**2.3 Presence of high-grade dysplasia or colorectal malignancies**

The presence of high-grade dysplasia (HGD) or colorectal cancer is another indication for elective RPC with IPAA in IC.

Colorectal surveillance in UC obeys specific rules (**Figure 6**) [10], and chromoendoscopy has an essential role in dysplasias identification (**Figure 7**) [11, 12]. In UC surveillance, the chromoendoscopy allows to split the cases in visible dysplasia and invisible dysplasia (**Figure 7**) [13, 14].

**Figure 6.** *Colorectal surveillance in UC (33 biopsies allow 90% accuracy in dysplasia diagnosis).*

**Figure 7.** *Role of chromoendoscopy in dysplasia endoscopic visiblility.*

Nowadays, dysplasia management in UC takes into account the grade and number of dysplasia, whether visible or not, and the presence of primary sclerosing cirrhosis (PSC) (**Figures 8** and **9**) [11, 15, 16].

*Restorative Proctocolectomy: When to Propose and When to Avoid DOI: http://dx.doi.org/10.5772/intechopen.98987*

**Figure 8.**

*Management of visible dysplasia in ulcerative colitis.*

**Figure 9.** *Management of invisible dysplasia in ulcerative colitis.*

#### **Table 2.** *CRC risk factors in ulcerative colitis.*

In a systematic review of the literature, Fumery et al. found that among patients with UC-LGD under surveillance, the annual incidence of progression to CRC was 0.8%. Concomitant primary sclerosing cholangitis, invisible dysplasia, distal location, and multifocal LGD are high-risk features associated with dysplasia progression [17].

In UC patients with high-grade dysplasia or colorectal cancer (CRC), the colon and rectum should be removed with *en bloc* oncologic resection of lymph nodes in all colonic segments due to the high risk of multiple synchronous tumors and preoperative under staging (ECCO statement 9A) [18].

The risk of colorectal cancer in UC is increased compared with the general population (**Table 2**) [19–24]. Moreover, it is estimated to be around 18% after 30 years of UC duration [20].

Occasionally, total abdominal colectomy with ileorectal rectal anastomosis (TAC-IRA) can be considered.


**3.8 Relative binding affinity of TauR2 towards neuronal specific tubulin isotypes**

The relative binding affinity of TauR2 towards neuronal specific tubulin isotypes (β/α/β) was analyzed by performing MMPBSA calculations for complexes

#### **Table 6.**

*Electrostatic interactions between different* β*/*α*/*β*-tubulin isotypes and TauR2 after molecular dynamics simulations.*

6CVN-tau, 6CVN\*-tau, βI/α/βI-tau, βIIb/α/βIIb-tau and βIII/α/βIII-tau etc. The energy components that govern the binding energy are recorded in **Table 7**. This analysis reveals that, βIII/α/βIII-tau complex shows most favorable interactions while 6CVN-tau complex is least favorable as supported by the binding energy values listed in **Table 7**. Thus, it is interesting to note the significance of C-terminal tail of the tubulin subunits in the stable binding of the tau repeat R2 to stabilize this complex. The order of calculated binding energy in between TauR2 with neuronal specific tubulin-TauR2 complexes is βIII/α/βIII > βIIb/α/βIIb >6CVN\* > βI/α/ βI > 6CVN. The electrostatic interactions in these complexes contribute significantly to the binding energy particularly in βIII/α/βIII-TauR2 and βIIb/α/βIIb-TauR2 complexes when compared to the 6CVN and βI/α/βI tubulin subunits (**Table 7**). The complex βI/α/βI-TauR2 exhibits higher binding energy leading to its weaker affinity towards TauR2. In addition to βIII/α/βIII-TauR2 the complex βIIb/α/βIIb-TauR2 also exhibits relatively higher affinity towards TauR2 compared to rest other complexes. Further, contribution of the individual residues in the binding energy has been investigated by calculating the decomposition energy for each residue. This analysis reveals that, residues from the H12 helix and C-terminal tail of tubulin subunits shows maximum contribution in the binding energy (**Figure 13**). The per-residue

**89**

Binding Energy

**Figure 12.**

*(E)* β*III/*α*/*β*III-TauR2.*

**Table 7.**

*in kcal/Mol.*

*Homology Modeling of Tubulin Isotypes to Investigate MT-Tau Interactions*

interactions energy (residue decomposition energy) calculated for various pairs of interacting residues highlights the importance of the interacting residues. The residues from the H12-helices and C-terminal tail region of complex βIII/α/βIII shows maximum contribution (most negative energy) in the non-bonded contacts leading to the stable and tight binding of the tauR2 to the βIII/α/βIII tubulin subunits.

*The relative binding energy of the tubulin-TauR2 complexes calculated using MMPBSA. All energies are given*

**System 6CVN 6CVN\*** β**I/**α**/**β**I** β**II/**α**/**β**II** β**III/**α**/**β**III** Vdw −97.25 ± 0.55 −131.17 ± 0.62 −133.38 ± 0.69 −124.36 ± 0.60 −125.24 ± 0.59 Elec −1232.33 ± 3.43 −1534.36 ± 3.12 −1423.07 ± 2.77 −1659.30 ± 4.68 −1768.65 ± 2.77 Polar 413.98 ± 4.73 349.43 ± 4.18 439.27 ± 2.95 433.79 ± 4.13 505.14 ± 2.92 SASA −12.35 ± 0.06 −15.12 ± 0.07 −17.05 ± 0.05 −15.66 ± 0.06 −16.04 ± 0.05

*The secondary structure changes during MD simulation using DSSP for TauR2. Secondary structure changes observed in (A) 6CVN-TauR2 (B) 6CVN\*-TauR2 (C)* β*I/*α*/*β*I-TauR2, (D)* β*IIb/*α*/*β*IIb-TauR2 and*

−927.87 ± 3.15 −1331.15 ± 3.19 −1134.13 ± 1.13 −1365.2.26 ± 2.26 −1404.7 ± 1.84

*DOI: http://dx.doi.org/10.5772/intechopen.95792*

*Homology Modeling of Tubulin Isotypes to Investigate MT-Tau Interactions DOI: http://dx.doi.org/10.5772/intechopen.95792*

#### **Figure 12.**

*Homology Molecular Modeling - Perspectives and Applications*

6CVN\*

**Systems Electrostatic interactions Distance (Å)** 6CVN-TauR2 D: LYS8:NZ - A: ALA430:O 4.04432

βI/α/βI-TauR2 D: LYS1: N - A: GLU421:OE1 2.86182

βIIb/α/βIIb-TauR2 A: LYS21:NZ - E: GLU434:OE2 4.3529

βIII/α/βIII-TauR2 A: LYS25:NZ - E: GLU434:OE2 2.68494

D: LYS21:NZ - B: SER439:O 4.66847 D: LYS25:NZ - B: GLU434:OE2 4.90999 D: LYS21:NZ - B: GLU434:OE1 5.38615

A: LYS7:NZ - E: GLU415:OE1 4.9846 A: LYS25:NZ - E: GLU441:OE1 5.12197 A: LYS17:NZ - E: ASP424:OD2 5.27557

D: LYS25:NZ - C: GLU412:OE1 4.31321 D: LYS7:NZ - B: GLU415:OE1 4.45715 D: LYS21:NZ - B: GLU434:OE2 4.75044

A: LYS8:NZ - E: ASP396:OD2 5.021

A: LYS25:NZ - E: GLU450:OE2 2.85019 A: LYS1: N - F: ASP417:OD2 2.91844 A: LYS1: N - F: GLU421:OE2 4.28381 A: LYS7:NZ - E: GLU415:OE1 4.31182 A: LYS21:NZ - E: GLU434:OE1 4.48844 A: LYS17:NZ - E: ASP424:OD2 4.70401 G: LYS392:NZ - A: ASP22:OD2 4.95323 A: LYS21:NZ - E: GLU450:OE2 5.37409

6CVN-tau, 6CVN\*-tau, βI/α/βI-tau, βIIb/α/βIIb-tau and βIII/α/βIII-tau etc. The energy components that govern the binding energy are recorded in **Table 7**. This analysis reveals that, βIII/α/βIII-tau complex shows most favorable interactions while 6CVN-tau complex is least favorable as supported by the binding energy values listed in **Table 7**. Thus, it is interesting to note the significance of C-terminal tail of the tubulin subunits in the stable binding of the tau repeat R2 to stabilize this complex. The order of calculated binding energy in between TauR2 with neuronal specific tubulin-TauR2 complexes is βIII/α/βIII > βIIb/α/βIIb >6CVN\* > βI/α/ βI > 6CVN. The electrostatic interactions in these complexes contribute significantly to the binding energy particularly in βIII/α/βIII-TauR2 and βIIb/α/βIIb-TauR2 complexes when compared to the 6CVN and βI/α/βI tubulin subunits (**Table 7**). The complex βI/α/βI-TauR2 exhibits higher binding energy leading to its weaker affinity towards TauR2. In addition to βIII/α/βIII-TauR2 the complex βIIb/α/βIIb-TauR2 also exhibits relatively higher affinity towards TauR2 compared to rest other complexes. Further, contribution of the individual residues in the binding energy has been investigated by calculating the decomposition energy for each residue. This analysis reveals that, residues from the H12 helix and C-terminal tail of tubulin subunits shows maximum contribution in the binding energy (**Figure 13**). The per-residue

*Electrostatic interactions between different* β*/*α*/*β*-tubulin isotypes and TauR2 after molecular dynamics*

**88**

**Table 6.**

*simulations.*

*The secondary structure changes during MD simulation using DSSP for TauR2. Secondary structure changes observed in (A) 6CVN-TauR2 (B) 6CVN\*-TauR2 (C)* β*I/*α*/*β*I-TauR2, (D)* β*IIb/*α*/*β*IIb-TauR2 and (E)* β*III/*α*/*β*III-TauR2.*

#### **Table 7.**

*The relative binding energy of the tubulin-TauR2 complexes calculated using MMPBSA. All energies are given in kcal/Mol.*

interactions energy (residue decomposition energy) calculated for various pairs of interacting residues highlights the importance of the interacting residues. The residues from the H12-helices and C-terminal tail region of complex βIII/α/βIII shows maximum contribution (most negative energy) in the non-bonded contacts leading to the stable and tight binding of the tauR2 to the βIII/α/βIII tubulin subunits.

**Figure 13.**

*The H12 and C-terminal tail regions show highest energy contribution for the binding of TauR2 in 6CVN\*,*  β*I/*α*/*β*I,* β*IIb/*α*/*β*IIb and* β*III/*α*/*β*III tubulin subunits except in case of 6CVN which does not have C-terminal tail region.*

Hence, relative binding energy calculations further support all other MD simulation results highlighting the tight binding of TauR2 to the βIII/α/βIII tubulin isotype which is predominantly expressed in the neuronal cells and brain.

## **4. Conclusion**

MTs are distributed across all types of cells and play an important role in the cellular functions. Structurally MTs are made up of α/β heterodimeric subunits. Large diversity of α and β-tubulin isotypes exists which are differently expressed in different types of cells, this makes MTs unique from one another in relative proportion of isotypes. The much elevated expression levels of βII and βIII tubulin isotypes about 58% and 25% respectively have been reported to in neuronal cells and brain [35]. The present study extensively uses molecular modeling approaches including homology modeling, MD simulation, binding energy to investigate the binding mode and interaction of neuronal specific tubulin isotypes with TauR2.

Extensive analysis on MD simulation trajectory shows a stable complex formation in between different tubulin isotype and TauR2. The stability of these complexes is mainly mediated by the interactions of H12 helix and C-terminal tail of the α/β tubulin isotypes with TauR2. TauR2 shows differential binding affinity towards various neuronal specific β-tubulin isotypes (βI, βII and βIII) the order of binding affinity is 'βIII> βIIb>βI'. Thus, it is found that TauR2 expresses greater binding affinity with βIII and βIIb tubulin isotypes which are abundantly expressed in neuronal cells and brain. The molecular modeling strategy adopted in this chapter could be potentially used to understand differential binding affinity of other tau repeats such as R1, R3, R4 towards β tubulin isotypes present in other cell lines. The structures for other repeats could be generated using homology modeling and their interactions with neuronal specific tubulin isotypes could also be studied using similar molecular modeling approach.

**91**

**Author details**

Vishwambhar Vishnu Bhandare

Bombay, Mumbai, India

**Acknowledgements**

**Conflict of interest**

Department of Biosciences and Bioengineering, Indian Institute of Technology

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*Address all correspondence to<EMAIL_ADDRESS>
provided the original work is properly cited.

*Homology Modeling of Tubulin Isotypes to Investigate MT-Tau Interactions*

lateral sclerosis and other tauopathy linked neurodegenerative disorders.

ture and functions using molecular modeling techniques.

http://creativecommons.org/licenses/by/4.0/

The author declares no conflict of interest.

I believe that the knowledge on precise molecular origin of differential binding affinity of tau with β tubulin isotypes present different cell types will pave the way for developing effective treatments against tau related disorders such as Alzheimers, Amyotrophic

Thus, homology modeling allows us to investigate important biomolecular interactions whose protein structures are not known and/or difficult to get by using biophysical experiments. This, homology modeling, computational tool has made it easier to address various challenging problems in understanding the basic phenomenon's/pathways in modern biology. Also, it has proven wide successful applications in determining the role of proteins in various genetic diseases, hormonal disorder cancers, neurological disorders and other diseases etc. by exploring protein struc-

VVB is thankful to IIT Bombay for Institute postdoctoral fellowship. Author

is also thankful to Prof. Ambarish Kunwar, Department of Biosciences and Bioengineering, IIT Bombay, Mumbai for fruitful discussion and providing necessary computational resources to perform this research work. Author also sincerely thanks Creative Commons license for giving permission to use data from my manuscript my published research article in Scientific Reports (https://doi.org/10.1038/ s41598-019-47249-7). A copy of creative commons license can be found at the link

*DOI: http://dx.doi.org/10.5772/intechopen.95792*

*Homology Modeling of Tubulin Isotypes to Investigate MT-Tau Interactions DOI: http://dx.doi.org/10.5772/intechopen.95792*

I believe that the knowledge on precise molecular origin of differential binding affinity of tau with β tubulin isotypes present different cell types will pave the way for developing effective treatments against tau related disorders such as Alzheimers, Amyotrophic lateral sclerosis and other tauopathy linked neurodegenerative disorders.

Thus, homology modeling allows us to investigate important biomolecular interactions whose protein structures are not known and/or difficult to get by using biophysical experiments. This, homology modeling, computational tool has made it easier to address various challenging problems in understanding the basic phenomenon's/pathways in modern biology. Also, it has proven wide successful applications in determining the role of proteins in various genetic diseases, hormonal disorder cancers, neurological disorders and other diseases etc. by exploring protein structure and functions using molecular modeling techniques.


**7. Boron-based fire retardant coatings**

char forming additives are still prominent solution to address the flammability and environ-

Cone calorimeter is a most commonly used bench-scale method to evaluate the flammability of wood. Shi and Chew have investigated the carbon monoxide (CO) yield of six species of wood samples under different external heat fluxes and moisture content by spontaneous ignition in a cone calorimeter. Spontaneous ignition is a complex phenomenon that combustible materials are ignited by internal heating, without the spark plug. As compare to piloted ignition, process of spontaneous ignition is much closer to the development of real fire. Results observed that thickness of wood has little effect to peak CO release rate, but the time to peak is postponed with a higher thickness. The peak CO release rate decreases with a higher external heat flux, but the decrease is not obvious when heat flux increases from 50 to 75 kW/

. Average CO yield is inversely proportional to external heat flux, thickness, and density. They concluded that both flame and moisture can also reduce CO release rate because energy used for water evaporation increases with high moisture content [25]. The effect of variable heat flux and oxygen concentrations (20.9, 18, 16 and 15%) on ignition time and mass loss rate of wood was investigated to obtain the kinetic parameters, activation energy and frequency factor. It was found that with increasing the oxygen concentration, the mass loss rate was increased, but the ignition time, the activation energy and the frequency factor were decreased [26]. Critical heat flux for ignition has been calculated to be between 10 and 13 kW/

for a range of wood products. Density, thickness and moisture content have a large influ-

The charring rate, speed at which charring depth advance in the material when exposed to high temperature, is a critical parameter for flammability of wooden samples because it allows the determination of the size of the residual section of wood. It depends on wood species, density, moisture content, permeability, composition and direction of burning [28]. For example, the charring rate of flame retardant-treated wood is linearly proportional to the applied heat flux in cone calorimeter and inversely proportional to the density of wood. Charred wood is bounded by the transition between the pyrolysis layer, the zone where thermal degradation of wood and char formation is actually occurring and the char layer, a zone of cracked charcoal that has no relevant strength or stiffness properties. Charring depth is the distance between the outer surface of the original member and the position of the char line. The base of char layer is widely occurs between 280 and 300°C. Beikircher et al. determined the charring rate, mass loss and temperature development of Norway wood coated with transparent and colored intumescent coatings using cone calorimeter and ISO 834 furnace test. They found that the intumescent coatings reduce the charring rate significantly at all irradiance and cellulosic fire exposure condition (ISO 834 test curve) in comparison with the uncoated (REF) wood sample (**Figure 2**). Intumescent coatings can delay the onset of charring

mental issues [24].

106 New Technologies in Protective Coatings

m2

m2

ence on the material dependent properties [27].

and reduce the charring rate of wood [29].

**6. Charring rate of wood**

Boric acid (H3 BO3 ) and borax (Na2 B4 O7 .10H2 O) are used as borates, which are water soluble and most commonly used flame retardants in wood products. Boron-containing formulations are also used to improve the service life of timbers, in terms of both increase in resistance to biological attacks and renders more resistant to burning. Atar and Keskin studied the flammability of varnish coated Uludag Fir wood and boron compound impregnation. The ASTM D1413-99 standard is used to impregnate the wood by vacuum technique using a mixture of boric acid and borax. The flammability of wood was characterized by ASTM E160-50. They found that boron impregnations showed decrease the flammability of wood as compared to varnish coated wood. It was suggested that the impregnation of wood with boron compounds before varnish coating can decrease the combustion temperature and provide security to wood structure. Further, they investigated the impact of boron compounds impregnation on combustion properties of the laminated veneer lumber obtained from European oak and Lombardy poplar woods. Because of the interaction of impregnation materials with wood structure, the lowest flame source combustion was observed in treated wood [30, 31].

Blasi et al. have investigated the pyrolysis products of fir wood impregnated with boric acid at heating temperatures of 377 and 527°C. It was found that the yields of char and water increase with boric acid concentration (below 2%), and the amounts of organic liquid products are reduced. The boric acid treatment lowers the activation energy and delayed the most important oxidation reaction of fir wood. The reaction temperature does not affect the pyrolysis product distribution but at lower temperature, the higher the char yields, water and non-flammable volatile products were observed [32]. Further, the effect of diammonium phosphate (DAP) and diammonium sulfate (DAS) treatment on the pyrolysis of wood was investigated. Two ammonium salts are widely used as flame retardants in wood substrate, and both are significantly alter the char reactivity. A lower activation energy and a higher reaction order are obtained for DAP-treated sample as compared to wood treated with DAS [33]. Both treatments produce an equal amount and composition of solid, liquid and gaseous products during decomposition. However, with increasing the concentration of salts and/or decreasing the heating temperature produce greater amount of char and water. It was concluded that DAP treatment showed better flame retardancy on the basis of the formation of higher yields of char, water and lower combustible flammable liquids. It also confirmed that the release of decomposed volatile products depends on the DAP concentration [34, 35]. The thermogravimetric analysis was carried out in air of wood and wood impregnated with DAP concentrations range up to 20% and heating rates between 5 and 20°C/min. Results showed a three step decompositions in sequence of wood decomposition, induction and char oxidation, and concluded that the estimated kinetic parameters are independent of the heating rate but vary with the DAP concentration. However, the activation energies of the various steps remain practically constant except for the decomposition of the cellulose component or the decomposition step, depending on the complexity of the mechanism [36].

The fire performance of Douglas fir wood was studied by both natural extractives and a mixture of boric acid and borax treatment. Dual treatments of wood with the natural extractives and borates were targeted to benefit from their potential cumulative protections, which are biological resistance and fire retardancy. It was observed that both treated wood specimens showed excellent fire retardant performance [37]. Tomark and Cavdar studied the effect of boron powder (BP), mixture of boric acid (BA) and borax (BX) and flame retardant agent (FA) based on liquid blend of limestone and silicone oil (SO) treatment on the oxygen index (OI) of Scots pine wood of bare and after leaching process. Leaching procedure was carried out to determine the permanent performance of the preservatives in wood. The oxygen index (OI) is the minimum percentage of oxygen required to continue flaming combustion of a sample under laboratory condition. Wood samples were initially vacuum treated with the preservative and then were subjected to leaching. **Figure 3** showed that the wood treated with flame retardants provided the best results, and moreover, leaching did not considerably change the

**Figure 3.** OI of un-leached and leached flame retardant-treated wood [38].

OI of wood. However, OI of treated sample was affected by leaching procedure, which may be due to the preservatives are not chemically adhered to the wood [38].

Disodium octaborate tetrahydrate (Na2 B8 O13.4H2 O) in waterborne paint treatment provides better fire retardant properties of Scot pine wood. The properties are further improved by tannin-based wood preservative solutions [39]. Further, the effect of wood preservative loading on the OI of fir wood was investigated. Wood preservatives have been widely used to extend the service life of wood. Study indicated that almost all treated samples showed higher OI values, and moreover, 3% copper-based preservative (Wolmanit-CB) was recommended [40]. The improvement in dimensional stability, durability and fire retardant properties of wood was investigated by using 1,3-dimethylol-4,5-dihydroxyethyleneurea treatment. The Oak wood showed considerable decrease in the pyrolysis temperature, heat release rate, and smoke production when methylolguanylurea phosphate and boric acid flame retardants were incorporated [41]. There is a current contentious toxicity problem with boron compounds, and as such, a need for wood products to move away from boron-based fire retardants is recognized.


**Review of Multilevel Voltage Source Inverter Topologies and Analysis of Harmonics Distortions in FC-MLI**

#### **Ronak A. Rana 1, Sujal A. Patel 1, Anand Muthusamy 1, Chee woo Lee 2,\* and Hee-Je Kim 2,\***

Received: 25 September 2019; Accepted: 6 November 2019; Published: 11 November 2019

**Abstract:** We review the most common topology of multi-level inverters. As is known, the conventional inverters are utilized to create an alternating current (AC) source from a direct current (DC) source. The two-level inverter provides various output voltages [(Vdc/2) and (−Vdc/2)] of the load. It is a successive method, but it makes the harmonic distortion of the output side, Electromagnetic interference (EMI), and high dv/dt. We solve this problem by constructing the sinusoidal voltage waveform. This is achieved by a "multilevel inverter" (MLI). The multilevel inverter creates the output voltage with multiple DC voltages as inputs. Many voltage levels are combined to produce a smoother waveform. During the last decade, the multilevel inverter has become very popular in medium and high-power applications with some advantages, such as the reduced power dissipation of switching elements, low harmonics, and low EMIs. We introduce the information about several multilevel inverters such as the diode-clamped multilevel inverter (DC-MLI), cascaded H-bridge multilevel inverter (CHB-MLI), and flying-capacitor multilevel inverter (FC-MLI) with Power systems CAD (PSCAD) simulation. It is shown that THD is 28.88% in three level FC-MLI while THD is 18.56% in five level topology. Therefore, we can decrease the total harmonic distortion adopting the higher-level topology.

**Keywords:** multilevel inverter; diode clamped multilevel inverter; flying capacitor multilevel inverter; cascade H bridge multilevel inverter; total harmonic distortion; PWM control techniques; PSCAD/MULTISIM simulation


*3.4. ABCA1, LDL-C and Triglyceride (TG) Serum Levels*

While the effect of ABCA1 on HDL-C plasma levels is clear, the effect of ABCA1 loss of function on other lipid traits is less evident. Several authors report that TD patients have significantly elevated plasma TG levels and reduced LDL-C concentrations than normal controls, although plasma TG levels vary in these patients [57–60]. Clee et al. reported overall higher TG levels in subjects heterozygous for *ABCA1* mutations than in controls, although TG levels were variable and not elevated in all mutation carriers [61]. Using an extreme phenotype approach, Frikke-Schmidt et al. described nine patients heterozygous for *ABCA1* mutations with very low HDL-C levels, six of which had elevated TG levels (>2.2 mmol/L) [12]. In contrast, heterozygous carriers of *ABCA1* mutations have no significant change in LDL-C levels [62–64].

Most GWAS have not reported *ABCA1* as a locus associated with TG and LDL-C levels [65–68]. However, recent multiethnic GWAS, including hundreds of thousands of cases and controls, have identified different *ABCA1* variants associated with TG (rs2575876, rs1799777, rs1883025 and rs1800978) and LDL-C levels (rs7873387, rs2575876, rs2740488, rs11789603, rs2066714) with genome-wide significance, although with small effect sizes [69–72]. In one of these studies, associations with TG levels were observed in current drinkers and/or regular drinkers [69]. In addition, several candidate gene studies also reported *ABCA1* SNPs associated with LDL-C and TG levels, with inconsistent results. While various studies failed to find associations of *ABCA1* gene variation with TG and/or LDL-C levels [40,73–75], *ABCA1* polymorphisms were associated with TG levels but not with LDL-C levels in Brazilians [76], Chinese [77], Turkish [78], Iranians [79] and Mexican school-aged children [80]. The functional *ABCA1*/R230C variant was associated with lower triglyceride levels only in Pimas and Mayans, but not in Mexican mestizos [41]. Moreover, *ABCA1* gene variants have been associated with LDL-C but not TG levels in a cohort of Greek nurses [81], and in male individuals with hypercholesterolemia [82]. In a large multiethnic cohort studying over 150 common variants, *ABCA1* was associated with both TG and LDL-C levels [83].

Postprandial hypertriglyceridemia is an important factor in developing atherosclerotic plaque and is closely related to the occurrence of cardiovascular events [84,85]. Although TG levels are usually estimated in a fasting state, several epidemiological studies have demonstrated that non-fasting hyperlipidemia is more harmful [86–88]. The high interindividual variability of TG levels observed in TD may be due to the inherent heterogeneity in individual triglyceride levels in different postprandial dietary lipid absorption states [89,90]. While several studies have documented single candidate SNPs associated with postprandial TG metabolism modulation [91,92], studies analyzing the effect of *ABCA1* gene variants on postprandial lipid metabolism are scarce. A recent study identified that most of the interindividual variability in the postprandial chylomicron TG response to dietary fat in healthy male adults could be explained by a combination of 42 SNPs in 23 genes, including *ABCA1* [91]. Moreover, Delgado-Lista et al. showed that major allele homozygotes for rs2575875 and rs4149272 had lower postprandial increases in TG and large-triglyceride rich lipoproteins, suggesting these variants may regulate the clearance of postprandial triglycerides [93].

It is evident that altered ABCA1 function and gene variation do not always affect TG levels. This may have to do with ethnicity, sex-specific effects and with interactions with other gene variants and environmental factors. In this regard, a small number of studies have reported interactions between *ABCA1* gene variants and dietary macronutrient proportions affecting plasma TG levels. In the Mexican population, premenopausal women carrying the *ABCA1*/R230C risk allele and consuming higher carbohydrate/lower fat diets

showed an unfavorable metabolic pattern including higher TG levels, with a statistically significant interaction [43]. An independent study in the Inuit population also reported an interaction between the *ABCA1*/R219K variant with saturated fat intake affecting plasma TG levels [94]. These facts indicate that gene-diet interactions may help better predict inter-individual variations in plasma lipid levels and may provide information useful to design diet intervention studies.


**5. Microbiology of bleb related infection**

The most common pathogens in blebitis are Staphylococcus aureus and Staphylococcus epidermidis [47, 54, 55]. The microbes most commonly associated with blebitis are less virulent than those in BRE, are part of normal lid/lacrimal flora, and produce no exotoxins; therefore, with successful treatment, visual prognosis is good. In a retrospective study, visual acuity was at least 20/25 in all successfully treated patients [17].

The microbes most commonly associated with early BRE include Staphylococcus epidermidis. Late onset BRE is associated with greater percentage of Streptococcus species 31%, and Gram-negatives such as Haemophilus influenzae 23%, Enterococcus 7%, Pseudomonas 7%, and fewer Staphylococcus species 7–22% [39, 48, 56].

When initiating antibiotic therapy for BRI, it is important to consider antibiotic resistance, which is particularly high in staphylococci; nearly half being resistant to methicillin with a high probability of concurrent resistance among methicillin resistant Staphylococcus aureus to other commonly used antibiotic classes [57]. In such cases it is useful to know that vancomycin is active against all gram-positive organisms, including all the methicillin-resistant staphylococci [57, 58].


**4. Results**

#### *4.1. Meteorological Conditions in the Base Year*

On the basis of calculations made with the WRF/CALMET model, the analysis of meteorological conditions significantly affecting the dispersion of pollutants in 2018 was performed (Figures 7–15). Both spatial variability of selected parameters per year and monthly variability were discussed based on selected locations—Bogatynia (the largest city in the commune), Sieniawka (located in the southwest of the examined area) and Działoszyn (located in the north of the examined area).

Wind as a parameter shaping the rate and direction of the pollution spread is one of the most important parameters for the dispersion process. With complex terrain, it can be highly variable, and when dealing with such a specific object as a deep open-pit mine, it is necessary to include it in the model as a field variable in space. This is clearly marked when analyzing the prevailing wind directions, where a significant change in the air flow occurs in the area of the open pit and, while the wind is southern for the most part of the area, in the pit, it changes direction to the west or east. The significant dynamics of the dominant wind direction can also be seen in the depression in which Zittau and Hrádek nad Nisou are located, where in 2018, winds from the western sector prevailed.

The calculations show that the wind field in the analyzed area is characterized by variability of annual mean speeds in the range of 3.8 to 4.4 m/s. The highest speeds (above 4.2 m/s) characterize the northwest and southeast parts of the analyzed area (Figure 7). Reduced wind speeds are characteristic of the valley areas (around Bogatynia, as well as Zittau and Hrádek nad Nisou).

Based on the hourly wind speeds and directions, annual wind roses were prepared for selected grids within meteorological domains representing the following cities: Bogatynia, Sieniawka and Działoszyn (Figure 8). The obtained calculation results indicate that, in 2018 in Bogatynia, winds from the southern sector (19%) definitely dominated; the highest speeds were also recorded in this sector. In Sieniawka, the share of winds from the southern sector was also the largest (13%), but the share of winds from the NW and WNW sectors was also significant (around 10% per year). In Działoszyn, apart from southern winds (13%), there was a large share of SSW winds (11%). Only in Działoszyn, the share of winds from the direction in which KWBT is located (in this case, the southern sector) was significant. The highest amount of calm winds was recorded in Bogatynia (1.8%); in other cities, this value was around 1%.

In the case of the analysis of wind speed values, higher values of monthly mean wind speeds (except for the summer months, i.e., June–August) were observed in Bogatynia than in Działoszyn and Sieniawka (Figure 9). According to the distribution of monthly mean wind speeds in 2018, higher wind speeds (above 5 m/s) occur in the autumn and winter months (October, January, November, and December). The spring–summer period (May–August) was characterized by lower wind speeds (below 3.5 m/s).

On the other hand, the classification of wind speeds for selected grids from the studied area shows that the most frequently occurring were the winds with speeds in the 3–5 m/s range (30.5–38.1%), referred to as mild winds (Figure 10). Weak winds, i.e., 1.5–3 m/s, and winds with speeds above 5 m/s occurred with similar frequency in all towns (around 21%–27%). In Bogatynia, more than 1% of winds with very high speeds >10.8 m/s were observed. In 2018, wind speeds less than 1.5 m/s occurred in 9.9% of cases in Działoszyn, 11% in Sieniawka and 12.6% in Bogatynia.

According to the Climate Monitoring Bulletin of Poland, published annually by the Institute of Meteorology and Water Management, 2018 has been classified as an extremely warm year [40,41]. The analyses show that the annual mean air temperature in 2018 in the studied area varied from around 9 ◦C to over 10 ◦C, while in most of the area, it was around 9.5 ◦C. Temperatures above 10 ◦C occurred in the northern part of KWBT and in the vicinity of ELT and in the northwest of the area (Figure 11). The coldest month in 2018 and the only one with the average temperature below 0 ◦C was February (around −4 ◦C). March was also quite cool (monthly mean around 0 ◦C) (Figure 12). The month with the highest mean (>20 ◦C) was August. At the same time, from April to October, monthly mean temperatures were above 10 ◦C. The characteristics of monthly mean temperatures indicate that the Bogatynia and Działoszyn regions are thermally similar, while the Sieniawka area is slightly cooler.

**Figure 7.** Spatial distribution of annual mean speeds and dominant wind direction determined by the WRF/CALMET model in 2018 (source: own study).

**Figure 8.** The distribution of wind directions and wind speeds determined by the WRF/CALMET model in the meshes of the meteorological grid corresponding to the location of selected towns in 2018 (Source: Own study): (**a**) Bogatynia, (**b**) Sieniawka, (**c**) Działoszyn.

**Figure 9.** Monthly mean wind speeds determined by the WRF/CALMET model in selected towns in 2018 (source: own study).

**Figure 10.** The frequency of wind speeds in specific ranges in selected towns in 2018 (source: own study).

**Figure 11.** Spatial distribution of annual mean air temperature values determined by WRF/CALMET in 2018 (source: own study).

**Figure 12.** The course of the monthly mean air temperature determined by the WRF/CALMET model in selected towns in 2018 (source: own study).

The Pasquill atmospheric stability classes, which describe the vertical air turbulence associated with temperature gradient and wind speed, are very important parameters for the dispersion of pollution. The model adopts six stability classes (PGT1–PGT6). Classes 1 and 2 are unfavorable for the dispersion of pollutants due to the fact that the trail of exhaust gases rises and falls due to intense turbulence. Classes 5 and 6, in which inverse conditions occur, are very unfavorable; the pollutants remain in the given area at low altitudes because they have no conditions for dispersion. The incidence of individual classes was determined for the towns of Sieniawka, Działoszyn and Bogatynia (Figure 13). The calculations show that, in the vicinity of the towns in question, in 2018, the most common was the atmospheric stability class 4, which represents neutral conditions (around or over 50% of cases). Class 1, defined as extremely unstable conditions, was very rare (less than 1% of cases). However, unfavorable classes 5 and 6 occurred in a total of around 21–30% cases during the year, most often in Sieniawka.

The year of 2018 was a dry year, which is also confirmed by the spatial distribution of the annual total precipitation in the area (Figure 14). Such conditions adversely affect the rise of dust pollutants, which, in the case of a large-scale object such as a mine, may contribute to the occurrence of high concentrations. In 2018, the annual rainfall totals in the studied area ranged from around 600 (in the west in the area of the Nysa Łu ˙zycka Valley) to 800 mm (in the east in the area of the Izera Mountains). The analysis of the annual rainfall totals in selected locations indicates a relatively small variability: from around 590 mm in Sieniawka to around 620 mm in Bogatynia and Działoszyn. The analysis of the variability of precipitation in 2018 shows that the lowest rainfall occurred in February and November—below 10 mm—while the highest was measured in June and December (77–97 mm) (Figure 15). In Sieniawka, high rainfall was noted also in January, where the total was around 30 mm higher than in Bogatynia and Działoszyn. For the remaining period of the year, rainfall totals in Sieniawka were slightly lower than for Bogatynia and Działoszyn, especially in May and June. In the remaining months of the year, the differences in the total precipitation between individual towns did not exceed 10 mm.

**Figure 13.** Share of the Pasquill atmospheric stability classes determined by the WRF/CALMET model in selected towns in 2018 (source: own study).

**Figure 14.** Spatial distribution of annual precipitation determined by the WRF/CALMET model in 2018 (source: own study).

**Figure 15.** Monthly precipitation totals determined by the WRF/CALMET model in selected towns in 2018 (source: own study).

#### *4.2. The Results of Air Quality Modeling*

Human health protection is the main criterion for air quality assessment. This study focuses on the analysis of long-term effects; therefore, the values of annual mean concentrations of PM10 and PM2.5 were assessed, with limit levels of 40 μg/m3 and 25 μg/m3, respectively. The assessment of changes resulting from the implementation of individual scenarios is presented as a relative difference.

Additionally, the shares of the main particulate matter emission sources in concentrations in two selected profiles of different emission nature were analyzed for scenarios 1 and 2. The first profile, around 40 km long, running from Działoszyn through Zatonie to Hrádek nad Nisou, clearly shows the impact of the energy complex. The second profile, around 26 km long, running from Olbersdorf through Zittau, Bogatynia and Hermanice to Frydlant, reflects the characteristics of the concentration field associated with emissions from household heating.

#### 4.2.1. Annual Mean PM10 Concentrations

The obtained results show that, in the year of diagnosis, the annual mean PM10 concentration practically in the entire analyzed area did not exceed the limit value (Figure 16). The area located near the ash storage area, where maximum concentrations reached over 100 μg/m3, was the exception. However, this area is located outside built-up areas, within a forest complex, so its range is limited. High concentrations also occur within the open pit, which is justified by the industrial characteristics of the area. Within the settlement area, the annual mean concentrations of PM10 are in the range of 18–26 μg/m3 (45–65% of the permissible level). The highest concentrations in built-up areas occurred in Bogatynia and reached 34 μg/m3 (85% of the permissible level). The lowest concentrations in the studied area occurred in its northwestern and southeastern regions (in elevated areas, marked in dark green).

The model calculations show that the implementation of corrective actions discussed in scenario 1 (Figure 16b) regarding the power complex facilities results in a maximum 70% reduction in concentrations nearby ash storage area. The greatest effectiveness is expected in the immediate vicinity of the ash stockyard (area marked with an arrow). Within a radius of 4 km from the main emission sources, a maximum reduction of 5% can be expected. The greatest effectiveness of actions in development areas is expected in the districts of Bogatynia–Zatonie (30–40%) and Trzciniec (10–15%), but also in Sieniawka (5–10%) and on the German side in the cities of Hirschfelde and Drausendorf and in eastern areas of Zittau (5–10%).

On the other hand, of the analyses carried out for activities indicated in scenario 2, they will be most effective in built-up areas (Figure 16c). In Bogatynia, as much as 20–40% decrease in annual mean PM10 concentrations is estimated. In larger cities, concentrations will fall by around 10–20%, and, in the remaining areas, the change will not exceed 5–10%.

The best effect was obtained for the compilation of scenarios 1 and 2, which is scenario 3 (Figure 16d), in which case at least a 10% decrease in concentrations can be expected basically in the entire analyzed area within the Polish borders. A small impact on the decrease in concentrations on the Czech and German side may, however, prove that the impact of both the energy complex and local emissions associated with the combustion of fuels in household heating devices is very limited.

Analyzing the share of emission sources in the annual mean PM10 concentrations in the profile between Działoszyn and Hrádek nad Nisou (Figure 17), it can be concluded that the inflow of pollutants from outside the computational domain has a very significant share, which is estimated at around 16 μg/m3 basically along the entire length of the profile. The concentrations related to household heating, which are clearly marked only on the Polish side of the border, are also an important component of the profile. The closer the sources of the power complex, the more significant the increase in their share; however, their range of influence is very limited (a few km). In the immediate vicinity of the ash storage area, its share is similar to the share of the inflow. The impact of KWBT is practically limited to industrial areas and may be associated with local high concentrations, even exceeding the target values. At the same time, it is clear that individual operations (transshipment at a coal yard, dumping or mining) have a significant impact basically in the place of their performance.

**Figure 16.** Annual mean PM10 concentrations in 2018: modeled values and relative differences for the analyzed scenarios (source: own study): (**a**) in 2018, (**b**) relative difference for scenario 1, (**c**) relative difference for scenario 2, (**d**) relative difference for scenario 3.

**Figure 17.** Profile of annual mean concentrations of PM10 between Działoszyn and Hrádek nad Nisou, considering the shares of individual source groups in 2018 (source: own study).

The implementation of the measures from scenario 1 will result in a very large decrease in concentrations, and so air quality standards will be met throughout the entire length of the analyzed profile (Figure 18). In this case, the most important factor shaping the air quality in the studied area will be the inflow of pollution. The impact of the power complex will be comparable to the current impact of emissions from household heating.

**Figure 18.** Profile of annual mean concentrations of PM10 between Działoszyn and Hrádek nad Nisou, considering the shares of individual source groups for scenario 1 (source: own study).

In the profile from Olbersdorf to Frydlant, the inflow of pollutants from outside of the studied area has the largest share in annual mean PM10 concentrations (Figure 19), similar to the profile analyzed earlier. However, in Poland, emissions related to household heating also have a very high share in concentration. This is particularly evident in Bogatynia, where concentrations from this type of emission can reach up to 12 μg/m3. Transport is the third most important group of sources in the studied profile (maximum annual mean PM10 concentrations reach up to around 3 μg/m3). The impact of the mine is relatively small, and it is significant only within the open pit (mining). At the same time, there are no exceedances of air quality standards virtually along the entire length of the profile.

The implementation of the anti-smog resolution will practically eliminate the impact of emissions from household heating, which will result in a significant reduction in the concentrations associated with it. This is clearly marked on the analyzed profile (Figure 20).

**Figure 19.** Profile of annual mean concentrations of PM10 between Działoszyn and Hrádek nad Nisou, considering the shares of individual source groups in 2018 (source: own study).

**Figure 20.** Profile of annual mean concentrations of PM10 between Olbersdorf and Frydlant, considering the shares of individual source groups in scenario 2 (source: own study).

#### 4.2.2. Annual Mean PM2.5 Concentrations

The results of the conducted model tests indicate that the lowest values of the annual mean PM2.5 concentration occurred in the eastern part of the area, where they do not exceed 14 μg/m3 (56% of the limit value) (Figure 21a). In the central part of the area, concentrations remain in the range of 14–16 μg/m3. Outside the industrial area, the highest annual mean PM2.5 concentrations occur in Bogatynia, where they reach around 23 μg/m3 (92% of the limit value). In other locations in the studied area, higher annual mean concentrations of PM2.5 were also recorded in Trzciniec Dolny (84% of the limit value), Zatonie (79% of the limit value), Sieniawka (76% of the limit value) and Działoszyn (70% of the limit value).

**Figure 21.** PM2.5 annual mean concentrations in 2018: modeled values and relative differences for the analyzed scenarios (source: own study): (**a**) in 2018, (**b**) relative difference for scenario 1, (**c**) relative difference for scenario 2, (**d**) relative difference for scenario 3.

Minimizing measures implemented in scenario 1 will locally (nearby ash storage area) result in a maximum 75% reduction in annual mean PM2.5 concentrations (Figure 21b). However, the range of maximum reductions is smaller than it was in the case of PM10, which is due to the nature of the dust associated with the emitters of the power complex (in particular, KWBT and ash storage area). Emissions from this type of facility primarily concern mineral dust with larger fractions and lower volatility. The greatest efficiency is expected in the immediate vicinity of the ash storage area. Within a radius of 1.5 km from the main sources, a maximum reduction of 5% can be expected. Analyzing the development areas, the direct significant impact of the application of the measures resulting from scenario 1 can only be seen in Zatonie and Trzciniec.

The implementation of scenario 2 will result in similar reductions in PM2.5 concentrations, as in the case of PM10, but the reduction range is greater (Figure 21c).

As in the case of PM2.5, the best effect was obtained for scenario 3: a 10% reduction in concentration values was obtained practically throughout the entire analyzed area within the Polish borders (Figure 21d).

In the profile between Działoszyn and Hrádek nad Nisou (Figure 22), there are no exceedances of air quality standards set for annual mean concentrations of PM2.5. Analyzing the shares of emission sources, it can be stated that, also in the case of this pollution, the inflow of pollutants from outside the computational domain has a very significant share, which is estimated at around 13 μg/m3 on the entire length of the profile. An important component of the profile is also concentrations related

to household heating. As the sources of the power complex approach, their share increases, and the impact is much smaller than it was in the case of PM10.

**Figure 22.** Profile of annual mean concentrations of PM2.5 between Działoszyn and Hrádek nad Nisou, considering the shares of individual source groups in 2018 (source: own study).

The emission reduction related to the implementation of scenario 1 will significantly reduce the annual mean concentrations of PM2.5 and the share of concentrations from local emissions will be lower than the concentrations from inflow (Figure 23). The impact of emissions related to the ash storage area will practically disappear and the impact of emissions from the mine will be limited to its area. The largest share of local emissions in concentrations will be associated with the impact of local heating sources.

**Figure 23.** Profile of annual mean concentrations of PM2.5 between Działoszyn and Hrádek nad Nisou, considering the shares of individual source groups for scenario 1 (source: own study).

In the profile between Olbersdorf and Frydlant, the annual mean concentration of PM2.5 also has the most significant share of pollution (Figure 24). Locally, however, in Bogatynia, there is a very large share of emissions associated with household heating systems. The concentrations in Bogatynia are approaching the limit value, but they do not exceed it. Other local sources (also emissions related to KWBT) are much less important.

**Figure 24.** Profile of annual mean concentrations of PM2.5 between Olbersdorf and Frydlant, considering the shares of individual source groups in 2018 (source: own study).

The implementation of the anti-smog resolution in the examined area will practically result in a very large reduction of local emissions and thus its impact on the formation of air quality in the examined area (Figure 25). The more significant impact of KWBT is practically limited to the open-pit area, but its share is similar to the share of emissions from local transport.

**Figure 25.** Profile of annual mean concentrations of PM2.5 between Olbersdorf and Frydlant, considering the shares of individual source groups in scenario 2 (source: own study).

#### *4.3. Assessment of the E*ff*ectiveness of the Implementation of Various Scenarios Based on the Results of Health Risk Analyses*

The obtained results of health risk assessment analyses indicate the 6% general improvement in air quality from the implementation of scenario 1 (all activities specified for the mine) in the entire commune leads to the reduction of health effects by nearly 5%. This confirms that the mine itself has a negligible impact on the health of residents (current estimated health impact—base scenario—is approximately 7%; see Table 7).

**Table 7.** PM2.5 concentration and related premature deaths calculated for emission scenarios.

A completely different situation is observed in the case of scenario 2 (introduction of provisions resulting from the implementation of regional measures, i.e., anti-smog resolution). A noticeable decrease of over 7% in the level of pollution in the commune when implementing scenario 2 causes over a two-fold higher (14.4%) decrease in health risk (premature deaths).

Both abovementioned scenarios can be implemented independently and simultaneously by separate units based on their competence (mine authorities and local government). The implementation of both scenarios together (scenario 3) causes a significantly higher improvement in air quality and reduction in health risk in the studied area (e.g., changes in the values of the weighted population annual average concentration). After implementing the scenario 3 measures in the analyzed area, the 18% decrease in the number of premature deaths can be expected (estimated according to the baseline scenario) when the concentration of average annual particulate matter is reduced by just over 13%.

In each case (scenarios), the spatial distribution of health effects reduction changes is not regular (Figures 26–28). The analysis of the obtained results of premature death changes distribution for the areas of the commune shows little impact on the populated area for scenario 1, where in the vast majority of areas (nearly 73% of the area), the observed changes do not exceed 5% (Figure 26). Despite this, in this scenario, there are close to 1% areas with over 30% improvement in health. Generally, in 7% of areas, the number of premature deaths is reduced by at least 15%.

The situation looks much better with the implementation of scenario 2 (Figure 27). For this scenario, a decrease in the number of premature deaths associated with long-term exposure to PM2.5 lower than 5% is already observed in nearly 58% of areas. An improvement in health—that is, at least a 15% reduction in premature deaths—has already been noticed in 12% of areas.

Implementation of scenarios 1 and 2 at the same time remains the most effective and health-promoting solution (for scenario 3, see Figure 28). Assessment results for scenario 3 show that only in 25% of the areas, the improvement in health is less than 5%, while a reduction in premature deaths of over 15% is observed almost in 33% of the commune's area.

**Figure 26.** Spatial distribution of relative changes (reductions) in the number of premature deaths for scenario 1 relative to the baseline scenario.

**Figure 27.** Spatial distribution of relative changes (reductions) in the number of premature deaths for scenario 2 relative to the baseline scenario.

**Figure 28.** Spatial distribution of relative changes (reductions) in the number of premature deaths for scenario 3 relative to the baseline scenario.

#### **5. Summary and Final Conclusions**

Mathematical modeling is one of the tools whose application within the air quality management system is crucial. Commonly, mathematical models apply, among others, when developing plans and programs of corrective actions aimed at achieving and/or maintaining air quality at an appropriate level; analyses of the effectiveness of implementing specific solutions; analyses of the impact of air pollution on various elements of the environment, including human health; air quality forecasting, considering changes in the activity of emission sources and meteorological conditions, and providing the public and decision-makers with adequate information. In the case of modeling systems, it is important that the input data used in the analyses (including emission, meteorological and topographic data) are current and accurate. This has a significant impact on the results obtained by modeling and their credibility and representativeness. An important element of this type of analysis is the assessment of discrepancies in the results of model calculations, including the relative error rate of the modeling result in relation to the results of measurements made at measuring stations using devices compatible with or equivalent to the reference method specified for a given pollutant. This type of procedure was undertaken as part of the work in which the selected case study was the area of the commune in Poland, whose character was considered unique and complex due to the geographical location and diversity of the terrain and the functioning energy complex. Analyses were carried out considering the defined activities for three emission reduction scenarios: (1) scenario related to changes in emissions in the analyzed mine resulting from the minimizing measures indicated in the report on the mine's environmental impact, (2) scenario resulting from the "anti-smog" resolution in force in the Lower Silesian Voivodship and (3) scenario compiling the abovementioned scenarios. Additionally, to demonstrate the effectiveness of planned preventive and corrective actions taken in the analyzed area, a health risk analysis was performed. All analyses were made considering the changes in the distribution of pollutant concentrations within the boundaries of the commune.

The results of the conducted analyses indicated that the lowest values of the annual mean PM2.5 concentration occurred in the eastern part of the studied area and did not exceed 14 μg/m3 (56% of the limit value). The implementation of activities resulting from the considered scenario 1 will result in a reduction in annual mean concentrations of PM2.5 (maximum 75% in industrial area), mainly due to the maximum reduction in activities carried out within the furnace ash storage area, as well as the construction of a new ash conveyor, thanks to which the storage area will be practically taken out of operation. The achieved range of maximum concentration reduction was smaller than in the case of PM10, which may be due to the nature of the dust associated with the emitters of the energy complex (in particular, KWBT and ash storage area). Emissions from this type of facility primarily concern mineral dust of larger fractions that are transported in the atmosphere to a much lesser extent. The greatest result is expected in the immediate vicinity of the ash storage area. Within a radius of 1.5 km from the main sources, a slight reduction in concentrations, not exceeding 5% of the current state, can be expected. For this reason, actions taken under this scenario do not have a major impact on the health of the surrounding residents.

The performed analyses have shown that the implementation of scenario 2 will result in similar levels of PM2.5 concentration reductions as PM10, but with a much vaster spatial range, which translates into a much higher impact on the population threat related to air quality, with an estimated 14% reduction.

The best e ffect was obtained for scenario 3, where, in total, the average 10% reduction in concentration values was obtained practically in the entire analyzed area within the borders of the community. Therefore, the implementation of both scenarios seems to be the most e ffective for limiting the health risk associated with the exposure of residents to particulate matter (estimated health e ffect reduction is almost 20%). The full implementation of scenario 3 shows that only in 25% of the area was the expected improvement of health lower than 5%. A significant decrease in health risk (more than 15%) was observed in as much as one third of the studied area.

Mathematical modeling as a tool should be disseminated, and the data used in the model should be available not upon special request but due to the obligation to provide access to information on the environmental impact of an installation, plant and/or the group of emitters in a given area.

**Author Contributions:** Conceptualization, I.S., M.P. and K.S.; methodology, I.S., M.P. and K.S.; software, M.P. and K.S.; validation, I.S., M.P. and K.S.; formal analysis, I.S., M.P., K.S., D.K., M.Z. and K.K.; investigation, I.S., M.P., K.S., D.K., M.Z. and K.K.; writing—original draft preparation, I.S., M.P., K.S., D.K., M.Z. and K.K.; writing—review and editing, I.S., M.P., K.S., D.K., M.Z. and K.K.; visualization, M.P. and K.S.; supervision, I.S. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was co-financed within the "Excellent Science" program of the Polish Ministry of Science and Higher Education.

**Acknowledgments:** The authors of the study thank for their cooperation: Anita Kuli´s from ONE WAY Anita Kuli´s (Zielonka, Poland), Rafał Skorupi ´nski, as well as Milena Gola-Kozak and Dorota Sucholas from PGE Górnictwo i Energetyka Konwencjonalna S.A., Kopalnia W˛egla Brunatnego Turów (Bogatynia, Poland).

**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.


**Chapter 4**

*Urban Horticulture - Necessity of the Future*

fault detection in hydroponics. IFAC Proceedings Volumes.

[17] Ferentinos KP, Albright LD. Predictive neural network modeling of pH and electrical conductivity in deep–trough hydroponics. Transactions

[18] Van LD, Lin YB, Wu TH, Lin YW, Peng SR, Kao LH, et al. PlantTalk: A smartphone-based intelligent hydroponic plant box. Sensors.

of ASAE. 2002;**45**(6):2007

[19] Kurashina Y, Yamashita T, Kurabayashi S, Takemura K, Ando K. Growth control of leaf lettuce with exposure to underwater ultrasound and dissolved oxygen supersaturation.

Ultrasonics Sonochemistry.

[20] Takahashi K, Saito Y, Oikawa R, Okumura T, Takaki K, Fujio T. Development of automatically controlled corona plasma system for inactivation of pathogen in hydroponic cultivation medium of tomato. Journal

of Electrostatics. 2018;**91**:61-69

[21] Talukder MR, Asaduzzaman M, Tanaka H, Asao T. Electro-degradation of culture solution improves growth, yield and quality of strawberry plants grown in closed hydroponics. Scientia Horticulturae. 2019;**243**:243-251

[22] Tanke NF, Long GA, Agrawal D, Valada A, Kantor GA. Automation of hydroponic installations using a robot with position based visual feedback. In: Proceedings of the International Conference of Agricultural Engineering

CIGR-AgEng. 2012. p. C1429

2001;**34**(26):37-42

2019;**19**(8):1763

2019;**51**:292-297

**50**


**10.1 Steroid versus steroid-free protocols**

The known toxicity of long-term steroid exposure has prompted the development of steroidfree immunosuppressive regimens. Benefits of the withdrawal or avoidance of steroids include normal growth in children, improved lipid profiles, improved blood pressure, better glycemic control, and a lower risk of bone disease.

The development of cyclosporine prompted attempts to develop steroid-free protocols. Initially, patients were doing well with cyclosporine monotherapy. Over time, 50% of these patients required steroids, usually for episodes of acute rejection. Strong randomized studies are undoubtedly needed to prove both the efficacy and the safety of these protocols.

Steroid withdrawal has been used as a strategy to avoid adverse steroid effects in transplanted patients. Recent data show that the risk of rejection is higher in patients withdrawn from steroids on a cyclosporine-based protocol. After tacrolimus became available, protocols with this drug showed that withdrawal of steroids after 6 months was successful 80% of the time. More recently, studies involving rapid steroid withdrawal (over 1-2 wk) in patients taking tacrolimus show similar graft survival rates compared with patients withdrawn after 3-6 months. Although the roles of sirolimus and MMF in steroidfree protocols have yet to be definitively determined, the future looks promising for greater use of steroid-free protocols.