This initial hydration reaction was thought to be due to the increase in the filling effect of the hydrate and the generation of C-S-H of the early age by the mass production of Ettringite.In the field of construction, securing the early strength of concrete (on the first and third days of aging) has been an important problem in deciding the mold release time . Therefore, the problem of reduced compressive strength in the early aging stage caused by mixing granulated blast furnace slag (GBFS) with concrete must certainly be resolved. In this study, we conduct experiments to explore methods for generating a concrete that develops an early strength equivalent to that of 100% OPC. The objective of this study is the development of an early-strength accelerator (ESA) made from an industrial by-product, for a GBFS-mixed cement mortar. This study also analyzes the mechanism of the early-strength generation in the concrete to evaluate the influence of the burning temperature of ESA on the optimal compressive strength of the concrete. According to the results of the experiment, GBFS, whose ESA is burnt at 800 °C, shows an activation factor of 102.6–104.7% in comparison with 100% OPC on the first and third days during early aging, thereby meeting the target compressive strength. The results of the micro-analytic experiment are as follows: ESA showed a pH of strongly alkaline. In addition, it was found that the content of SO Therefore, it is very important to use it more actively as an admixture for concrete. In view of the above, the use of GBFS is expected to expand more widely worldwide [Currently, eco-friendly and low-carbon products are being actively developed and efforts are being made to innovate their manufacturing processes in all the industrial fields in accordance with the green-growth policies implemented worldwide. In the construction industry, cement is an essential binder used for manufacturing concrete. However, the volume of limestone mining is expected to reach its limit soon, so that a rise in the manufacturing cost of cement is inevitable in the future because of the regulations on greenhouse gas emissions. Notably, the construction industry emits approximately 7–9% of COmissions ,2,3,4. Tmissions ,6,7. In orldwide ,11,12,13Portland Blast Furnace Slag Cement (PBFSC), which is a mixture of OPC and 20–40% of GBFS, is the most typical type of GBFS used in the construction industry. More recently, High-volume Blast Furnace Slag Cement (HBFSC), whose GBFS content is heightened to 60–70% by applying a cutting-edge technology, is being used for the reduction of the heat of hydration and improvement of seawater and chemical resistance performances ,12,13,142/g) and using an early-strength admixture [rength, rather than the early-strength (on the first and third day of aging). They also failed to clearly identify the mechanism of the hydration reaction triggered by alkali-activation.The methods for improving the early strength of a GBFS-mixed concrete include increasing the fineness of the powder , which can be mass-produced by applying a source technology, for a material that helps in the development of its early-strength (on the first and third day of aging) earlier than 100% OPC. The experiment for this study was conducted on the basis of the results obtained from preceding studies ,21.2-Al2O3 (Sludge), Chemical Gypsum (CG) is generated during the manufacturing process of titanium oxide [The industrial byproducts used in this study are: tap water, which is refined, and the remaining sludge. A High content of SiOum oxide ,23. Limeum oxide  that affum oxide  and the um oxide .After individually burning (0–1100 °C) each of the raw materials selected in this study, their chemical compositions and substances were analyzed. The experiment was conducted separately for the mortar level and cement paste level. The mortar experiment was designed to identify the flow performance and property of compressive strength development.The experiment with the cement paste was designed to identify the mechanism of the hydration reaction on the cement paste resulting from the use of ESA and mechanism of early compressive strength development via microanalysis. Mixtures of the substances used in the experiments are displayed in 2/g. For PBFSC, three types of GBFSs were mixed at 30% of the content .The type of OPC used possessed a fineness of 3450 cm2O3)/SiO2) was 1.79 and fineness was 4330 cm2/g. In consideration of the economic feasibility, OGE (70% OPC + 23% GBFS + 7% ESA) without natural anhydrous gypsum was used for the experiment. Its chemical composition is demonstrated in The basicity , Al2O3 (25–38%), and Fe2O3 (2–5%). When organic impurities are removed by burning, the sludge shows an advantage in contributing to an improved early-strength development of concrete. CG is a by-product generated during a chemical reaction that neutralizes acidic sulfur to lime, and whose main components are CaO (32–39%) and SO3 (45–50%). When the ignition is lost and impurities are removed, LP is the main component of OPC, which exists as CaCO3. Usually, it is converted into CaO during decarboxylation at a temperature > 900 °C. The pH of LP increases from 6 before burning to 12 after burning. It plays the role of a catalyst for the early hydration of Ca(OH)2 crystals and it accelerates the hydration of OPC particles [Based on articles . It was  as SiO2 –46%, Al2In the mixtures used for the experiments , the ratio of each binder and fine aggregates was set at 1:3. The ratio of water to binder was fixed at 50%. The 7% ESA mixture against the mass of cement was experimented at five levels (700–1100 °C). Curing was conducted in an isothermal-isohumidity room at a curing temperature of 20 °C ± 2 °C and with a high relative humidity of 95%. After one day of aging, the cured water was removed. The compressive strength was tested on the 1st, 3rd, 7th, 14th, and 28th day of aging and the compressive strength was determined by calculating the average of three compressive strength values measured for the day. Furthermore, its basic property was compared using the measuring flow. The cement paste experiment was conducted at seven levels: OPC, PBFSC, and OGE1 to OGE5. The ratio of water to cement (W/C) was fixed at 50%. The method of curing was the same as that of the mortar experiment. 2 was high in sludge. In the chemical composition of the sludge, the content of the SiO2 component was 45–55. LP existed as CaCO3 at 800 °C, and was then decarbonated at 900 °C and turned into CaO, which is a strong alkaline substance that accelerates the generation of Ca(OH)2 when reacting with water. It is thought to enable early hydration by removing the oxide coating of GBFS during the early stage.As can be seen from 3 content decreases, while the CaO and SiO2 content increases as the burning temperature increases. Such changes are thought to be attributed to the change in the chemical composition following the decarboxylation of LP and combustion of CO2. In comparison with OPC, the SO3 content in PBFSC is higher by approximately 2%. The SO3 content in OGE with ESA burnt at different temperatures is also greater by approximately 2% when compared to PBFSC.Among the major chemical components of ESA, the SOFurthermore, OGE has a similar chemical composition regardless of the burning temperature of ESA, which is considered to be due to the insignificant share of ESA in the entire OGE, at about 7%.3 at 700–800 °C and then into the peak of CaO at 900 °C or higher. ESA-mixed OGE shows the best compressive strength at 800 °C in terms of the burning temperature. In this region, XRDs of anhydrous gypsum, CaCO3, co-exist.4 content compared with the CaO content, the more effective that CaSO4 is as an effective activator for improved compressive strength in the early aging stage.When the burning temperature increases, the main peak point is turned into CaO from the anhydrous gypsum. The higher the CaSO2 peak, showing a typical hydration product of OPC. In contrast, ESA-mixed OGE generates Ettringite as a hydration product. The generation of Ettringite and C-S-H in early aging is thought to be the cause of the compressive strength development from its filling effect. On the third day of aging, C3S, which is a non-hydration product, decreases and Ca(OH)2 increases. The peak of Ettringite is generally reduced on the third day of aging, which is because when gypsum runs out in the process of hydrate generation of cement, it comes to exist as a monosulfate, which is a stable hydrate.According to A test (free-lime) on the stability of OGE at different burning temperatures of ESA was conducted. It was based on the formula below, by using the Ethylene Glycol method. As displayed in 2 crystals are generated after the reaction of C3S with water, which is correlated with the peak measured in the XRD analysis. In OGE 1 and OGE 2, the generation of Ca(OH)2 and C-S-H was observed. These are generated from the chemical bonding involving Ca2+ around the C3S particle. In OPC, a monosulfate was observed on the third day of aging. Generally, after one day of aging, gypsum is exhausted and turns into a low sulphate. The SO3 content in OGE 1 and OGE 2 is higher than in OPC, as shown in the table of chemical analysis, and SO3 is still observed on the third day of aging. In addition, their compressive strength is similar to that of OPC. OPC is thought to be attributable to the effect of GBFS, which has a higher level of fineness than OPC, as well as to the speed of hydration accelerated by the ESA that has a strongly alkaline pH. Another reason for this may be that the active C-S-H hydration reaction has a greater impact on Ettringite and the compressive strength than the generation of a large volume of Ca(OH)2 when compared with 100% OPC on the first day of aging.In the mortar experiment, the compressive strength decreased as the sintering temperature of ESA increased. The use of OGE 2 showed an equivalent compressive strength in OPC and early age. In addition, the compressive strength at 28 days was also excellent.3 decreases, leading to a rise in the content of CaO and SiO2.When the setting time was measured in the cement paste experiment, the OPC reaction was the fastest. As the burning temperature rises, the content of SO2 from the pH of the strongly alkaline ESA. In addition, the early strength development was also attributable to the generation and filling effect of C-S-H and Ettringite from the supply of SO3.In the XRD and XRF analysis, an increase in the early compressive strength development of OGE was caused by the continuous generation of Ca(OH)In the stability test, ESA-mixed GBFS was found to be stable in terms of excessive expansion and cracks were generated because of the existence of free-lime when applying a construction technology such as steam curing. As the content of free-lime in it is lower than that in OPC, ESA-mixed GBFS is thought to be available when applying the steam curing method such as Precast and when manufacturing special products.3 and apply alkaline-activation to improve the compressive strength at the mortar level, as a way of improving the early strength of GBFS-mixed concrete, which usually has the problem of a low early-strength.In conclusion, ESA developed by using an industrial by-product and industrial waste could be used to supply SO


Experimental and computational simulation methods are used to investigate the adsorption behavior of the surfactant nonylphenol ethoxylate (NPEO10), which contains 10 ethylene oxide groups, on the lignite surface. The adsorption of NPEO10 on lignite follow a Langmuir-type isotherm. The thermodynamic parameters of the adsorption process show that the whole process is spontaneous. X-ray photoelectron spectroscopic (XPS) analysis indicates that a significant fraction of the oxygen-containing functional groups on the lignitic surface were covered by NPEO10. Molecular dynamics (MD) simulations show that the NPEO10 molecules were found to adsorb at the water-coal interface. Moreover, polar interactions are the main effect in the adsorption process. The density distributions of coal, NPEO10, and water molecules along the Z axis show that the remaining hydrophobic portions of the surfactant extend into the solution, creating a more hydrophobic coal surface that repels water molecules. The negative interaction energy calculated from the density profiles of the head and tail groups along the three spatial directions between the surfactant and the lignitic surface suggest that the adsorption process is spontaneous. The self-diffusion coefficients show that the presence of NPEO10 causes higher water mobility by improving the hydrophobicity of lignite. Coal plays an important role in fulfilling the energy needs of our society. Lignite is a typical low-rank coal with very large deposits, which is easy to burn and has highly volatile components ,2. HowevIn recent years, molecular dynamics simulation has become a valuable tool to investigate the interactions of water/surfactant (collector)/mineral surfaces. Compared with experimental methods, computer simulations can directly provide microscopic details and fundamental understanding . Chen et10), which contained 10 ethylene oxide groups, on the surface of lignite using MD and X-ray photoelectron spectroscopy (XPS). The adsorption of NPEO10 on the model surface of lignite was investigated using MD simulations. Quantifying the molecular-scale structural and dynamic behavior of the water/surfactant/coal system is helpful to improve understanding of the interactions between NPEO10 and lignite. In addition, adsorption experiments between lignite and NPEO10 were performed to verify the simulation results.We investigated the fundamental properties and mechanism of the adsorption of nonylphenol ethoxylate  and linearized Freundlich Equation (2) can be represented as follows [b and mQ refer to the Langmuir constant, which is related to the affinity of the adsorption sites, and the maximum amount of NPEO10 per unit weight of adsorbent, and were calculated from the slope and intercept, respectively, of the straight lines of the plot eC/eq vs. eC. According to Equation (2), k and n refer to the Freundlich constant and can be determined from the linear plot of lgeq vs. eC. k is correlated to the adsorption capacity when the adsorbate equilibrium concentration of the adsorbate is equal to 1, and n represents the degree of dependence of the adsorption process on the equilibrium concentration. follows ,26,27,28mQ, b, and n are summarized in r2 values) are given in the same table. As shown in r2 values of the Langmuir equation are 0.9990, 0.9996, and 0.9992 at 308, 318, and 328 K, respectively, all higher than the r2 values of the Freundlich equation, suggesting that the adsorption of NPEO10 onto the coal sample closely follows the Langmuir model.The values of G°) can be calculated using the following equation [b, R, and T are the Langmuir constant, ideal gas constant, and the absolute temperature, respectively. The adsorption free energy calculated on a molar basis was −44.80, −45.28, and −45.88 kJ/mol at 308, 318, and 328 K, respectively ΔGo=A wide-scan spectrum in the binding energy range 0–1400 eV was obtained to identify and quantitatively analyze the surface elements present . A typic10. We found clear changes in the O 1s, N 1s, C 1s, S 2p, Si 2p, and Al 2p peaks after adsorption of NPEO10. Compared with the case before NPEO10 adsorption, the C 1s peak is greatly enhanced after adsorption of NPEO10. However, the O 1s peak showed a clear reduction in size, and the N 1s, S 2p, Si 2p, and Al 2p peaks were slightly weakened. Quantitative peak analysis was carried out to determine the surface elements’ concentrations, and the results are shown in 10.10 on a lignite surface for different simulation times are shown in 10, and water molecules along the Z axis are shown in The aggregated structures of NPEO10 peak appears at ~20 Å, close to the first peak corresponding to water. This water layer may consist of the near-surface water film controlled by the hydrogen bonding between adsorbed water molecules and the coal surface. The intensity of the first peak of the water is obviously weaker, meaning there are fewer water molecules in this region. Most water molecules appear at a distance along the Z-axis exceeding 40 Å. The NPEO10 molecules exist at the interface between water and coal. Water molecules are repelled from the coal surface because of the stronger hydrophobicity of the lignite surface after adsorbing NPEO10. The results also show that the densities of NPEO10 and the coal surface overlap, which does not necessarily mean that NPEO10 molecules penetrate the lignite. Instead, the overlap is partly caused by the roughness of the surface, whose microscopic valleys are filled with the surfactant molecules.The original configuration of NPEOs was in such a way with the polar head groups facing the lignite surface as can been seen in 10 were also calculated to survey the configuration of the adsorbed surfactant molecules on the coal surface, as shown in 10 and the hydrophilic sites on the coal surface is the main force affecting the adsorption process. In other words, the ethylene oxide groups of NPEO10 preferentially adsorb on the hydrophilic sites of lignite and leave the hydrophobic portion of the molecule exposed to the solution. This result indicates that there is a high oxygen content and an abundance of hydrophilic surface functional groups on the lignite surface.The Z-dependent mass density profiles for the head (ethoxylate) and tail (nonylphenol) groups of NPEOinter NPEO & coal). The value of Einter NPEO & coal between NPEO10 and the lignite surface can be calculated using Equation (4):total is the total energy of the system. Ecoal, ENPEO, and Ewater refer to the energies of the coal surface, NPEO10, and water, respectively. Ecoal + water, ENPEO + water, and Ecoal + NPEO are the total energy of coal and water, the total energy of NPEO10 and water, and the total energy of coal and NPEO10, respectively. The value of Einter NPEO & coal obtained from the simulation is −174.16 kJ/mol. The negative value of the interaction energy between the surfactant and coal means that the system becomes more stable after adsorption.The relative intensity and efficiency of the interaction between the surfactant and the coal surface is indicated by the interaction energy  represents the position vector at an initial time, and ir(t) represents the position vector after time t, and the angular brackets signify the ensemble average.The mean square displacement (MSD) is the statistical average of particle trajectories, and is a measurement of the average distance of particles from a given particle. The dynamic properties of water molecules can also be obtained from the MSD, which can be expressed as follows :(5)MSD=N10 are shown in 10. Obviously, the increase in diffusion strength is greater in the coal-water-NPEO10 system.The MSD curves of water molecules in the absence and presence of NPEO10. D can be expressed as follows according to Einstein’s equation [The self-diffusion coefficient (D) reflects the intensity of atomic mobility of water molecules and was calculated in mixed systems both with and without NPEOequation :(6)D=16NThe MSD and self-diffusion coefficient are closely related, as follows:−5 and 4.79 × 10−5 cm2/s in the mixed system with and without NPEO10, respectively. This result means that the mobility of water over the modified coal surface caused by the adsorption of NPEO10 is enhanced as compared to that of water over the surface of original coal. The high mobility of water molecules should contribute to their displacement from the modified coal surface and the attachment of air bubbles. These simulated results are consistent with those obtained from XPS analysis.The self-diffusion coefficients were calculated to be 5.67 × 10Mad), ash content on a dry basis (Aad), volatile content (Vad), and fixed carbon content (FCad) were 9.10%, 19.82%, 62.75%, and FCdaf = 37.25%, respectively.The lignite used in this study was provided by a colliery in China and was crushed to −0.5 mm. Analysis of the coal samples showed that its moisture content  with no further purification. The chemical structure of NPEO10 is shown in NPEO10 on the sample under investigation. The adsorption experiments were carried out in scintillation vials. Each vial contained surfactant solution (25 mL) of a known concentration and 0.5 g of the coal sample. The vials were agitated in a constant temperature water bath oscillator at 308, 318, and 328 K for 24 h, respectively, followed by suction filtration to obtain clear solutions. The surfactant concentrations in the solutions were determined using a spectrophotometer (Model UV757CRT) at a wavelength of 275 nm.The maximum adsorption density was measured for NPEOThe XPS experiments are carried out at room temperature in an ultra-high vacuum (UHV) system with the surface analysis system . The spectrum of the survey scan is recorded at the pass energy of 100 eV with the step size of 1.00 eV. The high resolution spectra are recorded at the pass energy of 20 eV with the step of 0.05 eV. The data processing (peak fitting) is performed with the XPS peak fit software, using a Smart-type background subtraction and Gaussian/Lorentzian peak shapes.3 as shown in Molecular dynamics simulations were conducted using the Materials Studio 8.0 package. The COMPASS force field was applied in all simulations . The mol−3 kcal/mol was used to account for the long-range electrostatic interactions. The coal surface was frozen during the simulation to save computational effort, while the surfactant and water were allowed to relax. A simulation was performed for 1 ns. The final results were calculated based on the outcome of simulations of a period of 500 ps after the equilibration period.The molecular dynamics simulations were run at the NVT ensemble level at 298 K using a Nose thermostat, and the time step was set to 1.0 fs. A van der Waals interaction cutoff of 12.5 Å was employed, and the Ewald summation method with an accuracy of 10Curves showing the fluctuation of energy during the processes of energy minimization and annealing are shown in 10) on the surface of lignite was investigated by experimental and computational simulation methods.The adsorption behavior of nonylphenol ethoxylate with 10 ethylene oxide groups  analyses show that most of the oxygen-containing functional groups on the lignitic coal surface were covered by NPEO10.The adsorption of NPEO10 on a model lignite surface. The NPEO10 molecules were found to adsorb at the water-coal interface. Moreover, the polar interactions between the ethoxylate group of NPEO10 and the hydrophilic sites on the lignitic coal surface were the main factor in the adsorption process. The density distributions of coal, NPEO10, and water molecules along the Z-axis direction showed that the remaining hydrophobic portions of surfactant, which extend into the solution, create a more hydrophobic coal surface to repel the water molecules.Molecular dynamics (MD) simulations were used to investigate the adsorption behavior of NPEO10 molecules was studied through the density profiles of the head and tail groups in the three spatial directions. The results showed that the negative interaction energy between the surfactant and the lignite surface suggest that the adsorption process is spontaneous, which is consistent with the thermodynamics of the experiment. The self-diffusion coefficients show that the presence of NPEO10 causes higher water mobility, improving the hydrophobicity of lignite.The aggregated structure of adsorbed NPEO


The aim of the present study was to evaluate the diameter, relationship and position of the posterior superior alveolar artery and its relationship with the alveolar ridge, the medial wall of the maxillary sinus, the prevalence of pathologic conditions and the maxillary sinus septa on CBCT images.A total of 200 CBCT images (400 maxillary sinuses) of patients over 20 years of age were evaluated. The distances between the lower border of the artery and the alveolar crest and between the artery and the medial wall of the sinus and the diameter of the artery were measured. The position of the artery, the presence of pathologic conditions and septa were recorded in the posterior region in: a) males edentulous in the posterior region; b) males having teeth in the posterior region; c) females edentulous in the posterior region; and d) females having teeth in the posterior region.P<0.05). The mean distance between the artery and the medial wall of the sinus was 11.65±1.21 mm, with no significant differences between the groups (P=0.796). The mean diameter of the canal was 1.37±0.44 mm, with no significant differences between the 4 groups (P=0.570). The position of the artery was intraosseous in 73.2%, beneath the sinus membrane in 21.7% and external to the lateral wall of the sinus in 4.9% of the cases. The overall prevalence rates of pathologic conditions and septa in the maxillary sinus were 45.7% and 26%, respectively.The mean distance between the artery and the alveolar crest, irrespective of groupings, was 16.17±1.63 mm, with significant differences between the groups (CBCT technique is useful for such evaluations and for possible variations in maxillary sinuses and presence of septa and pathologic entities in maxillary sinuses. Key words:Maxillary sinus, maxillary artery, Cone-Beam computed tomography. A written informed consent form, which is routinely obtained from each patient prior to imaging in our clinic, also included a clause for the use of images in this research.All the scans had a high quality to be included in this research and were taken using a scanner. CBCT images of maxillary sinuses that were damaged by tumors or severe traumas were excluded from this study. The images had been taken with a Planmeca Promax 3D CBCT unit  at kVp=84 and mA=16, using 1-mmm cross-sections. For intra-examiner calibration and determination of the reliability and reproducibility of the measurements, the images were re-evaluated by the same observer 2 weeks after the initial evaluation.-Data collection The scans were evaluated in the coronal dimension by a maxillofacial radiologist in three cross-sections: First in the axial cross-section in which the artery was observed for the first time; the second cross-section, after which the artery was not seen; and the third cross-section between these two cross-sections. The position of the artery was divided into: a) intraosseous; b) submembranous; c) on the external cortex of the lateral wall of the sinus. The male and female subjects were divided into 4 groups as follows: 1) males edentulous in the posterior region (n=42); 2) males dentate in the posterior region (n=32); 3) females edentulous in the posterior region (n=37); and 4) females dentate in the posterior region (n=31). The diameters of the artery in the three groups were as follows: a) less than 1 mm; b) 1-2 mm; c) over 2 mm. The distance between the inferior border of the artery and the alveolar crest and the distance between the artery and the medial wall of the sinus were determined.The presence of pathologic entities, including thickening of the membrane, chronic sinusitis and cysts, and the presence of sinus septa measuring at least 2 mm, were recorded. In addition, the canal diameter was recorded in relation to age, gender and location. To determine reliability, the scans were randomly re-evaluated after a month by the radiologist.-Statistical analysesSPSS 23 was used for statistical analyses. Kolmogorov-Smirnov test was used for the evaluation of normal distribution of data. Intra-class correlation coefficient (ICC) was used to determine agreement between the two observations.Means and standard deviations were used to show the distance between the inferior border of the artery and the alveolar crest and also the distance between the artery and the medial wall of the sinus. One-way ANOVA was used to evaluate differences between male and female subjects with and without teeth in the posterior region. In addition, the means and standard deviation of the diameter of arteries were calculated and divided into three groups based on percentages: a) less than 1 mm; b) 1-2 mm; and c) over 2 mm. One-way ANOVA was used to evaluate differences between males and females with and without teeth in the posterior region and the percentages of the location of the artery in terms of intraosseous, submembranous or on the external cortex of the lateral wall of the sinus were separately calculated. The presence of pathologic conditions irrespective of the etiology, including an increase in the thickness of the sinus mucosa to more than 2 mm and the percentage of the presence of sinus septa (at least 2 mm), was determined. The means and standard deviations of canal diameter were determined in male and female subjects. One-way ANOVA was used to evaluate differences between males and females with and without teeth in the posterior region. In addition, Pearson’s correlation coefficient was used to determine the correlation between age and the canal diameter.A total of 400 left and right maxillary sinuses were evaluated. The posterior superior alveolar artery canal was observed in 71% of the sinuses, with 73.2% of the arteries being intraosseous, 21.7% under the sinus membrane and 4.9% external to the lateral wall of the sinus. Location of PSAA is described in In general, the canal diameters were less than 1 mm in 30.2%, 1-2 mm in 59.1% and more than 2 mm in 10.5% of the cases. Range of diameter of the canal was 0.7- 2.7 mm in this research.The means in males and females with and without teeth in the posterior region are described in The mean distance between the artery and the alveolar crest, irrespective of the groups, was 16.17±1.63 mm. The distances in edentulous males, dentate males, edentulous females and dentate females were presented in The overall prevalence of pathologic conditions in the study groups is presented in et al. (2011), Ilgüy et al. (2013), Elian et al. (2005) and Kim et al. (2011) reported observation of the canal in 89.3%, 64.5%, 52.9% and 52% of the cases, respectively  reported observation of the canal in 100% of the cases . Consistent with the present study, Beretta et al. ; h , Neugebauer et al. (47%) and Lana (44.4%)  showed in a comparative study that CT was more accurate than CBCT  -27 and bhan CBCT . An anat (et al.  showed aThe present study recommends the use of the CBCT technique for the evaluation of the position and status of the posterior superior alveolar artery in order to prevent possible complications during implant placement.


A receptors. These data suggest that the molecular mechanism of the effect of Selank may also be related to its ability to affect the performance of the GABAergic system. To test this hypothesis, we studied the changes in expression of 84 genes involved in the functioning of the GABAergic system and in the processes of neurotransmission in the culture of neuroblastoma IMR-32 cells using qPCR method. As test substances, in addition to Selank, we selected the major GABAA receptor ligand, GABA, the atypical antipsychotic, olanzapine, and combinations of these compounds . We found no changes in the mRNA levels of the genes studied under the effect of Selank. The combined effect of GABA and Selank led to nearly complete suppression of changes in expression of genes in which mRNA levels changed under the effect of GABA. When Selank was used in conjunction with olanzapine, the expression alterations of more genes were observed compared with olanzapine alone. The data obtained indicate that Selank has no direct effect on the mRNA levels of the GABAergic system genes in neuroblastoma IMR-32 cells. At the same time, our results partially confirm the hypothesis that the peptide may affect the interaction of GABA with GABAA receptors. Our data also suggest that Selank may enhance the effect of olanzapine on the expression of the genes studied.Clinical studies have shown that Selank had an anxiolytic effect comparable to that of classical benzodiazepine drugs, which can enhance the inhibitory effect of GABA by allosteric modulation of GABA Drugs that are based on natural regulatory peptides are currently becoming more widely used. Synthetic analogs of regulatory peptides typically contain only natural amino acids in their structure, so that they practically do not have any toxic side effects. Drugs that are developed on the basis of regulatory peptides can provide directional effects on certain human body systems and are already used for the treatment of a variety of human diseases, such as cardiovascular disease  changes in the presence of Selank, and Selank preliminary intranasal administration causes a change in the number of GABA-specific binding sites but does not affect receptor affinity  with L-glutamine  supplemented with 10% fetal bovine serum (FBS) (PanEco), and gentamicin (50 mkg/ml) .The human neuroblastoma cell line, IMR-32, was obtained from the A.T.C.C. . The cells were maintained in a humidified atmosphere containing 5% COIMR-32 cells were seeded into 6-well plates  at 1–2 million cells per well in 4 ml of cell culture medium with Phenol Red per well, following incubation for 24 h at 37°C to allow the cells to adhere. After 24 h of incubation, physiological solution (50 mkl), Selank (1 nmol per well), GABA (1 nmol per well), olanzapine (1 nmol per well), a mixture of GABA and Selank (1 nmol of GABA and 1 nmol of Selank per well), or a mixture of Selank and olanzapine (1 nmol of Selank and 1 nmol of olanzapine per well) were added into the culture medium and the cells were incubated with the reagents for 1 h. The specified dose of Selank was selected as an optimum dose, that is used in studies of effects of peptides in cell cultures  according to the manufacturer's protocol. qPCR was performed using the Custom Human RT2 Profiler™ PCR Array: CAPH11633C (Qiagen). Amplification was carried out on the StepOnePlus™ Real-Time qPCR System  using the RT2 SYBR Green Mastermix . Thermal cycling was carried out as follows: (1) 95°C for 600 s, followed by (2) 40 cycles of 15 s at 95°C and 60 s at 60°C. All reactions were repeated three times for the cDNAs from each experimental and control cells. The qPCR study follows the MIQE guidelines.The lysates were incubated at −20°C for 1 h, then at +4°C for 1 h prior to RNA purification. Chloroform (0.1 ml) was added to each lysate. Tubes were shaken vigorously by hand for 15 s and incubated at room temperature for 3 min. After incubation, the samples were centrifuged at 12000 × g for 15 min at +4°C. The aqueous phase was placed into a new tube and the RNA isolation procedure was carried out using the QIAamp® RNA mini kit  according to the manufacturer's recommendations. RNA quality was monitored using an Experion automated electrophoresis system (Bio-Rad Laboratories). The RNA quality index was higher than 8.5 in all samples. First-strand cDNAs were synthesized using the RTCq) values obtained for the genes studied were normalized to the Cq-values of the four reference genes: TFRC, TSPO, B2M, and UBC. Statistical data analysis of the normalized Cq-values and identification of significant differences between the levels of expression of the genes studied in nerve cells in the human neuroblastoma cell line IMR-32 after the incubation with the physiological solution and in the cells after the incubation with the substances studied was performed using the RT2 Profiler PCR Array Data Analysis version 3.5 . Data analysis is based on the ΔΔCq method with normalization of the raw data to reference genes. Genes in which the mRNA level changed significantly (p ≤ 0.05) 1.5 times or more were taken into account in the analysis of the changes in expression under the action of the test compounds. A comparison of significant changes of gene expression after the incubation with the substances studied was performed using the Spearman's rank correlation coefficient with Statistica v8.0 software. The gene set enrichment analysis (GSEA) of the genes studied and visualization of functional relations between proteins, encoded by these genes, were performed using Pathway Studio version 11.2.5.9 .The threshold reaction cycle (Cq) of 15 genes studied  were higher than 35, which indicates the low representation of mRNA in cells examined. Therefore, these genes were excluded from further analysis.We studied the effects of Selank, GABA, olanzapine, as well as combinations of these compounds  on the changes of mRNA levels of the 84 genes involved in neurotransmission processes in nerve cells in the human neuroblastoma cell line IMR-32. Preliminary analysis showed that the values of threshold cycles , FOS (3 times), and JUNB (5.3 times). Four genes  showed an increase of expression of no more than 2-fold compared with the control cells. It should be noted that there were no changes in the mRNA levels of the genes studied under the effect of Selank in the IMR-32 cells.The results of the expression analysis of the effects of Selank, GABA, olanzapine, and their combinations on the expression of 69 genes are shown in Table JUNB, whose mRNA level decreased 1.7 times, was shown after incubation of the IMR-32 cells simultaneously with Selank and GABA. At the same time, changes in the mRNA levels of the greatest number of genes were shown after incubation of the IMR-32 cells simultaneously with Selank and olanzapine when compared with all compounds and their combinations studied. Significant changes in the expression of 35 of 69 genes chosen for the analysis were shown: 29 genes showed decreased mRNA levels, and transcript levels of 10 of them  decreased more than 3 times. The mRNA levels of six genes  increased after the incubation of the IMR-32 cells with Selank and olanzapine.Statistically significant change in the expression of only one gene, BIRC2, GABRA5, GABRG2, GNAQ, ODC1, and SNCA) were increased.The cumulative analysis of all obtained statistically significant data showed that after the incubation of IMR-32 neuroblastoma cells with all the compounds and their combinations a decrease in mRNA levels of most of the genes studied (31) was observed; in contrast, mRNA levels of only six genes .It should also be noted that the most pronounced change in expression was observed for two genes, Another interesting feature is that despite the fact that no statistically significant change in expression of the genes under study was observed under the effect of Selank, the combined effect of GABA and Selank led to nearly complete suppression of changes in expression of genes in which mRNA levels changed under the effect of GABA Figure . When Ser = 0.98, p ≤ 0.05).The correlation analysis was conducted for genes in which the mRNA levels significantly changed under the effect of the compounds studied. As a result, we discovered a very strong positive correlation between gene expression changes under the effect of GABA and those under the effect of olanzapine  of the genes which mRNA levels changed significantly in neuroblastoma cells IMR-32 after incubation with the mixture of Selank and olanzapine. The results are shown in Table A receptors. This suggests that the molecular mechanism of the effect of Selank may also be related to its ability to affect the GABA receptors.Clinical studies have shown that Selank is highly effective in the prevention and treatment of generalized anxiety disorder and neurasthenia, as well as stress and anxiety. This effect of the peptide is similar to that of classical benzodiazepine drugs  are present in the cell culture  played central role (Figure A receptors.Thus, the data obtained indicate that Selank has no direct effect on the expression of genes of the GABAergic system in neuroblastoma IMR-32 cells. We can assume, that difference between expression profiles after the incubation with GABA and mixture of Selank and GABA partially confirms the hypothesis that the peptide may affect the interaction of GABA with GABAEF, TK, ER, GP, and LA performed the experimental work. AK, AA, MS, and PS undertook all statistical analyses and helped with their interpretation. PS and MS designed the study. AK and MS wrote the first draft of the manuscript. MS and PS contributed to the final writing of the manuscript. SL and NM was involved in revising the manuscript critically for important intellectual content. All authors contributed to and have approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


A reader raised concerns about potential data duplication in several figures. Specifically, the reader identified regions of overlap among the following figure panels:Panels E25, E50, and D50 shown in Figure 4Panels C and D25 panels in Figure 4Panel C in Figure 4 (Migration) and Panel C in Figure 5 (Invasion)The authors acknowledged that there was an error in the preparation of these figures. However, they no longer have the data underlying the results shown in the panels in Figure 4, and they were unable to replicate these results using the same experimental conditions.Due to the concerns about the integrity of the results, and the absence of data reproducing the findings, the authors have concerns about the validity and robustness of the results reported and have requested the retraction of this article.PLOS ONE.The authors apologize to the readers and editors of


Dear Editor,-3.The utility of the various imaging methods in the evaluation and diagnosis ofmusculoskeletal disorders is well established, and those methods play a fundamental rolein the planning of the different treatments, be they conservative or surgical, providingimages that can be manipulated through specific software to create three-dimensional(3D) reconstructions. To date, however, such 3D reconstructions have been made availableonly as digital files, as images on radiographic films, or as prints on paper. Thesetraditional forms of image documentation do not always allow surgeons to have a realin-depth sensory notion and knowledge of the 3D anatomical relationships in the planningof different types of surgical procedures. Recently, 3D printing has come to be usedwith increasingly frequency to obtain a more realistic and more accurate analysis bycreating 3D modelsWhat really is 3D printing? The definition of 3D printing, also known as rapidprototyping, is the use of a set of methods to create solid three-dimensional objects(models or prototypes) from the data contained in digital files. There are differentforms of 3D printing, one of the most popular being the additive processing technique,in which the object is created layer by layer through successive depositions of a highlyresistant plastic polymer.How does 3D printing work? It all begins with the development of the 3D digital file. Thefile is obtained through the acquisition of sectional images through the use of magneticresonance imaging, computed tomography, or even (3D or 4D) ultrasound. The digital fileis then analyzed and processed with computer-aided design (CAD) software, according towhat is required in each situation. After developing the 3D digital file, the CADmodeling software divides the prototype into hundreds or thousands of thin horizontallayers, thus preparing the file for printing. The digital file can then be loaded into a3D printer for printing.-5. There has been rapid growth in the number of potential applications of3D printing in medicine, which has already been used in several situations, even inBrazil-8. We illustrate, as an example, a case in which 3Dprinting was employed at our facility for the preoperative planning of the surgicaltreatment of an osteolytic lesion in the mandible (Is 3D printing already a reality in clinical practice or only in experimental research?In several countries, it is already a part of the clinical routine, having been shown tohave a great impact on the precision and safety of surgical proceduresmandible .-9.What are the applications of 3D printing in musculoskeletal imaging? Among its manypotential applications in clinical practice and in the teaching of medicine, weemphasize in this article the use of the technique in musculoskeletal imaging. Wehighlight its application in the preoperative planning of complex surgical procedures,which require high precision, such as those employed in the treatment of spinaldeformities and complex fractures, as well as in the creation of models of orthotics andprostheses tailored to the anatomy and needs of each patientWe believe it to be inevitable that, in the coming years, there will be growth in theapplication of the 3D printing technique in the field of medicine as a whole, especiallyin the area of musculoskeletal imaging. The incorporation of this new technique willallow the optimization of protocols promoting good practices, offering greatereffectiveness to the professionals involved and allowing better results, withpotentially greater safety for patients.


Self-medication has been reported as an option which people choose to relieve the suffering of conditions that cause pain, however, this could delay the correct diagnosis and therapy.The aim of the present study was to determine the prevalence of self-medication among patients with Temporomandibular Disorder (TMD), and to analyze correlations with the severity of the disease.p<0.05.A prospective study was conducted with patients who had been diagnosed with TMD. The patients were submitted to anamnesis and a physical examination. This research also used the Fonseca`s Anamnestic Index (FAI) and a questionnaire that was developed specifically for this study, containing questions related to the first health professional contacted and self-medication. The data were analyzed using comparative and correlative analysis (Version 18.0 of SPSS software), with the level of significance set at Thirty-four patients were included, with a prevalence of females (91.2%) and a mean age of 39.76 years. Half of the patients claimed to have chosen their own medications at time, especially analgesics. Sodium dipyrone was used by 12 of the participants. Dentists were the most commonly contacted health professionals (55.5%). No correlation was found between self-medication and the severity of TMD according to the FAI. Furthermore, the time period between the onset of symptoms and the first consultation was not affected by self-medication.Self-medication seems to be highly prevalent among patients with TMD, although this practice does not seem to alter the severity of the disease. One of these options is self-medication, which can be defined as the use of medicines to treat disorders (self-diagnosed) or symptoms. One of the greatest problems with this practice is the absence of a clinical assessment by a qualified health professional, which can lead to delays in the diagnosis and adequate treatment, health risks, the inadequate use of medication, interaction with other prescribed medications and unnecessary spending .The use of medication (whether prescribed or not) has become more common as a form of therapy to reduce morbidity and improve the quality of life of many individuals. A part of this group are patients who suffer from conditions that generate chronic pain. It is believed that 12% of these people are affected by TMD and 5% of this group exhibit severe symptoms that require treatment  conPatients with TMD exhibit symptoms such as headache and tinnitus, which lead them to seek professional help from neurologists, otolaryngologists and physiotherapists. A number of patients receive their first treatment when the TMD is already severe, due to the delay in seeking specialized help. No previous studies were identified with the specific aim of assessing the prevalence of self-medication among patients with TMD, although some have dealt with this subject , 7. The 2A prospective study was conducted with patients complaining of pain and TMD in a dental clinic in the Paulista University . The following inclusion criteria were applied: patients with myofascial pain according to clinical examination, patients who appeared at the institution for the first time; male and female individuals; aged between 18 and 80 years; with a minimum classification of mild TMD according to the Fonseca`s Anamestic Index (FAI)  and 2). The present study was approved by the Research Ethics Committee of the Faculty of Dentistry of the UNIP.A questionnaire developed specifically for this research was also used. It contained questions related to the onset of symptoms, the first contact with a health professional and self-medication  for Windows . The Chi-square test was used to assess the relationship between the variables. The Kruskal-Wallis test was performed to compare the time period that had elapsed between the onset of symptoms and the initial consultation related to the severity of TMD. The Mann–Whitney U test was performed to compare the time period that had elapsed between the onset of symptoms and the initial consultation according to the groups of patients that report self –medication and not. The results were considered statistically significant for 31 shows the distribution of sample according to variables studied.The present study assessed 34 patients, with a prevalence of women , a mean (SD) age of 39.76 (14.86) years. Most of the patients had completed high school , followed by third level education  and primary education . Six categories were identified for the main pain complaint: pain in the TMJ ; headaches ; difficulty while chewing ; clicking and crackling noises in the TMJ ; bruxism and teeth clenching ; and tinnitus . Table Concerning the first health professional contacted after the onset of symptoms, a prevalence was recorded for dentists , followed by otolaryngologists , general doctors  and neurologists . The time period that elapsed between the onset of the symptoms and the first consultation ranged from 15 days to 4 years, with a mean (SD) value of 13.29 (14.88) months. Half of the patients (n=17) claimed to have self-medicated prior to seeking professional help. Most of this group used analgesics (n=15), particularly sodium dipyrone (n=12) and paracetamol (n=3), although the use of non-steroidal anti-inflammatories (n=5) and muscle relaxants (n=1) was also reported. Most of the patients used medication without an indication from another person (n=14), although two patients based their medication on the recommendations of a pharmacist and another asked a family member. In the sample, 15 patients exhibited systemic diseases. In total, 61.8% (21/34) of the patients currently take medication and of these, 90.5% (19/21) of the drugs were prescribed by a health professional. Six patients in the sample claimed to suffer from or had been diagnosed with, depression.2=0.810; p=0.667) or gender . Regarding the main complaint of patients and the health professional contacted, a dentist was most often contacted for complaints related to chewing difficulties (n=3), noises in the TMJ (n=3) and parafunction (n=4). For pain in the TMJ however, the distribution was similar among dentists (n=6) and otolaryngologists (n=4). A significant proportion of patients contacted a general practitioner for headaches (n=5).No statistical difference was recorded between self-medication and the level of education . The mean time period that had elapsed between the onset of symptoms and the initial consultation was longer among patients with severe TMD (17.13 months) than among those with moderate TMD (9.63 months) or mild TMD (14.75 months), although there were no statistically significant differences between the groups . No differences were found regarding the time period that had elapsed between the onset of symptoms and the first consultation when compared patients in self-medication group (11.46 months) with prescribed medication (14.6 months) .When using the Fonseca anamnestic index, the sample exhibited an even distribution among the levels of severity: mild (n=10); moderate (n=14); and severe (n=10). No statistically significant differences were found between the presence of severe TMD and self-medication  evaluated the use of analgesics in 145 patients with a headache diagnosed in Outpatient Headache Clinic. They found that 34% of patients performed self-medication  cThis was a preliminary study as it only involved one research center and a limited number of subjects. However, the aim of this research was to present a topic that should be explored using two easy-to-use and fast questionnaires. The limitations of the present study include the small size and heterogeneity of the sample and the absence of the patient´s clinical data.The idea of self-medicating before seeking professional help seems to be a common attitude among patients with TMD. However, for the sample studied and according to the Fonseca anamnestic index, this behavior was not correlated with the severity of the symptoms. The prevalence of self-medication seems not to be related to the time elapsed between the onset of symptoms and first consultation with a professional.


Vestibular dysfunction causes postural instability, which is prevalent in the elderly. We previously showed that an imperceptible level of noisy galvanic vestibular stimulation (nGVS) can improve postural stability in patients with bilateral vestibulopathy during the stimulus, presumably by enhancing vestibular information processing. In this study, we investigated the after-effects of an imperceptible long-duration nGVS on body balance in elderly adults. Thirty elderly participants underwent two nGVS sessions in a randomised order. In Session 1, participants received nGVS for 30 min twice with a 4-h interval. In Session 2, participants received nGVS for 3 h. Two-legged stance tasks were performed with eyes closed while participants stood on a foam rubber surface, with and without nGVS, and parameters related to postural stability were measured using posturography. In both sessions, the postural stability was markedly improved for more than 2 h after the cessation of the stimulus and tended to decrease thereafter. The second stimulation in Session 1 caused a moderate additional improvement in body balance and promoted the sustainability of the improvement. These results suggest that nGVS can lead to a postural stability improvement in elderly adults that lasts for several hours after the cessation of the stimulus, probably via vestibular neuroplasticity. The vestibular system, which is involved in the detection of linear and angular movements of the head, provides peripheral sensory input in the postural control system and contributes to stabilisation of body balanceGalvanic vestibular stimulation (GVS) transcutaneously delivers electrical current to vestibular hair cells and their afferents through electrodes placed over the mastoids356910The vestibular system exhibits strong neuroplasticity131516Given the strong neuroplasticity of the vestibular system, we hypothesised that nGVS would induce a sustained improvement in postural stability, even after the cessation of the stimulus. The purpose of this study was to determine whether nGVS has a post-stimulation effect on the improvement in body balance in elderly adults. We also examined the cumulative effect of nGVS on the improvement in postural stability using repeated application of nGVS. We revealed that nGVS has both post-stimulation and cumulative effects on improving postural stability in elderly adults that last for several hours. These participants obtained postural stabilisation without stimulation due to persistence of the post-stimulation effect.To examine the post-stimulation effect and the cumulative effect of nGVS, which was applied with electrodes on the right and left mastoids , on postThirty elderly healthy participants were randomly assigned to first undergo Session 1 and then Session 2 (Group A) or to first undergo Session 2 and then Session 1 (Group B) . Two parWe defined the normalised ratio (NR) as the ratio of the value of each parameter at the measurement time point to that at baseline. A representative participant who received nGVS at its optimal intensity for 30 min showed improvements in the NRs of all three parameters of COP just after the cessation of the stimulus . The impOverall, in Session 1, the NRs of the velocity, area, and RMS were significantly smaller at the immediate PST (0 h) than at baseline , in which low-intensity direct electrical currents are applied to the skull for several minutes, on human motor cortical excitability revealed that repeated cathodal tDCS during the post-stimulation effects of the first stimulus prolonged the duration of the post-stimulation effects, whereas repeated tDCS after the disappearance of the post-stimulation effects of the first stimulus did not have such effectsBV is a rare disorder that accounts for approximately 4% of vestibular disorders, with an increased frequency in the elderly3435This study has several limitations. First, the study was not placebo-controlled. It is possible that habituation of the participants due to the repeated posturography measurements affected the results of the post-stimulation effect of nGVS on postural stability. However, the improvement in the NRs of each parameter decreased after PST 2 h in both the 30-min and 3-h nGVS sessions. These results cannot be explained by the habituation effect and suggest the existence of the post-stimulation effect of nGVS and its attenuation. The second limitation is that we did not continue measuring the postural stability until the post-stimulation effect had completely disappeared. We showed that the NRs of all three parameters were improved for at least 3 h after 30-min nGVS and for at least for 2 h after 3-h nGVS, but the post-stimulation effects of nGVS might continue for more than 4 h.In conclusion, we revealed that nGVS can induce a long-term improvement in postural stability after the cessation of the stimulus due to a strong post-stimulation effect and that repetition of the stimulus can induce further improvement. These newly discovered effects could contribute to an increased applicability of nGVS for postural stabilisation in elderly adults.All procedures were conducted in accordance with the Helsinki Declaration and were approved by the Institutional Review Board of the University of Tokyo Hospital (P2114052-11Y). This trial was registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry . The date defining the periods of recruitment and follow-up was December 24, 2014. All participants gave written informed consent.Thirty healthy participants  were recruited from a human resource centre . ExclusiTo examine the post-stimulation and cumulative effects of nGVS on postural stability, we performed two experimental sessions, separated by an interval of 7 days, after determining the optimal intensity of nGVS . In Sess2; stretch percentage, 110%; thickness, 3.5 cm). Two-legged stance tasks were performed by healthy participants with eyes closed while participants stood on the foam rubber surface, with and without nGVS  with a foam rubber surface containing vertical force transducers. The data were plotted in a statokinesigram . The foam material consisted of natural rubber  78. GVS w7We determined the optimal intensity of nGVS for each participant before initiating each experimental session investigating the long-term effects. First, the value of each COP parameter with no stimulation (0 mA) for 30s was measured and defined as the baseline value. Then, nGVS was applied for 30s with peak amplitudes set at 50, 100, 200, 300, and 500 μA. The optimal intensity was defined as the one at which the value measured during the stimulation was simultaneously smaller than that at baseline in all of the three COP parametersIn Session 1, posturographic data were analysed at 0, 0.5, 1, 2, 3, and 4 h during the PST . In SessWe defined the normalised ratio (NR) as the ratio of the value of each parameter at the measurement time point to that at baseline. The primary endpoint was defined as the NRs of the velocity, area, and RMS at PST 4 h in the first part of Session 1 and Session 2. Secondary endpoints were defined as follows: (1) the NRs of the velocity, area, and RMS at PST 0 h in the first part of Session 1 and Session 2; (2) amount of change from baseline in the NRs of the velocity, area, and RMS in the first part of Session 1 and Session 2; (3) longitudinal change in the NRs of the velocity, area, and RMS in the first PST of Session 1 and the PST of Session 2; and (4) longitudinal change in the NRs of the velocity, area, and RMS in the first and second PST in Session 1.Data are expressed as mean ± standard error. Statistical analysis was performed using SAS software version 9.4 . A paired t-test was performed for the comparison of the NRs of the velocity, area, and RMS at a certain measurement time point during the PST between the first part of Session 1 and Session 2 and between the first and second parts of Session 1. Generalised linear mixed models were adopted for the comparison of longitudinal changes in the NRs of the velocity, area, and RMS between the first PST of Session 1 and the PST of Session 2. Generalised linear mixed models were also used for the comparison of the longitudinal change in the NRs of the velocity, area, and RMS between the first PST and second PST in Session 1. A one-sample t-test was performed to assess the change in the NRs of the velocity, area, and RMS from baseline. P < 0.05 was considered statistically significant.How to cite this article: Fujimoto, C. et al. Noisy galvanic vestibular stimulation induces a sustained improvement in body balance in elderly adults. Sci. Rep. 6, 37575; doi: 10.1038/srep37575 (2016).Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


Anchoring of heterochromatin to the nuclear envelope appears to be an important process ensuring the spatial organization of the chromatin structure and genome function in eukaryotic nuclei. Proteins of the inner nuclear membrane (INM) mediating these interactions are able to recognize lamina-associated heterochromatin domains (termed LAD) and simultaneously bind either lamin A/C or lamin B1. One of these proteins is the lamin B receptor (LBR) that binds lamin B1 and tethers heterochromatin to the INM in embryonic and undifferentiated cells. It is replaced by lamin A/C with specific lamin A/C binding proteins at the beginning of cell differentiation and in differentiated cells. Our functional experiments in cancer cell lines show that heterochromatin in cancer cells is tethered to the INM by LBR, which is downregulated together with lamin B1 at the onset of cell transition to senescence. The downregulation of these proteins in senescent cells leads to the detachment of centromeric repetitive sequences from INM, their relocation to the nucleoplasm, and distension. In cells, the expression of LBR and LB1 is highly coordinated as evidenced by the reduction of both proteins in LBR shRNA lines. The loss of the constitutive heterochromatin structure containing LADs results in changes in chromatin architecture and genome function and can be the reason for the permanent loss of cell proliferation in senescence. It has been well established that the spatial organization of chromatin plays a critical role in genome functions . The majHeterochromatin tethers support the essential organization of the structure and function of the chromatin ,14. EachCellular senescence is a cellular response to a variety of stresses ,19,20. Iink4a-pRb [INK4a is particularly prevalent in benign lesions, although is often lost upon malignancy [The onset and maintenance of the senescent state involve the action of two major tumor suppressive pathways, p53-p21 and p16nk4a-pRb ,30. Uprelignancy , and itslignancy ,33. Mostlignancy ,34. Theylignancy . It is aIn recent years, it was reported that lamin B1 (LB1) expression is reduced in replicative and oncogene-induced senescence, which delays cell proliferation and promotes cellular senescence via a p53- and Rb-dependent mechanism ,36,37,38Our results show  downreguLBR protein is known to contain specific regions for heterochromatin attachment, recognition of specific histone methylations, HP1γ and, in addition, the attachment of LB1 ,43,44,48It is very interesting that in undifferentiated and differentiated cells the higher order chromatin structure is set by the anchoring of heterochromatin to the INM by means of distinct proteins of the INM that simultaneously binds to one of the lamins: lamin B receptor binds to lamin B1 in undifferentiated and embryonic cells and different LEM-domain proteins and other transmembrane mediators bind to lamin A/C in various differentiated cells . This shGenome-wide mapping of LB1 has identified lamina-associated domains (LADs) that are gene poor and guanine–cytosine poor, enriched for histone repressive marks ,54 and rThe downregulation of LBR and LB1 in the beginning of senescence induces several consecutive changes that eventually lead to irreversible alterations in nuclear architecture. The evidence for this hypothesis comes from several experimental systems. In irradiated cancer cells, we observed detachment of peri/centromeric satellite heterochromatin (enriched in the epigenetic H3K9me3 mark) from the inner nuclear membrane and its relocation to the nucleoplasm . InteresThe results of further experiments will show whether our conclusions regarding the fate of senescent cells after the loss of constitutive heterochromatin structure are real or not and whether they could be found conditions for this structure restoration.


The aim of the study was to analyse the disturbances of the oro-pharyngeal swallowing phase of dysphagia in amyotrophic lateral sclerosis (ALS) patients with the use of specific manometric measurements and to evaluate their plausible association with the duration of the disease. Seventeen patients with ALS were evaluated with manometric examinations of the oral and pharyngeal part of the gastrointestinal tract. Tests were carried out by using the oesophageal balloon-based method with four balloon transducers located 5 cm away from each other. The following manometric parameters were analysed: the base of tongue contraction (BTC) and the upper oesophageal sphincter pressure (UESP), and the hypopharyngeal suction pump (HSP) as well as the oro-pharyngeal, pharyngeal and hypopharyngeal transit time and average pharyngeal bolus velocity , pharyngeal transit time (PTT), hypopharyngeal transit time (HTT) and average pharyngeal bolus velocity (APBV), respectively). Manomatric examinations during swallowing in patients with ALS showed significant weakness of BTC, a decrease of HSP and a decrease of the velocity of bolus transit inside the pharynx which were particularly marked between the first and the third examination. Manometric examinations of the oro-pharyngeal part of the gastrointestinal tract are useful and supportive methods in the analysis of swallowing disturbances in ALS patients. Abnormalities of deglutition in patients with amyotrophic lateral sclerosis (ALS) result from the weakness and discoordination of the muscles involved in the process of swallowing. Damage to the cranial nerves V, VII, IX, X and XII leads to abnormal mastication, inappropriate bolus formation and the impaired transit of the food bolus to the oesophagus. It has been shown so far that ALS patients suffer mainly from the abnormal oral phase of the swallowing  or the pharyngeal phase of the swallowing (particularly in case of predominant upper motor neuron damage) ,3,4,5,6.Damage to the lower motor neurons leads to the weakness of contraction within the base of the tongue, soft palate and muscles of the pharynx which results in the impaired tightness within the nasopharynx and regurgitation of food to the nasal cavity. Moreover, weakness of muscles that normally elevate the hyoid bone and larynx forwards and upwards decreases the opening of the upper oesophageal sphincter (UES), resulting in retention of the saliva, food and fluids within the piriform recess and the postcricoid area. Weakness of facial muscles  leads to the abnormal collection of saliva and precludes its removal from the oral cavity. Damage to the upper motor neurons results in the contraction of the cricopharyngeus muscle (being a part of the UES) or to its premature closure which consequently leads to the substantial impairment of the food passage, the retention of the food in pharynx and its aspiration to the respiratory tract.Manometric parameters related to the passage of the bolus through the pharynx and its velocity are rarely reported in patients with ALS. Robbins  analysedThe aim of the study was to assess the disturbances of the oral and pharyngeal phase of swallowing in patients with bulbar form of ALS, focused on the determination of the type, dynamic and duration of the disease. An objective description of swallowing disturbances in ALS could be important for the evaluation of the severity insufficiency among these patients, i.e., for their prognosis.The patient group consisted originally of five (29%) men and 12 (71%) women (mean age at entry: 54.5 ± 11.4 years (range: 23–76)). The mean age at onset of symptoms was 53.3 ± 8.5 years (range: 31–74) and the average interval between the onset of symptoms and the first examination within this study was 31.4 ± 17.5 months. Forty-seven patients (73.4%) were diagnosed with limb-onset ALS and a further 17 (26.6%) subjects were diagnosed with the bulbar form of the disease.n = 3:2 men and one women) or poor general health status (n = 3:1 men and two women) had a mean age of 62 ± 4.6 years and the duration of their disease at baseline ranged between 14 and 40 months (mean: 23.8). An additional four patients (one men and three women) who were examined twice and died before the third assessment were 64, 62, and 58 years of age, respectively, and at baseline, they had suffered from ALS for 28, 34 and 38 months, respectively.Patients who could be examined only once because of subsequent death  during dry and wet swallowing were substantially decreased among patients with ALS. Oropharyngeal transit time (OTT) and hypopharyngeal transit time (HTT) were markedly longer among patients than in controls, both during dry and wet swallowing.Mean values of particular parameters assessed during swallowing studies were compared in patients regarding the progression of abnormalities during the course of the disease. p = 0.007) and between the second and third examination (p = 0.026). UESP values increased between the first and third examination, as well as between the second and third one (p = 0.005). HSP significantly decreased between the first and second examination, as well as between the second and third one . APBV decreased significantly between the first and third (p = 0.006), second and third (p = 0.001) and between the first and second examination (p = 0.036).BTC decreased markedly between the first and third examination (p = 0.013), as well as between the first and second examination (p = 0.045). HTT was significantly longer in the third examination when compared with the first one (p = 0.002).OTT was significantly prolonged in the third examination when compared with the first one (p = 0.004), in the third examination versus the first one (p = 0.001), as well as in the third examination when compared with the second one (p = 0.041). Resting UESP was markedly higher in the third examination when compared with the first (p = 0.004) or second one (p = 0.009). HSP was significantly decreased in the third examination when compared with the second one only (p = 0.05), while APBV was lower in the third examination when compared with the first one (p = 0.007) and lower in the second examination in comparison to the first one (p < 0.001). Mean OTT and HTT did not change significantly over the course of the disease.BTC values were significantly lower in the second examination when compared with the first one  with definite  or probable  ALS diagnosed in the out-patient clinic for patients with ALS affiliated to the Department of Neurology, Jagiellonian University Medical College in Krakow. The diagnosis of definite or probable ALS was established by the same neurologist (BT) according to the El Escorial World Federation of Neurology criteria (1998).Inclusion criteria consisted of the informed consent of subject to participate and the age between 18 and 80. Exclusion criteria comprised the family history of ALS, swallowing difficulties resulting from conditions other than ALS, anatomical conditions of lips, oral cavity or pharynx that precluded objective testing, as well as swallowing difficulties assessed in Hillel scale as five points, i.e., the use of liquefied diet . Lack ofControl group for the manometric studies of the upper part of the gastrointestinal tract consisted of 30 volunteers (20 men and 10 women) at the mean age of 53.7 ± 9.5 years (range: 39–71 years). Controls were free of any detectable laryngeal disorders; they had no disorders related to anatomical abnormalities of oral cavity, pharynx or larynx.Study protocol was approved by the Bioethical Committee of Jagiellonian University (decision no. KBET/145/B/2006). All subjects provided their informed consent to participate in the study.Manometric examination was performed three times in each patient, i.e., at the baseline, and approximately 6 and 12 months after the first evaluation. All three examinations were performed in seven patients (41.2%). Three patients died before the term of the second examination, and further three patients could not be examined owing to the poor general health status, immobilisation, or increased severity of symptoms precluding testing. Four other patients died before the third examination.®, London/Enfield, UK) equipped with four balloon pressure sensors positioned in 5 cm intervals. All data from each examination were entered to the computerised database with Polygram 98/Polygram Net software .Manometric examination of the upper part of gastrointenstinal tract was performed with the use of Polygraf ID apparatus (Medtronic). Data were registered with the oesophageal tube Air Charge (LatitudeThe study was performed in the sitting position according to the technique described by Castell and Castell . The oesThe following parameters were measured: (1) Base of tongue contraction (BTC), expressed in mm Hg, being the pressure value produced by the backward movement of the base of tongue and its contact with posterior wall of the pharynx during the oral phase of the swallowing; (2) UES pressure (UESP), expressed in mm Hg; (3) Hypopharyngeal suction pump (HSP), expressed in mm Hg × sec, being the negative pressure measured in the postcricoid segment as the area limited by the curve of the negative pressure in UES and the pressure level of 0 mm Hg; (4) Average pharyngeal bolus velocity (APBV), expressed in cm/s, reflecting the time of bolus transit through pharynx at the distance of 10 cm ; and (5) Pharyngeal transit time (PTT), expressed in seconds, being the time of bolus transit through the 10 cm segment between the oropharynx and the UES. The last parameter is divided into two parts; oropharyngeal transit time (OTT)—time needed for the bolus transit between first and second balloon sensor, i.e., from the base of tongue to the entrance to the larynx (5 cm long) and hypopharyngeal transit time (HTT) between second and third balloon sensor, i.e., between entrance to the larynx and UES (5 cm long as well). Both BTC and UESP were measured according to the description provided by Walther , while Hp-value of ≤0.05 was considered statistically significant. Statistical analysis was performed with the use of STATISTICA v. 8.0 PL .Statistical analysis used non-parametric tests as the assumption of the normal distribution of variables was not met. Mann-Whitney test was used to compare quantitative variables  between patients and controls. Repeated measures within the studied group were analysed with Wilcoxon test. A Manometric examination of the upper part of the gastrointestinal tract is an effective method for the detection of abnormalities during the oral and pharyngeal phase of swallowing in patients with ALS. This study confirms the presence of substantial and severe disturbances of the swallowing act, including the abnormal base of tongue contraction, the hypopharyngeal suction pump and the time and velocity of bolus transit through the oral cavity and pharynx.Manometry of the upper part of the gastrointenstinal tract is a useful method in the assessment of the severity of deglutition disorders among patients with ALS.


The aims of this study were to assess and analysis of drinking water quality of Chabahar villages in Sistan and Baluchistan province by water quality index (WQI) and to investigate the water stability in subjected area. The results illustrated that the average values of LSI, RSI, PSI, LS, and AI was 0.5 (±0.34), 6.76 (±0.6), 6.50 (±0.99), 2.71 (±1.59), and 12.63 (±0.34), respectively. The calculation of WQI for groundwater samples indicated that 25% of the samples could be considered as excellent water, 50% of the samples were classified as good water category and 25% of the samples showed poor water category. Specifications TableValue of the data1.These data could be helpful for many organizations, such as rural water and wastewater organizations, water treatment plants, water resources management, and the Ministry of Energy, which need these to make decisions and adopt guidelines for water quality management.2.The zoning of the scaling and corrosion indices and water quality index (WQI) was done to provide a clear picture of the water quality in the water resources at the villages of Chabahar.3.In dry and semi-arid climates such as Iran, groundwater is almost the main source of water supply, therefore, the continuous monitoring of the quality of these valuable resources is very necessary.1The parameters and indices were calculated in the experiments are including chloride ion, sulfate, temperature, Electrical Conductivity (EC), Total Dissolved Solids (TDS), pH, total alkalinity, bicarbonate ions, and calcium hardness according to standard methods for examination of water and wastewater An important parameter for determining the water quality and its sustainability for drinking purposes is water quality index (WQI). In order to provide the composite influence of individual water quality parameters on the overall water quality WQI could be useful 22.12  according to physical and chemical parameters. 2.2.1To calculate the WQI, the weight for the physico-chemical parameters were assigned according to the relative importance of parameters in the overall quality of water for drinking purposes.Wi is the relative weightWi is the weight of each parametern is the number of parameters.Using the following equation, the relative weight was computed:qi is the quality ratingCi is the concentration of each chemical parameter in each sample in milligrams per literSi is the World Health Organization standard for eachChemical parameter in milligrams per liter according to the guidelines of the WHO 2011 The quality rating scale for each parameter is calculated by dividing its concentration in each water sample by its respective standards (World Health Organization 2011 SIi is the sub-index of it parameterqi is the rating based on concentration of it parametern is the number of parameters [2]For computing the final stage of WQI, the SI is first determined for each parameter. The sum of SI values gives the water quality index for each sample.


The composition and condition of membrane lipids, the morphology of erythrocytes, and hemoglobin distribution were explored with the help of laser interference microscopy (LIM) and Raman spectroscopy. It is shown that patients with cardiovascular diseases (CVD) have significant changes in the composition of their phospholipids and the fatty acids of membrane lipids. Furthermore, the microviscosity of the membranes and morphology of the erythrocytes are altered causing disordered oxygen transport by hemoglobin. Basic therapy carried out with the use of antiaggregants, statins, antianginals, beta-blockers, and calcium antagonists does not help to recover the morphofunctional properties of erythrocytes. Based on the results the authors assume that, for the relief of the ischemic crisis and further therapeutic treatment, it is necessary to include, in addition to cardiovascular disease medicines, medication that increases the ability of erythrocytes' hemoglobin to transport oxygen to the tissues. We assume that the use of LIM and Raman spectroscopy is advisable for early diagnosis of changes in the structure and functional state of erythrocytes when cardiovascular diseases develop. Nowadays diseases of the cardiovascular system occupy a leading place among the major causes of disabilities and mortality of the active labour force not only in Russia but throughout the world , 2. NotwThe pathophysiology of most cardiovascular diseases attributes one of the key places to hypoxia, which causes disorders of the gas-transport function of blood and, in many cases, reduces the efficiency of oxygen transport carried out by erythrocytes. The primary reason is attributed to the disorders in structure and function of endothelium of blood vessels, while the role of erythrocytes and their oxygen-transport ability in the development of vascular diseases remains insufficiently studied , 3.2). The use of Raman spectroscopy (RS) made it possible to identify changes in the conformation of hemoporphyrin in patients with severe arterial hypertension and under the therapeutic interval hypoxia in patients with stable effort [Oxygen-transport function of erythrocytes in peripheral blood depends on many factors, where of great importance is the change in conformation of hemoglobin (Hb) and its affinity to oxygen , The research was carried out following the approval of the Local ethics Committee of Mordovia State University on the basis at the Mordovian Republican Hospital of War Veterans in accordance with the principles of Good Clinical Practice. Having obtained informed consent for participation in the research, we examined 39 patients at the cardiology department, all males aged from 46 to 63 years (average age of 54.5 ± 3.8 years). Further inclusionary criteria required patients to be nonsmokers, with no history of hereditary anomalies and a body mass index ranging from 23 to 29. Patients were divided into 2 groups depending on disease:The research did not include patients with a history of liver, kidney, lung disease, diabetes, systemic diseases, or malignancy.The treatment was administered using a unified scheme and antianginal drugs, ACE inhibitors, angiotensin II antagonists, beta-blockers, calcium antagonists, electrolytes, antiaggregants, statins, and diuretics. The examination was carried out before and on the tenth day of treatment.The control group consisted of 19 apparently healthy male donors of the republican station of blood transfusion of a similar age (the average age being 50.5 ± 1.9 years), without evidence of CVD during preventative examinations.Research results were obtained from patients' blood samples, aseptically taken from the cubital vein in the volume of 5 mL in a fasting state.Erythrocytes were obtained by centrifugation of whole blood at 1500 ×g for 10 min; then a small portion of sediment was resuspended in the washing fluid; the latter was used for microscopy, while the other part was used to obtain membranes.2PO4; 0.5 mM PMSF (phenylmetylsulfonylfluoride) pH 8.0 (lysis solution). The ratio of erythrocyte sediment to lysis solution was 1 : 20 (V : V).To isolate membranes from human erythrocytes sediments of erythrocytes were hemolysed in a cooled to 0°C solution of 5 mM NaHThe mixture was left for 10 min at 4°C and then centrifuged at 20000 ×g for 40 minutes (temperature 0°C). The supernatant was removed; the sediment was resuspended in lysis solution and centrifuged at 20000 ×g for 40 minutes (temperature 0°C). The procedure was repeated three times.Extraction of membrane lipids was performed by using Bligh and Dyer's method . To sepaThe resulting phospholipids were eluted with a mixture of chloroform : methanol (2 : 1). Methylation of fatty acids was performed by using Morrison and Smith's method . Separat2PO4, 3.5 mm of KCl, 1.5 mm of MgCl2, 145 mm of NaCl, and 6 mm of glucose, pH 7.4). 1 mcL of the erythrocytes' suspension was placed on a mirror glass; a smear was prepared and covered with cover glass. The measurements were carried out at room temperature (18–22°C). For LIM examination we received image of 10 sites with a monolayer arrangement of cells in the interference channel and the reflected light in each sample. The resulting images of red blood cells were processed using FIJI [The structure of erythrocytes and hemoglobin content was found by method of laser interference microscopy (LIM) in vitro –30 with ing FIJI .The condition of human erythrocytes was assessed by registering the mean value of optical path difference (OPD) and the phase image area of erythrocyte, the value of which was calculated using FIJI software . To get S is the phase image area of erythrocyte, Φmean is mean value of the measured parameter, optical path difference (OPD), proportional to the thickness of erythrocyte, ncell is erythrocyte refraction index equal to 1,405, and nm is refraction index of normal saline that was equal to 1,333.Additionally we had to evaluate the phase volume of erythrocyte by the formula below:Conformation and properties of hemoglobin were defined by Raman spectroscopy on the device In Via Renishaw (UK) with short-focus extreme aperture lens monochromator (focus distance not more than 250 mm) , 32, 33.The erythrocytes suspension smear was studied on the object glass. Hemoglobin spectra bands were traced out at excitation by laser 532 nm and correlation of bands with variations of porphyrin links was carried out. For each sample the measurements were taken three times and the resulting values were averaged. The position and intensity of Raman scattering (RSc) bands of hemoglobin spectrum depend on variations of links in a porphyrin ring that allows you to estimate the conformation of hematoporphyrin (HP), which is directly related to hemoglobin's oxygen-binding properties [To analyse the conformation of hemoglobin's hematoporphyrin (HP) we took into account specific bands of RS spectrum, which allowed us to explore the conformation of HP in deoxyhemoglobin (d–Hb) and the ability of d-Hb to bind ligands, as well as the HP conformation in oxyhemoglobin (o–Hb) and the ability of o-Hb to reduce the oxygen.2–binding properties we drew on the following RS band spectra of blood (maximum positions indicated): 1355, 1375, 1550, and 1580 cm−1.In this paper to analyse the conformation and Hb's ОThe use of RS-peaks correlations and not their absolute values is explained by the fact that the absolute value of spectrum intensity depends on the amount of hemoglobin and thus amount of erythrocytes in the sample and in the laser's focus. Internal normalisation of peaks (on the intensity of other bands) ensures that the analysed parameters in different samples do not bear on the amount of hemoglobin and are determined only by the conformation of hemoglobin and the relative content of its various forms.The character of spectra in Raman scattering (RSc) of hemoprotein hemoglobin , 33 allo−1 is related to symmetrical oscillations of pyrrole rings in deoxyhemoglobin molecules and hemoglobin bound with ligands, respectively [2 in blood is 3-4 orders higher than the concentrations of other ligands , the intensity of the band 1375 cm−1 is mainly determined by the content of oxyhemoglobin. Therefore, the intensity ratio I1375/(I1355 + I1375) is proportionate to the relative amount of oxyhemoglobin in blood. Intensities of bands 1550 cm−1 and 1580 cm−1 characterise the spin state of iron in its deoxy- and oxyform, respectively, and thus are a marker, which assesses the structural characteristics of iron in a prosthetic group.The intensity of the spectrum bands 1355 and 1375 cmI1355/I1550 and I1375/I1580, evaluating the ability of molecules of hemoglobin in erythrocytes to bind and to release oxygen molecules, respectively, with account to the internal state of hemoglobin molecules. Dividing one ratio by another (I1355/I1550)/(I1375/I1580) one can obtain a parameter reflecting the affinity of the hemoglobin molecule to oxygen in native erythrocytes [This makes possible, using the relationship between the intensities of bands hrocytes , 32–35.Statistical processing of experimental results was carried out in several stages. The first phase evaluated the normality of the distribution of values for each of the samples; we used Geary's criterion . The secThe research results are presented as arithmetic means ± standard deviation (means ± SD).The findings showed that erythrocytic membranes of healthy people have 5 fractions of phospholipids (PL): sphingomyelin (SM), phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylethanolamine (PEA), and diacylglycerol (DAG). The composition of phospholipids' fatty acids (FA) of erythrocytic membranes included myristic (14:0), palmitic (16:0), palmitoleic (C16:1), stearic (C18:0), oleic (C18:1), linoleic (C18:2), linolenic (C18:3), arachidic (C20:0), gondoinic (C20:1), eicosadienoic (C20:2), and behenic (C22:0) acids.p < 0.05), respectively, compared to control values , respectively, compared to control values (Concurrent with this the content of lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPEA), and free fatty acids (FFA) increases by 20.8; 18.3; and 24.2% , respectively, compared to control values (p < 0.05), respectively, compared to control values  .p < 0.05), respectively, compared to control values. It should be noted that patients with stable angina on the background of hypertension demonstrate a more intensive activation of processes of lipid peroxidation (LPO): the level of DC and MDA in this variant of experiments increases by 38.9% and 52.6% (p < 0.05), respectively, compared with donors' erythrocytes  and malonic dialdehyde (MDA), the amount of which increases by 31.2 and 41.4%  and relative ability of hemoglobin to isolate ligands for ischemic heart disease patients in comparison with healthy donors' indicators .Among other things found is the decrease in relative quantity of oxyhemoglobin (o-Hb) and relative ability of hemoglobin to isolate ligands for ischemic heart disease patients in comparison with healthy donors' indicators .Also we found the increase in relative ability of hemoglobin to bind ligands (including oxygen) and affinities of hemoglobin to ligands  among SA patients (by 33.8% and 45.3% in comparison with donors' indicators) and SA with primary arterial hypertension patients (by 56.9% and 38.2% in comparison with donors' indicators).Increased affinity of hemoglobin to oxygen and ability of hemoglobin to bind oxygen further intensifies the hypoxic processes already present when ischemic heart disease develops. Deterioration in ability of hemoglobin to release ligands including oxygen leads to the same thing.It is possible to assume that the increased affinity of hemoglobin to oxygen and the arising hypoxia can be an important decisive pathogenetic sign of ischemic heart disease and arterial hypertension, as well as the cause of its exacerbation when hypertensive crises follow. The increased affinity of hemoglobin to oxygen reduces arteriovenous differences with reference to oxygen and, therefore, aggravates not only cerebral hypoxia, but also other organs and systems. Arising “vicious circles,” in their turn, can further worsen oxygen-transport function of blood . Based oTherefore, to raise the efficiency of pathogenetic comprehensive treatment of patients with stable stenocardia and arterial hypertension, it is necessary to include medication relieving disturbances in the oxygen-transport function of blood.The results of our own research and review of literature on the topic prove that the change in physicochemical properties of the lipid bilayer of erythrocytic membranes largely determines the development of ischemic heart disease (IHD).It is possible to identify a number of factors that influence the severity of the pathological processes in IHD: the accumulation of phospholipids' lysoforms (LPC and LPEA) and free fatty acids in the development of IHD may contribute to the “decondensation” of separate sections of the erythrocytic membrane lipid bilayer .Significant increase in the number of FFA also affects the packing of bilayer integrity, influencing the increase in passive ion transport. All these processes impair gradients of ions concentration and, as a consequence, disturb erythrocytes' ionic balance .Changes found in the content of PI and the simultaneous accumulation of DAG clearly point to the activation of the PI-cycle and, therefore, to the intensification of processes leading to the formation of secondary messengers which activate protein kinase C. This subsequently triggers phosphorylation and the activation of a large number of intracellular proteins.2+ permeability of erythrocytic membranes, which in its turn may trigger activation of Ca2+-dependent PLA2 [This enhances Caent PLA2 .The consequence of this is the strengthening of the destructive processes in the membrane of red blood cells in ischemic heart disease.Changes of membrane lipid composition, in particular, the increase of PS, DAG, and SM and reduction of PC, PEA, and PI and the increase of lysoforms, trigger the disruption of protein-lipid interactions in the membrane and change the surface charge on the membrane.In addition the change in the surface charge of the erythrocytic membrane can be attributed to experimentally found redistribution of charged fractions of phospholipids in patients with stable angina in favour of those neutral ones, located at the outer side of the plasma membrane  and negatively charged PS, which is part of the inner surface of the membrane.All these factors can also influence the transport of ions and change the oxygen-binding properties of the erythrocyte hemoglobin through the change in hematoporphyrin conformation , 48–50.Intensification of LPO processes, found in IHD patients' erythrocytes, firstly causes the decrease in the content of unsaturated fatty acids of phospholipids which is more marked in stable angina on the background of arterial hypertension. This triggers the increase in membranes' microviscosity and enhances their clusterisation. As a result the passive transport of ions including calcium ions increases due to the formation of nonspecific pores .In the end, the intensification of LPO processes along with enzymatic degradation of PL contributes to membranes' damage and changes their physicochemical properties. As a result the disintegration of membrane structures culminates in their destruction and eventual cell death may occur , 53.2 transport efficiency in the body and are signs of many pathologies, including cardiovascular diseases [Numerous processes in the lipid bilayer membrane lead to changes in morphometric characteristics of erythrocytes among patients with IHD, namely, the appearance of echinocytes, stomatocytes, and spherocytes with redistribution and condensation of hemoglobin within the cell. The changes in morphology of the erythrocyte and, as a consequence, distribution of hemoglobin within it, significantly affect the Odiseases .The revealed hemoglobin hematoporphyrin conformation disturbance in IHD patients' erythrocytes leads to the impaired oxygen-binding capacity of hemoglobin exemplified by the decrease in relative amount of oxyhemoglobin, relative ability of hemoglobin to drop ligands, the enhanced ability of hemoglobin to bind ligands, and the affinity of hemoglobin to ligands. This contributes to further intensification of the processes of hypoxia already present when IHD develops.Therefore, the above processes occurring in the lipid bilayer of erythrocytic membranes affect the entire cytoarchitectonics of a cell, conformation of hemoglobin, and, consequently, the core function of erythrocytes—transport of oxygen. This mechanism is probably one of the most important phases in the development of ischemic heart disease.The revealed changes in erythrocytes' properties may also worsen the tissue hypoxia and should be studied in further experiments.The research findings showed that erythrocytic membranes, cytoarchitectonics of formed elements, lipids forming lipid membranes bilayer, and also hemoglobin represent a uniform highly dynamic system responding to the changes happening in the human body.Based on findings and scientific literature it is possible to state that the prescribed therapy did not lead to normalisation of phospholipid and fatty acid structure of erythrocytic membranes. It requires a further search for natural compounds that can influence phospholipase activity and normalise processes of lipid peroxidation and, finally, the structure of hemoglobin. Traditional treatment does not affect one of the major phases of tissue oxygen supply or separate sites exposed to hypoxia. In order to advance the management of cardiovascular diseases it is necessary to take into account the possibility of administering medication improving the functional characteristics of both hemoglobin and erythrocytes.


DEAR EDITOR1 The depth of the labiomental groove is 4-6 mm and it is deeper for men than women.2The labiomental groove is the deepest point of contour change at the junction of the lower lip and chin. It defines the sublabiale point. The labiomental groove is located at about one third the distance from stomion to gnathion. It represents the level of vestibule, but, more pertinently, it is the superior attachments of the mentalis muscle. The chin composes about two thirds of this part of lower face, thus forming a ratio of 1:2, lower lip to chin.2,3 In lower lip- chin reconstruction, excision of lip–chin aesthetic unit and adequate release of the lower lip to completely cover the lower teeth, is performed and in the case of thick lower lip and a flattened mental prominence, debulking of lower lip, sculpting of labiomental groove and even chin implant insertion are recommended. The lip-chin unit is then resurfaced with full thickness or thick split thickness skin graft.2,4 But, what we see in a significant number of reconstructed lower faces is somewhat acceptable appearance of lip–chin unit in frontal view, but aesthetically unacceptable contour in lateral view  was needed , and theThe authors declare no conflict of interest.