Search results for: residual activity (Q2)

Authors: Maki Mizogami, Hironori Tsuchiya, Yoshiroh Hayabuchi, Kenji Shigemi

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Since drugs exhibit significant structure-dependent differences in activity and toxicity, their differentiation based on the mechanism of action should have implications for comparative drug efficacy and safety. We aimed to differentiate drug stereoisomers by their stereostructure-selective membrane interactions underlying pharmacological and toxicological effects. Biomimetic lipid bilayer membranes were prepared with phospholipids and sterols (either cholesterol or epicholesterol) to mimic the lipid compositions of neuronal and cardiomyocyte membranes and to provide these membranes with the chirality. The membrane preparations were treated with different classes of stereoisomers at clinically- and pharmacologically-relevant concentrations (25-200 μM), followed by measuring fluorescence polarization to determine the membrane interactivity of drugs to change the physicochemical property of membranes. All the tested drugs acted on lipid bilayers to increase or decrease the membrane fluidity. Drug stereoisomers could not be differentiated when interacting with the membranes consisting of phospholipids alone. However, they stereostructure-selectively interacted with neuro-mimetic and cardio-mimetic membranes containing 40 mol% cholesterol ((3β)-cholest-5-en-3-ol) to show the relative potencies being local anesthetic R(+)-bupivacaine > rac-bupivacaine > S(‒)-bupivacaine, α2-adrenergic agonistic D-medetomidine > rac-medetomidine > L-medetomidine, β-adrenergic antagonistic R(+)-propranolol > rac-propranolol > S(–)-propranolol, NMDA receptor antagonistic S(+)-ketamine > rac-ketamine, analgesic monoterpenoid (+)-menthol > (‒)-menthol, non-steroidal anti-inflammatory S(+)-ibuprofen > rac-ibuprofen > R(‒)-ibuprofen, and bioactive flavonoid (+)-epicatechin > (‒)-epicatechin. All of the order of membrane interactivity were correlated to those of beneficial and adverse effects of the tested stereoisomers. In contrast, the membranes prepared with epicholesterol ((3α)-chotest-5-en-3-ol), an epimeric form of cholesterol, reversed the rank order of membrane interactivity to be S(‒)-enantiomeric > racemic > R(+)-enantiomeric bupivacaine, L-enantiomeric > racemic > D-enantiomeric medetomidine, S(–)-enantiomeric > racemic > R(+)-enantiomeric propranolol, racemic > S(+)-enantiomeric ketamine, (‒)-enantiomeric > (+)-enantiomeric menthol, R(‒)-enantiomeric > racemic > S(+)-enantiomeric ibuprofen, and (‒)-enantiomeric > (+)-enantiomeric epicatechin. The opposite configuration allows drug molecules to interact with chiral sterol membranes enantiomer-selectively. From the comparative results, it is speculated that a 3β-hydroxyl group in cholesterol is responsible for the enantioselective interactions of drugs. In conclusion, the differentiation of drug stereoisomers by their stereostructure-selective membrane interactions would be useful for designing and predicting drugs with higher activity and/or lower toxicity.

Keywords: chiral membrane, differentiation, drug stereoisomer, enantioselective membrane interaction

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Authors: R. B. Mishra, Sudhakar Tripathi

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In this paper, the cable model of dendrites have been considered. The dendrites are cylindrical cables of various segments having variable length and reducing radius from start point at synapse and end points. For a particular event signal being received by a neuron in response only some dendrite are active at a particular instance. Initial current signals with different current flows in dendrite are assumed. Due to overlapping and coupling of active dendrite, they induce currents in the dendrite segments of each other at a particular instance. But how these currents are induced in the various segments of active dendrites due to coupling between these dendrites, It is not presented in the literature. Here the paper presents a model for induced currents in active dendrite segments due to mutual coupling at the starting instance of an activity in dendrite. The model is as discussed further.

Keywords: currents, dendrites, induction, simulation

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Authors: J. O. Alvarez, L. Y. Rivera

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Physical activity can reduce symptomatology in children with autism spectrum disorder (ASD). The sport of soccer has been widely applied as a therapeutic method for ASD children. However, empirical results from soccer programs are not widely known. This paper presents the case study of Golitos, the only dedicated soccer program for children on the island of Puerto Rico, and analyzes its results in the reduction of ASD social and emotional symptoms. The paper shows evidence that suggests that program approach, content, and community-based elements can make a notable difference in the effectiveness of using soccer or sports as therapeutic methods for children with ASD.

Keywords: autism, soccer, program, community

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Authors: Fatima Doganc, Hakan Goker

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Benzimidazole moiety is an important pharmacophore and privileged structure for the medicinal chemists, since it exhibits various important biological activities. Some clinically used drugs have benzimidazole moiety, such as omeprazole, astemizole, albendazole and domperidone. 2-(4-tert-Butylphenyl)benzimidazole, is a PGC-1α transcriptional regulator shown to have beneficial effects in diabetic mice. We planned to modify the structure of this compound for developing new antidiabetic drug candidates. Hence, a series of guanidino or amidino, benzo/pyrido/pyrimidino-imidazole derivatives were freshly prepared. Mass, 1H-NMR, 13C-NMR, 2D-NMR spectroscopy techniques were used for the new derivatives to clarify their structures and their purity was controlled through the elemental analysis. Antidiabetic activity studies of the synthesized compounds are under the investigation.

Keywords: antidiabetic agents, benzimidazole, imidazopyridine, imidazopyrimidine

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Authors: Jeffrey M. Byford

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The conceptualized theory of decision making on historical events often does not conform to uniform beliefs among students. When presented the opportunity, many students have differing opinions and rationales associated with historical events and outcomes. The intent of this paper was to provide students with the economic, social and political dilemmas associated with the autonomy of East Berlin. Students ranked seven possible actions from the most to least acceptable. In addition, students were required to provide both positive and negative factors for each decision and relative ranking. Results from this activity suggested that while most students chose a financial action towards West Berlin, some students had trouble justifying their actions.

Keywords: content-centered learning, cold war, Berlin, decision-making

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Authors: Ramachandran Manivannan, B. Sakthi Swaroop, Selvam Noyel Victoria

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Microbial corrosion of brass gauze by the aerobic film forming bacteria Arthrobacter sulfurous in neutral media was investigated using gravimetric studies. Maximum weight loss of 166.98 mg was observed for a period of 28 days of exposure to the bacterial medium as against the weight loss of 13.69 mg for control. The optical density studies for the bacterial culture was found to show attainment of stationary phase in 48 h. Scanning electron microscopy analysis of the samples shows the presence of pitting corrosion. The energy dispersive X-ray analysis of the samples showed increased oxygen and phosphorus content in the sample due to bacterial activity.

Keywords: Arthrobacter sulfureus, biocorrosion, brass, neutral medium

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Authors: Martin Juhas, Bohuslava Juhasova, Igor Halenar, Andrej Elias

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This article deals with the possibility of increasing efficiency, reliability and safety of the system for teledosimetric data collection management and their evaluation as a part of complex study for activity “Research of data collection, their measurement and evaluation with mobile and autonomous units” within project “Research of monitoring and evaluation of non-standard conditions in the area of nuclear power plants”. Possible weaknesses in existing system are identified. A study of available cluster solutions with possibility of their deploying to analysed system is presented.

Keywords: teledosimetric data, efficiency, reliability, safety, cluster solution

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Authors: Jamel Boukhatem, Mouldi Djelassi

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Contrary to the existing literature generally focusing on the role played by Sukuk in enhancing investors' and shareholders' wealth, this paper sheds some light on the Sukuk wealth effect across all economic agents: households, government, and investors by implementing a two-period life-cycle model with overlapping generations to show whether Sukuk is net wealth. The main findings are threefold: i) the effect of a change in Sukuk issuances on the consumers’ utility level will be different from one generation to another, ii) an increase in taxes due to the increase in Sukuk and rents is covered by transfers made by the members of generation 1 in the form of inheritance, and iii) the existence of a positive relationship between the asset prices representative of Sukuk and the real activity.

Keywords: Sukuk, households, investors, overlapping generations model, wealth, modeling

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Authors: Maria De Albuquerque Bercot, Caio Gustavo Mesquita Angelo, Daniela Maria Moreira Siqueira, Augusto Assucena De Vasconcellos, Rodrigo Studart Correa

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Mining is an important socioeconomic activity in Brazil although it negatively impacts the environment. Mineral operations cause irreversible changes in topography, removal of vegetation and topsoil, habitat destruction, displacement of fauna, loss of biodiversity, soil erosion, siltation of watercourses and have potential to enhance climate change. Due to the impacts and its pollution potential, mining activity in Brazil is legally subjected to environmental licensing. Unlicensed mining operations or operations that not abide to the terms of an obtained license are taken as environmental crimes in the country. This work reports a case analyzed in the Forensic Institute of the Brazilian Federal District Civil Police. The case consisted of detecting illegal aspects of sand exploitation from a licensed mine in Federal District, nearby Brasilia city. The fieldwork covered an area of roughly 6 ha, which was surveyed with an unmanned aerial vehicle (UAV) (PHANTOM 3 ADVANCED). The overflight with UAV took about 20 min, with maximum flight height of 100 m. 592 UAV georeferenced images were obtained and processed in a photogrammetric software (AGISOFT PHOTOSCAN 1.1.4), which generated a mosaic of geo-referenced images and a 3D model in less than six working hours. The 3D model was analyzed in a forensic software for accurate modeling and volumetric analysis. (MAPTEK I-SITE FORENSIC 2.2). To ensure the 3D model was a true representation of the mine site, coordinates of ten control points and reference measures were taken during fieldwork and compared to respective spatial data in the model. Finally, these spatial data were used for measuring mining area, excavation depth and volume of exploited sand. Results showed that mine holder had not complied with some terms and conditions stated in the granted license, such as sand exploration beyond authorized extension, depth and volume. Easiness, the accuracy and expedition of procedures used in this case highlight the employment of UAV imagery and computational photogrammetry as efficient tools for outdoor forensic exams, especially on environmental issues.

Keywords: computational photogrammetry, environmental monitoring, mining, UAV

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Authors: Divya Pradip Roy, Md. Zahirul Alam Chowdhury

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Electromyography (EMG) sensors are generally used to record the electrical activity produced by skeletal muscles. The conventional EMG sensors available in the market are expensive. This research suggests a low cost EMG sensor design which can be built with simple devices within our reach. In this research, one instrumentation amplifier, two high pass filters, two low pass filters and an inverting amplifier is connected sequentially. The output from the circuit exhibits electrical potential generated by the muscle cells when they are neurologically activated. This electromyography signal is used to control prosthetic devices, identifying neuromuscular diseases and for various other purposes.

Keywords: EMG, high pass filter, instrumentation amplifier, inverting amplifier, low pass filter, neuromuscular

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Authors: Teodorica G. Ani

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Economic activity requires an encouraging regulatory environment and effective rules that are transparent and accessible to all. The World Bank has been publishing the annual Doing Business reports since 2004 to investigate the scope and manner of regulations that enhance business activity and those that constrain it. A streamlined business environment supporting the development of competitive small and medium enterprises (SMEs) may expand employment opportunities and improve the living conditions of low income households. Asia has emerged as one of the most attractive markets in the world. Economies in East Asia and the Pacific were among the most active in making it easier for local firms to do business. The study aimed to describe the ease of doing business and its effect to economic growth among selected economies in Asia for the year 2014. The study covered 29 economies in East Asia, Southeast Asia, South Asia and Middle Asia. Ease of doing business is measured by the Doing Business indicators (DBI) of the World Bank. The indicators cover ten aspects of the ease of doing business such as starting a business, dealing with construction permits, getting electricity, registering property, getting credit, protecting investors, paying taxes, trading across borders, enforcing contracts and resolving insolvency. In the study, Gross Domestic Product (GDP) was used as the proxy variable for economic growth. Descriptive research was the research design used. Graphical analysis was used to describe the income and doing business among selected economies. In addition, multiple regression was used to determine the effect of doing business to economic growth. The study presented the income among selected economies. The graph showed China has the highest income while Maldives produces the lowest and that observation were supported by gathered literatures. The study also presented the status of the ten indicators of doing business among selected economies. The graphs showed varying trends on how easy to start a business, deal with construction permits and to register property. Starting a business is easiest in Singapore followed by Hong Kong. The study found out that the variations in ease of doing business is explained by starting a business, dealing with construction permits and registering property. Moreover, an explanation of the regression result implies that a day increase in the average number of days it takes to complete a procedure will decrease the value of GDP in general. The research proposed inputs to policy which may increase the awareness of local government units of different economies on the simplification of the policies of the different components used in measuring doing business.

Keywords: doing business, economic growth, gross domestic product, Asia

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Authors: Virendra Nath, Vipin Kumar

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Background: TypeII Diabetes mellitus is a foremost health problem worldwide, predisposing to increased mortality and morbidity. Undesirable effects of the current medications have prompted the researcher to develop more potential drug(s) against the disease. The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptors family and take part in a vital role in the regulation of metabolic equilibrium. They can induce or repress genes associated with adipogenesis, lipid, and glucose metabolism. Aims: Investigation of PPARα/γ agonistic hits were screened by hierarchical virtual screening followed by molecular dynamics simulation and knowledge-based structure-activity relation (SAR) analysis using approved PPAR α/γ dual agonist. Methods: The PPARα/γ agonistic activity of compounds was searched by using Maestro through structure-based virtual screening and molecular dynamics (MD) simulation application. Virtual screening of nuclear-receptor ligands was done, and the binding modes with protein-ligand interactions of newer entity(s) were investigated. Further, binding energy prediction, Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit along with the structural comparative analysis of approved PPARα/γ agonists with screened hit was done for knowledge-based SAR. Results and Discussion: The silicone chip-based approach recognized the most capable nine hits and had better predictive binding energy as compared to the reference drug compound (Tesaglitazar). In this study, the key amino acid residues of binding pockets of both targets PPARα/γ were acknowledged as essential and were found to be associated in the key interactions with the most potential dual hit (ChemDiv-3269-0443). Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit and found root mean square deviation (RMSD) stabile around 2Å and 2.1Å, respectively. Frequency distribution data also revealed that the key residues of both proteins showed maximum contacts with a potent hit during the MD simulation of 20 nanoseconds (ns). The knowledge-based SAR studies of PPARα/γ agonists were studied using 2D structures of approved drugs like aleglitazar, tesaglitazar, etc. for successful designing and synthesis of compounds PPARγ agonistic candidates with anti-hyperlipidimic potential.

Keywords: computational, diabetes, PPAR, simulation

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Authors: Bastian Vollrath, Hartwig Hubel

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In case of over-elastic and cyclic loading, strain may accumulate due to a ratcheting mechanism until the state of shakedown is possibly achieved. Load history dependent numerical investigations by a step-by-step analysis are rather costly in terms of engineering time and numerical effort. In the case of multi-parameter loading, where various independent loadings affect the final state of shakedown, the computational effort becomes an additional challenge. Therefore, direct methods like the Simplified Theory of Plastic Zones (STPZ) are developed to solve the problem with a few linear elastic analyses. Post-shakedown quantities such as strain ranges and cyclic accumulated strains are calculated approximately by disregarding the load history. The STPZ is based on estimates of a transformed internal variable, which can be used to perform modified elastic analyses, where the elastic material parameters are modified, and initial strains are applied as modified loading, resulting in residual stresses and strains. The STPZ already turned out to work well with respect to cyclic loading between two states of loading. Usually, few linear elastic analyses are sufficient to obtain a good approximation to the post-shakedown quantities. In a multi-dimensional load domain, the approximation of the transformed internal variable transforms from a plane problem into a hyperspace problem, where time-consuming approximation methods need to be applied. Therefore, a solution restricted to structures with four stress components was developed to estimate the transformed internal variable by means of three-dimensional vector algebra. This paper presents the extension to cyclic multi-parameter loading so that an unlimited number of load cases can be taken into account. The theoretical basis and basic presumptions of the Simplified Theory of Plastic Zones are outlined for the case of elastic shakedown. The extension of the method to many load cases is explained, and a workflow of the procedure is illustrated. An example, adopting the FE-implementation of the method into ANSYS and considering multilinear hardening is given which highlights the advantages of the method compared to incremental, step-by-step analysis.

Keywords: cyclic loading, direct method, elastic shakedown, multi-parameter loading, STPZ

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Authors: Dumont Maxime, Correia Carlos, Sauvage Jean-François, Schwartz Noah, Gray Morgan

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Context: The concept of the segmented telescope is unavoidable to build extremely large telescopes (ELT) in the quest for spatial resolution, but it also allows one to fit a large telescope within a reduced volume of space (JWST) or into an even smaller volume (Standard Cubesat). Cubesats have tight constraints on the computational burden available and the small payload volume allowed. At the same time, they undergo thermal gradients leading to large and evolving optical aberrations. The pupil segmentation comes nevertheless with an obvious difficulty: to co-phase the different segments. The CubeSat constraints prevent the use of a dedicated wavefront sensor (WFS), making the focal-plane images acquired by the science detector the most practical alternative. Yet, one of the challenges for the wavefront sensing is the non-linearity between the image intensity and the phase aberrations. Plus, for Earth observation, the object is unknown and unrepeatable. Recently, several studies have suggested Neural Networks (NN) for wavefront sensing; especially convolutional NN, which are well known for being non-linear and image-friendly problem solvers. Aims: We study in this paper the prospect of using NN to measure the phasing aberrations of a segmented pupil from the focal-plane image directly without a dedicated wavefront sensing. Methods: In our application, we take the case of a deployable telescope fitting in a CubeSat for Earth observations which triples the aperture size (compared to the 10cm CubeSat standard) and therefore triples the angular resolution capacity. In order to reach the diffraction-limited regime in the visible wavelength, typically, a wavefront error below lambda/50 is required. The telescope focal-plane detector, used for imaging, will be used as a wavefront-sensor. In this work, we study a point source, i.e. the Point Spread Function [PSF] of the optical system as an input of a VGG-net neural network, an architecture designed for image regression/classification. Results: This approach shows some promising results (about 2nm RMS, which is sub lambda/50 of residual WFE with 40-100nm RMS of input WFE) using a relatively fast computational time less than 30 ms which translates a small computation burder. These results allow one further study for higher aberrations and noise.

Keywords: wavefront sensing, deep learning, deployable telescope, space telescope

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Authors: Allulu Yousef Alturki, Raghad Abdullah Alshafi, Sara Abdulaziz Alghashem, Sahar Saleh Alghamdi, Rasha Saad Suliman, Zeyad Alehaideb, Rizwan Ali

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Cancer is recognized as a worldwide public health concern. Therefore, there is a continuous quest to discover new effective medications with less side-effects. In recent years, researchers have shown an increased interest in medicinal plants as several plant species have shown promising biological activities. Thus, we seek to investigate three medicinal herbs that are commonly-found in the Middle Easternregion and yet have not been explored in depth, including plants belonging to the Rhamnaceae, Polygonaceae, and Apocynaceaeplant families. Initially, we investigated using three types of cancer cell lines for breast, colorectal, and liver cancers. We performed high Content Imaging (HCI)-Apoptosis Assay and ApoTox-Glo™ Triplex Assay on KAIMRC2 and HCT8 cell lines. The highest activity of HCI-Apoptosis Assay was with Calligonumcomosum and Ziziphusnummularia in ethanol, followed by Calotropis procera and Ziziphusnummularia in ethyl acetate. The IC50values for the families of Rhamnaceae, Polygonaceae, and Apocynaceae in HepG2 and HCT8 cell lines ranged from 0.089 to 9.84mg/mL and 0.080to 15.08mg/mL, respectively. Further screening was conducted on an additional two cell lines, namely the MDA-MB-231 and KAIMRC2, for selected seven extracts with the highest activity having IC50values ranged from 0.058 to0.51mg/mL and 0.029 to0.19mg/mL, respectively. Continuous scientific investigations to isolate and characterize the potent bioactive phytochemical(s) are warranted. Funding: The authors acknowledge financial support from King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia. Institutional Review Board Statement: The study was approved by the Institutional Review Board of the Institutional Review Board of King Abdullah International Medical Research Center (SP21R/463/12, 24 January 2022). Acknowledgments: The authors want to express their gratitude to the College of Pharmacy (COP) at King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) and King Abdullah International Medical Research Center (KAIMRC) for their continued support.

Keywords: rhamnaceae, polygonaceae, apocynaceae, natural products

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Authors: Chen Yang, Jun Hu, Ping Li, Lili Xue

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Most companies pay careful attention to consumer feedback collection, so it is popular to find the ‘feedback’ button of all kinds of mobile apps. Yet it is much more changeling to analyze these feedback texts and to catch the true feelings of a consumer regarding either a problem or a complimentary of consumers who hands out the feedback. Especially to the Chinese content, it is possible that; in one context the Chinese feedback expresses positive feedback, but in the other context, the same Chinese feedback may be a negative one. For example, in Chinese, the feedback 'operating with loudness' works well with both refrigerator and stereo system. Apparently, this feedback towards a refrigerator shows negative feedback; however, the same feedback is positive towards a stereo system. By introducing Bradley, M. and Lang, P.'s Affective Norms for English Text (ANET) theory and Bucci W.’s Referential Activity (RA) theory, we, usability researchers at Pingan, are able to decipher the feedback and to find the hidden feelings behind the content. We subtract 2 disciplines ‘valence’ and ‘dominance’ out of 3 of ANET and 2 disciplines ‘concreteness’ and ‘specificity’ out of 4 of RA to organize our own rating system with a scale of 1 to 5 points. This rating system enables us to judge the feelings/emotion behind each feedback, and it works well with both single word/phrase and a whole paragraph. The result of the rating reflects the strength of the feeling/emotion of the consumer when he/she is typing the feedback. In our daily work, we first require a consumer to answer the net promoter score (NPS) before writing the feedback, so we can determine the feedback is positive or negative. Secondly, we code the feedback content according to company problematic list, which contains 200 problematic items. In this way, we are able to collect the data that how many feedbacks left by the consumer belong to one typical problem. Thirdly, we rate each feedback based on the rating system mentioned above to illustrate the strength of the feeling/emotion when our consumer writes the feedback. In this way, we actually obtain two kinds of data 1) the portion, which means how many feedbacks are ascribed into one problematic item and 2) the severity, how strong the negative feeling/emotion is when the consumer is writing this feedback. By crossing these two, and introducing the portion into X-axis and severity into Y-axis, we are able to find which typical problem gets the high score in both portion and severity. The higher the score of a problem has, the more urgent a problem is supposed to be solved as it means more people write stronger negative feelings in feedbacks regarding this problem. Moreover, by introducing hidden Markov model to program our rating system, we are able to computerize the scoring system and are able to process thousands of feedback in a short period of time, which is efficient and accurate enough for the industrial purpose.

Keywords: computerized scoring system, feeling/emotion of consumer feedback, referential activity, text mining

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Authors: Maxat Bokambayev, Bella Tussupova, Aisha Mamyrova, Erlan Izbasarov

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Optimization of business processes in trading companies is reviewed in the report. There is the presentation of the “Wholesale Customer Order Handling Process” business process model applicable for small and medium businesses. It is proposed to apply the algorithm for automation of the customer order processing which will significantly reduce labor costs and time expenditures and increase the profitability of companies. An optimized business process is an element of the information system of accounting of spare parts trading network activity. The considered algorithm may find application in the trading industry as well.

Keywords: business processes, discrete-event simulation, management, trading industry

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Authors: Achiron Anat, Mathilda Mandel, Mayust Sue, Achiron Reuven, Gurevich Michael

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Introduction: As coronavirus disease 2019 (COVID-19) vaccination is currently spreading around the world, it is of importance to assess the ability of multiple sclerosis (MS) patients to mount an appropriate immune response to the vaccine in the context of disease-modifying treatments (DMT’s). Objectives: Evaluate immunity generated following COVID-19 vaccination in MS patients, and assess factors contributing to protective humoral and cellular immune responses in MS patients vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) virus infection. Methods: Review our recent data related to (1) the safety of PfizerBNT162b2 COVID-19 mRNA vaccine in adult MS patients; (2) the humoral post-vaccination SARS-CoV2 IgG response in MS vaccinees using anti-spike protein-based serology; and (3) the cellular immune response of memory B-cells specific for SARS-CoV-2 receptor-binding domain (RBD) and memory T-cells secreting IFN-g and/or IL-2 in response to SARS-CoV2 peptides using ELISpot/Fluorospot assays in MS patients either untreated or under treatment with fingolimod, cladribine, or ocrelizumab; (4) covariate parameters related to mounting protective immune responses. Results: COVID-19 vaccine proved safe in MS patients, and the adverse event profile was mainly characterised by pain at the injection site, fatigue, and headache. Not any increased risk of relapse activity was noted and the rate of patients with acute relapse was comparable to the relapse rate in non-vaccinated patients during the corresponding follow-up period. A mild increase in the rate of adverse events was noted in younger MS patients, among patients with lower disability, and in patients treated with DMTs. Following COVID-19 vaccination protective humoral immune response was significantly decreased in fingolimod- and ocrelizumab- treated MS patients. SARS-CoV2 specific B-cell and T-cell cellular responses were respectively decreased. Untreated MS patients and patients treated with cladribine demonstrated protective humoral and cellular immune responses, similar to healthy vaccinated subjects. Conclusions: COVID-19 BNT162b2 vaccine proved as safe for MS patients. No increased risk of relapse activity was noted post-vaccination. Although COVID-19 vaccination is new, accumulated data demonstrate differences in immune responses under various DMT’s. This knowledge can help to construct appropriate COVID-19 vaccine guidelines to ensure proper immune responses for MS patients.

Keywords: covid-19, vaccination, multiple sclerosis, IgG

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Authors: Beata Jackowska-Zduniak

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We formulate and analyze a mathematical model describing dynamics of the hypothalamus-pituitary-thyroid homoeostatic mechanism in endocrine system. We introduce to this system two types of couplings and delay. In our model, feedback controls the secretion of thyroid hormones and delay reflects time lags required for transportation of the hormones. The influence of delayed feedback on the stability behaviour of the system is discussed. Analytical results are illustrated by numerical examples of the model dynamics. This system of equations describes normal activity of the thyroid and also a couple of types of malfunctions (e.g. hyperthyroidism).

Keywords: mathematical modeling, ordinary differential equations, endocrine system, delay differential equation

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Authors: Elda Maraj, Shkelqim Kuka

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Coronary heart disease causes many deaths in the world. Unfortunately, this problem will continue to increase in the future. In this paper, a fuzzy logic model to predict coronary heart disease is presented. This model has been developed with seven input variables and one output variable that was implemented for 30 patients in Albania. Here fuzzy logic toolbox of MATLAB is used. Fuzzy model inputs are considered as cholesterol, blood pressure, physical activity, age, BMI, smoking, and diabetes, whereas the output is the disease classification. The fuzzy sets and membership functions are chosen in an appropriate manner. Centroid method is used for defuzzification. The database is taken from University Hospital Center "Mother Teresa" in Tirana, Albania.

Keywords: coronary heart disease, fuzzy logic toolbox, membership function, prediction model

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Authors: Zhihui Liu, Dongmei Hao, Qian Qiu, Yang An, Lin Yang, Song Zhang, Yimin Yang, Xuwen Li, Dingchang Zheng

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Premature birth, defined as birth before 37 completed weeks of gestation is a leading cause of neonatal morbidity and mortality and has long-term adverse consequences for health. It has recently been reported that the worldwide preterm birth rate is around 10%. The existing measurement techniques for diagnosing preterm delivery include tocodynamometer, ultrasound and fetal fibronectin. However, they are subjective, or suffer from high measurement variability and inaccurate diagnosis and prediction of preterm labor. Electrohysterography (EHG) method based on recording of uterine electrical activity by electrodes attached to maternal abdomen, is a promising method to assess uterine activity and diagnose preterm labor. The purpose of this study is to analyze the difference of EHG signal features between term labor and preterm labor. Free access database was used with 300 signals acquired in two groups of pregnant women who delivered at term (262 cases) and preterm (38 cases). Among them, EHG signals from 38 term labor and 38 preterm labor were preprocessed with band-pass Butterworth filters of 0.08–4Hz. Then, EHG signal features were extracted, which comprised classical time domain description including root mean square and zero-crossing number, spectral parameters including peak frequency, mean frequency and median frequency, wavelet packet coefficients, autoregression (AR) model coefficients, and nonlinear measures including maximal Lyapunov exponent, sample entropy and correlation dimension. Their statistical significance for recognition of two groups of recordings was provided. The results showed that mean frequency of preterm labor was significantly smaller than term labor (p < 0.05). 5 coefficients of AR model showed significant difference between term labor and preterm labor. The maximal Lyapunov exponent of early preterm (time of recording < the 26th week of gestation) was significantly smaller than early term. The sample entropy of late preterm (time of recording > the 26th week of gestation) was significantly smaller than late term. There was no significant difference for other features between the term labor and preterm labor groups. Any future work regarding classification should therefore focus on using multiple techniques, with the mean frequency, AR coefficients, maximal Lyapunov exponent and the sample entropy being among the prime candidates. Even if these methods are not yet useful for clinical practice, they do bring the most promising indicators for the preterm labor.

Keywords: electrohysterogram, feature, preterm labor, term labor

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Authors: Claudio Lamilla, Andrés Santos, Vicente Llanquinao, Jocelyn Hermosilla, Leticia Barrientos

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The industry in general is very interested in improving and optimizing industrial processes in order to reduce the costs involved in obtaining raw materials and production. Thus, an interesting and cost-effective alternative is the incorporation of bioactive metabolites in such processes, being an example of this enzymes which catalyze efficiently a large number of enzymatic reactions of industrial and biotechnological interest. In the search for new sources of these active metabolites, Antarctica is one of the least explored places on our planet where the most drastic cold conditions, salinity, UVA-UVB and liquid water available are present, features that have shaped all life in this very harsh environment, especially bacteria that live in different Antarctic ecosystems, which have had to develop different strategies to adapt to these conditions, producing unique biochemical strategies. In this work the production of cellulolytic enzymes of seven bacterial strains isolated from marine sediments at different sites in the Antarctic was evaluated. Isolation of the strains was performed using serial dilutions in the culture medium at M115°C. The identification of the strains was performed using universal primers (27F and 1492R). The enzyme activity assays were performed on R2A medium, carboxy methyl cellulose (CMC)was added as substrate. Degradation of the substrate was revealed by adding Lugol. The results show that four of the tested strains produce enzymes which degrade CMC substrate. The molecular identifications, showed that these bacteria belong to the genus Streptomyces and Pseudoalteromonas, being Streptomyces strain who showed the highest activity. Only some bacteria in marine sediments have the ability to produce these enzymes, perhaps due to their greater adaptability to degrade at temperatures bordering zero degrees Celsius, some algae that are abundant in this environment and have cellulose as the main structure. The discovery of new enzymes adapted to cold is of great industrial interest, especially for paper, textiles, detergents, biofuels, food and agriculture. These enzymes represent 8% of industrial demand worldwide and is expected to increase their demand in the coming years. Mainly in the paper and food industry are required in extraction processes starch, protein and juices, as well as the animal feed industry where treating vegetables and grains helps improve the nutritional value of the food, all this clearly puts Antarctic microorganisms and their enzymes specifically as a potential contribution to industry and the novel biotechnological applications.

Keywords: antarctic, bacteria, biotechnological, cellulolytic enzymes

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Authors: Zachary Muthii Rukenya, James Mbaria, Peter Mbaabu, Kiama Stephen Gitahi, Ronald Onzago

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Aloe turkanensis is one of the widely used medicinal shrub and in Kenya the plant is mainly found in Baringo, Isiolo, Laikipia, Turkana and West Pokot Counties where it is used in ethno-medicine and ethno-veterinary medicine. The Turkana community uses the plant products to manage malaria, wounds, stomach ache, constipation, pain, skin infection, poultry diseases and retained afterbirth in cows. This evaluated the efficacy and safety of the plant obtained from Turkana County, Kenya. Preliminary data on the use of the plant in the county was collected through observation, photographing and interviews. A sample of the whole plant was harvested in Natira sublocation, in ex-Turkana west district in February 2012 after identification by Aloe-working group herbalists who voluntarily provided information on its medicinal uses. Botanical identification was done at Kenya Forest Research Centre in Karura where voucher specimen was deposited. Cold maceration using 70% methanol and distilled water was used for extraction. Bioassays were to determine the effects of the plant extracts on brine shrimp and selected bacterial and fungal cultures. The extracts were tested in-vitro activity against standard cultures of B. cereus (ATCC 11778), S. aureus (ATCC25923), P. aeroginosa (ATCC 27853), E. coli (ATCC 25922) and a human infections clinical isolate of C. albicans. The extracts of Aloe turkanensis inhibited the growth B. cereus (100-200 mg/ml), S. aureus (50-100 mg/ml), P. aeroginosa (200mg/ml), E. coli (400mg/ml) while C. albicans was not affected. The extracts also inhibited the growth of S. aureus and B. cereus with mean diameters of inhibition zones being 19.75±1 mm and 18.5±05 mm reapectively. Phytochemical screening showed the presence of alkaloids, tarpenoids, steroids, quinones, saponins and tannins in the plant extracts. The extract was found to be non-toxic at a concentration of 1000µg/ml with a 100% survival of Brine Shrimp larva. It was concluded that Aloe turkanensis growing the study area has metabolites that inhibit the growth of microorganisms and is however, there is need for further studies to validate the in-vivo bioactivity of the plant and more generate adequate toxicological data.to support conservation, value chain addition of its products and widespread use as a herbal remedy.

Keywords: Aloe turkanensis, bioactivity, cultivated, human infections

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Authors: Ashwini Patil

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Caudal block is one of the most commonly used regional anesthetic techniques in children. Currently, fentanyl is used as an adjuvant to bupivacaine to prolong analgesia but fentanyl is a narcotic. Dexamethasone, a glucocorticoid with strong anti-inflammatory effects provides improvement in post-operative analgesia and post-operative side effects. However, its analgesic efficacy and safety in comparison with fentanyl has not been extensively studied. So the objective of this randomized controlled study is to compare dexamethasone with fentanyl as an adjuvant to bupivacaine for caudal block in children in relation to the duration of caudal analgesia, post-operative analgesic requirement and incidence of post-operative nausea and vomiting. This study included 100 children, aged 1–6 years, undergoing lower abdominal surgeries. Patients were randomized into two groups, 50 each to receive a combination of dexamethasone 0.2 mg/kg along with 1 ml/kg bupivacaine 0.25% (group A) or combination of fentanyl (1 ug/kg) along with 1ml/kg bupivacaine 0.25% (group B). In the post-operative period, pain was assessed using a Modified Objective Pain Scale (MOPS) until 12 hr after surgery and rescue analgesia is administered when MOPS score 4 or more is recorded. Residual motor block, number of analgesic doses required within 24 hr after surgery, sedation scores, intra-operative and post-operative hemodynamic variables, post-operative nausea and vomiting (PONV), and other adverse effects were recorded. Data is analysed using unpaired t test and Significance level of P< 0.05 is considered statistically significant. Group A showed a significantly longer time to first analgesic requirement than group B (p<0.05). The number of rescue analgesic doses required in the first 24 h was significantly less in group A (p<0.05). Group A showed significantly lower MOPS scores than group B(p<0.05). Intra-operative and post-operative hemodynamic variables, Modified Bromage Scale scores, and sedation scores were comparable in both the groups. Group A showed significantly fewer incidences of PONV compared with group B(p<0.05). This study reveals that adding dexamethasone to bupivacaine prolongs the duration of postoperative analgesia and decreases the incidence of PONV as compared to combination of fentanyl to bupivacaine after a caudal block in pediatric patients.

Keywords: bupivacaine, caudal analgesia, dexamethasone, pediatric

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Authors: Fatih Sonmez

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease and it is the most common form of dementia that affects aged people. Acetylcholinesterase is a hydrolase involved in the termination of impulse transmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter ACh in the central and peripheral nervous system. Carvacrol (5-iso-propyl-2-methyl-phenol) is a main bioactive monoterpene isolated from many medicinal herbs, such as Thymus vulgaris, Monarda punctate and Origanum vulgare spp. It is known that carvacrol has been widely used as an active anti-inflammatory ingredient, which can inhibit the isoproterenol induced inflammation in myocardial infarcted rats. In this paper, a series of 12 carvacrol substituted carbamate derivatives (2a-l) was synthesized and their inhibitory activities on AChE and BuChE were evaluated. Among them, 2d exhibited the strongest inhibition against AChE with an IC50 value of 2.22 µM, which was 130-fold more than that of carvacrol (IC50 = 288.26 µM).

Keywords: Acetylcholinesterase, Butyrylcholinesterase, Carbamate, Carvacrol

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Authors: Aicha Bensouici, Assia Mili, Naouel Rdjem, Nacera Baali

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Copper oxide decorated reduced graphene oxide (GO) was obtained successfully using two steps route synthesis was used. Firstly, graphene oxide was obtained using a modified Hummers method by excluding sodium nitrate from starting materials. After washing-centrifugation routine pristine GO was decorated by copper oxide using a refluxation technique at 120°C during 2h, and an equal amount of GO and copper acetate was used. Three CuO-rGO nanocomposite samples types were obtained at 30min, 24h, and 7 day stirring time. TAC results show dose dependent behavior of CuO-rGO and confirm no influence of stirring time on antioxidant properties, 30min is considered as an optimal stirring condition.

Keywords: copper oxide, reduced graphene oxide, TAC, GO

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Authors: Jos Olijve

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Introduction and Purpose: Endotoxins are found in the outer membrane of gram-negative bacteria and have profound in vitro and in vivo responses. They can trigger strong immune responses and negatively affect various cellar activities particular cells expressing toll-like receptors. They are therefore unwanted contaminants of biomaterials sourced from natural raw materials, and their activity must be as low as possible. Collagen and gelatin are natural extracellular matrix components and have, due to their low allergenic potential, suitable biological properties, and tunable physical characteristics, high potential in biomedical applications. The purpose of this study was to determine the influence of autoclave sterilization of gelatin on physical properties and endotoxin level compared to surfactant purified gelatin. Methods: Type A gelatin from Sigma-Aldrich (G1890) with endotoxin level of 35000 endotoxin units (EU) per gram gelatin and type A gelatins from Rousselot Gent with endotoxin activity of 30000 EU per gram were used. A 10 w/w% G1890 gelatin solution was autoclave sterilized during 30 minutes at 121°C and 1 bar over pressure. The physical properties and the endotoxin level of the sterilized G1890 gelatin were compared to a type A gelatin from Rousselot purified with Triton X100 surfactant. The Triton X100 was added to a concentration of 0.5 w/w% which is above the critical micellar concentration. The gelatin surfactant mixtures were kept for 30-45 minutes under constant stirring at 55-60°C. The Triton X100 was removed by active carbon filtration. The endotoxin levels of the gelatins were measured using the Endozyme recombinant factor C method from Hyglos GmbH (Germany). Results and Discussion: Autoclave sterilization significantly affect the physical properties of gelatin. Molecular weight of G1890 decreased from 140 to 50kDa, and gel strength decreased from 300 to 40g. The endotoxin level of the gelatin reduced after sterilization from 35000 EU/g to levels of 400-500 EU/g. These endotoxin levels are however still far above the upper endotoxin level of 0.05 EU/ml, which resembles 5 EU/g gelatin based on a 1% gelatin solution, to avoid cell proliferation alteration. Molecular weight and gel strength of Rousselot gelatin was not altered after Triton X100 purification and remained 150kDa and 300g respectively. The endotoxin levels of Triton X100 purified Rousselot gelatin was < 5EU/g gelatin. Conclusion: Autoclave sterilization of gelatin is, in comparison to Triton X100 purification, not efficient to inactivate endotoxin levels in gelatin to levels below the upper limit to avoid cell proliferation alteration. Autoclave sterilization gave a significant decrease in molecular weight and gel strength which makes autoclave sterilized gelatin, in comparison to Triton X100 purified gelatin, not suitable for 3D printing.

Keywords: endotoxin, gelatin, molecular weight, sterilization, Triton X100

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Authors: Liubov Evstigneeva

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In this paper an attempt is made to establish causal nexuses between innovation and international trade in Russia. The topicality of this issue is determined by the necessity of choosing policy instruments for economic modernization and transition to innovative development. The vector auto regression (VAR) model and Granger test are applied for the Russian monthly data from 2005 until the second quartile of 2015. Both lagged import and export at the national level cause innovation, the latter starts to stimulate foreign trade since it is a remote lag. In comparison to aggregate data, the results by patent’s categories are more diverse. Importing technologies from foreign countries stimulates patent activity, while innovations created in Russia are only Granger causality for import to Commonwealth of Independent States.

Keywords: export, import, innovation, patents

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Authors: Assel E. Molzhigitova, Amankeldi K. Sadanov, Elvira T. Ismailova, Kulyash A. Iskandarova, Olga N. Shemshura, Ainur I. Seitbattalova

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Fire blight is a very harmful for commercial apple and pear production quarantine bacterial disease. To date, several different methods have been proposed for disease control, including the use of copperbased preparations and antibiotics, which are not always reliable or effective. The use of bacteria as biocontrol agents is one of the most promising and eco-friendly alternative methods. Bacteria with protective activity against the causal agent of fire blight are often present among the epiphytic microorganisms of the phyllosphere of host plants. Therefore, the main objective of our study was screening of local epiphytic bacteria as possible antagonists against Erwinia amylovora, the causal agent of fire blight. Samples of infected organs of apple and pear trees (shoots, leaves, fruits) were collected from the industrial horticulture areas in various agro-ecological zones of Kazakhstan. Epiphytic microorganisms were isolated by standard and modified methods on specific nutrient media. The primary screening of selected microorganisms under laboratory conditions to determine the ability to suppress the growth of Erwinia amylovora was performed by agar-diffusion-test. Among 142 bacteria isolated from the fire blight host plants, 5 isolates, belonging to the genera Bacillus, Lactobacillus, Pseudomonas, Paenibacillus and Pantoea showed higher antagonistic activity against the pathogen. The diameters of inhibition zone have been depended on the species and ranged from 10 mm to 48 mm. The maximum diameter of inhibition zone (48 mm) was exhibited by B. amyloliquefaciens. Less inhibitory effect was showed by Pantoea agglomerans PA1 (19 mm). The study of inhibitory effect of Lactobacillus species against E. amylovora showed that among 7 isolates tested only one (Lactobacillus plantarum 17M) demonstrated inhibitory zone (30 mm). In summary, this study was devoted to detect the beneficial epiphytic bacteria from plants organs of pear and apple trees due to fire blight control in Kazakhstan. Results obtained from the in vitro experiments showed that the most efficient bacterial isolates are Lactobacillus plantarum 17M, Bacillus amyloliquefaciens MB40, and Pantoea agglomerans PA1. These antagonists are suitable for development as biocontrol agents for fire blight control. Their efficacies will be evaluated additionally, in biological tests under in vitro and field conditions during our further study.

Keywords: antagonists, epiphytic bacteria, Erwinia amylovora, fire blight

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Authors: Ali Kamal M. Sami, Safa Almukhtar, Alaa Al-Krush, Ismael Hama-Amin Akha Weas, Ruqaya Ahmed Alqais

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Introduction and Objectives Lower urinary tract symptoms (LUTS) are common among men with benign prostatic hyperplasia (BPH). The combination of 5 alpha-reductase inhibitors and alpha-blockers has been used as a conservative treatment of male LUTS secondary to BPH. Nanotechnology structured water magnalife is a type of water that is produced by modulators and specific frequency and energy fields that transform ordinary water into this Nanowater. In this study, we evaluated the use of Nano-water with the conservative treatment and to see if it improves the outcome and gives better results in those patients with LUTS/BPH. Material and methods For a period of 3 months, 200 men with International Prostate Symptom Score (IPSS)≥13, maximum flow rate (Qmax)≤ 15ml/s, and prostate volume > 30 and <80 ccs were randomly divided into two groups. Group A 100 men were given Nano-water with the (tamsulosindutasteride) and group B 100 men were given ordinary bottled water with the (tamsulosindutasteride). The water bottles were unlabeled and were given in a daily dose of 20ml/kg body weight. Dutasteride 0.5mg and tamsulosin 0.4 mg daily doses. Both groups were evaluated for the IPSS, Qmax, Residual Urine (RU), International Index of Erectile Function–Erectile Function (IIEF-EF) domain at the beginning (baseline data), and at the end of the 3 months. Results Of the 200 men with LUTS who were included in this study, 193 men were followed, and 7 men dropped out of the study for different reasons. In group A which included 97 men with LUTS, IPSS decreased by 16.82 (from 20.47 to 6.65) (P<0.00001) and Qmax increased by 5.73 ml/s (from 11.71 to 17.44) (P<0.00001) and RU <50 ml in 88% of patients (P<0.00001) and IIEF-EF increased to 26.65 (from 16.85) (P<0.00001). While in group B, 96 men with LUTS, IPSS decreased by 8.74(from 19.59 to 10.85)(P<0.00001) and Qmax increased by 4.67 ml/s(from 10.74 to 15.41)(P<0.00001), RU<50 ml in 75% of patients (P<0.00001), and IIEF-EF increased to 21(from 15.87)(P<0.00001). Group A had better results than group B. IPSS in group A decreased to 6.65 vs 10.85 in group B(P<0.00001), also Qmax increased to 17.44 in group A vs 15.41 in group B(P<0.00001), group A had RU <50 ml in 88% of patients vs 75% of patients in group B(P<0.00001).Group A had better IIEF-EF which increased to 26.65 vs 21 in group B(P<0.00001). While the differences between the baseline data of both groups were statistically not significant. Conclusion The use of nanotechnology structured water magnalife gives a better result in terms of LUTS and scores in patients with BPH. This combination is showing improvements in IPSS and even in erectile function in those men after 3 months.

Keywords: nano water, lower urinary tract symptoms, benign prostatic hypertrophy, erectile dysfunction

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