**Charlotte Cambier 1,\*, Waldo Galle 1,2 and Niels De Temmerman 1**

Received: 30 June 2020; Accepted: 12 August 2020; Published: 18 August 2020

**Abstract:** To support the construction sector in its transition to a circular economy, many design instruments and decision support tools have been and are still being developed. This development is uncoordinated and raises confusion among building designers and advising engineers, slowing down the tools' adoption in practice. Moreover, it is unclear if the available design tools are able to fulfil the needs of design professionals at all. Therefore, this research identifies the knowledge challenges for the "supply and demand" of design tools for a circular construction practice. It focuses on Flanders, given the importance the topic receives in the region's policy programme and among practitioners. This study builds on a thorough literature review, and on inventorying and categorising instruments and ongoing developments. By comparing that review with the needs that were identified during interviews with a focus group, it was possible to pinpoint designers' needs for support tools and outline three urgent research tracks. More generally, it was found that the needs of our focus group are only partially reflected by the available design tools and the ongoing developments. This identified mismatch advocates for a more participatory and practice-oriented research approach when developing design support tools for circular building.

**Keywords:** design for circularity; design support tools; circular construction; circular economy


**3. Laboratory and other diagnostic tests**

Sputum examination is one of the best ways of differentiating bacterial pneumonia from pulmonary infarction. In bacterial pneumonia the sputum classically is purulent, occasionally foul smelling and may contain bright red fleck of blood. Gram's stain typically shows many bacteria and polymorphonuclear leukocytes. In pulmonary infarction, sputum, when present, usually is frankly blood with few bacteria or inflammatory cells. If the infarct becomes infected the sputum may be indistinguishable from that in bacterial pneumonia. Blood cultures often reveal the causative microorganism in the patients with bacterial pneumonia but show no growth in cases of bland pulmonary infarction (8).

Cavitation after bland pulmonary infarcts may result from either aseptic necrosis of the infracted lung or from secondary bacterial infection with subsequent abscess formation. It is infective almost as often as it is aseptic (9).

Two types of infected pulmonary infarct have been proposed based on the mode by which infection sets in (10). One is called "primary" because the infection is from a septic embolus. The other is called "secondary" because the infection is bronchigenic origin. Some authors suggest that the development of fever and/or purulent sputum following a pulmonary infarct is highly suspicious for secondary infection. The spectrum of causative agents for infected pulmonary infarct is similar to that of nosocomial pneumonia (3).

Total leukocyte count has limited discriminatory value. It usually is normal or slightly elevated in pulmonary infarction, but there is reports of leukocytes count higher than 40 000 per mm3 in patients with massive, bland necrosis of pulmonary tissue. Elevated serum lactic dehydrogenase (LDH) activity, normal aspartate aminotranspherase activity (AST) and increased serum bilirubin concentration forms a triad once considered a sensitive indicators of pulmonary embolism and infarction. However, subsequent studies have shown that these tests fail to differentiate pulmonary infarction from pneumonia and host of other disorders (8).

Electrocardiographic abnormalities that may appear are right ventricular conduction disturbances; right axis deviation; inverted T-waves with S-T segment deviation in the right precordial leads; peaked T-waves in leads II, III and AVF; various types of supraventricular and raraly ventricular arrhythmias and S1, Q3 or S1,S2, S3 patterns. Heart ultrasound may reveals right ventricular dilatation, septal deviation of left ventricle, tricuspidal regurgitation or right ventricle hypokinesis with wall thinning (8, 11).

Pulmonary function test and arterial blood gas studies provide data that are too variable and nonspecific to differentiate bacterial pneumonia from pulmonary infarction (8).


**Analysis of Online Conversations for Giving Sense to Sustainable Tourism in the Adriatic-Ionian Region to Sustainable Tourism in the Adriatic-Ionian Region**

**Analysis of Online Conversations for Giving Sense**

DOI: 10.5772/intechopen.70371

Gian Luigi Corinto and Fabio Curzi Gian Luigi Corinto and Fabio Curzi Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.70371

#### **Abstract**

[25] Davis RC, Marvin GR. Venice, the Tourist Maze: A Cultural Critique of the world's most Touristed City. Berkeley-Los Angeles-London: University of California Press; 2004 [26] Comune di Venezia. Annuario del Turismo 2015-Città di Venezia. Comune di Venezia,

[27] Razzini A.Venice port activities and the challenges of safeguarding Venice. In: Fletcher CA, Spencer T, editors. Flooding and Environmental Challenges for Venice and its Lagoon: State of Knowledge. Cambridge, UK: Cambridge University Press; 2005. pp. 263-265

[28] Terranova G, Citron M, Parolin A. The Port of Venice case study: Voluntary agreements to reduce air pollution from cruise ships. In: 2015 GreenPort Cruise Conference; October

[29] Moufakkir O, Burns PM, editors. Controversies in Tourism. Wallingford, UK: CABI; 2012 [30] Carić H, Mackelworth P. Cruise tourism environmental impacts - the perspective from

the Adriatic Sea. Ocean & Coastal Management. 2014;**102**:350-363

CPM Centro Produzione Multimediale; 2016

106 Mobilities, Tourism and Travel Behavior - Contexts and Boundaries

2015; Copenhagen; 2015

The role of online conversation analysis on tourism and sustainability is underrated, especially in policymaking and management of sustainability of tourist destinations. The paper reports an analysis of online conversations retrieved from Twitter during the 2016 peak season, referring to four main destinations located in the Adriatic-Ionian region. The focus is analyzing the meaning of the expression "sustainable tourism" as emerging from online texting. Findings are that private users do not talk about sustainability and features of sustainable tourism while using Twitter, enforcing the idea that sustainable tourism has popular "meaning" and "appeal" possibly different from scientific approach. Users tell exclusively on leisure features of destinations, and public bodies neglect the opportunity of using Twitter for image building and web listening. Private companies, public administrators, and policymakers should benefit from the exposed procedures for online conversation analyses in designing and organizing their respective tasks. Researchers and destination managers would be also interested in the existing divide between official documents and statements on sustainability and sustainable tourism and reality of popular perception of the issue.

**Keywords:** Adriatic-Ionian region, online conversations, sustainable tourism, text analysis, Blue Flag criteria


**5. Application of dNAD**

Compared to conventional NA detection methods, dNAD provides better sensitivity, better precision, higher tolerance, and the NA's absolute quantification. Until now, dNAD has been applied to a variety of research fields, including pathogen detection, food safety, clinical diagnosis (genetic instability estimation and early cancer), prenatal diagnosis, quantitative analysis of gene expression, and NGS library quantification. Although dPCR is still the most widespread type of dNAD, in resource-limited regions, it is confined due to the requirement of thermal cycling and robust temperature control. To overcome this awkwardness, dINAAs without thermal cycling are of great interest, which also enlarge the application of dNAD, especially for POCT. For this subchapter, the recent advances on application of dNAD will be narrated.

#### **5.1. Pathogen detection**

Honestly speaking, on pathogen detection, the advantages of most conventional NADs on both analytical sensitivity and specificity are inherited by the corresponding digital formats. In addition, dNAD has the capability of realizing NA's absolute quantification. Therefore, dNAD can be used as the ultrahigh sensitivity and more accurate method for viral load determination or bacterial quantification. Kelley et al. established a duplex ddPCR assay for high-precision methicillin-resistant *Staphylococcus aureus* (MRSA) analysis [76]. By assaying 397 clinical samples, a good agreement with the reference assay for both qPCR and ddPCR assays was indicated. Strain et al. demonstrated and estimated the application of ddPCR for a highly precise measurement of HIV DNA [77]. Total HIV DNA and episomal 2-LTR (long terminal repeat) circles in cells that were all isolated from infected patients were targeted. Compared to qPCR, ddPCR performed a significantly increased precision (5-fold for total HIV DNA and >20-fold for 2-LTR circles), making it an alternative for the measurement of HIV DNA from clinical specimens.

dNAD also enables the direct detection without NA extraction due to the ability of partitioning target NA and nontarget components (e.g., inhibitors) into different microwells. Pavšič et al. employed two dPCR platforms (QX100 ddPCR system from Bio-Rad Laboratories and the BioMark HD IFC cdPCR system from Fluidigm) for the direct quantification of two wholevirus materials of human cytomegalovirus (HCMV) without DNA extraction [78]. It was demonstrated that direct quantification by both dPCRs could provide repeatable measure‐ ments of viral DNA copy numbers, giving a closer agreement with the actual viral load than that with either dPCR or qPCR of extracted DNA.

Although dNAD certainly possesses the superiority of absolute quantitation, some reports fail to demonstrate the advantage, which calls for the requirement of optimization when estab‐ lishing dNAD. For instance, Boizeau et al. used ddPCR to provide an absolute quantitation of HBV genome molecules [79]. However, the results indicated that qPCR assays remained more sensitive than ddPCR when used for low HBV DNA levels, suggesting that optimization of ddPCR was still necessary, especially on accurately differentiating the positive from negative in samples with very low levels of target DNA molecules.

#### **5.2. Food safety**

If the precision of cdNAD is defined as the minimum difference in concentration (∆*λ*/*λ*) that is reliably detected with more than 99% true positive and more than 99% true negative rate, this situation corresponds to 4.6*σ* separation in the mean (*μ*) for two Gaussian distributions. That is to say, in the case with small ∆*λ*, ∆*μ*/∆*λ*=4.6*σ*. Then, ∂[*N*(1-*e* -*λ*)]∆*λ*/∂*λ*=*Ne* -*λ*∆*λ*=4.6[*Ne λ* (1-*e*-*λ*)]1/2, and ∆*λ*/*λ*=4.6(*e λ*-1)1/2/(*λN* 1/2). For different total chamber numbers (*N*) in chip panel,

Compared to conventional NA detection methods, dNAD provides better sensitivity, better precision, higher tolerance, and the NA's absolute quantification. Until now, dNAD has been applied to a variety of research fields, including pathogen detection, food safety, clinical diagnosis (genetic instability estimation and early cancer), prenatal diagnosis, quantitative analysis of gene expression, and NGS library quantification. Although dPCR is still the most widespread type of dNAD, in resource-limited regions, it is confined due to the requirement of thermal cycling and robust temperature control. To overcome this awkwardness, dINAAs without thermal cycling are of great interest, which also enlarge the application of dNAD, especially for POCT. For this subchapter, the recent advances on application of dNAD will be

Honestly speaking, on pathogen detection, the advantages of most conventional NADs on both analytical sensitivity and specificity are inherited by the corresponding digital formats. In addition, dNAD has the capability of realizing NA's absolute quantification. Therefore, dNAD can be used as the ultrahigh sensitivity and more accurate method for viral load determination or bacterial quantification. Kelley et al. established a duplex ddPCR assay for high-precision methicillin-resistant *Staphylococcus aureus* (MRSA) analysis [76]. By assaying 397 clinical samples, a good agreement with the reference assay for both qPCR and ddPCR assays was indicated. Strain et al. demonstrated and estimated the application of ddPCR for a highly precise measurement of HIV DNA [77]. Total HIV DNA and episomal 2-LTR (long terminal repeat) circles in cells that were all isolated from infected patients were targeted. Compared to qPCR, ddPCR performed a significantly increased precision (5-fold for total HIV DNA and >20-fold for 2-LTR circles), making it an alternative for the measurement of HIV DNA from

dNAD also enables the direct detection without NA extraction due to the ability of partitioning target NA and nontarget components (e.g., inhibitors) into different microwells. Pavšič et al. employed two dPCR platforms (QX100 ddPCR system from Bio-Rad Laboratories and the BioMark HD IFC cdPCR system from Fluidigm) for the direct quantification of two wholevirus materials of human cytomegalovirus (HCMV) without DNA extraction [78]. It was demonstrated that direct quantification by both dPCRs could provide repeatable measure‐

the precision (∆*λ*/*λ*) to expected molecules per chamber (*λ*) could be plotted.

**5. Application of dNAD**

142 Lab-on-a-Chip Fabrication and Application

narrated.

**5.1. Pathogen detection**

clinical specimens.

Food safety mainly refers to two parts: the minoring of foodborne pathogens and the detection of GMO. For example, human noroviruses (NoV) and hepatitis A virus (HAV) are two foodborne enteric viruses that have caused the vast majority of nonbacterial gastroenteritis or some fatal infectious hepatitis. Coudray-Meunier et al. conducted a comparative study of IFC RT-cdPCR and conventional RT-qPCR when quantifying the NoV and HAV from lettuce and water samples, proving that the IFC RT-cdPCR assay was more tolerant to inhibitory sub‐ stances from lettuce samples [80]. Also, the IFC RT-cdPCR may be useful for standardizing the quantification of enteric viruses in bottled water and lettuce samples. Fu et al. used the BioMark HD system equipped with a 48.770 digital array to develop cdPCR for GMO detection without pretreatment [81]. The CaMV35s promoter and the NOS terminator were selected as the targets, and nine events of GMOs (MON810, MON863, TC1507, MIR604, MIR162, GA21, T25, NK603, and Bt176) were collected to determine the specificity. The results showed that the cdPCR could achieve a discrimination of down to 0.1%, lower than the labeling threshold level of the EU, allowing highly sensitive, specific, and stable GMO screening detection. Dalmira et al. developed a duplex ddPCR assay to characterize the certified reference materials (CRMs) in terms of T-*nos*/*hmg* copy number ratio in maize [82]. After optimization using a central composite design, the duplex ddPCR method realized the absolute limit of detection (LOD) and limit of quantification (LOQ) of 11 and 23 copy number *T*-*nos*, namely, relative LOD of 0.034% and relative LOQ of 0.08%, respectively. The dynamic range of T-*nos*/*hmg* ratio ranged from 0.08% to 100%. The results indicated that the duplex ddPCR assay was useful for characterizing CRM candidates on T-*nos*/*hmg* ratio.

The bias caused by reliance on quantitative standards may have an impact on the results of qPCR, which is not beneficial for water monitoring and microbial source identification. Therefore, Cao et al. employed a duplex ddPCR to simultaneously quantify *Enterococcus* spp. and the human fecal-associated HF183 marker for evaluating the water quality [83]. The results demonstrated that ddPCR performed greater tolerance of inhibition than qPCR, with one to two orders of magnitude higher at inhibitor concentrations. Also, ddPCR brought about remarkably improved precision, although a lower upper LOQ than qPCR was indicated.

For food safety, it is indispensable to identify and quantify the meat products for unveiling species fraud and product mislabeling during food processing. Tian et al. used LTNP cdPCR to detect bovine meat in ovine meat [72]. Floren et al. successfully applied two-step ddPCR for precise quantification of cattle, horse, and pig in processed meat product, with the nuclear *F2* gene targeted [84].

#### **5.3. Clinical diagnosis**

At present, clinical diagnosis including genetic instability estimation and early cancer is also the main application field for dNAD. It has been clearly confirmed that the genetic instability of human cells is one of the causes of cancer, including somatic mutation, allelic imbalance, loss of heterozygosity, CNVs, and single nucleotide variations (SNVs). Accordingly, how to discriminate the rare mutant gene from abundant normal NAs attracts great concerns of researchers. Interestingly, it is also the question that initiates the concept formation of dNAD.

As *de novo* CNV may be caused by reprogramming somatic cells into induced pluripotent stem cells, Abyzov et al. used qPCR and ddPCR to detect and estimate this phenomenon. The results showed that, in parental fibroblasts, at least half of the CNVs are indicated as low-frequency somatic genomic variants [85]. Boettger et al. successfully applied a ddPCR approach to analyze father-mother-offspring trios from HapMap at specific sites within region 1 on the investigation of inference of complex CNV and single nucleotide polymorphism (SNP) haplotypes at the human 17q21.31 locus [86].

Detecting biomarkers associated with tumor formation, development, and drug evaluations on gene expression is the useful approach for early cancer diagnosis. Up to now, various biomarkers have been identified, and dNAD reflects the unique advantage of absolute quantitation of their gene expression [87]. Zhu et al. applied SPC cdPCR to the detection of three lung cancer-related genes (PLAU, ENO2, and PLAT). cdPCR yielded comparable results to qPCR, illustrating that the established platform had the ability of realizing absolute quantitation for gene expression [30]. Floren et al. employed ddPCR to detect the BRAF-V600E and V600K mutations in melanoma circulating tumor with high sensitivity [84]. The study demonstrated that ddPCR performed 200-fold increased sensitivity than competitive allelespecific PCR (castPCR), giving an LOD of 0.0005% when combined with whole-genome amplification (WGA). Through noninvasive analysis of circulating free plasma DNA, Geven‐ sleben et al. determined the presence of oncogenic amplification by developing a plasma DNA ddPCR assay targeting HER2 [88]. In the independent validation cohort, ddPCR could reach a positive and negative predictive value of 70% and 92%, respectively. The results suggested that ddPCR had the potential to the analysis of any locus amplified in cancer, not only in metastatic breast cancer. Beaver et al. also employed a ddPCR assay for the detection of circulating plasma tumor DNA (ptDNA) in patients with early-stage cancer [89]. A total of 30 tumors were first analyzed by Sanger sequencing for common PIK3CA mutations, and ddPCR was then used to analyze their extracted DNA for the same mutations. This ddPCR-based accurate mutation detection platform was demonstrated to be of great use for early-stage breast cancer.

As a new generation of cancer biomarkers, abnormally DNA methylation in the gene's regulatory regions can affect identical residues that may cause the cancer. The analysis of methylated genes therefore becomes more and more important in cancer research. For example, Li et al. developed a sensitive bead-based ddPCR for the quantification of DNA methylation, which could detect down to one methylated DNA molecule in approximately 5000 unmethylated DNA molecules from plasma or fecal samples [20]. Weisenberger et al. developed an improved DNA methylation detection with single-molecule high-resolution based on IFC cdPCR and successfully identified the breast cancer-specific hypermethylation phenomenon in the CpG islands of RUNX3, CLDN5, and FOXE1 [90].

#### **5.4. Prenatal diagnosis**

precise quantification of cattle, horse, and pig in processed meat product, with the nuclear *F2*

At present, clinical diagnosis including genetic instability estimation and early cancer is also the main application field for dNAD. It has been clearly confirmed that the genetic instability of human cells is one of the causes of cancer, including somatic mutation, allelic imbalance, loss of heterozygosity, CNVs, and single nucleotide variations (SNVs). Accordingly, how to discriminate the rare mutant gene from abundant normal NAs attracts great concerns of researchers. Interestingly, it is also the question that initiates the concept formation of dNAD. As *de novo* CNV may be caused by reprogramming somatic cells into induced pluripotent stem cells, Abyzov et al. used qPCR and ddPCR to detect and estimate this phenomenon. The results showed that, in parental fibroblasts, at least half of the CNVs are indicated as low-frequency somatic genomic variants [85]. Boettger et al. successfully applied a ddPCR approach to analyze father-mother-offspring trios from HapMap at specific sites within region 1 on the investigation of inference of complex CNV and single nucleotide polymorphism (SNP)

Detecting biomarkers associated with tumor formation, development, and drug evaluations on gene expression is the useful approach for early cancer diagnosis. Up to now, various biomarkers have been identified, and dNAD reflects the unique advantage of absolute quantitation of their gene expression [87]. Zhu et al. applied SPC cdPCR to the detection of three lung cancer-related genes (PLAU, ENO2, and PLAT). cdPCR yielded comparable results to qPCR, illustrating that the established platform had the ability of realizing absolute quantitation for gene expression [30]. Floren et al. employed ddPCR to detect the BRAF-V600E and V600K mutations in melanoma circulating tumor with high sensitivity [84]. The study demonstrated that ddPCR performed 200-fold increased sensitivity than competitive allelespecific PCR (castPCR), giving an LOD of 0.0005% when combined with whole-genome amplification (WGA). Through noninvasive analysis of circulating free plasma DNA, Geven‐ sleben et al. determined the presence of oncogenic amplification by developing a plasma DNA ddPCR assay targeting HER2 [88]. In the independent validation cohort, ddPCR could reach a positive and negative predictive value of 70% and 92%, respectively. The results suggested that ddPCR had the potential to the analysis of any locus amplified in cancer, not only in metastatic breast cancer. Beaver et al. also employed a ddPCR assay for the detection of circulating plasma tumor DNA (ptDNA) in patients with early-stage cancer [89]. A total of 30 tumors were first analyzed by Sanger sequencing for common PIK3CA mutations, and ddPCR was then used to analyze their extracted DNA for the same mutations. This ddPCR-based accurate mutation detection platform was demonstrated to be of great use for early-stage breast

As a new generation of cancer biomarkers, abnormally DNA methylation in the gene's regulatory regions can affect identical residues that may cause the cancer. The analysis of methylated genes therefore becomes more and more important in cancer research. For example, Li et al. developed a sensitive bead-based ddPCR for the quantification of DNA

gene targeted [84].

cancer.

**5.3. Clinical diagnosis**

144 Lab-on-a-Chip Fabrication and Application

haplotypes at the human 17q21.31 locus [86].

Prenatal diagnosis is usually carried out by invasive or noninvasive approaches [91]. The invasive method (e.g., amniocentesis) refers to inserting needles into the uterus, which is timeconsuming (several weeks required) and risky to the fetus [92]. In contrast, noninvasive method seems to be more rapid and safer. Currently, noninvasive prenatal diagnosis mainly involves ultrasonography of the womb or detecting cell-free fetal DNA (cffDNA) in maternal serum and plasma. The latter is also termed as noninvasive prenatal testing (NIPT). Appling dNAD to NIPT is the emerging noninvasive approach with high sensitivity and high precision [93–97]. Gu et al. employed the QX100 ddPCR system from Bio-Rad Laboratories to detect cffDNA for the risk of methylmalonic acidemia, confirming that ddPCR is a cost-effective and noninvasive prenatal method when diagnosing known mutations associated with Mendelian disorders [98]. Pornprasert and Prasing implemented a ddPCR for the deletion of α(0) thalassemia Southeast Asian (SEA)-type deletion [99]. The study showed that ddPCR might be an alternative technology to routine clinical diagnosis. Barrett et al. adopted 12×765 digital array chips to establish an IFC cdPCR to analyze the cffDNA for NIPT of sickle cell anemia [94]. The results suggested that the built IFC cdPCR is a useful method to determine the genotype of fetuses at risk for sickle cell anemia. Meantime, the report also illustrated that it was essential to optimize the fractional fetal DNA concentration.

Because most cffDNA fragments were approximately 200 bp in size and, in the early gestation, the cffDNA occupies low percentage (mostly <10%) in maternal plasma, efficient methods for the extraction of cffDNA are in great need. Holmberg et al. thereby estimated two commercial platforms to extract cffDNA: the Akonni Biosystems TruTip technology and the Circulating Nucleic Acids Kit from Qiagen [100]. Determined by QX100 ddPCR system and qPCR, the extracted products from two platforms performed similar results.

#### **5.5. NGS library quantification**

As known to all, the establishment of NGS libraries still leans mainly on manual bench-top procedures, which is slow and inefficient [101]. To solve it, Kim et al. invented an automated digital microfluidic LOC-based sample preparation for the NGS. Compared to the conven‐ tional methods, digital microfluidic LOC platform is cost-efficient and has high throughout [102]. Similarly, Thaitrong et al. integrated a droplet-based microfluidic LOC system with a unit of capillary-based reagent delivery and the quantitative CE module to develop an automated quality-control platform for NGS [103]. Besides, White et al. confirmed that dPCR is able to provide sensitive and absolute calibration for NGS, enabling direct sequencing without titration runs and with sufficient precision [11]. Fu et al. developed a picoliter-scaled droplet digital WGA (ddWGA) platform for realizing uniform and accurate single-cell sequencing, bringing about significantly improved amplification evenness and accuracy for the simultaneous detection of CNVs and SNVs in single-cell level [104]. Weisenberger et al. applied the Fluidigm BioMark Digital Array to establish digital bisulfite genomic DNA sequencing with high resolution and high sensitivity [105]. The results showed that IFC cdPCR was a fast and reliable method for the single-molecule-scaled detection of DNA methylation information.


**1. Introduction**

Konzo is a permanent and non-progressive paralytic disease that affects thousands of children and women of child-bearing age among millions of people who rely on cassava as their main source of food, mainly in Sub-Saharan Africa [1]. We recently showed that cognition may also be affected and subtle or pre-clinical forms of the paralytic disease may exist. Thus, the global burden of the disease may therefore have been underestimated, which raises serious concerns for the public health of millions of people for whom cassava is the main subsistence crop [2, 3].

The mechanisms underlying konzo remain unclear, although epidemiological studies have consistently shown an association between the occurrence of konzo and chronic dietary reliance on foodstuffs from insufficiently processed bitter cassava, with poor protein intake. Our recent studies suggest that disease development may be mediated through oxidative damage, findings that appear to be consistent with the putative effects of cyanide intoxication and/or chronic undernutrition [4]. Konzo is a permanent and irreversible condition with no treatment available. Improved processing methods to remove cyanogens from cassava prior to human consumption and enhancement of human cyanide detoxification capabilities perhaps through dietary supplementation may be critical to the prevention of the disease [5]. However, because of the chronic and heavy dietary reliance on bitter cassava as the main food source and the potential for continuous exposure to residual amounts of cyanogens due to variations in processing methods, chronic low-dose exposure to cyanide may persist, which may, possibly, lead to oxidative damage and neurocognitive deficits. It is therefore important that preventive measures are embedded in daily food practices and dietary habits to avoid the unnecessary burden of toxicity related to cyanide. The promotion of traditional or ethnic foods with potential health benefits may be useful in konzo-affected areas.

and some minerals and vitamins (vitamin C). The roots are a poor source of lipids and proteins. Manihot leaves contained anthocyanins, flavonoids and other polyphenols. All parts of the plant contained the cyanogenic glycosides (linamarin and lotaustralin) that constitute the

Traditional Foods as Putative Sources of Antioxidants with Health Benefits in Konzo

http://dx.doi.org/10.5772/intechopen.74523

119

In DR Congo, the dependence on cassava is particularly strong and it is estimated that cassava (*Manihot esculenta*) is "all good enough" for the Congolese people because they receive "the

Cassava contains cyanogenic glucosides (linamarin and lotaustralin) that are released as hydrogen cyanide, which are thought to protect the plants from insects and other animals. For human consumption, the plants need to be detoxified, usually by soaking, drying in the sun, boiling, fermentation, or grating with roasting. These processes allow the cyanogenic glucosides to be released, but depend upon traditional practices, time taken, and the availability of water. Major food crises following drought or war are the cause of konzo. In these situations, the traditional systems of processing cassava roots into flour and other derived products are completely modified by: (i) The reduction of cassava retting time that is achieved not in the river as practiced in traditional methods but within households in closed containers (ii) Reducing the drying time of roasted cassava, …(iii) Drying of cosettes or roasted cassava under a wood fire [8]. These changes in cassava root transformation expose the population to cyanide intoxication through the consumption of flour and other by-products with cyanide levels that exceed the WHO standards (maximum 10 parts per million: ppm). A 2011 survey of 123 households in Kahemba showed that the average cyanide level in cassava flour was 92.2 ± 56.2 ppm [9]. Neurotoxicity is associated with incompletely detoxified cassava, although the exact mechanisms by which these compounds cause neurological damage is unclear. Two neurological conditions are mainly associated with bitter cassava: a myeloneuropathy and konzo. The myeloneuropathy called tropical ataxic neuropathy (TAN) manifests as a slowly evolving bilateral sensory polyneuropathy, optic atrophy and sensorineural deafness, and sensory ataxia, is seen in adults (particularly elderly) who have a solely cassava diet. The toxicity of cyanide is reduced by its transformation to thiocyanate or cyanate, which requires sulfur donors, often limited in malnutrition. However, it has been shown that oxidative damage plays a crucial role in the pathogenesis of konzo [10].

antinutrient factors [7, 8].

bread of the roots and the meat of the leaves [7].

**Figure 1.** Leaves and roots of cassava (*Manihot esculenta*).

In this chapter, we report findings from a survey of food consumption and a subsequent phytochemical composition of relevant foods, aiming to identify foods with interesting antioxidant properties that could be used as functional foods or nutraceuticals in the prevention of chronic cassava cyanogenic poisoning, including konzo.