Search results for: Marina Chavleishvili
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 148

Search results for: Marina Chavleishvili

28 Adaptation of the Scenario Test for Greek-speaking People with Aphasia: Reliability and Validity Study

Authors: Marina Charalambous, Phivos Phylactou, Thekla Elriz, Loukia Psychogios, Jean-Marie Annoni

Abstract:

Background: Evidence-based practices for the evaluation and treatment of people with aphasia (PWA) in Greek are mainly impairment-based. Functional and multimodal communication is usually under assessed and neglected by clinicians. This study explores the adaptation and psychometric testing of the Greek (GR) version of The Scenario Test. The Scenario Test assesses the everyday functional communication of PWA in an interactive multimodal communication setting with the support of an active communication facilitator. Aims: To define the reliability and validity of The Scenario Test GR and discuss its clinical value. Methods & Procedures: The Scenario Test-GR was administered to 54 people with chronic stroke (6+ months post-stroke): 32 PWA and 22 people with stroke without aphasia. Participants were recruited from Greece and Cyprus. All measures were performed in an interview format. Standard psychometric criteria were applied to evaluate reliability (internal consistency, test-retest, and interrater reliability) and validity (construct and known – groups validity) of the Scenario Test GR. Video analysis was performed for the qualitative examination of the communication modes used. Outcomes & Results: The Scenario Test-GR shows high levels of reliability and validity. High scores of internal consistency (Cronbach’s α = .95), test-retest reliability (ICC = .99), and interrater reliability (ICC = .99) were found. Interrater agreement in scores on individual items fell between good and excellent levels of agreement. Correlations with a tool measuring language function in aphasia (the Aphasia Severity Rating Scale of the Boston Diagnostic Aphasia Examination), a measure of functional communication (the Communicative Effectiveness Index), and two instruments examining the psychosocial impact of aphasia (the Stroke and Aphasia Quality of Life questionnaire and the Aphasia Impact Questionnaire) revealed good convergent validity (all ps< .05). Results showed good known – groups validity (Mann-Whitney U = 96.5, p < .001), with significantly higher scores for participants without aphasia compared to those with aphasia. Conclusions: The psychometric qualities of The Scenario Test-GR support the reliability and validity of the tool for the assessment of functional communication for Greek-speaking PWA. The Scenario Test-GR can be used to assess multimodal functional communication, orient aphasia rehabilitation goal setting towards the activity and participation level, and be used as an outcome measure of everyday communication. Future studies will focus on the measurement of sensitivity to change in PWA with severe non-fluent aphasia.

Keywords: the scenario test GR, functional communication assessment, people with aphasia (PWA), tool validation

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27 Biological Institute Actions for Bovine Mastitis Monitoring in Low Income Dairy Farms, Brazil: Preliminary Data

Authors: Vanessa Castro, Liria H. Okuda, Daniela P. Chiebao, Adriana H. C. N. Romaldini, Harumi Hojo, Marina Grandi, Joao Paulo A. Silva, Alessandra F. C. Nassar

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The Biological Institute of Sao Paulo, in partnership with a private company, develops an Animal Health Family Farming Program (Prosaf) to enable communication among smallholder farmers and scientists, on-farm consulting and lectures, solving health questions that will benefit agricultural productivity. In Vale do Paraiba region, a dairy region of Sao Paulo State, southern Brazil, many of these types of farms are found with several milk quality problems. Most of these farms are profit-based business; however, with non-technified cattle rearing systems and uncertain veterinary assistance. Feedback from Prosaf showed that the biggest complaints from farmers were low milk production, sick animals and, mainly, loss of selling price due to a high somatic cell count (SCC) and a total bacterial count (TBC). The aims of this study were to improve milk quality, animal hygiene and herd health status by adjustments into general management practices and introducing techniques of sanitary control and milk monitoring in five dairy farms from Sao Jose do Barreiro municipality, Sao Paulo State, Brazil, to increase their profits. A total of 119 milk samples from 56 animals positive for California Mastitis Test (CMT) were collected. The positive CMT indicates subclinical mastitis, therefore laboratorial exams were performed in the milk (microbiological, biochemical and antibiogram test) detect the presence of Staphylococcus aureus (41.8%), Bacillus sp. (11.8%), Streptococcus sp. (2.1%), nonfermenting, motile and oxidase-negative Gram-negative Bacilli (2.1%) and Enterobacter (2.1%). Antibiograms revealed high resistance to gentamicin and streptomycin, probably due to indiscriminate use of antibiotics without veterinarian prescription. We suggested the improvement of hygiene management in the complete milking and cooling tanks system. Using the results of the laboratory tests, animals were properly treated, and the effects observed were better CMT outcomes, lower SCCs, and TBCs leading to an increase in milk pricing. This study will have a positive impact on the family farmers from Sao Paulo State dairy region by improving their market milk competitiveness.

Keywords: milk, family farming, food quality, antibiogram, profitability

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26 Knowledge Transfer through Entrepreneurship: From Research at the University to the Consolidation of a Spin-off Company

Authors: Milica Lilic, Marina Rosales Martínez

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Academic research cannot be oblivious to social problems and needs, so projects that have the capacity for transformation and impact should have the opportunity to go beyond the University circles and bring benefit to society. Apart from patents and R&D research contracts, this opportunity can be achieved through entrepreneurship as one of the most direct tools to turn knowledge into a tangible product. Thus, as an example of good practices, it is intended to analyze the case of an institutional entrepreneurship program carried out at the University of Seville, aimed at researchers interested in assessing the business opportunity of their research and expanding their knowledge on procedures for the commercialization of technologies used at academic projects. The program is based on three pillars: training, teamwork sessions and networking. The training includes aspects such as product-client fit, technical-scientific and economic-financial feasibility of a spin-off, institutional organization and decision making, public and private fundraising, and making the spin-off visible in the business world (social networks, key contacts, corporate image and ethical principles). On the other hand, the teamwork sessions are guided by a mentor and aimed at identifying research results with potential, clarifying financial needs and procedures to obtain the necessary resources for the consolidation of the spin-off. This part of the program is considered to be crucial in order for the participants to convert their academic findings into a business model. Finally, the networking part is oriented to workshops about the digital transformation of a project, the accurate communication of the product or service a spin-off offers to society and the development of transferable skills necessary for managing a business. This blended program results in the final stage where each team, through an elevator pitch format, presents their research turned into a business model to an experienced jury. The awarded teams get a starting capital for their enterprise and enjoy the opportunity of formally consolidating their spin-off company at the University. Studying the results of the program, it has been shown that many researchers have basic or no knowledge of entrepreneurship skills and different ways to turn their research results into a business model with a direct impact on society. Therefore, the described program has been used as an example to highlight the importance of knowledge transfer at the University and the role that this institution should have in providing the tools to promote entrepreneurship within it. Keeping in mind that the University is defined by three main activities (teaching, research and knowledge transfer), it is safe to conclude that the latter, and the entrepreneurship as an expression of it, is crucial in order for the other two to comply with their purpose.

Keywords: good practice, knowledge transfer, a spin-off company, university

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25 A Theragnostic Approach for Alzheimer’s Disease Focused on Phosphorylated Tau

Authors: Tomás Sobrino, Lara García-Varela, Marta Aramburu-Núñez, Mónica Castro, Noemí Gómez-Lado, Mariña Rodríguez-Arrizabalaga, Antía Custodia, Juan Manuel Pías-Peleteiro, José Manuel Aldrey, Daniel Romaus-Sanjurjo, Ángeles Almeida, Pablo Aguiar, Alberto Ouro

Abstract:

Introduction: Alzheimer’s disease (AD) and other tauopathies are primary causes of dementia, causing progressive cognitive deterioration that entails serious repercussions for the patients' performance of daily tasks. Currently, there is no effective approach for the early diagnosis and treatment of AD and tauopathies. This study suggests a theragnostic approach based on the importance of phosphorylated tau protein (p-Tau) in the early pathophysiological processes of AD. We have developed a novel theragnostic monoclonal antibody (mAb) to provide both diagnostic and therapeutic effects. Methods/Results: We have developed a p-Tau mAb, which was doped with deferoxamine for radiolabeling with Zirconium-89 (89Zr) for PET imaging, as well as fluorescence dies for immunofluorescence assays. The p-Tau mAb was evaluated in vitro for toxicity by MTT assay, LDH activity, propidium iodide/Annexin V assay, caspase-3, and mitochondrial membrane potential (MMP) assay in both mouse endothelial cell line (bEnd.3) and cortical primary neurons cell cultures. Importantly, non-toxic effects (up to concentrations of p-Tau mAb greater than 100 ug/mL) were detected. In vivo experiments in the tauopathy model mice (PS19) show that the 89Zr-pTau-mAb and 89Zr-Fragments-pTau-mAb are stable in circulation for up to 10 days without toxic effects. However, only less than 0.2% reached the brain, so further strategies have to be designed for crossing the Brain-Blood-Barrier (BBB). Moreover, an intraparenchymal treatment strategy was carried out. The PS19 mice were operated to implement osmotic pumps (Alzet 1004) at two different times, at 4 and 7 months, to stimulate the controlled release for one month each of the B6 antibody or the IgG1 control antibody. We demonstrated that B6-treated mice maintained their motor and memory abilities significantly compared with IgG1 treatment. In addition, we observed a significant reduction in p-Tau deposits in the brain. Conclusions /Discussion: A theragnostic pTau-mAb was developed. Moreover, we demonstrated that our p-Tau mAb recognizes very-early pathology forms of p-Tau by non-invasive techniques, such as PET. In addition, p-Tau mAb has non-toxic effects, both in vitro and in vivo. Although the p-Tau mAb is stable in circulation, only 0.2% achieve the brain. However, direct intraventricular treatment significantly reduces cognitive impairment in Alzheimer's animal models, as well as the accumulation of toxic p-Tau species.

Keywords: alzheimer's disease, theragnosis, tau, PET, immunotherapy, tauopathies

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24 Importance of Different Spatial Parameters in Water Quality Analysis within Intensive Agricultural Area

Authors: Marina Bubalo, Davor Romić, Stjepan Husnjak, Helena Bakić

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Even though European Council Directive 91/676/EEC known as Nitrates Directive was adopted in 1991, the issue of water quality preservation in areas of intensive agricultural production still persist all over Europe. High nitrate nitrogen concentrations in surface and groundwater originating from diffuse sources are one of the most important environmental problems in modern intensive agriculture. The fate of nitrogen in soil, surface and groundwater in agricultural area is mostly affected by anthropogenic activity (i.e. agricultural practice) and hydrological and climatological conditions. The aim of this study was to identify impact of land use, soil type, soil vulnerability to pollutant percolation, and natural aquifer vulnerability to nitrate occurrence in surface and groundwater within an intensive agricultural area. The study was set in Varaždin County (northern Croatia), which is under significant influence of the large rivers Drava and Mura and due to that entire area is dominated by alluvial soil with shallow active profile mainly on gravel base. Negative agricultural impact on water quality in this area is evident therefore the half of selected county is a part of delineated nitrate vulnerable zones (NVZ). Data on water quality were collected from 7 surface and 8 groundwater monitoring stations in the County. Also, recent study of the area implied detailed inventory of agricultural production and fertilizers use with the aim to produce new agricultural land use database as one of dominant parameters. The analysis of this database done using ArcGIS 10.1 showed that 52,7% of total County area is agricultural land and 59,2% of agricultural land is used for intensive agricultural production. On the other hand, 56% of soil within the county is classified as soil vulnerable to pollutant percolation. The situation is similar with natural aquifer vulnerability; northern part of the county ranges from high to very high aquifer vulnerability. Statistical analysis of water quality data is done using SPSS 13.0. Cluster analysis group both surface and groundwater stations in two groups according to nitrate nitrogen concentrations. Mean nitrate nitrogen concentration in surface water – group 1 ranges from 4,2 to 5,5 mg/l and in surface water – group 2 from 24 to 42 mg/l. The results are similar, but evidently higher, in groundwater samples; mean nitrate nitrogen concentration in group 1 ranges from 3,9 to 17 mg/l and in group 2 from 36 to 96 mg/l. ANOVA analysis confirmed statistical significance between stations that are classified in the same group. The previously listed parameters (land use, soil type, etc.) were used in factorial correspondence analysis (FCA) to detect importance of each stated parameter in local water quality. Since stated parameters mostly cannot be altered, there is obvious necessity for more precise and more adapted land management in such conditions.

Keywords: agricultural area, nitrate, factorial correspondence analysis, water quality

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23 Skull Extraction for Quantification of Brain Volume in Magnetic Resonance Imaging of Multiple Sclerosis Patients

Authors: Marcela De Oliveira, Marina P. Da Silva, Fernando C. G. Da Rocha, Jorge M. Santos, Jaime S. Cardoso, Paulo N. Lisboa-Filho

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Multiple Sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by neurodegeneration, inflammation, demyelination, and axonal loss. Magnetic resonance imaging (MRI), due to the richness in the information details provided, is the gold standard exam for diagnosis and follow-up of neurodegenerative diseases, such as MS. Brain atrophy, the gradual loss of brain volume, is quite extensive in multiple sclerosis, nearly 0.5-1.35% per year, far off the limits of normal aging. Thus, the brain volume quantification becomes an essential task for future analysis of the occurrence atrophy. The analysis of MRI has become a tedious and complex task for clinicians, who have to manually extract important information. This manual analysis is prone to errors and is time consuming due to various intra- and inter-operator variability. Nowadays, computerized methods for MRI segmentation have been extensively used to assist doctors in quantitative analyzes for disease diagnosis and monitoring. Thus, the purpose of this work was to evaluate the brain volume in MRI of MS patients. We used MRI scans with 30 slices of the five patients diagnosed with multiple sclerosis according to the McDonald criteria. The computational methods for the analysis of images were carried out in two steps: segmentation of the brain and brain volume quantification. The first image processing step was to perform brain extraction by skull stripping from the original image. In the skull stripper for MRI images of the brain, the algorithm registers a grayscale atlas image to the grayscale patient image. The associated brain mask is propagated using the registration transformation. Then this mask is eroded and used for a refined brain extraction based on level-sets (edge of the brain-skull border with dedicated expansion, curvature, and advection terms). In the second step, the brain volume quantification was performed by counting the voxels belonging to the segmentation mask and converted in cc. We observed an average brain volume of 1469.5 cc. We concluded that the automatic method applied in this work can be used for the brain extraction process and brain volume quantification in MRI. The development and use of computer programs can contribute to assist health professionals in the diagnosis and monitoring of patients with neurodegenerative diseases. In future works, we expect to implement more automated methods for the assessment of cerebral atrophy and brain lesions quantification, including machine-learning approaches. Acknowledgements: This work was supported by a grant from Brazilian agency Fundação de Amparo à Pesquisa do Estado de São Paulo (number 2019/16362-5).

Keywords: brain volume, magnetic resonance imaging, multiple sclerosis, skull stripper

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22 Differences in Preschool Educators' and Parents' Interactive Behavior during a Cooperative Task with Children

Authors: Marina Fuertes

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Introduction: In everyday life experiences, children are solicited to cooperate with others. Often they perform cooperative tasks with their parents (e.g., setting the table for dinner) or in school. These tasks are very significant since children may learn to turn taking in interactions, to participate as well to accept others participation, to trust, to respect, to negotiate, to self-regulate their emotions, etc. Indeed, cooperative tasks contribute to children social, motor, cognitive and linguistic development. Therefore, it is important to study what learning, social and affective experiences are provided to children during these tasks. In this study, we included parents and preschool educators. Parents and educators are both significant: educative, interactive and affective figures. Rarely parents and educators behavior have been compared in studies about cooperative tasks. Parents and educators have different but complementary styles of interaction and communication. Aims: Therefore, this study aims to compare parents and educators' (of both genders) interactive behavior (cooperativity, empathy, ability to challenge the child, reciprocity, elaboration) during a play/individualized situation involving a cooperative task. Moreover, to compare parents and educators' behavior with girls and boys. Method: A quasi-experimental study with 45 dyads educators-children and 45 dyads with parents and their children. In this study, participated children between 3 and 5 years old and with age appropriate development. Adults and children were videotaped using a variety of materials (e.g., pencils, wood, wool) and tools (e.g., scissors, hammer) to produce together something of their choice during 20-minutes. Each dyad (one adult and one child) was observed and videotaped independently. Adults and children agreed and consented to participate. Experimental conditions were suitable, pleasant and age appropriated. Results: Findings indicate that parents and teachers offer different learning experiences. Teachers were more likely to challenged children to explore new concepts and to accept children ideas. In turn, parents gave more support to children actions and were more likely to use their own example to teach children. Multiple regression analysis indicates that parent versus educator status predicts their behavior. Gender of both children and adults affected the results. Adults acted differently with girls and boys (e.g., adults worked more cooperatively with girls than boys). Male participants supported more girls participation rather than boys while female adults allowed boys to make more decisions than girls. Discussion: Taking our results and past studies, we learn that different qualitative interactions and learning experiences are offered by parents, educators according to parents and children gender. Thus, the same child needs to learn different cooperative strategies according to their interactive patterns and specific context. Yet, cooperative play and individualized activities with children generate learning opportunities and benefits children participation and involvement.

Keywords: early childhood education, parenting, gender, cooperative tasks, adult-child interaction

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21 Study of the Kinetics of Formation of Carboxylic Acids Using Ion Chromatography during Oxidation Induced by Rancimat of the Oleic Acid, Linoleic Acid, Linolenic Acid, and Biodiesel

Authors: Patrícia T. Souza, Marina Ansolin, Eduardo A. C. Batista, Antonio J. A. Meirelles, Matthieu Tubino

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Lipid oxidation is a major cause of the deterioration of the quality of the biodiesel, because the waste generated damages the engines. Among the main undesirable effects are the increase of viscosity and acidity, leading to the formation of insoluble gums and sediments which cause the blockage of fuel filters. The auto-oxidation is defined as the spontaneous reaction of atmospheric oxygen with lipids. Unsaturated fatty acids are usually the components affected by such reactions. They are present as free fatty acids, fatty esters and glycerides. To determine the oxidative stability of biodiesels, through the induction period, IP, the Rancimat method is used, which allows continuous monitoring of the induced oxidation process of the samples. During the oxidation of the lipids, volatile organic acids are produced as byproducts, in addition, other byproducts, including alcohols and carbonyl compounds, may be further oxidized to carboxylic acids. By the methodology developed in this work using ion chromatography, IC, analyzing the water contained in the conductimetric vessel, were quantified organic anions of carboxylic acids in samples subjected to oxidation induced by Rancimat. The optimized chromatographic conditions were: eluent water:acetone (80:20 v/v) with 0.5 mM sulfuric acid; flow rate 0.4 mL min-1; injection volume 20 µL; eluent suppressor 20 mM LiCl; analytical curve from 1 to 400 ppm. The samples studied were methyl biodiesel from soybean oil and unsaturated fatty acids standards: oleic, linoleic and linolenic. The induced oxidation kinetics curves were constructed by analyzing the water contained in the conductimetric vessels which were removed, each one, from the Rancimat apparatus at prefixed intervals of time. About 3 g of sample were used under the conditions of 110 °C and air flow rate of 10 L h-1. The water of each conductimetric Rancimat measuring vessel, where the volatile compounds were collected, was filtered through a 0.45 µm filter and analyzed by IC. Through the kinetic data of the formation of the organic anions of carboxylic acids, the formation rates of the same were calculated. The observed order of the rates of formation of the anions was: formate >>> acetate > hexanoate > valerate for the oleic acid; formate > hexanoate > acetate > valerate for the linoleic acid; formate >>> valerate > acetate > propionate > butyrate for the linolenic acid. It is possible to suppose that propionate and butyrate are obtained mainly from linolenic acid and that hexanoate is originated from oleic and linoleic acid. For the methyl biodiesel the order of formation of anions was: formate >>> acetate > valerate > hexanoate > propionate. According to the total rate of formation these anions produced during the induced degradation of the fatty acids can be assigned the order of reactivity: linolenic acid > linoleic acid >>> oleic acid.

Keywords: anions of carboxylic acids, biodiesel, ion chromatography, oxidation

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20 Ecological and Historical Components of the Cultural Code of the City of Florence as Part of the Edutainment Project Velonotte International

Authors: Natalia Zhabo, Sergey Nikitin, Marina Avdonina, Mariya Nikitina

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The analysis of the activities of one of the events of the international educational and entertainment project Velonotte is provided: an evening bicycle tour with children around Florence. The aim of the project is to develop methods and techniques for increasing the sensitivity of the cycling participants and listeners of the radio broadcasts to the treasures of the national heritage, in this case, to the historical layers of the city and the ecology of the Renaissance epoch. The block of educational tasks is considered, and the issues of preserving the identity of the city are discussed. Methods. The Florentine event was prepared during more than a year. First of all the creative team selected such events of the history of the city which seem to be important for revealing the specifics of the city, its spirit - from antiquity to our days – including the forums of Internet with broad public opinion. Then a route (seven kilometers) was developed, which was proposed to the authorities and organizations of the city. The selection of speakers was conducted according to several criteria: they should be authors of books, famous scientists, connoisseurs in a certain sphere (toponymy, history of urban gardens, art history), capable and willing to talk with participants directly at the points of stops, in order to make a dialogue and so that performances could be organized with their participation. The music was chosen for each part of the itinerary to prepare the audience emotionally. Cards for coloring with images of the main content of each stop were created for children. A site was done to inform the participants and to keep photos, videos and the audio files with speakers’ speech afterward. Results: Held in April 2017, the event was dedicated to the 640th Anniversary of the Filippo Brunelleschi, Florentine architect, and to the 190th anniversary of the publication of Florence guide by Stendhal. It was supported by City of Florence and Florence Bike Festival. Florence was explored to transfer traditional elements of culture, sometimes unfairly forgotten from ancient times to Brunelleschi and Michelangelo and Tschaikovsky and David Bowie with lectures by professors of Universities. Memorable art boards were installed in public spaces. Elements of the cultural code are deeply internalized in the minds of the townspeople, the perception of the city in everyday life and human communication is comparable to such fundamental concepts of the self-awareness of the townspeople as mental comfort and the level of happiness. The format of a fun and playful walk with the ICT support gives new opportunities for enriching the city's cultural code of each citizen with new components, associations, connotations.

Keywords: edutainment, cultural code, cycling, sensitization Florence

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19 The Impact of Gestational Weight Gain on Subclinical Atherosclerosis, Placental Circulation and Neonatal Complications

Authors: Marina Shargorodsky

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Aim: Gestational weight gain (GWG) has been related to altering future weight-gain curves and increased risks of obesity later in life. Obesity may contribute to vascular atherosclerotic changes as well as excess cardiovascular morbidity and mortality observed in these patients. Noninvasive arterial testing, such as ultrasonographic measurement of carotid IMT, is considered a surrogate for systemic atherosclerotic disease burden and is predictive of cardiovascular events in asymptomatic individuals as well as recurrent events in patients with known cardiovascular disease. Currently, there is no consistent evidence regarding the vascular impact of excessive GWG. The present study was designed to investigate the impact of GWG on early atherosclerotic changes during late pregnancy, using intima-media thickness, as well as placental vascular circulation and inflammatory lesions and pregnancy outcomes. Methods: The study group consisted of 59 pregnant women who gave birth and underwent a placental histopathological examination at the Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Israel, in 2019. According to the IOM guidelines the study group has been divided into two groups: Group 1 included 32 women with pregnancy weight gain within recommended range; Group 2 included 27 women with excessive weight gain during pregnancy. The IMT was measured from non-diseased intimal and medial wall layers of the carotid artery on both sides, visualized by high-resolution 7.5 MHz ultrasound (Apogee CX Color, ATL). Placental histology subdivided placental findings to lesions consistent with maternal vascular and fetal vascular malperfusion according to the criteria of the Society for Pediatric Pathology, subdividing placental findings to lesions consistent with maternal vascular and fetal vascular malperfusion, as well as the inflammatory response of maternal and fetal origin. Results: IMT levels differed between groups and were significantly higher in Group 1 compared to Group 2 (0.7+/-0.1 vs 0.6+/-0/1, p=0.028). Multiple linear regression analysis of IMT included variables based on their associations in univariate analyses with a backward approach. Included in the model were pre-gestational BMI, HDL cholesterol and fasting glucose. The model was significant (p=0.001) and correctly classified 64.7% of study patients. In this model, pre-pregnancy BMI remained a significant independent predictor of subclinical atherosclerosis assessed by IMT (OR 4.314, 95% CI 0.0599-0.674, p=0.044). Among placental lesions related to fetal vascular malperfusion, villous changes consistent with fetal thrombo-occlusive disease (FTOD) were significantly higher in Group 1 than in Group 2, p=0.034). In Conclusion, the present study demonstrated that excessive weight gain during pregnancy is associated with an adverse effect on early stages of subclinical atherosclerosis, placental vascular circulation and neonatal complications. The precise mechanism for these vascular changes, as well as the overall clinical impact of weight control during pregnancy on IMT, placental vascular circulation as well as pregnancy outcomes, deserves further investigation.

Keywords: obesity, pregnancy, complications, weight gain

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18 Association of Temperature Factors with Seropositive Results against Selected Pathogens in Dairy Cow Herds from Central and Northern Greece

Authors: Marina Sofia, Alexios Giannakopoulos, Antonia Touloudi, Dimitris C Chatzopoulos, Zoi Athanasakopoulou, Vassiliki Spyrou, Charalambos Billinis

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Fertility of dairy cattle can be affected by heat stress when the ambient temperature increases above 30°C and the relative humidity ranges from 35% to 50%. The present study was conducted on dairy cattle farms during summer months in Greece and aimed to identify the serological profile against pathogens that could affect fertility and to associate the positive serological results at herd level with temperature factors. A total of 323 serum samples were collected from clinically healthy dairy cows of 8 herds, located in Central and Northern Greece. ELISA tests were performed to detect antibodies against selected pathogens that affect fertility, namely Chlamydophila abortus, Coxiella burnetii, Neospora caninum, Toxoplasma gondii and Infectious Bovine Rhinotracheitis Virus (IBRV). Eleven climatic variables were derived from the WorldClim version 1.4. and ArcGIS V.10.1 software was used for analysis of the spatial information. Five different MaxEnt models were applied to associate the temperature variables with the locations of seropositive Chl. abortus, C. burnetii, N. caninum, T. gondii and IBRV herds (one for each pathogen). The logistic outputs were used for the interpretation of the results. ROC analyses were performed to evaluate the goodness of fit of the models’ predictions. Jackknife tests were used to identify the variables with a substantial contribution to each model. The seropositivity rates of pathogens varied among the 8 herds (0.85-4.76% for Chl. abortus, 4.76-62.71% for N. caninum, 3.8-43.47% for C. burnetii, 4.76-39.28% for T. gondii and 47.83-78.57% for IBRV). The variables of annual temperature range, mean diurnal range and maximum temperature of the warmest month gave a contribution to all five models. The regularized training gains, the training AUCs and the unregularized training gains were estimated. The mean diurnal range gave the highest gain when used in isolation and decreased the gain the most when it was omitted in the two models for seropositive Chl.abortus and IBRV herds. The annual temperature range increased the gain when used alone and decreased the gain the most when it was omitted in the models for seropositive C. burnetii, N. caninum and T. gondii herds. In conclusion, antibodies against Chl. abortus, C. burnetii, N. caninum, T. gondii and IBRV were detected in most herds suggesting circulation of pathogens that could cause infertility. The results of the spatial analyses demonstrated that the annual temperature range, mean diurnal range and maximum temperature of the warmest month could affect positively the possible pathogens’ presence. Acknowledgment: This research has been co‐financed by the European Regional Development Fund of the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH–CREATE–INNOVATE (project code: T1EDK-01078).

Keywords: dairy cows, seropositivity, spatial analysis, temperature factors

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17 Analysis of the Development of Mining Companies Social Corporate Responsibility Based on the Rating Score

Authors: Tatiana Ponomarenko, Oksana Marinina, Marina Nevskaya

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Modern corporate social responsibility (CSR) is a sphere of multilevel responsibility of a company toward society represented by various stakeholders. The relevance of CSR management grows due to the active development of socially responsible investing (principles for responsible investment) taking into account factors of environmental, social and corporate governance (ESG), growing attention of the investment community in general to the long-term stability of companies and the quality of control of nonfinancial risks. The modern approach to CSR strategic management is aimed at the creation of trustful relationships with stakeholders, on the basis of which a contribution to the sustainable development of companies, regions, and national economics is insured. However, the practical concepts of social responsibility in mining companies are different, which leads to various degrees of application of CSR. A number of companies implement CSR using a traditional (limited) understanding of responsibility toward employees and counteragents, the others understand CSR much wider and try to use leverages of efficient cooperation. As in large mining companies the scope of CSR measures is diverse and characterized by different indices, the study was aimed at evaluating CSR efficiency on the basis of a proprietary methodology and determining the level of development of CSR management in terms of anti-crisis, reactive and proactive development. The methodology of the research includes analysis of integrated global reporting initiative (GRI) reports of large mining companies; choice of most representative sectoral agents by a criterion of the regularity of issuance and publication of reports; calculation of indices of evaluation of CSR level of the selected companies in dynamics. The methodology of evaluation of CSR level is based on a rating score of changes in standard indices of GRI reports by economic, environmental, and social directions. Result. By the results of the analysis, companies of fuel and energy and metallurgic complexes, in overwhelming majority, reflecting three indices out of a wide range of possible indicators of SDGs (Sustainable Development Goals), were selected for the study. The evaluation of the scopes of CSR of the companies Gazprom, LUKOIL, Metalloinvest, Nornikel, Rosneft, Severstal, SIBUR, SUEK corresponds to the reactive type of development according to a scale of CSR strategic management, which is the average value out of the possible values. The chief drawback is that companies, in the process of analyzing global goals, often choose the goals which relate to their own activities, paying insufficient attention to the interests of the stakeholders inside the country. This fact evidences the necessity of searching for more effective mechanisms of CSR control. Acknowledgment: This article is prepared within grant support of the RFBR, project 19-510-44013 'Development of the concept of mineral resources value formation in the context of sustainable development in resource-oriented economies'.

Keywords: sustainable development, corporate social responsibility, development strategies, efficiency assessment

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16 Dynamic Changes in NT-proBNP Levels in Unrelated Donors during Hematopoietic Stem Cells Mobilization

Authors: Natalia V. Minaeva, Natalia A. Zorina, Marina N. Khorobrikh, Philipp S. Sherstnev, Tatiana V. Krivokorytova, Alexander S. Luchinin, Maksim S. Minaev, Igor V. Paramonov

Abstract:

Background. Over the last few decades, the Center for International Blood and Marrow Transplant Research (CIBMTR) and the World Marrow Donor Association (WMDA) have been actively working to ensure the safety of the hematopoietic stem cell (HSC) donation process. Registration of adverse events that may occur during the donation period and establishing a relationship between donation and side effects are included in the WMDA international standards. The level of blood serum N-terminal pro-brain natriuretic peptide (NT-proBNP) is an early marker of myocardial stress. Due to the high analytical sensitivity and specificity, laboratory assessment of NT-proBNP makes it possible to objectively diagnose myocardial dysfunction. It is well known that the main stimulus for proBNP synthesis and secretion from atrial and ventricular cardiac myocytes is myocyte stretch and increasement of myocardial extensibility and pressure in the heart chambers. Аim. The aim of the study was to assess the dynamic changes in the levels of blood serum N-terminal pro-brain natriuretic peptide of unrelated donors at various stages of hematopoietic stem cell mobilization. Materials. We have examined 133 unrelated donors, including 92 men and 41 women, that have been included into the study. The NT-proBNP levels were measured before the start of mobilization, then on the day of apheresis, and after the donation of allogeneic HSC. The relationship between NT-proBNP levels and body mass index (BMI), ferritin, hemoglobin, and white blood cells (WBC) levels was assessed on the day of apheresis. The median age of donors was 34 years. Mobilization of HSCs was managed with filgrastim administration at a dose of 10 μg/kg daily for 4-5 days. The first leukocytapheresis was performed on day 4 from the start of filgrastim administration. Quantitative values of the blood serum NT-proBNP level are presented as a median (Me), first and third quartiles (Q1-Q3). Comparative analysis was carried out using the t-test and correlation analysis as well by Spearman method. Results. The baseline blood serum NT-proBNP levels in all 133 donors were within the reference values (<125 pg/ml) and equaled 21,6 (10,0; 43,3) pg/ml. At the same time, the level of NT-proBNP in women was significantly higher than that of men. On the day of the HSC apheresis, a significant increase of blood serum NT-proBNP levels was detected and equald 131,2 (72,6; 165,3) pg/ml (p<0,001), with higher rates in female donors. A statistically significant weak inverse correleation was established between the level of NT-proBNP and the BMI of donors (-0.18, p = 0,03), as well as the level of hemoglobin (-0.33, p <0,001), and ferritin levels (-0.19, p = 0,03). No relationship has been established between the magnitude of WBC levels achieved as a result of the mobilization of HSC on the day of leukocytapheresis. A day after the apheresis, the blood serum NT-proBNP levels still exceeded the reference values, but there was a decreasing tendency. Conclusion. An increase of the blood serum NT-proBNP level in unrelated donors during the mobilization of HSC was established. Future studies should clarify the reason for this phenomenon, as well as its effects on donors' long-term health.

Keywords: unrelated donors, mobilization, hematopoietic stem cells, N-terminal pro-brain natriuretic peptide

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15 Computer Based Identification of Possible Molecular Targets for Induction of Drug Resistance Reversion in Multidrug Resistant Mycobacterium Tuberculosis

Authors: Oleg Reva, Ilya Korotetskiy, Marina Lankina, Murat Kulmanov, Aleksandr Ilin

Abstract:

Molecular docking approaches are widely used for design of new antibiotics and modeling of antibacterial activities of numerous ligands which bind specifically to active centers of indispensable enzymes and/or key signaling proteins of pathogens. Widespread drug resistance among pathogenic microorganisms calls for development of new antibiotics specifically targeting important metabolic and information pathways. A generally recognized problem is that almost all molecular targets have been identified already and it is getting more and more difficult to design innovative antibacterial compounds to combat the drug resistance. A promising way to overcome the drug resistance problem is an induction of reversion of drug resistance by supplementary medicines to improve the efficacy of the conventional antibiotics. In contrast to well established computer-based drug design, modeling of drug resistance reversion still is in its infancy. In this work, we proposed an approach to identification of compensatory genetic variants reducing the fitness cost associated with the acquisition of drug resistance by pathogenic bacteria. The approach was based on an analysis of the population genetic of Mycobacterium tuberculosis and on results of experimental modeling of the drug resistance reversion induced by a new anti-tuberculosis drug FS-1. The latter drug is an iodine-containing nanomolecular complex that passed clinical trials and was admitted as a new medicine against MDR-TB in Kazakhstan. Isolates of M. tuberculosis obtained on different stages of the clinical trials and also from laboratory animals infected with MDR-TB strain were characterized by antibiotic resistance, and their genomes were sequenced by the paired-end Illumina HiSeq 2000 technology. A steady increase in sensitivity to conventional anti-tuberculosis antibiotics in series of isolated treated with FS-1 was registered despite the fact that the canonical drug resistance mutations identified in the genomes of these isolates remained intact. It was hypothesized that the drug resistance phenotype in M. tuberculosis requires an adjustment of activities of many genes to compensate the fitness cost of the drug resistance mutations. FS-1 cased an aggravation of the fitness cost and removal of the drug-resistant variants of M. tuberculosis from the population. This process caused a significant increase in genetic heterogeneity of the Mtb population that was not observed in the positive and negative controls (infected laboratory animals left untreated and treated solely with the antibiotics). A large-scale search for linkage disequilibrium associations between the drug resistance mutations and genetic variants in other genomic loci allowed identification of target proteins, which could be influenced by supplementary drugs to increase the fitness cost of the drug resistance and deprive the drug-resistant bacterial variants of their competitiveness in the population. The approach will be used to improve the efficacy of FS-1 and also for computer-based design of new drugs to combat drug-resistant infections.

Keywords: complete genome sequencing, computational modeling, drug resistance reversion, Mycobacterium tuberculosis

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14 Assessing of Social Comfort of the Russian Population with Big Data

Authors: Marina Shakleina, Konstantin Shaklein, Stanislav Yakiro

Abstract:

The digitalization of modern human life over the last decade has facilitated the acquisition, storage, and processing of data, which are used to detect changes in consumer preferences and to improve the internal efficiency of the production process. This emerging trend has attracted academic interest in the use of big data in research. The study focuses on modeling the social comfort of the Russian population for the period 2010-2021 using big data. Big data provides enormous opportunities for understanding human interactions at the scale of society with plenty of space and time dynamics. One of the most popular big data sources is Google Trends. The methodology for assessing social comfort using big data involves several steps: 1. 574 words were selected based on the Harvard IV-4 Dictionary adjusted to fit the reality of everyday Russian life. The set of keywords was further cleansed by excluding queries consisting of verbs and words with several lexical meanings. 2. Search queries were processed to ensure comparability of results: the transformation of data to a 10-point scale, elimination of popularity peaks, detrending, and deseasoning. The proposed methodology for keyword search and Google Trends processing was implemented in the form of a script in the Python programming language. 3. Block and summary integral indicators of social comfort were constructed using the first modified principal component resulting in weighting coefficients values of block components. According to the study, social comfort is described by 12 blocks: ‘health’, ‘education’, ‘social support’, ‘financial situation’, ‘employment’, ‘housing’, ‘ethical norms’, ‘security’, ‘political stability’, ‘leisure’, ‘environment’, ‘infrastructure’. According to the model, the summary integral indicator increased by 54% and was 4.631 points; the average annual rate was 3.6%, which is higher than the rate of economic growth by 2.7 p.p. The value of the indicator describing social comfort in Russia is determined by 26% by ‘social support’, 24% by ‘education’, 12% by ‘infrastructure’, 10% by ‘leisure’, and the remaining 28% by others. Among 25% of the most popular searches, 85% are of negative nature and are mainly related to the blocks ‘security’, ‘political stability’, ‘health’, for example, ‘crime rate’, ‘vulnerability’. Among the 25% most unpopular queries, 99% of the queries were positive and mostly related to the blocks ‘ethical norms’, ‘education’, ‘employment’, for example, ‘social package’, ‘recycling’. In conclusion, the introduction of the latent category ‘social comfort’ into the scientific vocabulary deepens the theory of the quality of life of the population in terms of the study of the involvement of an individual in the society and expanding the subjective aspect of the measurements of various indicators. Integral assessment of social comfort demonstrates the overall picture of the development of the phenomenon over time and space and quantitatively evaluates ongoing socio-economic policy. The application of big data in the assessment of latent categories gives stable results, which opens up possibilities for their practical implementation.

Keywords: big data, Google trends, integral indicator, social comfort

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13 Associated Factors the Safety of the Patient in Hemodialysis Clinics of a Brazilian Municipality: Cross-Sectional Study

Authors: Magda Milleyde de Sousa Lima, Letícia Lima Aguiar, Marina Guerra Martins, Erika Veríssimo Dias Sousa, Lizandra Sampaio de Oliveira, Lívia Moreira Barros, Joselany Áfio Caetano

Abstract:

Patients with chronic kidney disease are vulnerable to episodes which make the safety of their health vulnerable, mainly due to the treatment process that exposes them to high rates of interventions during hemodialysis sessions. Some factors associated with health care contribute to the risk of death and complications. However, there are a small number of scientific studies evaluating the level of safety of hemodialysis clinics, and the sociodemographic characteristics of patients and professionals associated with this safety. Therefore, the present study aims to examine the level of patient safety in hemodialysis clinics in the Brazilian capital, to identify the sociodemographic and clinical factors of patients and nursing staff associated with the level of safety. This is an observational, descriptive and quantitative research conducted in three hemodialysis clinics placed in the city of Fortaleza-CE, Brazil, from September to November 2019. The sample was formed after a sample calculation for finite inhabitants of correlation with 200 chronic renal patients, 30 nursing technicians and seven nurses. Conventional sampling was used based on the inclusion criteria: being present at the hemodialysis session on the day the researcher performed the data collection and being 18 years of age or older. Participants who presented communication difficulties to listen to and/or answer the sociodemographic and clinical questionnaire were excluded. Two instruments were applied: sociodemographic and clinical characterization form and Chronic Renal Patient Safety Assessment Scale on Hemodialysis (EASPRCH). The data were analyzed using the Kruskal Walls Test for categorical variables and Spearman correlation coefficient for non-categorical variables, using the Statistical Package SPSS version 20.0. The present study respected the ethical and legal principles determined by resolution 466/2012 of the National Health Council, under the approval of the Ethics and Research Committee with an opinion number: 3,255,635. The results showed that a hemodialysis clinic presented unsafe care practices of 32 points in the EASPRCH (p=0.001). A statistical association was identified between the level of safety and the variables of the patients: level of education (p=0.018), family income (p=0.049), type of employment (p=0.012), venous access site (p=0.009), use of medication during the session (p=0.008) and time of hemodialysis (p=0.002). When evaluating the profile of nurses, a statistical association was evidenced between the level of safety with the variables: marital status (p=0.000), race (p=0.017), schooling (p= 0.000), income (p=0.013), age (p=0.000), clinic workload (p=0.000), time working with hemodialysis (p=0.000), time working in the clinic (p= 0.007) and clinic sizing (p=0.000). In order, the sociodemographic factors of nursing technicians associated with the level of patient safety were: race (p= 0.001) and weekly workload at (p=0.010). Therefore, it is concluded that there is a non-conformity in the level of patient safety in one of the clinics studied and, that sociodemographic and clinical factors of patients and health professionals corroborate the level of safety of the health unit.

Keywords: hemodialysis, nursing, patient safety, quality improvement

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12 'iTheory': Mobile Way to Music Fundamentals

Authors: Marina Karaseva

Abstract:

The beginning of our century became a new digital epoch in the educational situation. Last decade the newest stage of this process had been initialized by the touch-screen mobile devices with program applications for them. The touch possibilities for learning fundamentals of music are of especially importance for music majors. The phenomenon of touching, firstly, makes it realistic to play on the screen as on music instrument, secondly, helps students to learn music theory while listening in its sound elements by music ear. Nowadays we can detect several levels of such mobile applications: from the basic ones devoting to the elementary music training such as intervals and chords recognition, to the more advanced applications which deal with music perception of non-major and minor modes, ethnic timbres, and complicated rhythms. The main purpose of the proposed paper is to disclose the main tendencies in this process and to demonstrate the most innovative features of music theory applications on the base of iOS and Android systems as the most common used. Methodological recommendations how to use these digital material musicologically will be done for the professional music education of different levels. These recommendations are based on more than ten year ‘iTheory’ teaching experience of the author. In this paper, we try to logically classify all types of ‘iTheory’mobile applications into several groups, according to their methodological goals. General concepts given below will be demonstrated in concrete examples. The most numerous group of programs is formed with simulators for studying notes with audio-visual links. There are link-pair types as follows: sound — musical notation which may be used as flashcards for studying words and letters, sound — key, sound — string (basically, guitar’s). The second large group of programs is programs-tests containing a game component. As a rule, their basis is made with exercises on ear identification and reconstruction by voice: sounds and intervals on their sounding — harmonical and melodical, music modes, rhythmic patterns, chords, selected instrumental timbres. Some programs are aimed at an establishment of acoustical communications between concepts of the musical theory and their musical embodiments. There are also programs focused on progress of operative musical memory (with repeating of sounding phrases and their transposing in a new pitch), as well as on perfect pitch training In addition a number of programs improvisation skills have been developed. An absolute pitch-system of solmisation is a common base for mobile programs. However, it is possible to find also the programs focused on the relative pitch system of solfegе. In App Store and Google Play Market online store there are also many free programs-simulators of musical instruments — piano, guitars, celesta, violin, organ. These programs may be effective for individual and group exercises in ear training or composition classes. Great variety and good sound quality of these programs give now a unique opportunity to musicians to master their music abilities in a shorter time. That is why such teaching material may be a way to effective study of music theory.

Keywords: ear training, innovation in music education, music theory, mobile devices

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11 Expression of Fibrogenesis Markers after Mesenchymal Stem Cells Therapy for Experimental Liver Cirrhosis

Authors: Tatsiana Ihnatovich, Darya Nizheharodava, Mikalai Halabarodzka, Tatsiana Savitskaya, Marina Zafranskaya

Abstract:

Liver fibrosis is a complex of histological changes resulting from chronic liver disease accompanied by an excessive production and deposition of extracellular matrix components in the hepatic parenchyma. Liver fibrosis is a serious medical and social problem. Hepatic stellate cells (HSCs) make a significant contribution to the extracellular matrix deposition due to liver injury. Mesenchymal stem cells (MSCs) have a pronounced anti-inflammatory, regenerative and immunomodulatory effect; they are able to differentiate into hepatocytes and induce apoptosis of activated HSCs that opens the prospect of their use for preventing the excessive fibro-formation and the development of liver cirrhosis. The aim of the study is to evaluate the effect of MSCs therapy on the expression of fibrogenesis markers genes in liver tissue and HSCs cultures of rats with experimental liver cirrhosis (ELC). Materials and methods: ELC was induced by the common bile duct ligation (CBDL) in female Wistar rats (n = 19) with an average body weight of 250 (220 ÷ 270) g. Animals from the control group (n = 10) were sham-operated. On the 56th day after the CBDL, the rats of the experimental (n = 12) and the control (n = 5) groups received intraportal MSCs in concentration of 1×106 cells/animal (previously obtained from rat’s bone marrow) or saline, respectively. The animals were taken out of the experiment on the 21st day. HSCs were isolated by sequential liver perfusion in situ with following disaggregation, enzymatic treatment and centrifugation of cell suspension on a two-stage density gradient. The expression of collagen type I (Col1a1) and type III (Col3a1), matrix metalloproteinase type 2 (MMP2) and type 9 (MMP9), tissue inhibitor of matrix metalloproteinases type 1 (TIMP1), transforming growth factor β type 1 (TGFβ1) and type 3 (TGFβ3) was determined by real-time polymerase chain reaction. Statistical analysis was performed using Statistica 10.0. Results: In ELC rats compared to sham-operated animals, a significant increase of all studied markers expression was observed. The administration of MSCs led to a significant decrease of all detectable markers in the experimental group compared to rats without cell therapy. In ELC rats, an increased MMP9/TIMP1 ratio after cell therapy was also detected. The infusion of MSCs in the sham-operated animals did not lead to any changes. In the HSCs from ELC animals, the expression of Col1a1 and Col3a1 exceeded the similar parameters of the control group (p <0.05) and statistically decreased after the MSCs administration. The correlation between Col3a1 (Rs = 0.51, p <0.05), TGFβ1 (Rs = 0.6, p <0.01), and TGFβ3 (Rs = 0.75, p <0.001) expression in HSCs cultures and liver tissue has been found. Conclusion: Intraportal administration of MSCs to rats with ELC leads to a decreased Col1a1 and Col3a1, MMP2 and MMP9, TIMP1, TGFβ1 and TGFβ3 expression. The correlation between the expression of Col3a1, TGFβ1 and TGFβ3 in liver tissue and in HSCs cultures indicates the involvement of activated HSCs in the fibrogenesis that allows considering HSCs to be the main cell therapy target in ELC.

Keywords: cell therapy, experimental liver cirrhosis, hepatic stellate cells, mesenchymal stem cells

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10 Implementation of Synthesis and Quality Control Procedures of ¹⁸F-Fluoromisonidazole Radiopharmaceutical

Authors: Natalia C. E. S. Nascimento, Mercia L. Oliveira, Fernando R. A. Lima, Leonardo T. C. do Nascimento, Marina B. Silveira, Brigida G. A. Schirmer, Andrea V. Ferreira, Carlos Malamut, Juliana B. da Silva

Abstract:

Tissue hypoxia is a common characteristic of solid tumors leading to decreased sensitivity to radiotherapy and chemotherapy. In the clinical context, tumor hypoxia assessment employing the positron emission tomography (PET) tracer ¹⁸F-fluoromisonidazole ([¹⁸F]FMISO) is helpful for physicians for planning and therapy adjusting. The aim of this work was to implement the synthesis of 18F-FMISO in a TRACERlab® MXFDG module and also to establish the quality control procedure. [¹⁸F]FMISO was synthesized at Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN/Brazil) using an automated synthesizer (TRACERlab® MXFDG, GE) adapted for the production of [¹⁸F]FMISO. The FMISO chemical standard was purchased from ABX. 18O- enriched water was acquired from Center of Molecular Research. Reagent kits containing eluent solution, acetonitrile, ethanol, 2.0 M HCl solution, buffer solution, water for injections and [¹⁸F]FMISO precursor (dissolved in 2 ml acetonitrile) were purchased from ABX. The [¹⁸F]FMISO samples were purified by Solid Phase Extraction method. The quality requirements of [¹⁸F]FMISO are established in the European Pharmacopeia. According to that reference, quality control of [¹⁸F]FMISO should include appearance, pH, radionuclidic identity and purity, radiochemical identity and purity, chemical purity, residual solvents, bacterial endotoxins, and sterility. The duration of the synthesis process was 53 min, with radiochemical yield of (37.00 ± 0.01) % and the specific activity was more than 70 GBq/µmol. The syntheses were reproducible and showed satisfactory results. In relation to the quality control analysis, the samples were clear and colorless at pH 6.0. The spectrum emission, measured by using a High-Purity Germanium Detector (HPGe), presented a single peak at 511 keV and the half-life, determined by the decay method in an activimeter, was (111.0 ± 0.5) min, indicating no presence of radioactive contaminants, besides the desirable radionuclide (¹⁸F). The samples showed concentration of tetrabutylammonium (TBA) < 50μg/mL, assessed by visual comparison to TBA standard applied in the same thin layer chromatographic plate. Radiochemical purity was determined by high performance liquid chromatography (HPLC) and the results were 100%. Regarding the residual solvents tested, ethanol and acetonitrile presented concentration lower than 10% and 0.04%, respectively. Healthy female mice were injected via lateral tail vein with [¹⁸F]FMISO, microPET imaging studies (15 min) were performed after 2 h post injection (p.i), and the biodistribution was analyzed in five-time points (30, 60, 90, 120 and 180 min) after injection. Subsequently, organs/tissues were assayed for radioactivity with a gamma counter. All parameters of quality control test were in agreement to quality criteria confirming that [¹⁸F]FMISO was suitable for use in non-clinical and clinical trials, following the legal requirements for the production of new radiopharmaceuticals in Brazil.

Keywords: automatic radiosynthesis, hypoxic tumors, pharmacopeia, positron emitters, quality requirements

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9 A Qualitative Anthropological Analysis of Competing Health Perceptions in Chagas-Related Consultations in Non-Endemic Geneva

Authors: Marina Gold, Yves Jackson, David Parrat

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The high predominance of Latin American migrants in Geneva from countries where Chagas disease is endemic (Bolivia, Brazil, Argentina, Colombia) is increasing the incidence of chronic Chagas-related problems, especially cardiovascular complications. The precarious migratory status of what are mostly undocumented migrants complicates access to health and affects patients’ and doctors’ health perceptions regarding screening, treatment and monitoring of Chagas-related health concerns. This project results from a 3 year collaboration between the Geneva University Hospital and the NGO Mundo Sano to understand the following questions: 1) how do Latin American migrants perceive their health? 2) What do they understand from Chagas disease? 3) Are patients’ and doctors’ health perceptions similar or do they have competing agendas? This paper aims to present the results of a long-term study that interrogates health perceptions among Latin American migrants in Geneva. The first phase consisted in completing surveys at three community screening events (2016, 2017. 2018), and the results of these surveys reveal the subordination of the importance of health to that of having met economic family obligation. That is, health is important only when it becomes an impediment to economic gain. The contradictory result emerged that people are aware of the importance of health prevention in order to ensure long-term health, but they do not always have agency over their life-style habits (healthy food, regular exercise, emotional stability). The second phase of the research collected open-ended interviews with selected participants, in order to explore in more detail how Latin American migrants deal with Chagas in a different socio-political and economic context to that of endemic countries. These interviews (5 in total) reveal mixed methods of managing health: social networks, access to health care transnationally (in Geneva, Spain and back in their home country), and different valuations of health problems in each situation. The third phase consisted in observations of doctor-patient consultations and further extended interviews with patients to determine doctor/patient health perceptions around Chagas disease. This phase is ongoing, but it has yielded preliminarily observations regarding the expectations that patients’ have of doctors, and the understanding of doctors’ to patients’ complex situations. Positive and complementary health perceptions include patients’ feeling that doctors in Geneva are more understanding, more knowledgeable and less racist than those in their home country, who do not provide detailed information about Chagas or its treatment and discriminate against them for being indigenous or from poor rural areas, enabling a better communication between doctors and patients. Possible conflicting health perceptions include patients addressing their health concerns more holistically and encountering the specialist’s limitations to only treating one health concern, given time limitations and lack of competition with their colleagues (the general practitioner that referred the patient, for example). The implications of this study extend the case of Chagas disease in Geneva and is relevant for all chronic concerns and migratory contexts of precarity.

Keywords: chagas disease, health perceptions, Latin American Migrants, non-endemic countries

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8 „Real and Symbolic in Poetics of Multiplied Screens and Images“

Authors: Kristina Horvat Blazinovic

Abstract:

In the context of a work of art, one can talk about the idea-concept-term-intention expressed by the artist by using various forms of repetition (external, material, visible repetition). Such repetitions of elements (images in space or moving visual and sound images in time) suggest a "covert", "latent" ("dressed") repetition – i.e., "hidden", "latent" term-intention-idea. Repeating in this way reveals a "deeper truth" that the viewer needs to decode and which is hidden "under" the technical manifestation of the multiplied images. It is not only images, sounds, and screens that are repeated - something else is repeated through them as well, even if, in some cases, the very idea of repetition is repeated. This paper examines serial images and single-channel or multi-channel artwork in the field of video/film art and video installations, which in a way implies the concept of repetition and multiplication. Moving or static images and screens (as multi-screens) are repeated in time and space. The categories of the real and the symbolic partly refer to the Lacan registers of reality, i.e., the Imaginary - Symbolic – Real trinity that represents the orders within which human subjectivity is established. Authors such as Bruce Nauman, VALIE EXPORT, Ragnar Kjartansson, Wolf Vostell, Shirin Neshat, Paul Sharits, Harun Farocki, Dalibor Martinis, Andy Warhol, Douglas Gordon, Bill Viola, Frank Gillette, and Ira Schneider, and Marina Abramovic problematize, in different ways, the concept and procedures of multiplication - repetition, but not in the sense of "copying" and "repetition" of reality or the original, but of repeated repetitions of the simulacrum. Referential works of art are often connected by the theme of the traumatic. Repetitions of images and situations are a response to the traumatic (experience) - repetition itself is a symptom of trauma. On the other hand, repeating and multiplying traumatic images results in a new traumatic effect or cancels it. Reflections on repetition as a temporal and spatial phenomenon are in line with the chapters that link philosophical considerations of space and time and experience temporality with their manifestation in works of art. The observations about time and the relation of perception and memory are according to Henry Bergson and his conception of duration (durée) as "quality of quantity." The video works intended to be displayed as a video loop, express the idea of infinite duration ("pure time," according to Bergson). The Loop wants to be always present - to fixate in time. Wholeness is unrecognizable because the intention is to make the effect infinitely cyclic. Reflections on time and space end with considerations about the occurrence and effects of time and space intervals as places and moments "between" – the points of connection and separation, of continuity and stopping - by reference to the "interval theory" of Soviet filmmaker DzigaVertov. The scale of opportunities that can be explored in interval mode is wide. Intervals represent the perception of time and space in the form of pauses, interruptions, breaks (e.g., emotional, dramatic, or rhythmic) denote emptiness or silence, distance, proximity, interstitial space, or a gap between various states.

Keywords: video installation, performance, repetition, multi-screen, real and symbolic, loop, video art, interval, video time

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7 Sustainability in the Purchase of Airline Tickets: Analysis of Digital Communication from the Perspective of Neuroscience

Authors: Rodríguez Sánchez Carla, Sancho-Esper Franco, Guillen-Davo Marina

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Tourism is one of the most important sectors worldwide since it is an important economic engine for today's society. It is also one of the sectors that most negatively affect the environment in terms of CO₂ emissions due to this expansion. In light of this, airlines are developing Voluntary Carbon Offset (VCO). There is important evidence focused on analyzing the features of these VCO programs and their efficacy in reducing CO₂ emissions, and findings are mixed without a clear consensus. Different research approaches have centered on analyzing factors and consequences of VCO programs, such as economic modelling based on panel data, survey research based on traveler responses or experimental research analyzing customer decisions in a simulated context. This study belongs to the latter group because it tries to understand how different characteristics of an online ticket purchase website affect the willingness of a traveler to choose a sustainable one. The proposed behavioral model is based on several theories, such as the nudge theory, the dual processing ELM and the cognitive dissonance theory. This randomized experiment aims at overcoming previous studies based on self-reported measures that mainly study sustainable behavioral intention rather than actual decision-making. It also complements traditional self-reported independent variables by gathering objective information from an eye-tracking device. This experiment analyzes the influence of two characteristics of the online purchase website: i) the type of information regarding flight CO₂ emissions (quantitative vs. qualitative) and the comparison framework related to the sustainable purchase decision (negative: alternative with more emissions than the average flight of the route vs. positive: alternative with less emissions than the average flight of the route), therefore it is a 2x2 experiment with four alternative scenarios. A pretest was run before the actual experiment to refine the experiment features and to check the manipulations. Afterward, a different sample of students answered the pre-test questionnaire aimed at recruiting the cases and measuring several pre-stimulus measures. One week later, students came to the neurolab at the University setting to be part of the experiment, made their decision regarding online purchases and answered the post-test survey. A final sample of 21 students was gathered. The committee of ethics of the institution approved the experiment. The results show that qualitative information generates more sustainable decisions (less contaminant alternative) than quantitative information. Moreover, evidence shows that subjects are more willing to choose the sustainable decision to be more ecological (comparison of the average with the less contaminant alternative) rather than to be less contaminant (comparison of the average with the more contaminant alternative). There are also interesting differences in the information processing variables from the eye tracker. Both the total time to make the choice and the specific times by area of interest (AOI) differ depending on the assigned scenario. These results allow for a better understanding of the factors that condition the decision of a traveler to be part of a VCO program and provide useful information for airline managers to promote these programs to reduce environmental impact.

Keywords: voluntary carbon offset, airline, online purchase, carbon emission, sustainability, randomized experiment

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6 Development and Implementation of An "Electric Island" Monitoring Infrastructure for Promoting Energy Efficiency in Schools

Authors: Vladislav Grigorovitch, Marina Grigorovitch, David Pearlmutter, Erez Gal

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The concept of “electric island” is involved with achieving the balance between the self-power generation ability of each educational institution and energy consumption demand. Photo-Voltaic (PV) solar system installed on the roofs of educational buildings is a common way to absorb the available solar energy and generate electricity for self-consumption and even for returning to the grid. The main objective of this research is to develop and implement an “electric island” monitoring infrastructure for promoting energy efficiency in educational buildings. A microscale monitoring methodology will be developed to provide a platform to estimate energy consumption performance classified by rooms and subspaces rather than the more common macroscale monitoring of the whole building. The monitoring platform will be established on the experimental sites, enabling an estimation and further analysis of the variety of environmental and physical conditions. For each building, separate measurement configurations will be applied taking into account the specific requirements, restrictions, location and infrastructure issues. The direct results of the measurements will be analyzed to provide deeper understanding of the impact of environmental conditions and sustainability construction standards, not only on the energy demand of public building, but also on the energy consumption habits of the children that study in those schools and the educational and administrative staff that is responsible for providing the thermal comfort conditions and healthy studying atmosphere for the children. A monitoring methodology being developed in this research is providing online access to real-time data of Interferential Therapy (IFTs) from any mobile phone or computer by simply browsing the dedicated website, providing powerful tools for policy makers for better decision making while developing PV production infrastructure to achieve “electric islands” in educational buildings. A detailed measurement configuration was technically designed based on the specific conditions and restriction of each of the pilot buildings. A monitoring and analysis methodology includes a large variety of environmental parameters inside and outside the schools to investigate the impact of environmental conditions both on the energy performance of the school and educational abilities of the children. Indoor measurements are mandatory to acquire the energy consumption data, temperature, humidity, carbon dioxide and other air quality conditions in different parts of the building. In addition to that, we aim to study the awareness of the users to the energy consideration and thus the impact on their energy consumption habits. The monitoring of outdoor conditions is vital for proper design of the off-grid energy supply system and validation of its sufficient capacity. The suggested outcomes of this research include: 1. both experimental sites are designed to have PV production and storage capabilities; 2. Developing an online information feedback platform. The platform will provide consumer dedicated information to academic researchers, municipality officials and educational staff and students; 3. Designing an environmental work path for educational staff regarding optimal conditions and efficient hours for operating air conditioning, natural ventilation, closing of blinds, etc.

Keywords: sustainability, electric island, IOT, smart building

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5 Pedagogical Opportunities of Physics Education Technology Interactive Simulations for Secondary Science Education in Bangladesh

Authors: Mohosina Jabin Toma, Gerald Tembrevilla, Marina Milner-Bolotin

Abstract:

Science education in Bangladesh is losing its appeal at an alarming rate due to the lack of science laboratory equipment, excessive teacher-student ratio, and outdated teaching strategies. Research-based educational technologies aim to address some of the problems faced by teachers who have limited access to laboratory resources, like many Bangladeshi teachers. Physics Education Technology (PhET) research team has been developing science and mathematics interactive simulations to help students develop deeper conceptual understanding. Still, PhET simulations are rarely used in Bangladesh. The purpose of this study is to explore Bangladeshi teachers’ challenges in learning to implement PhET-enhanced pedagogies and examine teachers’ views on PhET’s pedagogical opportunities in secondary science education. Since it is a new technology for Bangladesh, seven workshops on PhET were conducted in Dhaka city for 129 in-service and pre-service teachers in the winter of 2023 prior to data collection. This study followed an explanatory mixed method approach that included a pre-and post-workshop survey and five semi-structured interviews. Teachers participated in the workshops voluntarily and shared their experiences at the end. Teachers’ challenges were also identified from workshop discussions and observations. The interviews took place three to four weeks after the workshop and shed light on teachers’ experiences of using PhET in actual classroom settings. The results suggest that teachers had difficulty handling new technology; hence, they recommended preparing a booklet and Bengali YouTube videos on PhET to assist them in overcoming their struggles. Teachers also faced challenges in using any inquiry-based learning approach due to the content-loaded curriculum and exam-oriented education system, as well as limited experience with inquiry-based education. The short duration of classes makes it difficult for them to design PhET activities. Furthermore, considering limited access to computers and the internet in school, teachers think PhET simulations can bring positive changes if used in homework activities. Teachers also think they lack pedagogical skills and sound content knowledge to take full advantage of PhET. They highly appreciated the workshops and proposed that the government designs some teacher training modules on how to incorporate PhET simulations. Despite all the challenges, teachers believe PhET can enhance student learning, ensure student engagement and increase student interest in STEM Education. Considering the lack of science laboratory equipment, teachers recognized the potential of PhET as a supplement to hands-on activities for secondary science education in Bangladesh. They believed that if PhET develops more curriculum-relevant sims, it will bring revolutionary changes to how Bangladeshi students learn science. All the participating teachers in this study came from two organizations, and all the workshops took place in urban areas; therefore, the findings cannot be generalized to all secondary science teachers. A nationwide study is required to include teachers from diverse backgrounds. A further study can shed light on how building a professional learning community can lessen teachers’ challenges in incorporating PhET-enhanced pedagogy in their teaching.

Keywords: educational technology, inquiry-based learning, PhET interactive simulations, PhET-enhanced pedagogies, science education, science laboratory equipment, teacher professional development

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4 Probability Modeling and Genetic Algorithms in Small Wind Turbine Design Optimization: Mentored Interdisciplinary Undergraduate Research at LaGuardia Community College

Authors: Marina Nechayeva, Malgorzata Marciniak, Vladimir Przhebelskiy, A. Dragutan, S. Lamichhane, S. Oikawa

Abstract:

This presentation is a progress report on a faculty-student research collaboration at CUNY LaGuardia Community College (LaGCC) aimed at designing a small horizontal axis wind turbine optimized for the wind patterns on the roof of our campus. Our project combines statistical and engineering research. Our wind modeling protocol is based upon a recent wind study by a faculty-student research group at MIT, and some of our blade design methods are adopted from a senior engineering project at CUNY City College. Our use of genetic algorithms has been inspired by the work on small wind turbines’ design by David Wood. We combine these diverse approaches in our interdisciplinary project in a way that has not been done before and improve upon certain techniques used by our predecessors. We employ several estimation methods to determine the best fitting parametric probability distribution model for the local wind speed data obtained through correlating short-term on-site measurements with a long-term time series at the nearby airport. The model serves as a foundation for engineering research that focuses on adapting and implementing genetic algorithms (GAs) to engineering optimization of the wind turbine design using Blade Element Momentum Theory. GAs are used to create new airfoils with desirable aerodynamic specifications. Small scale models of best performing designs are 3D printed and tested in the wind tunnel to verify the accuracy of relevant calculations. Genetic algorithms are applied to selected airfoils to determine the blade design (radial cord and pitch distribution) that would optimize the coefficient of power profile of the turbine. Our approach improves upon the traditional blade design methods in that it lets us dispense with assumptions necessary to simplify the system of Blade Element Momentum Theory equations, thus resulting in more accurate aerodynamic performance calculations. Furthermore, it enables us to design blades optimized for a whole range of wind speeds rather than a single value. Lastly, we improve upon known GA-based methods in that our algorithms are constructed to work with XFoil generated airfoils data which enables us to optimize blades using our own high glide ratio airfoil designs, without having to rely upon available empirical data from existing airfoils, such as NACA series. Beyond its immediate goal, this ongoing project serves as a training and selection platform for CUNY Research Scholars Program (CRSP) through its annual Aerodynamics and Wind Energy Research Seminar (AWERS), an undergraduate summer research boot camp, designed to introduce prospective researchers to the relevant theoretical background and methodology, get them up to speed with the current state of our research, and test their abilities and commitment to the program. Furthermore, several aspects of the research (e.g., writing code for 3D printing of airfoils) are adapted in the form of classroom research activities to enhance Calculus sequence instruction at LaGCC.

Keywords: engineering design optimization, genetic algorithms, horizontal axis wind turbine, wind modeling

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3 Facies, Diagenetic Analysis and Sequence Stratigraphy of Habib Rahi Formation Dwelling in the Vicinity of Jacobabad Khairpur High, Southern Indus Basin, Pakistan

Authors: Muhammad Haris, Syed Kamran Ali, Mubeen Islam, Tariq Mehmood, Faisal Shah

Abstract:

Jacobabad Khairpur High, part of a Sukkur rift zone, is the separating boundary between Central and Southern Indus Basin, formed as a result of Post-Jurassic uplift after the deposition of Middle Jurassic Chiltan Formation. Habib Rahi Formation of Middle to Late Eocene outcrops in the vicinity of Jacobabad Khairpur High, a section at Rohri near Sukkur is measured in detail for lithofacies, microfacies, diagenetic analysis and sequence stratigraphy. Habib Rahi Formation is richly fossiliferous and consists of mostly limestone with subordinate clays and marl. The total thickness of the formation in this section is 28.8m. The bottom of the formation is not exposed, while the upper contact with the Sirki Shale of the Middle Eocene age is unconformable in some places. A section is measured using Jacob’s Staff method, and traverses were made perpendicular to the strike. Four different lithofacies were identified based on outcrop geology which includes coarse-grained limestone facies (HR-1 to HR-5), massive bedded limestone facies (HR-6 HR-7), and micritic limestone facies (HR-8 to HR-13) and algal dolomitic limestone facie (HR-14). Total 14 rock samples were collected from outcrop for detailed petrographic studies, and thin sections of respective samples were prepared and analyzed under the microscope. On the basis of Dunham’s (1962) classification systems after studying textures, grain size, and fossil content and using Folk’s (1959) classification system after reviewing Allochems type, four microfacies were identified. These microfacies include HR-MF 1: Benthonic Foraminiferal Wackstone/Biomicrite Microfacies, HR-MF 2: Foramineral Nummulites Wackstone-Packstone/Biomicrite Microfacies HR-MF 3: Benthonic Foraminiferal Packstone/Biomicrite Microfacies, HR-MF 4: Bioclasts Carbonate Mudstone/Micrite Microfacies. The abundance of larger benthic Foraminifera’s (LBF), including Assilina sp., A. spiral abrade, A. granulosa, A. dandotica, A. laminosa, Nummulite sp., N. fabiani, N. stratus, N. globulus, Textularia, Bioclasts, and Red algae indicates shallow marine (Tidal Flat) environment of deposition. Based on variations in rock types, grain size, and marina fauna Habib Rahi Formation shows progradational stacking patterns, which indicates coarsening upward cycles. The second order of sea-level rise is identified (spanning from Y-Persian to Bartonian age) that represents the Transgressive System Tract (TST) and a third-order Regressive System Tract (RST) (spanning from Bartonian to Priabonian age). Diagenetic processes include fossils replacement by mud, dolomitization, pressure dissolution associated stylolites features and filling with dark organic matter. The presence of the microfossils includes Nummulite. striatus, N. fabiani, and Assilina. dandotica, signify Bartonian to Priabonian age of Habib Rahi Formation.

Keywords: Jacobabad Khairpur High, Habib Rahi Formation, lithofacies, microfacies, sequence stratigraphy, diagenetic history

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2 Investigation of the Controversial Immunomodulatory Potential of Trichinella spiralis Excretory-Secretory Products versus Extracellular Vesicles Derived from These Products in vitro

Authors: Natasa Ilic, Alisa Gruden-Movsesijan, Maja Kosanovic, Sofija Glamoclija, Marina Bekic, Ljiljana Sofronic-Milosavljevic, Sergej Tomic

Abstract:

As a very promising candidate for modulation of immune response in the sense of biasing the inflammatory towards an anti-inflammatory type of response, Trichinella spiralis infection was shown to successfully alleviate the severity of experimental autoimmune encephalomyelitis, the animal model of human disease multiple sclerosis. This effect is achieved via its excretory-secretory muscle larvae (ES L1) products which affect the maturation status and function of dendritic cells (DCs) by inducing the tolerogenic status of DCs, which leads to the mitigation of the Th1 type of response and the activation of a regulatory type of immune response both in vitro and in vivo. ES L1 alone or via treated DCs successfully mitigated EAE in the same manner as the infection itself. On the other hand, it has been shown that T. spiralis infection slows down the tumour growth and significantly reduces the tumour size in the model of mouse melanoma, while ES L1 possesses a pro-apoptotic and anti-survival effect on melanoma cells in vitro. Hence, although the mechanisms still need to be revealed, T. spiralis infection and its ES L1 products have a bit of controversial potential to modulate both inflammatory diseases and malignancies. The recent discovery of T. spiralis extracellular vesicles (TsEVs) suggested that the induction of complex regulation of the immune response requires simultaneous delivery of different signals in nano-sized packages. This study aimed to explore whether TsEVs bare the similar potential as ES L1 to influence the status of DCs in initiation, progression and regulation of immune response, but also to investigate the effect of both ES L1 and TsEVs on myeloid derived suppressor cells (MDSC) which present the regular tumour tissue environment. TsEVs were enriched from the conditioned medium of T. spiralis muscle larvae by differential centrifugation and used for the treatment of human monocyte-derived DCs and MDSC. On DCs, TsEVs induced low expression of HLA DR and CD40, moderate CD83 and CD86, and increased expression of ILT3 and CCR7 on treated DCs, i.e., they induced tolerogenic DCs. Such DCs possess the capacity to polarize T cell immune response towards regulatory type, with an increased proportion of IL-10 and TGF-β producing cells, similarly to ES L1. These findings indicated that the ability of TsEVs to induce tolerogenic DCs favoring anti-inflammatory responses may be helpful in coping with diseases that involve Th1/Th17-, but also Th2-mediated inflammation. In MDSC in vitro model, although both ES L1 and TsEVs had the same impact on MDSC phenotype i.e., they acted suppressive, ES L1 treated MDSC, unlike TsEVs treated ones, induced T cell response characterized by the increased RoRγT and IFN-γ, while the proportion of regulatory cells was decreased followed by the decrease in IL-10 and TGF-β positive cells proportion within this population. These findings indicate the interesting ability of ES L1 to modulate T cells response via MDSC towards pro-inflamatory type, suggesting that, unlike TsEVs which consistently demonstrate the suppresive effect on inflammatory response, it could be used also for the development of new approaches aimed for the treatment of malignant diseases. Acknowledgment: This work was funded by the Promis project – Nano-MDCS-Thera, Science Fund, Republic of Serbia.

Keywords: dendritic cells, myeloid derived suppressor cells, immunomodulation, Trichinella spiralis

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1 A Computational Investigation of Potential Drugs for Cholesterol Regulation to Treat Alzheimer’s Disease

Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang

Abstract:

Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.

Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation

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