**6. Concluding remarks from a systems biology perspective**

The dynamic interactions between environmental factors and epigenetic mechanisms that involve multiple pathways and processes suggest the need for a system-based approach to understand MS physiopathology and to implement new pharmacological therapies.

Targeting neuroprotection is always ambitious, not only in MS, but in neurology in general, mostly because of a poor understanding of the complexity of interconnections between different cellular and molecular processes. In complex diseases such as MS there is a milieu of dynamical interplay between networks of genes and signaling proteins, lipids, carbohydrate molecules that can have concomitant roles in inflammation, immune systems reactivity, demyelination, neurodegeneration, neuroprotection, remyelination. For example, the network of p38 mitogen-activated protein kinase (MAPK) signaling pathway can trigger both inflam‐ mation and neuroprotection. MAPK is activated by cell stress, playing a key role in immune responses and has been intensively investigated in relation with EAE pathogenesis [102]. Taking in account this multitude of interactions, the currently trend is to inhibit/potentiate selectively a single molecular pathway, for example, acting only on p38α MAPK and not also on p38β MAPK [103].

However, over-selective interventions have an important disadvantage. Imbalances in complex systems always affect concomitant different subsystems between which there is a significant cross-talk. This leads to several pathological outcomes, for example, to inflamma‐ tion, demyelination, and neurodegeneration which potentiate each other, so targeting a single pathway seems senseless. Additionally, some of these processes occur as compensatory mechanisms and become maladaptive and trigger the emergence and expansion of vicious circles due to the alteration of modulatory mechanisms. For example, in a demyelinated axon, homeostatic plasticity that involves the redistribution of ion channels occurs, and this redis‐ tribution contributes to the failure of AP conduction and finally generates a metabolic crisis. Intercorrelation between the molecular mechanisms that underlie inflammation, apoptosis, oxidative stress, increased Ca2+ load, mitochondrial dysfunction, microglial activation, and blood–brain barrier dysfunction is responsible for the expansion of vicious circles that generate a nonlinear pattern of clinical evolution. From this perspective, the traditional idea of a "magic bullet" seems too simplistic to achieve sufficient neuroprotection.

An interesting explanation of these mechanisms derives from the theory of complex biological systems, which are characterized by criticality and degeneracy. Degeneracy describes the ability of structurally and functionally distinct pathways to produce the same output. This characteristic supports the existence of multifunctional components that can perform similar functions under certain conditions. A direct consequence of degeneracy is the assurance of quick compensation if one of these mechanisms fails. However, in pathological conditions, degeneracy can lead to a chronic, robust state in which a unimodal therapeutic approach that targets a single pathway will fail to ensure the sustainable irreversibility of the pathological process. According to this idea, the combination of therapies that utilize pharmacological compounds with synergic effects but different mechanisms of action or individual multimodal, pleiotropic therapies, with modulatory properties that can target as many pathways as possible offer a feasible therapeutic approach.

Last, but not least, it is very important to take in account that everyone has a different genetic polymorphism that leads to different phenotypes which can have an important influence upon the reactivity of molecular networks. This patient inter-variability may be responsible for both heterogeneity in disease progression and treatment response, leading to an open door to metabolomics [104].

### **Author details**

Dafin F. Muresanu1,2\*, Maria Balea1,2, Olivia Rosu1 , Anca Buzoianu3 and Dana Slavoaca1,2

\*Address all correspondence to<EMAIL_ADDRESS>
1 Department of Clinical Neurosciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania

2 "RoNeuro" Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania

3 Department of Clinical Pharmacology and Toxicology, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania

## **References**

mechanisms and become maladaptive and trigger the emergence and expansion of vicious circles due to the alteration of modulatory mechanisms. For example, in a demyelinated axon, homeostatic plasticity that involves the redistribution of ion channels occurs, and this redis‐ tribution contributes to the failure of AP conduction and finally generates a metabolic crisis. Intercorrelation between the molecular mechanisms that underlie inflammation, apoptosis, oxidative stress, increased Ca2+ load, mitochondrial dysfunction, microglial activation, and blood–brain barrier dysfunction is responsible for the expansion of vicious circles that generate a nonlinear pattern of clinical evolution. From this perspective, the traditional idea of a "magic

An interesting explanation of these mechanisms derives from the theory of complex biological systems, which are characterized by criticality and degeneracy. Degeneracy describes the ability of structurally and functionally distinct pathways to produce the same output. This characteristic supports the existence of multifunctional components that can perform similar functions under certain conditions. A direct consequence of degeneracy is the assurance of quick compensation if one of these mechanisms fails. However, in pathological conditions, degeneracy can lead to a chronic, robust state in which a unimodal therapeutic approach that targets a single pathway will fail to ensure the sustainable irreversibility of the pathological process. According to this idea, the combination of therapies that utilize pharmacological compounds with synergic effects but different mechanisms of action or individual multimodal, pleiotropic therapies, with modulatory properties that can target as many pathways as possible

Last, but not least, it is very important to take in account that everyone has a different genetic polymorphism that leads to different phenotypes which can have an important influence upon the reactivity of molecular networks. This patient inter-variability may be responsible for both heterogeneity in disease progression and treatment response, leading to an open door to

1 Department of Clinical Neurosciences, "Iuliu Hatieganu" University of Medicine and

2 "RoNeuro" Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania

3 Department of Clinical Pharmacology and Toxicology, "Iuliu Hatieganu" University of

, Anca Buzoianu3

and Dana Slavoaca1,2

bullet" seems too simplistic to achieve sufficient neuroprotection.

offer a feasible therapeutic approach.

Dafin F. Muresanu1,2\*, Maria Balea1,2, Olivia Rosu1

\*Address all correspondence to<EMAIL_ADDRESS>
Medicine and Pharmacy, Cluj-Napoca, Romania

Pharmacy, Cluj-Napoca, Romania

metabolomics [104].

296 Trending Topics in Multiple Sclerosis

**Author details**

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*2.3. The Proposed Methodology*

The proposed methodology starts from the green energy audit, then adding specifications in terms of:

A phase of monitoring energy values post-intervention is added at the end of the process. The effects of the energy requalification interventions are introduced to the scheme, where the auditor examines indicators such as energy consumption for heating, cooling, or domestic hot water.

The green energy audit aims to improve the sustainability of the building. For this reason, the selection of intervention measures must be evaluated according to the contribution in terms of energy savings, economic costs, and environmental impacts. This evaluation should be assessed by the adoption of a rating system that certifies a level of sustainability with a global score determined by the adopted design strategy and the achievement of selected credits, so, the proposal is to follow the environmental assessment on the basis of LEED O+M scheme. A workflow is proposed for achieving the certification score using a new classification of prerequisites and credits that consider the points of

credits and the document to be delivered. This method references previous studies [40] that aimed to identify the credits necessary to achieve the minimum score to attain the certification label with the better use of resources in term of time and costs. This step consists of two phases:

	- (a) Sub-phase 2A involves the selection of credits
	- (b) Sub-phase 2B applies a credits classification according to the same approach in phase 1.

All the sections described for each prerequisite and credit are considered, for example, intent, requirements, relations, score, and options, according to the structure fixed by the LEED rating system (Figure 1).

**Figure 1.** Structure of prerequisites and credits according to the LEED rating system definition [16].

Subsequently, a scoring system, described in Table 1, was developed considering the following parameters: the number of required documents, (listed in the required documentation section), the connected prerequisites (listed in the related credit tips section), and the effort level to fulfil the forms requested by USGBC (as described in the intent and requirement section).

**Table 1.** Scoring system for prerequisites according to options: parameters are the requirements in each prerequisite and the score is the score system. In detail: 1 point is assigned for each document required for the achievement of the intent; 1 point is assigned for each prerequisite listed in the section of related credits tips; different points are assigned related to the procedure of the performance period; different points are assigned in relation to the different levels of commitment difficulty in completing and collecting data.

As an example, the possible score for the prerequisite p2 of the Minimum Energy Performance (EA category, Table 2) is presented with two options requiring a total amount of four or eight documents to be completed according to the chosen option; there are two related prerequisites: EA p1 Energy Efficiency Best Management Practices and EA p3 Building-Level Energy Metering. The performance period requires 12 continuous months of metered energy data collected before the end of the performance period; the form includes the data collected to fulfil the Energy Star Rating or similar energy audit. Therefore, a partial score could be achieved for each prerequisite option by the application of the method, as explained in Table 1, and the total score of the prerequisite is determined by the average values of the options.

**Table 2.** Example of a score calculation for prerequisite EA p2 Minimum Energy Performance: the number of options proposed by the prerequisite requirement; the amount of documentation, listed in the documentation required section; the number and types of prerequisites; period and description of performance period; forms requested from USGBC; partial score for each option; and normalization of total score through calculation of average partial scores.

As shown for prerequisite EA p2, the procedure concludes with the assignment of a final score for each prerequisite, obtained by the normalization of the partial score and the number of options contained in the prerequisite description.

The result is a classification of prerequisites for LEED O+M v.4 (Figure 2), organized from higher to lower scores, also listing the relationships. It represents a workflow for applying the certification process as it lists the prerequisites in order of importance. In case of a correlation (for example EA p3, EA p1, and EQ p1 with EA p2) the prerequisites with a lower score (EA p1 and EQ p1) lose the score because the relationship allows pursuing the same documentation and data for the item with

the higher score (EA p2), receiving the same higher score and the same relevance in the classification and workflow.

**Figure 2.** Work classification of prerequisites for LEED O+M; scores of prerequisites related to other prerequisites are struck through. LEED's goals drive the weighting of points toward certification. Each credit is allocated points based on the relative importance of its contribution toward the goals. The results present a weighted average: credits that most directly address the most important goals are assigned the highest weight [42].

The classification proposed in Figure 2 reveals the most important areas for attaining the certification according to the LEED O+M perspective. The main area of concern for the management of energy performance, the EA category, is the most important topic, followed by signed policies such as requested in the EQ and MR category.

After pursuing mandatory prerequisites, credits allow receiving a score to determine the level of certification: USGBC assigns different points to each option of each credit. Since the complexity of the requirements and the large number of credits and documents, this study tries to simplify the selection process with the aim of receiving higher LEED certification by evaluating the minimum number of documentations for each credit and its relevance to the system. A calculation was developed for assessing the weighing of each credit and for credit selection considering the following parameters: score, relationship, and frequency. Relationship considers the number of credits listed in the related credit tips section of the same credit; frequency counts the quotes for the considered credit in the related credit tips section of other credits.

Phase 2A involves selection process. First, credits are listed and ranked in relation to the number of documents/reports to be completed according to the options. Then, the methodology proposes a new parameter called the "summary credit", as defined in Equation (1), which considers the maximum points achievable (score), the number of correlated prerequisites and credits (relationship), and the quote in other prerequisites/credits (frequency):

$$\text{Summary } \text{credit} = \text{point} + \text{frequency} + \text{relationship} \tag{1}$$

The method identifies a choice of credits with the best value as defined using Equation (2). Considering the required documentation (*y*) and the calculated summary credit (*x*), the result is a list of best credits (Figure 3) for LEED O+M v.4:

$$y \le 3/10 \text{ x} \tag{2}$$

**Figure 3.** Selection of 10 important credits: on x axis, number of summary credit, on y axis, number of documents, in particular minimum documents in (**a**) minimum documents and (**b**) maximum documents; the chosen credits lay below the line, according to function *y* ≤ 3/10*x*.

Credits are organized in phase 2B, developing a score system that considers the internal options (Table 3) in the requirement for the credit structure: one point is assigned for each requested document, for each connection with prerequisites and credits; different points are assigned based on the performance period and on the level of complexity and difficulty in completing the forms requested from USGBC.

**Table 3.** Scoring system for credits according to internal options: parameters are the requirements for each credit and score is the scoring system. The system is the same for prerequisites, but more points are assigned in relation to the number of prerequisites and credits listed in the tips section.

While the previous analysis was only dedicated to the prerequisites, this process was also developed for classifying the credits. The classification of credits has been implemented with the correlation between both credits and prerequisites (Figure 4).

**Figure 4.** Work classification of credits for LEED O+M; scores of credits related to other credits are crossed out.

The credits classification shows how the management of energy use is relevant, as with the prerequisite classification. Particular relevance is assigned to the human health topic presented in the EQ and LT categories, as listed in the management of air quality, the interior lighting, and the incentive to use alternative transportation.

The methodology identifies a list of 10 credits. The application and calculation of the requirements of these credits could achieve a total score of 53 points according to the scorecard, achieving the Silver level of certification [41] for LEED O+M systems, achievable when a project earns 50–59 points.


*Article* **How to Obtain Maximum Environmental Applicability from Natural Silicates**

**Daliborka Popadi´c 1, Nemanja Gavrilov 2, Ljubiša Ignjatovi´c 2, Danina Krajišnik 3, Slavko Mentus 2, Maja Milojevi´c-Raki´c 2,\* and Danica Bajuk-Bogdanovi´c 2**

**Abstract:** Unmodified natural silicates (bentonite, kaolin, clinoptilolite and diatomites) were tested as adsorbents for the organic pollutants in water tables using Methylene Blue (MB) as the model adsorbate. Among the selected materials, bentonite adsorbed as much as 237 mg/g, confirming its excellent suitability for pollutant removal. Spectral evidence confirmed successful MB immobilization at the bentonite surface. Furthermore, the thermal treatment of MB-saturated adsorbent in an inert atmosphere at 700 ◦C produced a carbon/silicate composite. EDX confirmed the formation of the nitrogen-doped carbon overlay on the silica scaffold and the obtained composite material was probed as an electrode material for oxygen reduction in an alkaline solution. Reduction proceeded via a two-electron mechanism with the main product being HO2 −, a known nucleophile, which was subsequently used to degrade/demethylate MB. The composite showed a considerable 70% MB removal rate after an hour of electrochemical treatment. The synergy between the processes of adsorption of MB and the surface-generated HO2 − dictates the efficiency of the method and points to a possible route for spent adsorbent reuse in the form of a durable product for environmental protection.

**Keywords:** bentonite; methylene blue; oxygen reduction reaction; spent adsorbent

#### **1. Introduction**

The search for advanced materials that have favorable properties for the adsorption/degradation of various pollutants from water is still ongoing. Costly, complicated and time-consuming synthesis procedures may not always produce materials with high adsorption capacity/degradation efficiency and therefore the researcher's attention is drawn to the use/modification of abundant and low-cost natural materials [1,2]. In the environmental application field, aluminosilicates represent the most important class of minerals and Earth's crust constituents. Clinoptilolite, hydrated alkali aluminosilicate, is one of the most abundant minerals and is readily available and implemented as incipients/carriers [3–6]. Other crust ingredients are clay minerals with several candidates for targeted applications in adsorption studies. Bentonite is a highly applicable clay [7] mainly composed of montmorillonite, a clay mineral from the smectite group [8]. The characteristics of bentonite depend on the amount of smectite and exchangeable cations in the interlayer space. Due to their structural characteristics of 2:1 tetrahedral SiO2/octahedral Al2O3 layers with substantial voids, bentonites are perceived as good adsorbents. One of the main characteristics of these materials is the swelling ability and high cation exchange capacity. Kaolin's (white clay) main component is kaolinite, a clay mineral of a 1:1 kaolinite group, with tightly distributed tetrahedral and octahedral layers. Diatomites are sedimentary rock silicates that mainly

**Citation:** Popadi´c, D.; Gavrilov, N.; Ignjatovi´c, L.; Krajišnik, D.; Mentus, S.; Milojevi´c-Raki´c, M.; Bajuk-Bogdanovi´c, D. How to Obtain Maximum Environmental Applicability from Natural Silicates. *Catalysts* **2022**, *12*, 519. https://doi.org/10.3390/ catal12050519

Academic Editor: Roman Bulánek

Received: 12 April 2022 Accepted: 4 May 2022 Published: 5 May 2022

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consist of opal and cristobalite. These materials are light, finely porous rocks consisting mainly of small opal skeletons (or parts thereof) of diatomaceous algae with interesting physico-chemical and biomedical applications [9,10].

Natural material does not necessarily imply efficiency in pollutant removal. Among the affordable and readily available minerals, it is necessary to examine the influence of their different structures, morphologies and composition on adsorption properties, and environmental applicability in general [11,12].

Various dyes were investigated as model pollutants, such as methylene blue (MB), a cationic thiazine dye, which finds its way into essentially different fields—from pharmacology to the dye/textile industry. This multifunctionality arises from versatile functional groups present in its structure. The fact that it can mimic nitrogen/sulfur-containing pollutants in the environment makes MB an excellent candidate for probe testing for resolving environmental threats.

Not only is it important to find an efficient material [13–15] but the question is also what to do with the saturated adsorbent after the adsorption. Materials after adsorption can be further exploited for the preparation of nanoparticles, but this often requires the addition of metal precursors [16]. An attractive approach was proposed by Tian et al. for hydrothermal treatment of dye-saturated palygorskite/Ag nanoparticles. Obtained carbon composites efficiently adsorbed different dyes and pharmaceuticals [17]. Another proposal for spent MB dye biosorbents is their transformation to biochar, which could be subsequently used for additional dye adsorption [18]. MB dye can be used for the functionalization of cellulose gum sorbent to suit the removal of anionic dye [19]. If the intention is shifted toward applications different from reiterating adsorption cycles after burn-off, incorporation of metal ions is necessary, either as a precursor or as a pollutant adsorbate. For instance, a fuel cell setup may benefit from bio sorbent previously used for platinum adsorption [20]. For metal-free electroactive material production, MB is also a good candidate, as graphene dye functionalization leads to highly active and stable electrode material for charge storage application [21].

Here, we propose natural aluminosilicates selection (bentonite, kaolin, clinoptilolite and diatomites) for the adsorption application of MB as a model pollutant in water tables. MB dye removal was studied in detail in the literature employing natural silicates in raw and modified forms [22–28]. Considering that natural samples have different compositions depending on their origin, we examined different samples to find the optimal adsorbent of the highest capacity that can be further processed. Thus, the universal application of the preferred spent adsorbent may be proposed. After carbonization, the selected MBsaturated silicate sample will be used for the electrocatalytic application. Electrochemical dye degradation on various electrode materials is addressed in the literature as an efficient method [29–31]. To establish a comprehensive environmental approach, this novel electrode material will be employed for the degradation of MB in an electrolytic cell by electrogenerated hydroperoxyl radical to extend the lifecycle of such spent adsorbents.

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

#### *2.1. Thermal, Spectral and Structural Properties of Investigated Minerals*

Thermal profiles of the investigated silicates are given in Figure 1a. Diatomite samples DK and DP are stable with small differences after a physically adsorbed water loss. Kaoline undergoes a phase transformation to metakaolin at around 500 ◦C [32], while the BE profile consists of two segments, characteristic of smectite mineral. The first step of mass loss up to 200 ◦C is related to physisorbed water removal, which is followed by dehydration of Ca2+ coordinated water and thermal removal of structural OH groups up to over 600 ◦C [33]. Clinoptilolite displays a continuous mass decrease up to 700 ◦C in accordance with previous studies [34].

**Figure 1.** TG profiles (**a**) and FTIR spectra (**b**) of natural silicates—clinoptilolite (CL), Peru diatomite (DP), Kolubara diatomite (DK), kaolin (KA) and bentonite (BE).

Spectral profiles of the tested silicates were analyzed and the FTIR spectra are presented in Figure 1b.

In line with the TG results, the diatomite samples DK and DT express the least resolved band at 3450 cm−1 and 1637 cm−1 attributed to O–H stretching and H–O–H deformation vibration. These bands are evident in the BE and CL samples, accompanied by a sharp band at about 3630 and 3620 cm−1, respectively (stretching of the structural hydroxyl groups). The most complex spectral features in this region are associated with KA, with four resolved bands of the structural OH groups (3695, 3670, 3650 and 3620 cm−1) [35], characteristic of the kaolinite mineral, indicating its significant structural ordering.

In addition to the absorption bands of structural OH, Si–O groups play an important role in the differentiation of silicate minerals [36].

The FTIR spectra of the diatomaceous earth samples, DK and DP, give a very strong absorption band at 1100 cm−1 with a shoulder at 1230 cm−1 are attributed to the Si–O–Si stretching vibration. The absorption band at 795 cm−1 evolves from the corresponding inter tetrahedral Si–O–Si bending. The absorption peak at around 469 cm−1 corresponded to the Si–O–Si bending vibration [37]. The bentonite spectrum reveals strong bands attributed to Si–O elongation in the 1100–1000 cm−1 region, characteristic of the layered montmorillonite structure. The bands corresponding to the Al–Al–OH bending vibrations are observed at 915 cm−1, Al–O–Si at 525 cm−1 and Si–O–Si bending vibrations at 469 cm−1. The band at 620 cm−1 is assigned to coupled Al–O and Si–O out-of-plane vibrations [38]. The band at 1458 cm−1 is assigned to the asymmetric stretching vibration of the present carbonate impurity [39] and other, less pronounced bands in the spectrum originate from clay components. Figure S1 gives a bentonite diffractogram to resolve phase content. Reflections at 6.7◦, 19.9◦ and 35.0◦ 2θ correspond to the montmorillonite (JCPDS 29-1498), while other reflections correspond to low amounts of feldspar in the form of the albite (JCPDS 09-0466) and quartz phase (JCPDS 46-1045) [40].

The 1120–1000 cm−1 region resolves several strong absorption bands related to Si–O stretching vibrations in the kaolin sample. Two strong bands at 1032 cm−1 and 1008 cm−1 belong to the antisymmetric in-plane Si–O–Si stretching. The symmetric Si–O stretching band is located at 1115 cm−1 while Al2OH bending modes are positioned at 935 and 913 cm−1 ascribed to inner surface/OH groups. Two low-intensity bands at the 750 and 697 cm−1 are associated with perpendicular Si–O modes and possibly surface hydroxyls. The Si–O–Al and Si–O–Si bending are located at 540 and 470 cm−1, in that order [41].

In the clinoptilolite spectrum, an intense 1059 cm−1 band is ascribed to the asymmetric stretching vibration modes of internal T–O bonds in TO4 tetrahedra (T = Si and Al). The 795 cm−1 and 469 cm−1 bands are attributed to the stretching vibration modes of O–T–O groups and the bending vibration modes of T–O bonds, respectively [42].

#### *2.2. Methylene Blue Adsorption-Quantitative, Spectral and Elemental Analysis*

The UV–Vis spectrum of MB shows two characteristic absorption bands at 662 and 607 nm with their intensities dependent on the monomer–dimer structure and the dimer development [43]. Low MB concentration up to 70 ppm gives dominantly monomers/dimmers, while higher concentrations allow aggregation/stacking, thus changing the spectral profile. As the tested concentration range is rather wide, differences in the intensity ratio of the monomer/dimmer band are evident in Figure S2a. Thus, for accurate quantification of MB, the calibration curves are based on the integral band surface instead of the absorbance value.

For MB tested concentrations below 100 ppm, clinoptilolite (CL), diatomite (DP) and bentonite (BE) samples completely and instantly adsorb MB while Kolubara diatomite (DK) and kaolin (KA) enter saturation and therefore, were excluded from further testing. Kaolin's non-expanding structure is fixed without interlayer space, which is the reason for its low adsorption capacity. The CL is getting to its saturation level at 100 ppm while the BE and DP samples retain excellent adsorption performance, (Figure 2a). Furthermore, DP lowered the adsorbed quantity of MB to 54 mg/g, while bentonite demonstrated the best adsorption capacity for the starting MB concentration of 200 ppm. To test the extent of available adsorption sites on bentonite, this sample was further investigated in suspensions with 300, 400 and 500 ppm MB solutions. Complete MB removal was witnessed up to 500 ppm, where 236.6 mg of MB was adsorbed per gram of bentonite adsorbent, approximately 95% of the starting MB quantity. The excellent adsorption performance of bentonite is attributed to its interlayered structure, which is susceptible to expansion and swelling in an aqueous environment, thus forcing the layers apart. To conclude, a mineral from the expending smectite group is a highly superior adsorbent compared to other tested silicate materials. A cationic dye such as MB readily interacts with clay minerals by cation exchange of extra-framework cations in an aluminosilicate structure [44].

**Figure 2.** Retained quantities of MB on investigated minerals, recorded for different initial MB concentrations (**a**); Langmuir–Freundlich adsorption isotherm for MB adsorption on bentonite sample (**b**).

Adsorption isotherm testing (Figure 2b) for several additional starting MB concentrations revealed the Langmuir–Freundlich isotherm model [45] is better suited for the

description of the adsorption process (correlation coefficient 0.98) in comparison to the less realistic Langmuir equation [45] Yang (correlation coefficient 0.91). This finding is in accordance with presumed nearly equivalent adsorption centers and the excellent adsorption behavior of the bentonite sample.

The MB post-adsorption spectral investigation (Figure 3) reveals no change in the structure of the tested silicates upon adsorption. The most intense pristine MB bands are located at 1592 and 1386 cm−1. These bands can be observed in the BE spectra at 1604 and 1398 cm−1 after MB adsorption. The transition of band positions to higher wavenumbers is a result of band shortening due to MB immobilization on the BE surface.

**Figure 3.** FTIR spectra of MB and BE adsorbent before and after MB adsorption (MB@BE).

As the bentonite sample proved to be the utmost MB adsorbent, carbonization of the saturated adsorbent was the next step in this investigation. In such a way, carbonaceous material comprising heteroatoms was obtained. Raman microanalysis confirmed that the amorphous carbon phase is obtained by thermal treatment of the MB-saturated bentonite sample. The characteristic G (stretching modes, 1585 cm−1) and D (breathing modes, 1373 cm−1) bands are clear indications of MB carbonization with an evident structural disorder [46]. The FTIR spectra give additional information on the preservation of aluminosilicate structure, as witnessed in Figure S3.

To confirm its elemental composition, EDX measurements were performed on the carbonized sample, and the atomic % of dominant elements (>1%) is summarized in Figure 4. The absence of carbon and nitrogen in pristine bentonite is evidenced, while after carbonization, a high portion of the surface is made up of carbon (34 at.%) and nitrogen (7 at.%) atoms. Additionally, the ratio between carbon and nitrogen atoms matches that within the MB molecule. The N-doped carbon phase is evenly present at the aluminosilicate surface in the amount of 25 wt. % carbon and 6 wt. % N, corresponding well to the alreadymeasured highly adsorbed MB quantity.

The favorable elemental composition supports subsequent electroactive testing of this novel material derived from the saturated adsorbent.

**Figure 4.** EDX map (**a**) and elemental composition change for carbonized MB-saturated bentonite (C-MB@BE) in comparison to pristine bentonite (BE) sample (**b**).

#### *2.3. Electro-Applicability of Spent Adsorbent*

After carbonization of the MB dye, adsorbed on bentonite, the silicate scaffold was covered with layers of nitrogen-doped carbon, as seen by Raman, FTIR and EDX. Doped carbons are well known for their activity towards ORR in alkaline solution, albeit somewhat lower than those for transition metals and their oxides [47]. Spent biochar adsorbents of heavy metals can also be transferred to electrocatalysts for ORR [48]. Figure 5 contains the CVs for carbonized saturated adsorbent displaying clear dependence of the measured current on the rate of rotation, indicating that the process of oxygen reduction is diffusioncontrolled at more negative potential. Koutecký–Levich (K–L) analysis was conducted to assess the number of exchanged electrons per oxygen molecule and to distinguish between the 2e−4e− ORR mechanisms [47,49].

**Figure 5.** Background-corrected CVs for ORR in 0.1 M KOH at different rotation rates (**a**); dependence of the apparent number of exchanged electrons on the given potential, according to K–L analysis (**b**).

Calculated values for the apparent number of exchanged electrons show that 2e− are being consumed in the potential region of interest and that, at a moderately negative potential, HO2 − is formed according to reaction O2(g) + H2O(aq) + 2e− ↔ HO2 −(aq) + OH−(aq).

Katafias et al. [50] investigated chemical MB degradation in base and base/peroxide systems and reported that HO2 − nucleophile in alkaline solutions may be an efficient phenothiazine derivative degradation agent. This prompted us to check whether electrogenerated HO2 − in the adlayer near or at the electrode surface could be used to reduce MB or degrade it. MB can be involved in a fast, reversible, 2e− redox process where MB transforms to a reduced, colorless leuco-MB form [51] or can be demethylated via nucleophile attack [50,52]. Electron transfer enables versatile applications of MB, which can be followed and analyzed by electrochemical methods [53,54].

After preparation of the initial solution of MB standard in KOH, the potential of the electrode was fixed at an HO2 − generating potential for three consecutive runs with aliquots taken for spectrophotometric measurements. The UV range monitoring was required to differentiate whether the process is only decolorization (due to colorless leuco-MB evolution) [55] or whether we achieved actual MB degradation and if the formed associated colored degradation products [50,52] decreased. Therefore, withdrawn volumes were used to measure the decrease in absorbance characteristics for both MB species, as presented in Figure 6. The decrease in the spectral response of quiescent KOH/MB (without the electrode present) amounted to 14% after 1 h and served as a baseline/guideline for degradation studies, Figure 6a. Interestingly, there is no rise in the UV absorption band due to MB reduction to leuco-MB. Although not resolved due to the stronger MB signal overlap, this characteristic band at 255 nm of leuco-MB form [56] did not contribute to the UV absorption rising. This means that the portion of MB transferred to leuco-MB is moderately low and that a major quantity of MB is degraded in the alkaline environment by HO2 −.

Figure 6b depicts a slight effect of adsorption upon rotating the electrode due to increased mass flow of the MB solution towards the electrode. Concurrent adsorption and inherent KOH bleaching decreased the signal by 23.1%. Importantly, this decrease is simultaneously seen for both UV and Vis absorption bands, suggesting an actual MB solution concentration decrease without the evolution of the leuco-MB form.

The intended effect of electrogenerated HO2 − towards MB degradation is seen by a gross 65.9% calculated from a decrease in MB absorption bands in the 450–750 nm region (42.8% when corrected for inherent degradation and effect of rotation) within an hour when potential is held at −0.8 V, Figure 6c. The results can be interpreted in accordance with the literature whereby MB is positively charged [57], suggesting that it will readily adsorb electrostatically on a negative electrode surface. Maintaining the HO2 − generation at −0.8 V vs. SCE will have the additional effect of attracting MB towards the surface. Once there, MB will simultaneously adsorb at the electrode and be in close proximity to the generated HO2 −, a known proton donor, with electrons from the electrode enabling successful MB degradation by demethylation/deamination via OH- and HO2 − intermediates resulting in colored products (Azure A/B/C and Methylene violet) [50]. A rotating disc electrode (RDE) forces the convection of the MB molecules as well as oxygen from the bulk of the solution towards the electrode surface.

Increased convection results in the formation of significantly more HO2 −, seen as an increase in measured current, and more MB molecules near the surface. By integrating current with respect to time, the amount of charge spent on HO2 − generation could be assessed and amounted to (0.46, 0.60 and 0.61 C) recalculated to 2.37, 3.10, and 3.14 μmol of HO2 −, which was sufficient to account for the decrease in initial MB content (0.18 μmol). The combined effect is the significant decrease in MB concentration indicating successful degradation by in situ electrogenerated nucleophile attack.

Using a test reaction with MB, it was demonstrated that the new carbonized material derived from the saturated adsorbent can be successfully used for the generation of HO2 −. In addition to bleaching, electro-generated HO2 − could be used for wider environmental applications, such as a non-selective oxidant in water purification systems.

**Figure 6.** Spectro-electrochemical results on MB degradation in (A) KOH electrolyte (**a**); (A + B) KOH-filled electrolytic cell with rotating electrode (**b**) and (A + B + C) KOH-filled electrolytic cell with rotating electrode and potential applied (**c**).

#### **3. Materials and Methods**

#### *3.1. Materials*

The natural zeolite, clinoptilolite (CL), used in this study originates from the Zlatokop deposit (Vranje, Serbia). Diatomite samples were examined from two sites, one of domestic origin, the Kolubara basin Serbia (DK), and the other originating from South America,

Peru (DP sample, food-grade diatomaceous earth, freshwater source). The DP sample was neat and used as is, while the DK sample was used after thermal treatment (at 550 ◦C for 4 h). Bentonite (BE) obtained from Fagron (Greece) and kaolin (KA) from Sigma-Aldrich (St. Louis, MI, USA), were both of the pharmaceutical (Ph. Eur.) grade.

#### *3.2. Characterization of the Natural Silicates*

Infrared spectroscopy with Fourier analysis was performed in the range 4000–400 cm−1 with 32 scans per spectrum and a 4 cm−1 resolution on Nicolet iS20 spectrometer (Thermo Scientific, Waltham, MA, USA) using KBr pellet technique.

X-ray diffraction (XRD) at room temperature was performed on a D8 Advance diffractometer (Bruker, Karlsruhe, Germany) using Cu Kα radiation, at a 40 kV voltage and 40 mA current. Diffraction data were collected in the 2–50◦ 2θ range with a 0.02◦ step and 0.1 s retention time per step. Data collection was guided by DIFFRAC Plus Commander v.2.6.1 software (Bruker, Germany).

UV–Vis absorption spectra were recorded on an Evolution 220 spectrometer (Thermo Scientific, Waltham, MA, USA) in a quartz cuvette with an optical path of 1 cm or 0.1 cm, in the 200–800 nm range.

The investigated minerals were subjected to thermogravimetry (TG) on thermobalance SDT 2960 (TA Instruments, New Castle, DE, USA). Measurements were performed up to 900 ◦C with the heating rate 10 ◦C min−1 in a synthetic air atmosphere with a flow rate of 80 mL min−1.

#### *3.3. Methylene Blue Adsorption, Adsorbents Treatment and Characterization*

The natural silicates were tested as adsorbents for MB from aqueous solutions. The batch adsorption suspensions comprised 10 mg of solid adsorbent and 5 mL volume of MB (Reag. Ph. Eur., Merck, Kenilworth, NJ, USA) solution. The suspensions were placed in an ultrasonic bath for 2 × 10 min. For lower MB concentrations (20–80 ppm), 1 mL of the suspension was centrifuged for 5 min at 13,400 rpm and UV–Vis spectra were recorded after 1 h equilibration time. In the case of higher concentrations (100–500 ppm), spectra were recorded after 24 h equilibration time.

All samples were tested for adsorption in 100 ppm and 200 ppm MB concentrations. As bentonite was the only material that completely adsorbed 200 ppm MB, this sample was further investigated for retention of higher concentrations—300, 400 and 500 ppm.

Upon adsorption of Methylene Blue, the selected sample was heated in a tubular furnace within argon atmosphere for 2 h at 700 ◦C, and 10 ◦C/min rate. The carbonized sample was denoted C-MB@BE.

In addition to FTIR measurements, a DXR Raman spectrometer with a microscope (Thermo Scientific, Waltham, MA, USA), was employed for spectral analysis of carbonized saturated adsorbent. Laser wavelength was 532 nm and power set at 2.0 mW, with 10 × 10 s exposure time, 900 lines/mm grating and 50 μm aperture.

The elemental composition of the carbonized sample was investigated by an energydispersive X-ray spectrometer (EDX) coupled with a Phenom ProX scanning electron microscope (Thermo Scientific, Waltham, MA, USA).

#### *3.4. Electrochemical Measurements*

Glassy carbon (GC) electrode coated with a thin film of the carbonized sample was used for electrochemical measurements. Liquid ink suspension was arranged by sonicating 5 mg of C-MB@BE in 0.5 mL of ethanol/water/Nafion mixture. Loading of 250 μg cm−2 was achieved by drop-casting 5 μL of the suspension on top of the GC disk (5 mm diameter). Oxygen reduction reaction (ORR) activity and MB degradation were evaluated using cyclic voltammetry (CV) in a conventional three-electrode cell with Pt wire as a counter and a saturated calomel electrode (SCE) as a reference electrode, in 0.1 M KOH aqueous solution as supporting electrolyte. An Ivium VO1107 potentiostat/galvanostat was used to impose the desired potential and measure the current response. Before and during the

measurements, slight oxygen flow was kept through the electrolyte to keep the solution saturated with oxygen. The baseline was recorded by purging nitrogen through the cell to eliminate oxygen and concurrently all processes that use oxygen. Measurements were performed at standard pressure and ambient temperature. Koutecký–Levich analysis (K–L) (Equation (1)) was used to define the mechanism of ORR and determine the number of exchanged electrons per oxygen molecule:

$$\frac{1}{i\_m} = \frac{1}{i\_k} + \frac{1}{B\omega^{1/2}}\tag{1}$$

where *im* is the measured current, *ik* is the kinetic current from the electrochemical reaction, *B* is the Levich constant and *ω* is the angular rotation rate.

Spectro-electrochemical measurements were performed by dissolving 1 mL of 500 ppm MB aqueous solution in 249 mL 0.1 M KOH. Generation of species was carried out at a constant potential (−0.8 V vs. SCE), at 2400 rpm, with 5 mL aliquots being drawn for UV–Vis measurements every 1200 s, three successive times.

#### **4. Conclusions**

Herein, we propose a straightforward selection of the best adsorbent of methylene blue (MB) in aqueous solutions among natural aluminosilicates (bentonite, kaolin, clinoptilolite and diatomites). Nitrogen-rich MB was selected for investigation as a model pollutant in water tables.

Complete MB removal (cca. 95%) was witnessed up to a 500 ppm starting concentration, where 236.6 mg MB was adsorbed per gram of bentonite, while other silicates showed significantly lower capacities. The excellent adsorption performance of bentonite is attributed to its interlayered structure with evenly distributed adsorption sites. The MB interaction with the bentonite sample was confirmed by FTIR analysis along with mineral structure preservation and insight into possible adsorption centers. MB-saturated bentonite was further heated in an inert atmosphere to carbonize the adsorbate. Raman spectral analysis confirmed the amorphous carbon phase on the bentonite sample, and FTIR spectra evidenced the preservation of the aluminosilicate structure. The obtained carbonaceous material comprises N and S as confirmed by the EDX investigation.

The doped carbon material was tested for its activity toward oxygen reduction in an alkaline solution. The Koutecký–Levich analysis confirmed that 2e− are consumed in the selected potential region, therefore, confirming HO2 − formation. To exploit nucleophile generation, in situ, three complementary experiments were conducted in three 20 min runs. As a baseline, in the absence of rotation, a decrease in MB concentration matches that naturally occurring in an alkaline MB solution in the amount of 14%. In the presence of rotation of the carbonized MB-saturated bentonite electrode, but without the applied potential, MB concentration decreases by 23% due to electrode adsorption in addition to MB alkaline bleaching. Finally, the effect of electrogenerated HO2 − on MB degradation is seen by a 66% decrease within an hour. For successful MB degradation, the generation of a significant local concentration of HO2 − is needed in the presence of a reasonable concentration of MB near or at the surface. This local, electro-generated HO2 − concentration surpasses that found in the solution and successful degradation prefers intimate contact of pollutant molecules and HO2 − at the electrode surface.

The combined effect of convection and oxygen reduction enables successful degradation of pollutants by in situ electrogenerated nucleophile attack, placing this procedure as a method of choice for spent adsorbent employment.

**Supplementary Materials:** The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/catal12050519/s1, Figure S1: XRD pattern of bentonite sample; Figure S2: Calibration curve for MB in (a) an aqueous solution and (b) KOH, based on integral absorption band surface area; Figure S3: Raman and FTIR spectra of carbonized C-MB@BE sample.

**Author Contributions:** Conceptualization, D.P., M.M.-R. and D.B.-B.; methodology, D.P., D.K., N.G. and L.I.; formal analysis, D.P.; investigation, D.P., S.M. and N.G.; resources, L.I., S.M. and D.K.; data curation, D.P., D.B.-B. and N.G.; writing—original draft preparation, D.P., D.B.-B. and N.G.; writing—review and editing, M.M.-R., D.B.-B. and N.G.; visualization, M.M.-R.; supervision, D.B.-B. and N.G. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by the Ministry of Education, Science and Technological Development of the Republic of Serbia, grant numbers 451-03-68/2022-14/200146 and 451-03-68/2022-14/200161.

**Data Availability Statement:** Data are contained within the article or Supplementary Materials.

**Conflicts of Interest:** The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

#### **References**


3. A review of international studies and phonological processing/speed

International researchers have investigated many of the most important factors identified in fluent reading. In Dutch, Vaessen and Blomert found that RAN

contributed uniquely and substantially to the development of word reading fluency from grade 1 to grade 6 in primary school students [24], and when both accuracy and speed measures were considered in French, readers with dyslexia displayed deficiency in word-level reading skills [25]. A similar speed deficit of lexical and sub-lexical reading was also suggested by findings in French dyslexic children. The suggestion here being that the sub-lexical route shares with the lexical one the initial processing of the letter string, but then the lexical processing applies graphemephoneme rules in a serial mode [26]. This deficiency in sub-lexical processing is also a crucial feature in American dyslexic definitions and treatment, a language system known for its irregular words and "exceptions to the rule".

in Grades 1–4. Park and Uno [36] found that the contribution of phonological awareness to Hangul reading accuracy appears to occur only during the first 2 years of schooling, and RAN speed significantly predicted word-reading accuracy only in Grade 1. Further, the results of path analysis revealed that receptive vocabulary contributed exclusively and substantially to Hangul word-reading accuracy in Grades 1–4. This is unusual in light of the accepted idea that vocabulary plays a more important role in reading in less consistent orthographies [17]. Park and Uno argue that these results may be due to characteristics of the Hangul writing system that support the decoding of two-syllable words based on partial decoding and knowledge of the phonological and lexical aspects of a known, corresponding spoken word. In this case, the strategies needed to read accurately and with speed in Hangul differ with expertise and reading experience. A recent cross-language investigation measured reading performance (both reading accuracy and fluency), phonological short-term memory, RAN, receptive vocabulary and non-verbal intelligence in grade 2 children in five European countries (Finland, France, Hungary, Netherlands, and Portugal). While it is often proposed that extensive familiarity with the words of a language affects reading performance, the results here suggest that vocabulary was not a unique predictor of reading accuracy and fluency in these

In conclusion, phonological awareness represents the main predictive factor in normal and disabled readers of different languages. However, it may be less relevant in consistent orthographies, especially for reading accuracy where language –specific patterns appear to exist [39]. Research in German [40], Dutch [41], Norwegian [42], Italian [33], Greek [43], Finnish [44], Hungarian [45], and Hebrew [46], shows that most dyslexics in these languages attain high levels of reading accuracy but remain slow. It is possible that orthographies that are relatively regular in their letter-sound correspondences such as the Arabic require rapid development of the "direct access route". Perhaps it is only with increasing practice that improvements in efficiency lead to the reliable use of "direct access processes". Consequently, it is unclear whether the sub-lexical route accesses semantics after the phonology is assembled, and it is still debated whether direct visual access can occur without phonological mediation [47]. See Table 1 for a time-ordered summary of the international studies cited regarding phonological processing.

> Year Subjects- age or grade

Wimmer Germany 1993 Grades 2, 3, 4 German dyslexics attain high

Netherlands 1993 Mean age: 10.2 years Dutch dyslexics attain high levels

Norway 1996 Grade 3 Norwegian dyslexics attain high

1997 8 year olds English children seem more

6.9 years; Dyslexic: 9.1 years

Major findings

levels of reading accuracy but remain slow in processing speed.

of reading accuracy but remain slow in processing speed.

levels of reading accuracy but remain slow in processing speed.

Hebrew dyslexics attain high levels of reading accuracy but remain slow in processing speed.

impaired because of orthographic differences; German children had few problems with accuracy after the first year of instruction.

languages, except for Finnish [38].

The Neurobiological Development of Reading Fluency DOI: http://dx.doi.org/10.5772/intechopen.82806

Researchers National

Yap, Van der Leij

Bjaalid, Hoien, Lundberg

Landerl, Wimmer, Frith

93

origin of subjects

Breznitz Israel 1997 Normal mean age:

Germany, England

Researchers have proposed that between English and German dyslexic children with the same underlying phonological processing deficit, the English children show more severe reading impairment because of differences in orthographic consistency [27]. Mann and Wimmer [28] assessed readers in English and German at the end of kindergarten, and regression analyses showed that the only significant predictor of reading accuracy and speed in English was phonological awareness. Initial studies in German children found few problems with accuracy after the first year of instruction in contrast to English-based research and led to a German-English dyslexia comparison [27]. However, the reading fluency deficit of German dyslexic readers (found for all types of reading tasks) was found to be highly persistent [29] and hard to remediate [30].

Extensive research with German and Italian dyslexic children found reduced reading fluency as the main dyslexic impairment [6, 31]. Impairment on tasks that require implicit phonological processing, such as those evaluating verbal short-term memory, has been identified most clearly in transparent orthographies such as Italian and German [32]. Italian is a relatively shallow orthography, characterized by a high consistency of grapheme-phoneme correspondences and a simple syllabic structure. Also there are few irregular words and non-homographic homophones [15]. In spite of this regular orthography, Italian children with Developmental Dyslexia still present with a relevant difficulty which is primarily a deficit in reading speed [33] markedly affected by stimulus length [34]. Tobia and Marzocchi worked to define the cognitive profile of Italian children with Developmental Dyslexia. They found that 43.7% of children with DD had a profile that included deficits in both verbal and nonverbal domains. Some measures (visual search, syllable blending, and syllable deletion) were not significantly different among the three groups: dyslexic children, typically developing children of the same age (CA) and a control group of younger children equated for reading ability. Phoneme blending was the only variable that showed a large effect size [35].

The viability of accuracy/fluency-based typology of reading impairments has been investigated in Hebrew by Shany and Share [2]. Using a full battery of behavioral assessments including "pointed texts" (with all diacritical vowel markings included) and "unpointed texts" (with partial vowel markings included), these researchers found clear processing differences between the performances of students identified as rate-disabled and those identified as accuracy-disabled. Especially for word reading, the doubly-disabled subgroup of students was the most severely incapacitated with the lowest accuracy and reading rates.

The Korean handwriting system is an "alpha-syllabic" orthography, called Hangul. There are 24 graphemes, 14 are consonants and 10 are basic vowels. Hangul graphemes consistently represent sounds with a one-to-one correspondence and are combined in a limited number of patterns [36]. In a study using Hangul, researchers investigated the association of RAN and regular/irregular words in 4- and 5-yearold Korean children and found that RAN was uniquely associated with reading ability of both regular and irregular words [37]. Other research examined the cognitive abilities that predict reading and spelling performance in Korean children


**Author details**

Albert Sabban1,2

1 Department of Electrical Engineering, Ort Braude College, Karmiel, Israel

2 Senior RF and communication systems researcher and consultant in High Tech Companies, Haifa, Israel

\*Address all correspondence to<EMAIL_ADDRESS>
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*Green Wearable Sensors for Medical, Energy Harvesting, Communication, and IoT Systems DOI: http://dx.doi.org/10.5772/intechopen.112352*


**About the Editors**

**Heather Piper** Entering academic research following a career in Social Work, individually and with colleagues Heather Piper is responsible for over 40 refereed journal articles and a substantial number of monographs and edited collections. Her work is characterised by a contrarian perspective on mainstream approaches to a variety of issues, including citizenship education, animal abuse and human violence, women and violence, false allegations, intergenerational touch and *in loco parentis* relationships in the context of extreme concern around child abuse and protection, and ethical issues relating to such concerns.

**Else-Marie Buch Leander** is close to finishing a PhD on the unintended cultural, institutional, social, and discursive consequences of the current significant fear of child sexual abuse (CSA) in western societies. She particularly focuses on changes in practice in childcare institutions, the stigmatization of male childcare staff and the problematization of children's nudity and doctor games.

## **Preface to "Challenging Academia: A Critical Space for Controversial Social Issues"**

The call for papers for this Special Issue was intended to attract authors who may have been prevented from or are fearful of researching, speaking, or writing on certain topics. Increasingly in recent years (and perhaps in some societies more than others) there have been many instances of "no platforming" in academic arenas, often supported by social media campaigns against some alleged "offence". Such instances include individuals and groups with a particular commitment and/or self-interest who have sought to silence academics, and others who may seek to question their particular view of a controversial issue; this has been especially evident in matters concerning gender and transgender individuals. Examples of such silencing include: Rachel Ara, a feminist artist, was due to talk at Oxford Brookes University (UK) in 2019, but her talk was cancelled as she was condemned for being a Trans Exclusionary Radical Feminist (TERF); Selina Todd, a Professor of Modern History, and others, have faced petitions for them to be sacked from Oxford University (UK) for being critical of gender self-identification, and were accused of being transphobic [1].

In some instances, journal referees and reviewers can exercise a form of censorship, as senior academics resist challenges to particular orthodoxies that they have a direct interest in protecting as the mainstream approach. Such cases of censoring have included the defence of concepts such as the cycle of abuse, i.e., the inevitability that those who harm animals when young will harm people when older, or that societal factors will always trump genetics—a contentious area, but one that is worth exploring, especially in relation to health issues. In some cases, powerful and well-resourced organisations with a particular self-interest exercise pressure on the academy and practitioners to ensure that certain behaviours prevail (e.g., some child care charities, unions etc who advocate that teachers, sport coaches, and child care workers must not touch children, even young ones in their care, or must touch them only in prescribed ways), this has been articulated in the US context by Johnson [2], and the UK by Piper et al. [3,4] and now by Buch-Leander et al. (see this Special Issue). Similarly, research applications frequently have to be reviewed by practitioners who hold particular views and who can prevent certain research from taking place by both negative reviews and/or the withholding of funds.

Beyond such actions based, at least in part, on personal, professional, or organisational self-interest, many restrictive trends have been explained as a consequence of identity politics, and the relatively new understanding that if someone says they experience something as true, or offensive, then this cannot be challenged. As a result, disagreements on secular issues are conceived in quasi-religious terms, with harsh outcomes for perceived "heretics." In response to such silencing, a group in the USA, the Heterodox Academy, has been established, with a focus on achieving viewpoint diversity, seeking to encourage academics to confront these issues. In the UK, *The Journal of Controversial Ideas* has been launched, which aims to publish papers submitted pseudonymously, "in order to protect [authors] from threats to their careers or physical safety". However, some regard such anonymity as a retrograde step which could become part of the problem rather than the solution.

We should acknowledge that this an arena of public perception and debate where certainty is hard to achieve, where grey areas proliferate, and in which participants will have very different perceptions and understandings. Further, we would not claim that the perceived problem derives from only one source, and there is certainly no basis for holding either "the left" or "the right" responsible. Some commentators who would place themselves in the latter category may complain that "woke warriors" are "snowflakes" who seek to restrict open debate and scholarship, but may engage or collude in restrictive behaviour of their own, for instance, against those who seek to explore and highlight the degree to which the prosperity of many western democracies is based on wealth derived from slavery and self-interested colonialism. However, we believe there is a difference between situations where the substantial majority of expert opinion judges a particular area of work and argument (e.g., climate change denial) to be wholly beyond the pale, and where particular contributions are silenced through the actions of relatively small interest and pressure groups who manage to punch above their weight through single-minded moral outrage or disproportionate media coverage. Against this challenging background, this edition aims to help expand debate in "silenced" areas, and tackle areas that have been subject to "no platforming" or biased reviewing, and to challenge and intervene in defensive academic and professional practices resulting from fear.

The brief was necessarily eclectic and inclusive, but we were specifically hoping to attract papers addressing issues including "no platforming" (how can this be challenged and discouraged in so-called democracies?); transgender issues (e.g., should young children be encouraged to seek medical interventions? Should teachers and care workers be instructed to call young children "they"?); #metoo (has this movement had any negative consequences for women? Does it encourage vulnerability and victimhood and, if so, is this a price worth paying? Despite some good this movement has brought, has it also damaged men and the process of justice? Has it frozen sexual relations between the sexes?); national narratives (critical and/or revisionist accounts of, e.g., colonialism; is it appropriate to rename historic buildings and remove "offensive" public monuments?). Many of these issues have gathered publicity and pace in recent years.

To some extent, we were unsuccessful in attracting papers addressing such controversies, in spite of some direct targeting of authors we knew had raised and debated these issues, to their detriment. The fear factor was perhaps even greater even than we had expected. While preparing this preface, we noticed a timely and powerful article [5] which problematised the trend in some jurisdictions towards conflating sex and 'gender identity', thus removing sex as a discrete political and legal concept. It has profound consequences; when words change meaning or are conflated, concepts vanish. The anti-science denial of the difference between sex and 'gender identity' raises many problems. Women's oppression has been 'on the basis of sex', prompting the fight for sex-based rights which become harder to defend if permitted terminology erases women's material reality. Gender neutral terms cannot erase biology, but they can remove the analytical tools to understand and address it. In the UK cases of sexual abuse against children by women doubled between 2015 and 2019, from 1.5% to 3% of all cases, but around 38% of sexual offenders in women's prisons are transwomen. There are surely some fertile research areas here!

We did, however, attract a range of papers covering a number of areas (see below), and characterised by a broad international focus. While, on the face of it, many of these papers were less controversial than we had anticipated, nevertheless, a key theme emerged in many: there is often a clear and identifiable (yet unacknowledged) contradiction between key practices in various professional and institutional settings and what is either normally expected, formally required or endorsed by the relevant professions or institutions, or even legal in the relevant national context. For example, it is an expectation that graduate and post-graduate study will include an element of criticality in order to reach the required level of scholarship, yet there are certain topics and perspectives being excluded from such academic scrutiny (see the published papers for examples).

With some submitted papers which did attempt to address controversial areas, we had our own difficulties at the reviewing stage. At least one excellent paper was rejected; it challenged Sweden's

response to the Covid virus and was clearly deemed heretical by one reviewer who considered it in mid-2020. However, the early, low-key response to the pandemic in Sweden is now acknowledged as flawed even at the governmental level. A paper that was eventually published attracted diametrically opposed reviewer's comments, ranging from "the project [was] poorly conceived and executed" (and this reviewer additionally raised confidential ethical concerns) to "I would like to express my appreciation . . . in which critical thinking is applied to both the training and the method of the proper discipline of [named discipline]". Another paper, also eventually published, attracted two very positive sets of reviewers' comments, including one who stated that the paper was addressing a previously taboo area, but a third which claimed "the insufficiency of the text is of such a degree and nature that no revision will make it fit for a publication in an academic context". While differing reviewer's opinions are always to be expected, the extent and severity of the gatekeeping for this Special Issue was greater than any experienced previously by the editors.

These difficulties, when viewed in retrospect and with the aid of the analytic overview proffered by Laurent Dubreuil in his post-scriptum, become easier to understand. The extent to which questions of identity now pervade understanding and debates within and beyond the academy can hardly be over-stated. Indeed, as he demonstrates, the consequences of the narrowing politics of identity can be discerned even in areas of research, policy, and practice where issues of identity are not immediately obvious. In combination with longer-standing restrictive practices, based on inflexibility, defensiveness, and sometimes self-interest, this reality suggests a difficult future experience for academics and researchers determined to swim against the tide of mainstream assumptions and opinions.

However, to end on a more optimistic note, it has been widely noted that, over time, things that seem set in stone do change as, in the words of Plato, "All is flux: nothing stays still". Similarly, Leonard Cohen keeps us cheerful with his reminder that 'There is a crack, a crack in everything. That's how the light gets in. . . " We hope that change and illumination is not too slow in coming to many contested areas, and that academic debate from all perspectives is encouraged for the good of us all.


**2. Double arterial translocation with preservation of the pulmonary valve, surgical technique**

This procedure was achieved employing cardiopulmonary bypass with hypothermia at 25°C and myocardial protection with warm induction blood cardioplegic solution at a proportion of 3:1 followed by hypothermic cardioplegic solution and modified ultrafiltration. Initially an incision inferior to the aortic valve was made, excising the ascending aorta (including aortic valve and coronary arteries) beneath the annular level of aortic valve from the right ventricle. Then we performed the excision of the pulmonary root, including pulmonary valve, beneath the annular level of the pulmonary valve from the left ventricle [figure 1]. After section of the infundibular septum in direction to the VSD, the LVOT and the VSD was closed with glutharaldeide-fixed bovine pericardium patch [figure 2]. The resulting gap of the aortic translocation was partially closed with fresh autologous pericardium. Finally the ascending aorta with the aortic valve and the coronary arteries were sutured into the left ventricle outflow and the pulmonary root with the pulmonary valve was sutured into the right ventricular outflow [figure 3].

Correction of Transposition of Great Arteries with Ventricular Septal Defect and Left Outflow

Tract Obstruction with Double Arterial Translocation with Preservation of the Pulmonary Valve 211

Fig. 3. Double arterial translocation with preservation of the pulmonary valve. The resulting opening from resection of the ascending aorta was partially closed to the right with a fresh autologous pericardial patch. The ascending aorta with the coronary arteries and the aortic valve was sutured to the left ventricle outflow tract and the pulmonary trunk with the

Between November 1994 and June 2011, a total of 212 consecutive children with TGA were submitted to surgical treatment at the Hospital São Joaquim da Real e Benemérita Associação Portuguesa de Beneficência as follows: simple TGA (n = 110; 51,8%); TGA, VSD (n = 66; 31,1%); TGA, VSD and LVOTO (n = 34; 16,0%). The diagnosis was based on color echodopplercardiographic findings. The following procedures were used in children with TGA, VSD and LVOTO: modified BT shunt (n = 10), Rastelli procedure (n = 13), Jatene procedure (n = 3) and arterial translocation procedure (n = 8), with two further divisions modified Nikaidoh (n = 5) and double arterial translocation with preservation of pulmonary

In the modified BT shunt group, the VSD was not committed in two patients. Two patients had mitral valve straddling. Two patients had sistemic-pulmonar collateral arteries and one patient had multiple VSD. Seven patients were neonates, one was 2 months old and two patients were 1 year old. The mean weight was 4,3 kg (range 1,8 kg – 8,8 kg). In the Rastelli group three patients had previous modified BT shunt. Two patients had restrictive VSD. One patient had mitral valve insuficience and one patient had right pulmonary artery stenosis. Five patients were neonates, five patients were younger than 1 year of age (mean age was 6,2 months; range 2 months-eleven months), three patients were older than 1 year of age (mean age was 5,6 years; range 3 years – ten years). The mean weight was 7,9 kg (range 3,0 kg – 28,0 kg). In the Jatene procedure two patients were neonates and one patient was 4 months old. The mean weight was 3,8 kg (range 2,9 kg – 5,2 kg). In the arterial translocation group two patients had previous modified BT shunt and one patient had two

pulmonary valve was sutured to the right ventricle outflow tract

**2.1 Patients, general**

valve (n = 3).

Fig. 1. Double arterial translocation with preservation of the pulmonary valve. Withdrawal of the ascending aorta with the aortic valve and coronary arteries from the right ventricle and removal of the pulmonary trunk with the pulmonary valve from the left ventricle

Fig. 2. Double arterial translocation with preservation of the pulmonary valve. After section of the pulmonary ring and infundibular septum toward the interventricular communication, an enlargement of the left ventricle outflow tract and a closure of interventricular communication was carried out using a glutaraldehyde-fixed bovine pericardium graft

Fig. 3. Double arterial translocation with preservation of the pulmonary valve. The resulting opening from resection of the ascending aorta was partially closed to the right with a fresh autologous pericardial patch. The ascending aorta with the coronary arteries and the aortic valve was sutured to the left ventricle outflow tract and the pulmonary trunk with the pulmonary valve was sutured to the right ventricle outflow tract

### **2.1 Patients, general**

210 Aortic Valve Surgery

Fig. 1. Double arterial translocation with preservation of the pulmonary valve. Withdrawal of the ascending aorta with the aortic valve and coronary arteries from the right ventricle and removal of the pulmonary trunk with the pulmonary valve from the left ventricle

Fig. 2. Double arterial translocation with preservation of the pulmonary valve. After section of the pulmonary ring and infundibular septum toward the interventricular communication,

an enlargement of the left ventricle outflow tract and a closure of interventricular communication was carried out using a glutaraldehyde-fixed bovine pericardium graft Between November 1994 and June 2011, a total of 212 consecutive children with TGA were submitted to surgical treatment at the Hospital São Joaquim da Real e Benemérita Associação Portuguesa de Beneficência as follows: simple TGA (n = 110; 51,8%); TGA, VSD (n = 66; 31,1%); TGA, VSD and LVOTO (n = 34; 16,0%). The diagnosis was based on color echodopplercardiographic findings. The following procedures were used in children with TGA, VSD and LVOTO: modified BT shunt (n = 10), Rastelli procedure (n = 13), Jatene procedure (n = 3) and arterial translocation procedure (n = 8), with two further divisions modified Nikaidoh (n = 5) and double arterial translocation with preservation of pulmonary valve (n = 3).

In the modified BT shunt group, the VSD was not committed in two patients. Two patients had mitral valve straddling. Two patients had sistemic-pulmonar collateral arteries and one patient had multiple VSD. Seven patients were neonates, one was 2 months old and two patients were 1 year old. The mean weight was 4,3 kg (range 1,8 kg – 8,8 kg). In the Rastelli group three patients had previous modified BT shunt. Two patients had restrictive VSD. One patient had mitral valve insuficience and one patient had right pulmonary artery stenosis. Five patients were neonates, five patients were younger than 1 year of age (mean age was 6,2 months; range 2 months-eleven months), three patients were older than 1 year of age (mean age was 5,6 years; range 3 years – ten years). The mean weight was 7,9 kg (range 3,0 kg – 28,0 kg). In the Jatene procedure two patients were neonates and one patient was 4 months old. The mean weight was 3,8 kg (range 2,9 kg – 5,2 kg). In the arterial translocation group two patients had previous modified BT shunt and one patient had two

Correction of Transposition of Great Arteries with Ventricular Septal Defect and Left Outflow

**2.1.2 Surgical technique**

arterial translocation operation.

difference between all groups (p = 0.811).

avoids early reoperation to change the valved conduit.

**3. Results**

**4. Comments**

Tract Obstruction with Double Arterial Translocation with Preservation of the Pulmonary Valve 213

The palliative BT shunt was made by median sternotomy in seven patients, by right thoracotomy in two patients and by left thoracotomy in one patient. The interposition of a polytetrafluoroethylene (PTFE) tube was made between the innominate artery and the right pulmonary artery in nine patients, and between the left subclavian artery and the left pulmonary artery in one patient. In seven patients the diameter of the PTFE tube was 4 mm, and in three patients it was 5 mm. The Rastelli, Jatene and modified Nikaido procedures and double arterial translocation with preservation of the pulmonary valve were made by median sternotomy and moderate hypothermic cardiopulmonary bypass and myocardial protection with warm cardioplegic induction, followed by hypothermic blood cardioplegic solution at a proportion of 3:1 every 20 minutes. In the Rastelli procedure, the VSD was repaired through the right ventriculotomy in such a way to connect the left ventricle to aorta. The reconstruction of the pulmonary artery was performed with a glutaraldehydefixed bovine pericardium valved conduit in eight patients and with a glutaraldehyde-fixed bovine-valved jugular vein in six patients. In the Jatene group, the LVOTO was a subvalvar fibromuscular ridge. After aorta transection was performed resection of the localized LVOTO. The pulmonary trunk was transected proximal to its bifurcation. After the LeCompte maneuver, a button of the left and right coronary artery was excised from its sinus, and was inserted into the neoaorta. Coronary type was Yacoulb I in all patients. The reconstruction of the neopulmonar was done with a single, fresh autologous pericardium patch. In the modified Nikaidoh group the aorta was translocated with the aortic valve and coronary arteries to the left ventricle, after an enlargement of the left ventricle outflow tract and closure of VSD with a single glutaraldehyde-fixed preserved bovine pericardium patch. In this series of patients we used a valved conduit to reconstruct the right ventricular outflow. This approach was different from the original technique, in which the pulmonary trunk is used without a valve. We used a glutharaldeide-fixed valved bovine jugular vein in three patients. In one patient a glutharaldeide-fixed valved bovine pericardium conduit was used, and in one patient a Lhydro porcine valved pulmonary trunk [8]. During the analyzed period there was a change in the surgical procedure. At first, modified BT technique prevailed; later, Rastelli operation and Jatene operation were performed, and finally the

Two patients died in the modified BT shunt group (20%), three patients died in the Rastelli group (23,0%) and one patient died in the arterial translocation group (20%). All patients in the Jatene group and in the double arterial translocation with preservation of the pulmonary valve all patients survived. The statistical analyses (Fisher's Exact Test) showed no

The surgical management of TGA with VSD and LVOTO is a surgical challenge. The Rastelli

The most appropriate timing of the Rastelli operation is controversial. When it is performed during early infancy, it is a physiologic correction and avoids systemic hypoxemia. On the other hand, the palliative procedure of modified BT shunt performed during early infancy

operation remains the most applied procedure for this congenital cardiopathy.

previous modified BT shunt. Three patients were neonates, one patient was 6 months old and four patients were older than 1 year of age (mean age was 1,6 years; range 1 year – 2 years). The mean weight was 7,0 kg (range 2,6 kg – 11,3 kg).

#### **2.1.1 Patients, double arterial translocation with preservation of the pulmonary valve**

Three children with TGA with perimembranous VSD and LVOTO type-fibromuscular tubular obstruction associated to hypoplasia of the pulmonary valve ring underwent doble arterial translocation with preservation of the pulmonary valve: Patient 1, female, aged two years, weighing 10.8 kg, underwent two previous Blalock-Taussig shunt surgeries. Preoperative color Doppler echocardiography revealed a LVOTO gradient of 40 mmHg. CPB time was 195 minutes and the aortic clamping time was 123 minutes. Pressure measurement after surgical correction revealed a ratio of systolic pressure between the RV and LV (RV/LV) of 0.6 and a pulmonary gradient of 25 mmHg. The postoperative Doppler echocardiography revealed a pulmonary transvalvular gradient of 42 mmHg; Patient 2, male, aged 6 months, weighting 7.3 kg. Preoperative Doppler echocardiography revealed LVOT gradient of 65 mmHg. CPB time was 184 minutes and aortic clamping time was 140 minutes. Pressure measurement after surgical correction revealed RV/LV systolic pressure of 0.8 and pulmonary transvalvular gradient of 30 mmHg. Postoperative Doppler echocardiography revealed a pulmonary transvalvular gradient of 31 mmHg. Heart computaticional angiotomography (CT) performed during the immediate postoperative period showed appropriate positioning of the pulmonary trunk, pulmonary artery and aorta in both patients (Figure 4).

Patient 3, male, aged 1 year, weighting 8.0 kg. Preoperative Doppler echocardiography revealed LVOT gradient of 31 mmHg. CPB time was 182 minutes and aortic clamping time was 155 minutes. Pressure measurement after surgical correction revealed RV/LV systolic pressure of 0.7 and pulmonary transvalvular gradient of 30 mmHg.

Fig. 4. Double arterial translocation with preservation of the pulmonary valve. CT angiography performed in the immediate postoperative period showed appropriate positioning of the pulmonary artery and pulmonary branches as well as the ascending aorta