instruments inside the cannula is straight, the "elbow" and "shoulder" make triangulation possible inside the body. It has cleared FDA for urologic procedures. The other applications which the company is aiming at are rectum [11], laryngeal [12, 13] (through natural orifice), and other abdominal procedures.


*Article* **Fractional-Order Interval Observer for Multiagent Nonlinear Systems**

**Haoran Zhang, Jun Huang \* and Siyuan He**

The School of Mechanical and Electrical Engineering, Soochow University, Suzhou 215131, China<EMAIL_ADDRESS>(H.Z<EMAIL_ADDRESS>(S.H.)

**\*** Correspondence<EMAIL_ADDRESS>
**Abstract:** A framework of distributed interval observers is introduced for fractional-order multiagent systems in the presence of nonlinearity. First, a frame was designed to construct the upper and lower bounds of the system state. By using monotone system theory, the positivity of the error dynamics could be ensured, which implies that the bounds could trap the original state. Second, a sufficient condition was applied to guarantee the boundedness of distributed interval observers. Then, an extension of Lyapunov function in the fractional calculus field was the basis of the sufficient condition. An algorithm associated with the procedure of the observer design is also provided. Lastly, a numerical simulation is used to demonstrate the effectiveness of the distributed interval observer.

**Keywords:** distributed interval observer; fractional-order multiagent systems; monotone system theory


**3.4.4 Color, power doppler**

114 Prostate Cancer – Diagnostic and Therapeutic Advances

they may supplement each other, will become important source of research endeavours in the future. HistoScanning manufacturer intends to use the technology also for other cancers, like ovary, thyroid and breast, which may be advantageous as prostate diagnosis may benefit from multidisciplinary team. On the other side, C-TRUS ANNA was developed by urologists for urologists, can be used in almost any setting (any digital ultrasound machine is good) and seems to have at present more peer reviewed data. HistoScanning is not aiming only towards prostate biopsy guidance, but also aims at other potentially useful predictions regarding prostate cancer and seems to have larger research base with groups from different countries (UK, Germany) who study its potential applications. Whether one or both

Real time transrectal ultrasonoelastograpy of the prostate is aimed at discrimination between harder and softer areas of prostate tissue. MRI elastography technology was also developed (S. Li et al., 2011), but here only ultrasound is described. Back-scattered ultrasound waves are displaced with compression or decompression of tissue (approximately 2%), harder areas showing less displacement compared to softer (Salomon et al., 2008). Elastography is performed in real-time, at the time of biopsy – no previous transrectal ultrasound examination (as for C-TRUS ANNA) is necessary. By subjectively observing US elastography picture, operator aims at evaluating symmetry of stiffness, focal areas of hardness and persistence of stiffness with probe tilting, aiming at stiff nodule more than 5 mm in diameter and persistence of stiffness after probe tilting (Giurgiu et al., 2011). There are different scoring systems (Salomon et al., 2009), some focus on identifying smaller lesions and potentially showing increased sensitivity (Kamoi et al., 2008). Technique of elastography is still improving, better differentiation markers are being developed constantly (Zhang et al., 2011). Further, standardization of compression with idea of leaving this part to the machine is also in testing (Tsutsumi et al., 2010). Regarding companies which provide elastography equipment, most studies have been performed using Hitachi machine, which is commercially available for prostate applications and most tested, although other manufacturers also offer this technology. Among target-biopsy techniques elastograpy seems at present most widely spread as technology is also in use for breast cancer (primarily) and investment needed is only in US machine and probe, there are no perinvestigation charges as for C-TRUS ANNA. Elastography procedure is also much simpler compared to MRI-US fusion. Another advantage of elastography is in its compatibility with power/color doppler techniques for image guidance, which can be performed simultaneously, therefore gaining from two sources. There are quite a few published studies describing experience with prostate elastograpy from different parts of the world. Study results are positive and seem to support claims that elastography improves cancer detection rate. One of the very appealing studies, from USA, analyzed help of elastograpy in biopsy of men with PSA values between 1.25 and 4 and free/total PSA ratio less than 18% (Aigner et al., 2010). They were able to detect 24% of cancers using 5 cores with elastography guidance compared to 5.1% cancers using 10 systematic biopsies. Another study, from Romania, used and compared in the same set of patients gray scale, doppler and elastograpyh data (Giurgiu et al., 2011). They found, in a series of 65 patients and 43% of them with identified cancer on biopsy, sensitivity of elastograpy to be 68% and specificity 62%. Particularly promising was elastography in a subgroup of older than 70 years, where sensitivity

techniques will stand the test of time and what role they will play remains open.

**3.4.3 Elastography**

Angiogenesis is important in development of cancer and increased vascularity was detected in tumors in general and in radical prostatectomy specimens, therefore use of ultrasound to detect those changes was proposed. Color doppler imaging estimates mean frequency shift of doppler signal to determine velocity and direction of flow. Power doppler shows total energy of the signal by integrating it, therefore resulting in sig`nal with homogenous background and more precise detection of smaller and low flow vessels (Remzi et al., 2004). Study of usefulness of power and color doppler for evaluation of hypoechoic lesions showed 80% sensitivity and 82% specificity for detecting prostate cancer (Cho et al., 2000). Standardized criteria for scoring different degrees and distributions of prostatic vascularity were developed and also subjective scales seem to work well (Mitterberger et al., 2010), however this points to high subjectivity of the method, which is its drawback.

Power doppler was used for evaluation of peripheral prostatic capsular vessels, parenchymal vessels and vessels anastomosing with extraprostatic vessels (Sauvain et al., 2003). Criteria for suspicion of cancer in this study were increase in number of intra-lesional vessels, disoriented vessels or verticalized vessels in peripheral gland, asymmetrical blood flow, mass effect on the intraprostatic perilesional vessels and vessels in peripheral margins. Analyzing all those criteria, they aimed at estimation of prostate cancer stage by dividing lesions into three groups: absent extracapsular involvement, undetermined extracapsular involvement and presumably present extracapsular involvement. In this series, 55.7% patients had cancer and sensitivity of power doppler ultrasound was claimed to be 92%, specificity 72% (compared to 88% and 58% for ultrasound only). Group with ultrasound estimated lack of extracapsular involvement had this found in final pathology in 11%, while group with ultrasound suspicious for extracapsular involvement had it confirmed in 87%. Authors (Sauvain et al., 2003) conclude power doppler ultrasound improves accuracy of ultrasound imaging in the diagnosis of cancer, can increase detection rate, optimize number of biopsy cores and also predict extracapsular invasion by identification of capsule perforating vessels.

When using ultrasound for evaluation of minor differences in prostate blood flow between cancerous and benign areas, many factors can interfere with the results – for example position of the patient – it was shown left decubitus position caused flow asymmetry resulting in more biopsies directed toward left side without improving detection rate (Halpern et al., 2002).

Future of Prostate Biopsy: Who Will Get It and How? 117

nomogram (Remzi et al., 2005), as it is obvious higher number of cores gives better sampling and improves detection. Later, while some still questioned Vienna nomogram's usefulness (Lecuona & Heyns, 2010), it became obvious number of biopsy detected cancers is related to sampling density, which is a quotient between prostate size and number of cores taken. A lot of nomograms, which predict probability of positive prostate biopsy, take sampling density into account (Chun et al., 2007). Regarding number of cores, it went up from six at first to eight, later ten, later twelve (a lot of us still using this number at present for majority of patients for first biopsy), fifteen, eighteen... up to twenty-one (Guichard et al., 2007) core per biopsy session. This number seems to be highest present routine extended systematic biopsy scheme, simply because twenty-four or more cores is called saturation biopsy (Ahyai et al., 2010). Many have also argued they were unable to increase their cancer detection rate after increasing number of cores from for example 12 to 18. This underscores importance not only of

**3.6 Free hand systematic biopsy, targeted biopsy, prostatic mapping or combination**  Goal of prostate biopsy is not only to find "some" cancer in the prostate, as it was in the past. Now, it has not only to provide representative sample of DIL (dominant intraprostatic lesion), but also to show all "important" cancer areas in the prostate, describe precisely where they are and ensure other regions are cancer free. This is in contrast to efforts of targeted biopsies which claim they may reduce pain and burden of biopsy by reducing

Prostate-mapping biopsy approaches, for example TargetScann, have different approach – they aim at precisely sampling predefined sections of prostate with larger number of cores. Electronic doppler ultrasound probes are becoming increasingly complex and sensitive to detect blood flow signals in the prostate to help guiding biopsy. TargetScan's device ultrasound probe is sector and at present can not be used for image-guided approaches, but seems to provide relatively reliable results regarding prostate mapping, which is very important for all targeted therapy approaches (Andriole et al., 2007). "Robotic" probes (ultrasound systems, which are just inserted into rectum by physician and then guided by

We have therefore a mix of partly competing, some probably complementary and some excluding technologies aiming at improving prostate cancer detection and staging. Which will find its way into every-day practice and to what extent, remains open. It seems at present repeat biopsy yield is about 20%-40% and targeted biopsy methods claim, in repeat, previously negative setting, yield of 50%. All those new approaches need evaluation and confirmation. One way may be showing significantly better performance of targeted or mapping approaches compared to prediction of nomograms for repeat biopsy setting (Chun

Overall, it seems at present first biopsy should be 10-18 laterally directed cores (depending on prostate size, for prostates larger than 50 ml minimum 14). Targeted biopsy only, with less than 6 cores, may generally not be appropriate for the first biopsy, as it is far from 100%

For second and later biopsies, as targeted opinions are becoming more and more widespread and therefore accessible and are not untested technical glitches any more, we may in 2011 suggest any of the recently developed opinions, depending on local availability,

pressing buttons, are being developed also by other manufacturers.

number, but also direction of cores.

number of cores.

et al., 2007).

as follows.

and we need to assess whole prostate.

Different pharmaceutical interventions were proposed to increase difference between cancer and benign tissue: improved view with contrast agent, increased flow with phosphodiesterase inhibitor (vardenafil) (Morelli et al., 2011) or decreased flow with 5 alpha reductase inhibitor or combination of 5-alpha reductase inhibitor with contrast agent (Mitterberger et al., 2008).

Contrast enhanced transrectal prostate ultrasound was extensively evaluated in multiple research projects (Wink et al., 2008). Microbubbles act as additional reflectors in bloodstream and increase sensitivity of color and power doppler imaging. Newer techniques, for example harmonic imaging, were also tested. Use of ultrasound contrast agent is associated with only minimal side effects, like alterations in taste, flush or pain at the injection site. However, it costs additional money for contrast. It should be performed in 4 minutes after contrast injection (half life of bubbles). Further drawback is strong operator-dependence of the technique. Contrast enhanced ultrasound enables visualisation of prostate cancer (in up to 78% of cases), but sensitivity and specificity are not enough to avoid systematic biopsies. Targeted biopsies using this technique are claimed to allow lower number of cores per session without decrease in detection rate (Wink et al., 2008).

Use of 5-alpha reductase inhibitor was proposed in two staged approach: first color/power doppler evaluation of prostate is followed by 1-3 week of dutasteride and than reevaluation and biopsy guided to areas, where vascular signals have not decreased after treatment. Additional sextant systematic sample was also taken. Researchers claimed increased yield in targeted cores (20%) compared to sextant cores (8%) (Ives et al., 2005).

#### **3.5 Biopsy schemes and number of cores**

After finger guided biopsy strategies were replaced with ultrasound guided, it soon became clear (group around dr. Stamey, Stanford) 6 cores, taken in a systematic fashion, finds more cancer than aiming at hypo-echoic areas or randomly (Hodge et al., 1989). Standard approach, which hold for more than 10 years, was established: six cores were taken in parasagittal plane, one at the base, one mid-gland and one at apex. However, patients with negative biopsies and still suspicious for cancer, had repeat biopsies, which were almost as often positive as first biopsy – therefore it was obvious the system was not perfect. Aim should be – perform biopsy – if it is negative, then there is no cancer. Reality was – perform classic sextant scheme biopsy – if it is negative, then there is almost the same probability for cancer as before biopsy. So – search has begun for improvement of systematic biopsy scheme (mainly searching for optimal number of cores and location of cores) and this search has not settled yet. As this text aims at the future, not past, only some examples will be pointed out. Inadequacy of sextant scheme was proven many times, for example (Norberg et al., 1997) and also recent larger and longer retrospective data analyzes still turn to this question, for example regarding sextant biopsy's ability to predict unilateral disease (Mayes et al., 2011). First it became clear biopsies should be directed more laterally in the peripheral zone of the prostate (Eskew et al., 1997). Later, it seemed transitional zone inclusion may improve cancer detection, however this was abandoned for initial biopsy, because of inferior gain from transitional zone directed cores compared to more sampling toward far lateral mid-gland and anterior-apical areas. A lot of cancers are located on anterior horn of prostate. With repeat biopsy, of course, anterior transitional zone is also sampled (Chun et al., 2010). Innumerous analyzes have shown – more cores – more cancer. Prostate size has a role (Taneja, 2006). Nomogram was developed to optimize number of cores needed in relation to prostate size – so called Vienna

Different pharmaceutical interventions were proposed to increase difference between cancer and benign tissue: improved view with contrast agent, increased flow with phosphodiesterase inhibitor (vardenafil) (Morelli et al., 2011) or decreased flow with 5 alpha reductase inhibitor or combination of 5-alpha reductase inhibitor with contrast

Contrast enhanced transrectal prostate ultrasound was extensively evaluated in multiple research projects (Wink et al., 2008). Microbubbles act as additional reflectors in bloodstream and increase sensitivity of color and power doppler imaging. Newer techniques, for example harmonic imaging, were also tested. Use of ultrasound contrast agent is associated with only minimal side effects, like alterations in taste, flush or pain at the injection site. However, it costs additional money for contrast. It should be performed in 4 minutes after contrast injection (half life of bubbles). Further drawback is strong operator-dependence of the technique. Contrast enhanced ultrasound enables visualisation of prostate cancer (in up to 78% of cases), but sensitivity and specificity are not enough to avoid systematic biopsies. Targeted biopsies using this technique are claimed to allow lower number of cores per

Use of 5-alpha reductase inhibitor was proposed in two staged approach: first color/power doppler evaluation of prostate is followed by 1-3 week of dutasteride and than reevaluation and biopsy guided to areas, where vascular signals have not decreased after treatment. Additional sextant systematic sample was also taken. Researchers claimed increased yield in

After finger guided biopsy strategies were replaced with ultrasound guided, it soon became clear (group around dr. Stamey, Stanford) 6 cores, taken in a systematic fashion, finds more cancer than aiming at hypo-echoic areas or randomly (Hodge et al., 1989). Standard approach, which hold for more than 10 years, was established: six cores were taken in parasagittal plane, one at the base, one mid-gland and one at apex. However, patients with negative biopsies and still suspicious for cancer, had repeat biopsies, which were almost as often positive as first biopsy – therefore it was obvious the system was not perfect. Aim should be – perform biopsy – if it is negative, then there is no cancer. Reality was – perform classic sextant scheme biopsy – if it is negative, then there is almost the same probability for cancer as before biopsy. So – search has begun for improvement of systematic biopsy scheme (mainly searching for optimal number of cores and location of cores) and this search has not settled yet. As this text aims at the future, not past, only some examples will be pointed out. Inadequacy of sextant scheme was proven many times, for example (Norberg et al., 1997) and also recent larger and longer retrospective data analyzes still turn to this question, for example regarding sextant biopsy's ability to predict unilateral disease (Mayes et al., 2011). First it became clear biopsies should be directed more laterally in the peripheral zone of the prostate (Eskew et al., 1997). Later, it seemed transitional zone inclusion may improve cancer detection, however this was abandoned for initial biopsy, because of inferior gain from transitional zone directed cores compared to more sampling toward far lateral mid-gland and anterior-apical areas. A lot of cancers are located on anterior horn of prostate. With repeat biopsy, of course, anterior transitional zone is also sampled (Chun et al., 2010). Innumerous analyzes have shown – more cores – more cancer. Prostate size has a role (Taneja, 2006). Nomogram was developed to optimize number of cores needed in relation to prostate size – so called Vienna

agent (Mitterberger et al., 2008).

session without decrease in detection rate (Wink et al., 2008).

**3.5 Biopsy schemes and number of cores**

targeted cores (20%) compared to sextant cores (8%) (Ives et al., 2005).

nomogram (Remzi et al., 2005), as it is obvious higher number of cores gives better sampling and improves detection. Later, while some still questioned Vienna nomogram's usefulness (Lecuona & Heyns, 2010), it became obvious number of biopsy detected cancers is related to sampling density, which is a quotient between prostate size and number of cores taken. A lot of nomograms, which predict probability of positive prostate biopsy, take sampling density into account (Chun et al., 2007). Regarding number of cores, it went up from six at first to eight, later ten, later twelve (a lot of us still using this number at present for majority of patients for first biopsy), fifteen, eighteen... up to twenty-one (Guichard et al., 2007) core per biopsy session. This number seems to be highest present routine extended systematic biopsy scheme, simply because twenty-four or more cores is called saturation biopsy (Ahyai et al., 2010). Many have also argued they were unable to increase their cancer detection rate after increasing number of cores from for example 12 to 18. This underscores importance not only of number, but also direction of cores.

### **3.6 Free hand systematic biopsy, targeted biopsy, prostatic mapping or combination**

Goal of prostate biopsy is not only to find "some" cancer in the prostate, as it was in the past. Now, it has not only to provide representative sample of DIL (dominant intraprostatic lesion), but also to show all "important" cancer areas in the prostate, describe precisely where they are and ensure other regions are cancer free. This is in contrast to efforts of targeted biopsies which claim they may reduce pain and burden of biopsy by reducing number of cores.

Prostate-mapping biopsy approaches, for example TargetScann, have different approach – they aim at precisely sampling predefined sections of prostate with larger number of cores. Electronic doppler ultrasound probes are becoming increasingly complex and sensitive to detect blood flow signals in the prostate to help guiding biopsy. TargetScan's device ultrasound probe is sector and at present can not be used for image-guided approaches, but seems to provide relatively reliable results regarding prostate mapping, which is very important for all targeted therapy approaches (Andriole et al., 2007). "Robotic" probes (ultrasound systems, which are just inserted into rectum by physician and then guided by pressing buttons, are being developed also by other manufacturers.

We have therefore a mix of partly competing, some probably complementary and some excluding technologies aiming at improving prostate cancer detection and staging. Which will find its way into every-day practice and to what extent, remains open. It seems at present repeat biopsy yield is about 20%-40% and targeted biopsy methods claim, in repeat, previously negative setting, yield of 50%. All those new approaches need evaluation and confirmation. One way may be showing significantly better performance of targeted or mapping approaches compared to prediction of nomograms for repeat biopsy setting (Chun et al., 2007).

Overall, it seems at present first biopsy should be 10-18 laterally directed cores (depending on prostate size, for prostates larger than 50 ml minimum 14). Targeted biopsy only, with less than 6 cores, may generally not be appropriate for the first biopsy, as it is far from 100% and we need to assess whole prostate.

For second and later biopsies, as targeted opinions are becoming more and more widespread and therefore accessible and are not untested technical glitches any more, we may in 2011 suggest any of the recently developed opinions, depending on local availability, as follows.

Future of Prostate Biopsy: Who Will Get It and How? 119

AUA guidelines (www.auanet.org, 2008 edition, reviewed 2010) also confirm prophylaxis is indicated in all patients as randomized controlled trials have confirmed significantly lower rates of complications in antibiotic groups. They also claim single dose may be adequate. A lot depends on local antibiotic resistance patterns. For example, if TMP+SMX regimen is not used even for non-complicated urinary tract infections in one area, one would not use it for prostate biopsy prophylaxis either. One can never predict for sure future development of antibiotic resistance. Therefore, constant vigilance is needed and monitoring rates of infectious complications is necessary. Special attention should focus on repeat biopsies and this setting may sometimes deserve different antibiotic scheme or previous culture and susceptibility analysis. Later may be performed in two ways – patients with catheters or other urinary tract insertions may be screened using urine culture (Bruyere et al., 2010), but all who need screening should have their stools sample cultured for resistant strains. Resistant strains do occur and may significantly contribute to complications (Liss et al., 2011). Due to high probability of E.coli resistance to quinolones in cases of patients returning to hospital after prostate biopsy with quinolone prophylaxis, it is wise to use another antibiotic before cultures are known (although it seems obvious, people do often get prescribed flouroquinolone again). If there is no or low risk for ESBL, cephalosporines

(probably third generation) may be the best initial guess (Zaytoun et al., 2011).

accepting single dose only approach.

the environment for longer time.

flouroquinolone resistance or intolerance is present.

gentamicin may be method of choice for single dose regimens.

Although single dose is claimed useful, in our and many other situations most patients can be considered not low risk regarding infectious risk classifications (more than 65 years of age, concomitant diseases, like diabetes and lower urinary tract symptoms, incomplete bladder emptying). Therefore typical scheme (as we use it and others, for example (Campos-Fernandes et al., 2009), uses ciprofloxacin 500 mg twice daily started before biopsy and continued for three days. It was shown to decrease rate of complications after biopsy (Schaeffer et al., 2007). As every single infectious complication, even most minor, requiring any health-service contact, even only consultation, is seen as a big problem and aim is to avoid any complication, there are many patients who probably benefit from short course and not single dose antibiotic and this may be further reason why urologists are reluctant in

Metronidazol is added in some centers routinely, but most do not use it at present. However, it might be useful for specific patients, with specific predisposing conditions and in combination with other antibiotics (for example cephalosporins, although subjective experience shows more complications with their use for this purpose), when

Instead of 1-2 hour prior to procedure fluoroquinolone orally, same use parenteral aminogylcoside (gentamicin or amikacin) or aminopenicilline with betalactamase inhibitor (co-amoxiclav) at the time of biopsy, which is followed by oral antibiotic (often fluoroquinolone, but also others) at home. This scheme is used in some centers and may be helpful when compliance with oral regimen prior to biopsy is questionable or for allergy and non-tolerance to quinolones or in areas with high resistance to quinolones (Kehinde et al., 2008). Combination of periprocedural oral dose of ciprofloxacine with iv dose of

Additional important recent problem regarding fluoroquinolones was finding significantly different serum concentrations of active drug comparing different generic manufacturers (Kehinde et al., 2010). Apart from probable reason for higher complication rate, substandard antibiotics preparations also contribute to resistance development as longer courses are needed and as a consequence low concentrations of drug are present in


**Volatile Organic Compounds from Basil Essential Oils: Plant Taxonomy, Biological Activities, and Their Applications in Tropical Fruit Productions**

**Tibet Tangpao 1,2, Nutthawut Charoimek 2, Patipon Teerakitchotikan 2, Noppol Leksawasdi 3,4, Kittisak Jantanasakulwong 3,4, Pornchai Rachtanapun 3,4, Phisit Seesuriyachan 3,4, Yuthana Phimolsiripol 3,4, Thanongsak Chaiyaso 3,4, Warintorn Ruksiriwanich 5,6, Pensak Jantrawut 5,6, Hien Van Doan 7,8, Ratchadawan Cheewangkoon 8,9,\* and Sarana Rose Sommano 1,2,\***

**Abstract:** Basils of the genus *Ocimum* are aromatic plants grown widely throughout the tropical and temperate regions. The essential oils obtained from their aerial parts are enriched with volatile organic compounds with high market demand for food and pharmaceutical industries. The volatile organic compounds have been shown to exhibit biological activities. Therefore, their novel applications have been extensively explored in the last few decades. The most widely available basils in the tropical areas include white holy basil (*O. sanctum* var. Shyama), red holy basil (*O. sanctum* var. Rama), Thai basil (*O. basilicum* var. thyrsiflorum), lemon basil (*O. citriodorum*), and tree basil (*O. gratissimum*). Over 60 volatiles of different classes have been exclusively described, and some of them could be useful as biomarkers for genotype specification. The major volatile ingredient is the phenylpropanoids, such as methyl eugenol, which has the potential as a natural product for mitigating Oriental fruit fly (*Bactrocera dorsalis*) during tropical fruit production. Moreover, basil essential oils are also used to control diseases of the fruits during post-harvest storage. As a result, the application of basil essential oils as a sustainable defect control strategy for tropical fruit value chains seems intriguing. This review provides comprehensive information on plant taxonomy and volatile compositions of the essential oil fractions from different basil species. Their biological activities and applications are also discussed, mainly during the pre- and post-production of tropical fruits. Additionally, the available techniques to enhance the efficacy of the volatile active compounds are also described.

**Keywords:** essential oil; integrated pest management; Oriental fruit fly; pomology; post-harvest disease control

**Citation:** Tangpao, T.; Charoimek, N.; Teerakitchotikan, P.; Leksawasdi, N.; Jantanasakulwong, K.; Rachtanapun, P.; Seesuriyachan, P.; Phimolsiripol, Y.; Chaiyaso, T.; Ruksiriwanich, W.; et al. Volatile Organic Compounds from Basil Essential Oils: Plant Taxonomy, Biological Activities, and Their Applications in Tropical Fruit Productions. *Horticulturae* **2022**, *8*, 144. https://doi.org/10.3390/ horticulturae8020144

Academic Editors: Dasha Mihaylova, Aneta Popova and Isabel Lara

Received: 28 December 2021 Accepted: 5 February 2022 Published: 8 February 2022

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

191


**Author details**

Kristi M. Soileau1,2

1 Private Periodontal Practice, New Orleans, LA, USA

2 Louisiana State University Health School of Dentistry, New Orleans, LA, USA

\*Address all correspondence to<EMAIL_ADDRESS>
© 2021 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.

**81**

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*Why Are We Missing the Teeth? Addressing Oral Care Neglect in the Palliative Patient*

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*Why Are We Missing the Teeth? Addressing Oral Care Neglect in the Palliative Patient DOI: http://dx.doi.org/10.5772/intechopen.95606*


**Meet the editor**

Professor Kunihiro Sakuma, PhD, currently works at the Institute for Liberal Arts, Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He received his sports science diploma in 1995 from the University of Tsukuba and started scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism

of congenital muscular dystrophy and normal muscle regeneration. His interest was later changed to the molecular mechanism and attenuating strategy of sarcopenia (age-related muscle atrophy). His aim is to attenuate sarcopenia by improving autophagic defects using nutrient- and pharmaceutical-based treatments.

Contents

**Preface IX**

**Muscle Tissue 3** Kunihiro Sakuma

**Contractions 19**

Chapter 6 **Hereditary Myopathies 81**

María Cárdenas Díaz

**Section 2 Plasticity of the Skeletal Muscle 7**

Chapter 1 **Introductory Chapter: Current Status of Research Field in**

Chapter 2 **The Role of Glucose and Fatty Acid Metabolism in the**

Chapter 3 **Molecular and Cellular Markers in Skeletal Muscle Damage**

Chapter 4 **Multinuclear Magnetic Resonance Spectroscopy of Human**

Chapter 5 **Skeletal Muscle Fiber Types in Neuromuscular Diseases 65**

Satu O.A. Koskinen and Maarit Lehti

**Section 3 The Characteristics of Neuromuscular Disease 63**

Jennifer Glaser and Masatoshi Suzuki

**Development of Insulin Resistance in Skeletal Muscle 9** Sithandiwe Eunice Mazibuko-Mbeje, Phiwayinkosi V. Dludla, Bongani B. Nkambule, Nnini Obonye and Johan Louw

**after Acute Voluntary Exercise Containing Eccentric Muscle**

**Skeletal Muscle Metabolism in Training and Disease 33** Ladislav Valkovič, Radka Klepochová and Martin Krššák

Arlek Marion González-Jamett, Jorge Alfredo Bevilacqua and Ana

**Section 1 Introduction 1**


**2.4.2 Activation of neuroendocrine pathways**

Activation of the sympathetic Nervous System (SNS) leads to the release of adrenal hormones (catecholamines), which can have an effect on sleep (Guggisberg, 2007). Furthermore, the production of catecholamines may stimulate the production of inflammatory cytokines. Inflammatory processes are modulated by numerous feedback and feed forward mechanisms. The Hypothalamic-pituitary-adrenal axis also regulates inflammatory processes via cortisol secretion, which is secreted in a diurnal manner following the sleep-wake cycle. Cortisol can suppress the production of pro-inflammatory cytokines and, as part of the negative feedback mechanism designed to prevent uncontrolled inflammation, pro-inflammatory cytokines stimulate the HPA axis to produce cortisol. However, as in the case of SDB and the resulting hypoxia, plasma cortisol is chronically raised (Meerlo et al, 2000). Prolonged cortisol secretion leads the glucocorticoid receptors becoming desensitised and results in a decrease in the protective effects of cortisol against inflammation (Sapolsky et al, 2000). Disrupted sleep can lead to mild stimulation of the HPA axis and increased inflammation, thus providing another mechanism whereby disrupted sleep in pregnancy may lead to dysregulation of normal homeostatic processes and potentially lead to adverse pregnancy outcomes (Okun et al, 2009).

#### **2.4.3 Insulin resistance**

Accumulating evidence suggests that both poor sleep quantity and quality are associated with impaired glucose tolerance and diabetes (Cappuccio et al, 2010a). Until recently little has been known about the effect of poor sleep during pregnancy on glucose tolerance and gestational diabetes. Qui et al interviewed a large cohort of 1,290 women during early pregnancy. They collected information regarding sleep duration and snoring during pregnancy. They obtained information on gestational diabetes mellitus (GDM) from the screening and test results in their medical records. They found that those women who slept 4 hours or less had a greater risk of GDM than those sleeping 9 hours per night. Furthermore they observed that whilst the increased relative risk was 3.23 (95% CI 0.34-

Sleep and Pregnancy: Sleep Deprivation,

**2.6 Implications for public health**

environment can improve sleep for new mothers.

duration or quality.

**3. Conclusion**

Sleep Disturbed Breathing and Sleep Disorders in Pregnancy 13

In the general population sleep duration has been declining. Women now occupy an increasingly prominent position in the workplace but often they do so without any reduction in their home responsibilities. Consequently sleep needs are often of low priority. Preterm birth is a major public health priority and is a common adverse outcome in pregnancy. Sleep quantity and quality are not only important determinants of maternal and foetal health but are also important for general health and need to be particularly addressed in the post-partum period where sleep disruption is likely to be very common. There is also some evidence to suggest that the effects of sleep deprivation may be greater in women than in men. Despite this, the majority of studies undertaken are in men and there is now a clear

There is also a paucity of studies evaluating sleep disturbances in the post-partum period and research is required to look at the effects of sleep deprivation on both maternal and paternal functioning and the effect on maternal-infant interaction. Factors such as the type of delivery, the type of infant feeding, return-to-work time and infant temperament may be important, along with the degree of support from the father or other family members. A recent randomised trial set out to investigate if modification to the bedroom environment could improve the sleep of new parents (Lee & Gay, 2011). They evaluated a modified sleep hygiene intervention for new parents (infant proximity, noise masking, and dim lighting) in anticipation of night-time infant care in two samples of new mothers of different socioeconomic status. They were randomized to the experimental intervention or attention control, and sleep was assessed in late pregnancy and first 3 months postpartum using actigraphy and the General Sleep Disturbance Scale. The investigators observed that whilst the sleep hygiene strategies evaluated did not benefit the more socioeconomically advantaged women or their partners they did improve postpartum sleep among the less advantaged women suggesting that simple inexpensive changes to the bedroom

Further studies are required fully to investigate the effects of smoking on sleep and associated adverse pregnancy outcomes but meanwhile educational programmes could be used to educate women on the possible harmful effects. Research to determine if other health behaviours could have beneficial effects on sleep in pregnant women is also required. For example, physical activity is recommended to pregnant women for health benefits but as yet there are insufficient studies to determine if this has any effect on improving sleep

A lack of sleep is known to affect both our physical and mental health. The few studies that have investigated sleep in pregnancy have found both an increase in total sleep time and an increase in daytime sleepiness in the first trimester whereas the third trimester appears to be associated with a decrease in sleep time and an increase in the number of awakenings. Sleep has an important impact on maternal and foetal health. It has been associated with an increased duration and pain perception in labour, with a higher rate of caesarean delivery and with preterm labour. Some pregnant women develop sleep disorders such as RLS or OSA or insomnia and others develop postpartum depression. Longitudinal studies are required to fully evaluate the effect of sleep deprivation on maternal and foetal outcome.

need for more, large, multicentre, prospective studies to be performed in women.

30.41) for lean women (<25 kg/m2) this was increased to 9.83 (95% CI 1.12-86.32) for overweight women (> or = 25 kg/m2). Snoring was also associated with a 1.86-fold increased risk of GDM and the risk of GDM was 6.9 xs higher in overweight than lean women (Qiu et al, 2010). These findings are consistent with data in non-pregnant women and warrant further investigation to determine the effect on pregnancy outcome.

#### **2.4.4 Passive smoking**

In Japan, two surveys were conducted to determine if passive smoking might have any effect on the sleep disturbances observed in pregnant women. 16,396 pregnant women were surveyed in 2002 and 19,386 in 2006. This is particularly important as 80% of passive environmental smoking comes from the spouse and in Japan there is a very high smoking rate amongst men (53%). The results indicated that passive smoking is independently associated with increased sleep disturbances during pregnancy. They observed that pregnant woman who were exposed to passive smoking were likely to suffer from difficulty in initiating sleep, short sleep, and snoring; those women who smoked suffered from the same disturbances and also reported early morning awakenings and excessive daytime sleepiness (Ohida et al, 2007). The authors suggest that some of the negative health outcomes observed in pregnant women may be mediated by the effect of active and passive smoking on sleep.

#### **2.5 Diagnosis and management of sleep disorders in pregnancy**

There are many different ways in which sleep data can be collected, the gold standard, however, is to measure sleep using polysomnography (PSG) as this provides an objective assessment of the sleep-wake cycle over the entire sleep period (Baker et al, 1999). Much of the data regarding sleep in pregnancy is limited to self-administered questionnaires and to diaries: very few recent studies have used PSG. However, it is recognised that undertaking multiple sleep studies at different time points during pregnancy is difficult. Despite this there is evidence to suggest that sleep disorders in pregnancy can in certain individuals have adverse outcomes for the mother or baby and therefore it would be useful to develop a screening tool that could be administered quickly by health professionals during routine pregnancy consultations. A simple and cost-effective alternative to PSG is to use actigraphy and sleep diaries. There are now many wrist-watch style actigraphs available. They are activated by movement and can differentiate when a person is awake or asleep, many also now have light monitors incorporated in them as well. They are useful in identifying night time awakenings and for determining their subsequent duration. When used in conjunction with self-recorded sleep diaries, actigraphs can help to establish a very detailed sleep pattern. Questionnaires administered to a bed partner can also help to establish a diagnosis of sleep disordered breathing. OSA is a common but often unrecognised condition in women of childbearing age. The likelihood is increased however in women with a past or current history of polycystic ovary syndrome, depression, hypertension, diabetes, hypothyroidism, metabolic syndrome, obesity (Champagne et al, 2010). The diagnostic test of choice would be a PSG, and referral to a sleep specialist to confirm and treat primary sleep disorders may be required. Further research is also required to establish if the management thresholds for treatment of OSA in non-pregnant women are applicable to pregnant women.

Pharmacological treatment of sleep disorders in pregnancy needs to be viewed with caution, given the potential for harm to the foetus. Similar caution needs to extend to women who are breastfeeding.

### **2.6 Implications for public health**

12 Sleep Disorders

30.41) for lean women (<25 kg/m2) this was increased to 9.83 (95% CI 1.12-86.32) for overweight women (> or = 25 kg/m2). Snoring was also associated with a 1.86-fold increased risk of GDM and the risk of GDM was 6.9 xs higher in overweight than lean women (Qiu et al, 2010). These findings are consistent with data in non-pregnant women

In Japan, two surveys were conducted to determine if passive smoking might have any effect on the sleep disturbances observed in pregnant women. 16,396 pregnant women were surveyed in 2002 and 19,386 in 2006. This is particularly important as 80% of passive environmental smoking comes from the spouse and in Japan there is a very high smoking rate amongst men (53%). The results indicated that passive smoking is independently associated with increased sleep disturbances during pregnancy. They observed that pregnant woman who were exposed to passive smoking were likely to suffer from difficulty in initiating sleep, short sleep, and snoring; those women who smoked suffered from the same disturbances and also reported early morning awakenings and excessive daytime sleepiness (Ohida et al, 2007). The authors suggest that some of the negative health outcomes observed in pregnant women

There are many different ways in which sleep data can be collected, the gold standard, however, is to measure sleep using polysomnography (PSG) as this provides an objective assessment of the sleep-wake cycle over the entire sleep period (Baker et al, 1999). Much of the data regarding sleep in pregnancy is limited to self-administered questionnaires and to diaries: very few recent studies have used PSG. However, it is recognised that undertaking multiple sleep studies at different time points during pregnancy is difficult. Despite this there is evidence to suggest that sleep disorders in pregnancy can in certain individuals have adverse outcomes for the mother or baby and therefore it would be useful to develop a screening tool that could be administered quickly by health professionals during routine pregnancy consultations. A simple and cost-effective alternative to PSG is to use actigraphy and sleep diaries. There are now many wrist-watch style actigraphs available. They are activated by movement and can differentiate when a person is awake or asleep, many also now have light monitors incorporated in them as well. They are useful in identifying night time awakenings and for determining their subsequent duration. When used in conjunction with self-recorded sleep diaries, actigraphs can help to establish a very detailed sleep pattern. Questionnaires administered to a bed partner can also help to establish a diagnosis of sleep disordered breathing. OSA is a common but often unrecognised condition in women of childbearing age. The likelihood is increased however in women with a past or current history of polycystic ovary syndrome, depression, hypertension, diabetes, hypothyroidism, metabolic syndrome, obesity (Champagne et al, 2010). The diagnostic test of choice would be a PSG, and referral to a sleep specialist to confirm and treat primary sleep disorders may be required. Further research is also required to establish if the management thresholds for treatment of

Pharmacological treatment of sleep disorders in pregnancy needs to be viewed with caution, given the potential for harm to the foetus. Similar caution needs to extend to women who

and warrant further investigation to determine the effect on pregnancy outcome.

may be mediated by the effect of active and passive smoking on sleep.

**2.5 Diagnosis and management of sleep disorders in pregnancy**

OSA in non-pregnant women are applicable to pregnant women.

are breastfeeding.

**2.4.4 Passive smoking**

In the general population sleep duration has been declining. Women now occupy an increasingly prominent position in the workplace but often they do so without any reduction in their home responsibilities. Consequently sleep needs are often of low priority. Preterm birth is a major public health priority and is a common adverse outcome in pregnancy. Sleep quantity and quality are not only important determinants of maternal and foetal health but are also important for general health and need to be particularly addressed in the post-partum period where sleep disruption is likely to be very common. There is also some evidence to suggest that the effects of sleep deprivation may be greater in women than in men. Despite this, the majority of studies undertaken are in men and there is now a clear need for more, large, multicentre, prospective studies to be performed in women.

There is also a paucity of studies evaluating sleep disturbances in the post-partum period and research is required to look at the effects of sleep deprivation on both maternal and paternal functioning and the effect on maternal-infant interaction. Factors such as the type of delivery, the type of infant feeding, return-to-work time and infant temperament may be important, along with the degree of support from the father or other family members. A recent randomised trial set out to investigate if modification to the bedroom environment could improve the sleep of new parents (Lee & Gay, 2011). They evaluated a modified sleep hygiene intervention for new parents (infant proximity, noise masking, and dim lighting) in anticipation of night-time infant care in two samples of new mothers of different socioeconomic status. They were randomized to the experimental intervention or attention control, and sleep was assessed in late pregnancy and first 3 months postpartum using actigraphy and the General Sleep Disturbance Scale. The investigators observed that whilst the sleep hygiene strategies evaluated did not benefit the more socioeconomically advantaged women or their partners they did improve postpartum sleep among the less advantaged women suggesting that simple inexpensive changes to the bedroom environment can improve sleep for new mothers.

Further studies are required fully to investigate the effects of smoking on sleep and associated adverse pregnancy outcomes but meanwhile educational programmes could be used to educate women on the possible harmful effects. Research to determine if other health behaviours could have beneficial effects on sleep in pregnant women is also required. For example, physical activity is recommended to pregnant women for health benefits but as yet there are insufficient studies to determine if this has any effect on improving sleep duration or quality.

### **3. Conclusion**

A lack of sleep is known to affect both our physical and mental health. The few studies that have investigated sleep in pregnancy have found both an increase in total sleep time and an increase in daytime sleepiness in the first trimester whereas the third trimester appears to be associated with a decrease in sleep time and an increase in the number of awakenings. Sleep has an important impact on maternal and foetal health. It has been associated with an increased duration and pain perception in labour, with a higher rate of caesarean delivery and with preterm labour. Some pregnant women develop sleep disorders such as RLS or OSA or insomnia and others develop postpartum depression. Longitudinal studies are required to fully evaluate the effect of sleep deprivation on maternal and foetal outcome.

Sleep and Pregnancy: Sleep Deprivation,

Gynecol, Vol.88, pp. 797-800.

Rev, Vol.14, No.2, pp. 107-14.

Med, Vol.68, pp. 938-946

Vol.131, pp. 285-301

pp. d3649.

pp. 708–714

Sleep Disturbed Breathing and Sleep Disorders in Pregnancy 15

Cappuccio, F. P.; Stranges, S.; Kandala, N.-B.; Miller, M. A.; Taggart, F. M.; Kumari, M.;

Cappuccio, F. P., Taggart, F. M., Kandala, N.-B., Currie, A., Peile, E., Stranges, S., & Miller,

Cappuccio, F.P. & Miller, M.A. (2011a). Is prolonged lack of sleep associated with obesity?

Cappuccio, F.P.; Cooper, D.; D'Elia, L.; Strazzullo, P. & Miller, M.A. (2011b). Sleep duration

Carbonne B., Benachi A., Leveque M.L., Cabrol D., Papiemik E. (1996). Maternal position

Champagne, K.A.; Kimoff, R.J.; Barriga, P.C. & Schwartzman, K. (2010). Sleep disordered

Chang, J.J.; Pien, G.W.; Duntley, S.P. & Macones, G.A. (2010). Sleep deprivation during

Chappel L.C., Smith G.C.S. (2011). Should pregnant women sleep on their left? BMJ, Vol.342,

Dayan, J.; Creveuil, C.; Marks, M.N.; Conroy, S.; Herlicoviez, M.; Dreyfus, M. & Tordjman,

Evans, M.L.; Dick, M.J. & Clark, A.S. (1995). Sleep during the week before labor: relationships to labor outcomes. Clin Nurs Res.,Vol.4, No.3, pp. 238-249 Facco, F.L.; Kramer, J.; Ho, K.H.; Zee, P.C. & Grobman, W.A. (2010). Sleep disturbances in

Ferrie, J. E.; Shipley, M. J.; Cappuccio, F. P.; Brunner, E.; Miller, M. A.; Kumari, M. &

with mortality in the Whitehall II cohort. Sleep, Vol.30, No.12, pp. 1659-1666 Fluhr, H.; Krenzer, S.; Stein, G.M., et al. (2007). Interferon-gamma and tumor necrosis factor-

Freeman, D.J.; McManus, F.; Brown, E.A., et al. (2004). Short and long-term changes in

Gavin, N.I.; Gaynes, B.N.; Lohr, K.N.; Meltzer-Brody, S.; Gartlehner, G. & Swinson, T. (2005).

Goel, N.; Kim, H. & Lao, R.P. (2005). Gender differences in polysomnographic sleep in

young healthy sleepers. Chronobiol Int, Vol.22, No.5, pp. 905-915

The Whitehall II Study. Hypertension, Vol.50, No.4, pp. 694-701

adolescents and adults. Sleep, Vol.31, No.5, pp. 619-626

prospective studies. Eur Heart J,Vol.32, No.12, pp.1484-1492.

BMJ, Vol. 26, pp. 342:d3306. doi: 10.1136/bmj.d3306.

pregnancy. Obstet Gynecol. Vol.115, No.1, pp. 77-83

mediated apoptosis. J Cell Sci,Vol.120, pp. 4126–4133

Gynecol, Vol.106, No.5 Pt 1, pp. 1071-1083.

Ferrie, J. E.; Shipley, M. J.; Brunner, E. J., & Marmot, G. (2007). Gender-Specific Associations of Short Sleep Duration with Prevalent and Incident Hypertension.

M. A. (2008). Meta-analysis of short sleep duration and obesity in children,

predicts cardiovascular outcomes: a systematic review and meta-analysis of

during labor: effect on fetal oxygen saturation measured by pulse oximetry. Obstet

breathing in women of childbearing age & during pregnancy. Indian J Med Res,

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S. (2006). Prenatal depression, prenatal anxiety, and spontaneous preterm birth: A prospective cohort study among women with early and regular care. Psychosom

Marmot, M. G. (2007). A prospective study of change in sleep duration: associations

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plasma inflammatory markers associated with preeclampsia. Hypertension, Vol.44,

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Better methods to measure sleep disturbances in pregnancy are required along with evaluation of the underlying cause so that appropriate and effect treatment can be administered. Particular attention needs to be given to women who develop leg complaints, who are overweight or become obese during pregnancy or develop conditions such as diabetes or PIH.


**2.2. Mechanography**

The ruminal contractions were analyzed using the electronic tensometric recorder PIT 212 (COMT, Bialystok, Poland). The analysis of mechanograms and calculations of results were performed similarly as in a case of electromyographic recording [32]. The number of the rumen motor activity was determined by the frequency on mechanograms, with 5 min intervals before and after the DD40.


*IV. Typology*

The *Nakba* is an unbound and ongoing event of displacement. As its physical expression and material evidence, Dheisheh Refugee Camp represents the suffering of millions of Palestinians.

2 http://whc.unesco.org/archive/2008/whc08-32com-9e.pdf

Palestinian refugee camps remain a fundamental issue undermining peace between states, cultures, and religions in the region. The camp itself is the materialization of a crime and is in itself a question that calls for justice, land restitution and a change of power relations. In a moment in history in which sixty million refugees around the world are actively navigating identities defined by their exclusion from statehood, Dheisheh offers a historical perspective onto the contemporary condition of refugeehood and the culture of exile.

The perpetuation of legal exceptionality in Dheisheh has created a unique urban condition. The camp is not ephemeral, but it is not a city either. Refugees forced to live in this suspended condition have developed distinctive systems of civic management outside of state and municipal institutions. The camp exists in a limbo where fundamental juridical categories such as public and private do not and cannot exist. Despite the fact that refugees build their own homes and have lived in them for generations, they cannot technically own their house or the land it sits on. This has led to the development of an exceptional form of life in common: *al masha*. 3

The camp's inhabitants follow an underlying system of informal processes and interpersonal negotiations to make decisions concerning both individual and collective problems. These self-regulated means of conflict management and resolution did not emerge by choice, but rather in the absence of official mechanisms and as a reaction to decades of military and police violence. Constant internal debate—over building new houses, extending properties, encroaching onto pathways and alleys, closing streets for celebrations, etc.—has played a great role in shaping the camp.

The camp is subdivided by the inhabitants into different neighborhoods that maintain the name of their places of origin: Zakaria, Ras Abu Amara, Al Walajeh, Beit Jibrin, and Beit I'tab. Within the camp, there is great value placed on social capital. Norms that have helped deal with adversity over time, such as collective participation and the maintenance of social relations between families, are strongly respected. Networks of mutual support have emerged, such as the "economic safety net" set up by families originating from the village of Zakaria, who regularly pay a certain amount of money into a communal fund that can be accessed for accessing higher education.

3 As a term, *al masha* comes from the form of life that emerged during the Ottoman empire under the conditions in which people did not own the land but had the right to use it, to cultivate it together.

Photo: Luca Capuano with Carlo Favero.

### *VI. Associations*

Dheisheh is not only representative of the strength of millions who resisted annihilation and erasure from history through their immutable belief in the right of return, but it is also where we can understand the right of return as essentially the claim for the freedom of movement and the freedom to decide where to live. Refugees are forced to identify either with their village of origin or their site of exile. Yet how can one ask a young refugee born in a camp in Lebanon whether she is more Palestinian or Lebanese? The belief in the right of return opens a different political space that allows refugees to be multinational: Palestinian *and* Lebanese; Palestinian *and* Jordanian; Palestinian *and* Syrian, Palestinian *and* ... The aspiration for return is a civic form of cohabitation that is not based on ethnic, cultural, or religious division, but instead involves all states where exiled Palestinians live.

Palestinian refugee camps are the only space through which we can start to imagine and practice a political community beyond the idea of the nation-state. Refugee camps are by definition exceptional spaces, carved out from state sovereignty. Since their creation in 1949 and 1967, Palestinian refugee camps have been directly excluded by the creation of national boundaries. As the Outstanding Universal Value of a World Heritage property depends on its ability to "transcend national boundaries," Dheisheh transcends these boundaries through its lived reality of statelessness, refugeehood, and exile.

#### **3.1.c. Statement of Integrity**

The integrity of Dheisheh is marked by a consistent and purposeful act of collective refusal. From the very beginning, several actors have exercised their power to preserve the camp as it is. The camp therefore became a battlefield, where every transformation—from something as simple as opening a window to changing a roof—has served as a political statement about the right of return. Its integrity has been preserved not by freezing the development of the camp but rather by its transformation and continual opposition to normalization and resistance to settling (*tawtin*). Dheisheh's social fabric furthermore draws strength from its refusal to integrate into the urban life of Bethlehem. The camp is thus an architecture of exile; its reality is double. Dheisheh's existence is the material connection to other places: the place of origins.

#### **3.1.d. Statement of Authenticity**

The camp has an undisputable origin in the *Nakba* of 1948 and the forty-six villages families were relocated from. The original urban structure of the camp was a military-like grid adapted to the topography. Without municipal involvement and state governance, residents were largely left to determine the evolution of their urban environment according to the values they themselves willed. Over time, the grid has been modified, contested, and absorbed by the lives of its inhabitants. In adapting to urban conditions, unique systems of civic management were developed to preserve elements of the rural cultures residents brought with them.

In opposition to the city, Dheisheh has developed a unique spatial and social structure. It is an entirely distinct property system where refugees own the right to live in a house, but not the land itself. The high density of the camp gives it a similar feeling to a historic town center, with small alleys and tightly woven social relationships. The architecture of Dheisheh can be characterized as "low profile", in that any bold formal gesture is interpreted as a statement against the right of return. Dheisheh's basic materiality is constituted by cement blocks. The low cost and versatility of the material allowed refugees to replace UNRWA (United Nations Relief and Works Agency) shelters with more durable structures. The simplicity of the blocks enables the camp to maintain its form and design as both permanent and temporary. Always on the verge of being destroyed, Dheisheh's half-constructed, half-ruined form serves to oppose settlement and protect the right of return.

Photo: Luca Capuano with Carlo Favero.


**2.3. Micropropagation to produce sanitated plants**

Systemic buildup of infections particularly diseases (viral, bacterial and fungal) affect plant vigor and health. Unavailability of an efficient *in vitro* mass multiplication system in sugarcane is a major constraint in the provision of disease free elite germplasm [21]. Sugarcane has long breeding cycle and it requires 10–15 years to complete selection cycle. Fuzz multiplication rate of newly released sugarcane varieties is always slow 1:6–1:8 [22] and diseases accumulate in the seed sets during multiplication. Unavailability of disease free planting material is a major limitation in the improvement of sugarcane crop. Normally, sugarcane reproduces vegetatively but seed propagation is also there under particular climatic conditions [23]. Nodal cuttings are being used for the propagation of commercial sugarcane. In this method of multiplication, meristematic or non-meristematic tissues are used as explant. Sugarcane plants have been regenerated directly from apical and axillary meristems and also from immature leaf tissues [24].

*In vitro* propagation of sugarcane through meristematic tissues responded better as compared with other types of plant tissues. Therefore, significant efforts have been made to explore meristematic tissues for mass multiplication. In the beginning of twenty-first century, some reports highlighted direct regeneration of sugarcane genotypes through thin layer culture of cells from immature leaf or inflorescence [24]. They reported to lessen the time span required for *in vitro* propagation. Significant efforts have been made to establish protocols for direct or indirect sugarcane regeneration. Almost each part of the sugarcane plant has been exploited for callus induction but only inflorescence and immature leaves [25] responded better to morphogenic callus. Callus based regeneration gained significance with the prediction that *in-vitro* induced mutations can play some key role in sugarcane improvement [26]. *In vitro* induced variability is beneficial for the development of new varieties but it becomes undesirable when true-to-type plants are required. Only fewer examples have been quoted to highlight useful variations in callus-derived plants. Meristem culture was successfully used to eradicate chlorotic streak disease, sugarcane mosaic virus [27], white leaf disease and ratoon stunting disease. Combination of meristem culture and heat treatment have proved very effective to eradicate pathogens of Fiji disease [28], SCMV [27] and downy mildew. It is an effective method to eliminate most of the bacterial and fungal diseases and is commonly used to eradicate diseases of unknown etiology as well. Disease free planting material of sugarcane obtained from apices culture is now routinely used for the international exchange of this crop. Researchers have explored that plants regenerated from thin cell layer culture can be used to produce disease free sugarcane plants from the infected ones with *Leifsonia xyli*, SCMV and FDV. *In vitro* culture techniques are used in Brazil and USA to produce healthy planting material for commercial applications. Cryotherapy has also appeared as a proficient method to eliminate phytoplasma from the crop plants and has also been used for long term storage of germplasm or production of disease free plants [29].

#### **2.4. Germplasm conservation**

their approval or field establishment. Various high yielding, early maturing, high sucrose content and smut resistant varieties with good ratooning ability have also been developed

Somaclonal variation have been employed to improve cane-quality, sugar recovery, yield, drought tolerance and disease resistance. To increase the incidence of genetic variation and to get positive modifications in the target plant genome, physical (ion beams, gamma rays) and chemical (sodium azide, sodium nitrite and ethylmethane sulfonate (EMS) mutagens have been tested [15]. Introduction of selection pressure at cellular level has been successful to isolate mutants with desired characters. For fungal pathogen resistance inoculation with fungal pathotoxins or culture filtrates has been very effective. Somaclonal variants of sugarcane were developed against eye spot disease by Larkin and Scowcroft. Mutagenesis has been used by various researchers to isolate embryogenic cells and plants tolerant against red rot [16].

Similarly, for abiotic stress tolerance polyethylene glycol, mannitol and sodium chloride has been used for the selection of plants against drought/salinity tolerance [17]. Various studies were conducted to evaluate the level of variability and transmission of variations into the next generation by vegetative propagation. These studies verified the occurrence of considerable variations in *in-vitro* derived plants. However, extensive field experiments showed that tissue culture derived phenotypic variations were often temporary as most of the variants relapsed to the parental phenotype in the first ratoon crop [18]. Few other studies also supported somaclonal variations but to little extent. Chowdhury and Vasil [19] were not able to recognize any considerable variation in the DNA of plants regenerated from cell suspension, protoplasts and callus cultures. Taylor et al. [20] performed random amplified polymorphic DNA (RAPD) analyses of plants regenerated from embryogenic culture. Only a few polymorphisms were observed. Anyhow, there are different opinions about the somaclonal variations and their transmission to next generation. Most of the researchers are of the view that these variations depend upon the genetic makeup and experimental conditions under which plants are screened and selected.

Systemic buildup of infections particularly diseases (viral, bacterial and fungal) affect plant vigor and health. Unavailability of an efficient *in vitro* mass multiplication system in sugarcane is a major constraint in the provision of disease free elite germplasm [21]. Sugarcane has long breeding cycle and it requires 10–15 years to complete selection cycle. Fuzz multiplication rate of newly released sugarcane varieties is always slow 1:6–1:8 [22] and diseases accumulate in the seed sets during multiplication. Unavailability of disease free planting material is a major limitation in the improvement of sugarcane crop. Normally, sugarcane reproduces vegetatively but seed propagation is also there under particular climatic conditions [23]. Nodal cuttings are being used for the propagation of commercial sugarcane. In this method of multiplication, meristematic or non-meristematic tissues are used as explant. Sugarcane plants have been regenerated directly from apical and axillary meristems and also

through somatic embryogenesis.

**2.3. Micropropagation to produce sanitated plants**

from immature leaf tissues [24].

**2.2. Somaclonal variations**

116 Sugarcane - Technology and Research

Another important application of *in vitro* techniques that attracted researchers is germplasm conservation [30]. *In-vitro* storage of sugarcane germplasm had been established at the Centre de Cooperation Internationale en Recherche Agronomique pour le Development (CIRAD) in France, Sugarcane Breeding Institute in India, and BSES Limited (formerly the Bureau of Sugar Experiment Stations) in Australia. More than 200 hybrid clones of *Saccharum* spp. were preserved at 18°C for 12 months and no phenotypic modifications were observed in the recovered plants. However, with the advancements in tissue culture techniques, *in vitro* preservation became more valuable for the preservation of genetic resources especially of sugarcane [31]. The minimal medium used in *in vitro* preservation has been used successfully during short and medium term preservation, especially for meristems and shoot apices. Decline in explants metabolic activity is usually achieved by changing physical environment or composition of the media used [32]. The commonly used approaches are: lowering of incubation temperature and use of osmotically active compounds such as sorbitol, mannitol and sucrose. Moreover, growth inhibitors like abscisic acid (ABA) is also frequently used. Various factors i.e. vitamins, salts, osmotic stress and others have been explored by different researchers. Survival rate varied in all these experiments but nobody exploited genetic or cytological studies to assess the genetic stability of *in vitro* plants. For diploid species, Simple Sequence Repeat (SSR), Amplified Fragment Length Polymorphism (AFLP) and Inter-Simple Sequence Repeat (ISSR) have been used successfully to assess genetic stability of *in-vitro* plants [33]. But, for plants like sugarcane which has complex polyploid genome, these tools are inappropriate as interpretation of the results become tricky [34]. Using microscopic techniques for sugarcane is also difficult because of small size and large number of chromosomes and also due to the presence of various cytotypes [35]. In this context flow cytometry has got attraction as it ensures estimation of relative amounts of plants nuclear DNA quickly and precisely [36]. Cytometry is able to discriminate between plants derived different culture techniques and has extensively been used, in many economically important species such as *Gossypium hirsutum*, *Vitis vinifera*, *Passiflora* spp., *Elaeis guineensis*, *Musa acuminata* and *Prunus cerasus* [37]. Flow cytometric analysis of shoots was performed after every 6 months of storage. As a consequence, a discrete behavior of tested varieties was observed during storage and on average approximately 80% cultures were able to recover. From these findings it is concluded sugarcane genotypes can be maintained in minimal growth condition for extensive periods but may lead to genetic variations.

between coding genes strongly support the extension of genome in grasses. Transposons and retrotransposons are two categories of transposable elements. In plants, the most abundant retroelements are LTR (long terminal repeats) retrotransposons. Transposase proteins are involved in insertion-deletion mechanisms. Active sites of the transcription control the movement of retrotransposons, which reinsert them into the genome after each propagation cycle to increase copy number. Recent studies show that there exists a gene remodeling mechanism which results in the generation of new genes. As a result of gene remodeling, gene expression is altered by new regulatory networks [41]. The study of transposable elements in wheat and barley [42] provided close relationship of transposable elements with genome structure. The transposable elements in sugarcane can be activated and evaluated by functional transcriptomic approaches. The major limitation in sugarcane genetic improvement is its genome size. To sequence the genome of an organism Bacterial Artificial Chromosomes (BAC) are used. BAC (Bacterial Artificial Chromosomes) library was constructed with Hin*d*III partial digestion for sugarcane cultivar 'R570' having more than 100,000 clones with 130 mega base pairs (Mb) insert size [43]. For map-based cloning of sugarcane, BAC resources will be highly esteemed and physical map of sorghum (http://www.genome.clemson.edu/tools/contig\_viewer/index.

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Transcriptomic approaches have emerged as an effective tool for functional characterization of unknown genes. In combination with proteomics and metabolomics, these approaches are very useful for the development of improved sugarcane clones. It reduces the complexity of data and targets. Only active genes in the cell or tissues are considered at the time of sampling. By employing transcriptomic approaches, one can easily compare similar type of tissues at different developmental stages in different organisms growing in different conditions [44].

Due to large size and complexity of genome, the whole genome sequence of sugarcane was not available. The genome size of its modern cultivar is considered to be more than 10 GB. From 12th July, 2017, NCBI database has 83,138 GSSs (genome survey sequences), 285,216 ESTs (expressed sequence tags) and 13,382 nucleotide sequences including 491 sequences of mRNA under the search of "*Saccharum*". There are three main groups of ESTs including a large group resulting from a modern variety of sugarcane and two small groups from *Saccharum officinarum* and *Saccharum arundinaceum* (**Table 1**). Majority of ESTs belong to six cultivars from different countries including Australia (Q117), USA (CP72-2086), India (CoS 767, Co 1148) and Brazil (SP80-3280, SP70-1143). Most of the ESTs are from mixed tissue samples of Brazilian varieties i.e. P57150-4 x PB5211 or SP83-5077, RB80-5028; SP80-87432, RB855205, CB47-89, RB845298,

Many projects have been executed for sequencing sugarcane ESTs (expressed sequence tags) in Brazil (http://sucest.lad.ic.unicamp.br/en), South Africa and Australia [46]. Until now more than 0.3 million (300,000) ESTs have been generated. A database holding 0.238 million (238,000) ESTs (constructed from diverse organs and tissues) from 37 libraries was erected by

SP803280 x SP81-5441, SP80-185, SP80-3280 and SP87-396 [45].

html) will be used as complementary tool.

**3.2. Transcriptomics**

**3.3. ESTs**