Search results for: technology trade effect
Commenced in January 2007
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Edition: International
Paper Count: 21659

Search results for: technology trade effect

239 Harnessing Nature's Fury: Hyptis Suaveolens Loaded Bioactive Liposome for Photothermal Therapy of Lung Cancer

Authors: Sajmina Khatun, Monika Pebam, Aravind Kumar Rengan

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Photothermal therapy, a subset of nanomedicine, takes advantage of light-absorbing agents to generate localized heat, selectively eradicating cancer cells. This innovative approach minimizes damage to healthy tissues and offers a promising avenue for targeted cancer treatment. Unlike conventional therapies, photothermal therapy harnesses the power of light to combat malignancies precisely and effectively, showcasing its potential to revolutionize cancer treatment paradigms. The combined strengths of nanomedicine and photothermal therapy signify a transformative shift toward more effective, targeted, and tolerable cancer treatments in the medical landscape. Utilizing natural products becomes instrumental in formulating diverse bioactive medications owing to their various pharmacological properties attributed to the existence of phenolic structures, triterpenoids, and similar compounds. Hyptis suaveolens, commonly known as pignut, stands as an aromatic herb within the Lamiaceae family and represents a valuable therapeutic plant. Flourishing in swamps and alongside tropical and subtropical roadsides, these noxious weeds impede the development of adjacent plants. Hyptis suaveolens ranks among the most globally distributed alien invasive species. The present investigation revealed that a versatile, biodegradable liposome nanosystem (HIL NPs), incorporating bioactive molecules from Hyptis suaveolens, exhibits effective bioavailability to cancer cells, enabling tumor ablation upon near-infrared (NIR) laser exposure. The components within the nanosystem, specifically the bioactive molecules from Hyptis, function as anticancer agents, aiding in the photothermal ablation of highly metastatic lung cancer cells. Despite being a prolific weed impeding neighboring plant growth, Hyptis suaveolens showcases therapeutic benefits through its bioactive compounds. The obtained HIL NPs, characterized as a photothermally active liposome nanosystem, demonstrate a pronounced fluorescence absorption peak in the NIR range and achieve a high photothermal conversion efficiency under NIR laser irradiation. Transmission electron microscopy (TEM) and particle size analysis reveal that HIL NPs possess a spherical shape with a size of 141 ± 30 nm. Moreover, in vitro assessments of HIL NPs against lung cancer cell lines (A549) indicate effective anticancer activity through a combined cytotoxic effect and hyperthermia. Tumor ablation is facilitated by apoptosis induced by the overexpression of ɣ-H2AX, arresting cancer cell proliferation. Consequently, the multifunctional and biodegradable nanosystem (HIL NPs), incorporating bioactive compounds from Hyptis, provides valuable perspectives for developing an innovative therapeutic strategy originating from a challenging weed. This approach holds promise for potential applications in both bioimaging and the combined use of phyto-photothermal therapy for cancer treatment.

Keywords: bioactive liposome, hyptis suaveolens, photothermal therapy, lung cancer

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238 Towards a Measuring Tool to Encourage Knowledge Sharing in Emerging Knowledge Organizations: The Who, the What and the How

Authors: Rachel Barker

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The exponential velocity in the truly knowledge-intensive world today has increasingly bombarded organizations with unfathomable challenges. Hence organizations are introduced to strange lexicons of descriptors belonging to a new paradigm of who, what and how knowledge at individual and organizational levels should be managed. Although organizational knowledge has been recognized as a valuable intangible resource that holds the key to competitive advantage, little progress has been made in understanding how knowledge sharing at individual level could benefit knowledge use at collective level to ensure added value. The research problem is that a lack of research exists to measure knowledge sharing through a multi-layered structure of ideas with at its foundation, philosophical assumptions to support presuppositions and commitment which requires actual findings from measured variables to confirm observed and expected events. The purpose of this paper is to address this problem by presenting a theoretical approach to measure knowledge sharing in emerging knowledge organizations. The research question is that despite the competitive necessity of becoming a knowledge-based organization, leaders have found it difficult to transform their organizations due to a lack of knowledge on who, what and how it should be done. The main premise of this research is based on the challenge for knowledge leaders to develop an organizational culture conducive to the sharing of knowledge and where learning becomes the norm. The theoretical constructs were derived and based on the three components of the knowledge management theory, namely technical, communication and human components where it is suggested that this knowledge infrastructure could ensure effective management. While it is realised that it might be a little problematic to implement and measure all relevant concepts, this paper presents effect of eight critical success factors (CSFs) namely: organizational strategy, organizational culture, systems and infrastructure, intellectual capital, knowledge integration, organizational learning, motivation/performance measures and innovation. These CSFs have been identified based on a comprehensive literature review of existing research and tested in a new framework adapted from four perspectives of the balanced score card (BSC). Based on these CSFs and their items, an instrument was designed and tested among managers and employees of a purposefully selected engineering company in South Africa who relies on knowledge sharing to ensure their competitive advantage. Rigorous pretesting through personal interviews with executives and a number of academics took place to validate the instrument and to improve the quality of items and correct wording of issues. Through analysis of surveys collected, this research empirically models and uncovers key aspects of these dimensions based on the CSFs. Reliability of the instrument was calculated by Cronbach’s a for the two sections of the instrument on organizational and individual levels.The construct validity was confirmed by using factor analysis. The impact of the results was tested using structural equation modelling and proved to be a basis for implementing and understanding the competitive predisposition of the organization as it enters the process of knowledge management. In addition, they realised the importance to consolidate their knowledge assets to create value that is sustainable over time.

Keywords: innovation, intellectual capital, knowledge sharing, performance measures

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237 Microfluidic Plasmonic Device for the Sensitive Dual LSPR-Thermal Detection of the Cardiac Troponin Biomarker in Laminal Flow

Authors: Andreea Campu, Ilinica Muresan, Simona Cainap, Simion Astilean, Monica Focsan

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Acute myocardial infarction (AMI) is the most severe cardiovascular disease, which has threatened human lives for decades, thus a continuous interest is directed towards the detection of cardiac biomarkers such as cardiac troponin I (cTnI) in order to predict risk and, implicitly, fulfill the early diagnosis requirements in AMI settings. Microfluidics is a major technology involved in the development of efficient sensing devices with real-time fast responses and on-site applicability. Microfluidic devices have gathered a lot of attention recently due to their advantageous features such as high sensitivity and specificity, miniaturization and portability, ease-of-use, low-cost, facile fabrication, and reduced sample manipulation. The integration of gold nanoparticles into the structure of microfluidic sensors has led to the development of highly effective detection systems, considering the unique properties of the metallic nanostructures, specifically the Localized Surface Plasmon Resonance (LSPR), which makes them highly sensitive to their microenvironment. In this scientific context, herein, we propose the implementation of a novel detection device, which successfully combines the efficiency of gold bipyramids (AuBPs) as signal transducers and thermal generators with the sample-driven advantages of the microfluidic channels into a miniaturized, portable, low-cost, specific, and sensitive test for the dual LSPR-thermographic cTnI detection. Specifically, AuBPs with longitudinal LSPR response at 830 nm were chemically synthesized using the seed-mediated growth approach and characterized in terms of optical and morphological properties. Further, the colloidal AuBPs were deposited onto pre-treated silanized glass substrates thus, a uniform nanoparticle coverage of the substrate was obtained and confirmed by extinction measurements showing a 43 nm blue-shift of the LSPR response as a consequence of the refractive index change. The as-obtained plasmonic substrate was then integrated into a microfluidic “Y”-shaped polydimethylsiloxane (PDMS) channel, fabricated using a Laser Cutter system. Both plasmonic and microfluidic elements were plasma treated in order to achieve a permanent bond. The as-developed microfluidic plasmonic chip was further coupled to an automated syringe pump system. The proposed biosensing protocol implicates the successive injection inside the microfluidic channel as follows: p-aminothiophenol and glutaraldehyde, to achieve a covalent bond between the metallic surface and cTnI antibody, anti-cTnI, as a recognition element, and target cTnI biomarker. The successful functionalization and capture of cTnI was monitored by LSPR detection thus, after each step, a red-shift of the optical response was recorded. Furthermore, as an innovative detection technique, thermal determinations were made after each injection by exposing the microfluidic plasmonic chip to 785 nm laser excitation, considering that the AuBPs exhibit high light-to-heat conversion performances. By the analysis of the thermographic images, thermal curves were obtained, showing a decrease in the thermal efficiency after the anti-cTnI-cTnI reaction was realized. Thus, we developed a microfluidic plasmonic chip able to operate as both LSPR and thermal sensor for the detection of the cardiac troponin I biomarker, leading thus to the progress of diagnostic devices.

Keywords: gold nanobipyramids, microfluidic device, localized surface plasmon resonance detection, thermographic detection

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236 Cross-Sectional Associations between Deprivation Status and Physical Activity, Dietary Behaviours, Health-Related Variables, and Health-Related Quality of Life among Children Aged 9-11 Years

Authors: Maria Cardova

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Aim and objectives: The purpose of this studywas to explore to what extent the deprivation statusinfluenced children’s physical activity, dietary behaviour, and health outcomes such as weight status. Background: The United Kingdom’s childhood obesity rates are currently ranked among the highest in Europe. North West England deals with highest rates of childhood obesity. Data from the UK Millennium Cohort Study suggested a deprivation gradient to childhood obesity in England, with obesity rates being the highest in the most deprived areas. Traditionally, it has been individual conception of health, but the contemporary stance is that health behaviours affecting obesity are influenced by a broad range of factors operating at multiple levels. According to socio-ecological model of health behaviour, differences in obesity rates and health outcomes are likely explained by differences in lifestyle behaviours including physical activity and diet behaviours. However, higher rates of obesity among deprived children are not due to physical inactivity, in fact, most socially disadvantaged children are the most physically active. Poor diet including high consumption of fast food and sugar-sweetened beverages and low consumption of fruit and vegetables was found to be the most prevalent among adolescents living in poverty. Methods: This study adopted quantitative approach. It consisted of combination of basic demographic data, anthropometry, and questionnaires. Children (N = 165, mean age = 10.04 years; 53.33% female; 46.66% male) completed survey packs during school day including KIDSCREEN, Youth Activity Profile, Beverage and Snack Questionnaire, and Child Body Image Scale questionnaires as well as had anthropometric measurements taken including Body mass index, waist circumference, weight, and height. Children’s deprivation status was based on the English Indices of Multiple Deprivation scores of the school they attended. Results: Children from more deprived areas had higher weight status, waist circumference. Deprivation status had also effect on some dimensions of the KIDSCREEN questionnaire, such as that those from more deprived areas felt less socially accepted and bullied by their peers, had worse feelings about themselves such as body image, and more difficulty with school and learning. Children from more deprived areas reported higher rates of physical activity and also differences in snack and fruit and vegetable intake than their more affluent peers. Conclusion: Results demonstrated that, children living in the most-deprived areas appear to be at greater risk of unfavourable health-related variables and behaviours and are exposed to home and neighbourhood environments that are less conducive to health-promoting behaviours compared to their peers from less deprived areas. These findings indicate that children living in highly deprived areas represent an important group for future interventions designed to promote health-behaviours that would impact on the quality of life of the child and other health variables such as weight status.

Keywords: children, dietary behaviour, health, obesity, physical Activity, weight Status

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235 Formulation and Optimization of Self Nanoemulsifying Drug Delivery System of Rutin for Enhancement of Oral Bioavailability Using QbD Approach

Authors: Shrestha Sharma, Jasjeet K. Sahni, Javed Ali, Sanjula Baboota

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Introduction: Rutin is a naturally occurring strong antioxidant molecule belonging to bioflavonoid category. Due to its free radical scavenging properties, it has been found to be beneficial in the treatment of various diseases including inflammation, cancer, diabetes, allergy, cardiovascular disorders and various types of microbial infections. Despite its beneficial effects, it suffers from the problem of low aqueous solubility which is responsible for low oral bioavailability. The aim of our study was to optimize and characterize self-nanoemulsifying drug delivery system (SNEDDS) of rutin using Box-Behnken design (BBD) combined with a desirability function. Further various antioxidant, pharmacokinetic and pharmacodynamic studies were performed for the optimized rutin SNEDDS formulation. Methodologies: Selection of oil, surfactant and co-surfactant was done on the basis of solubility/miscibility studies. Sefsol+ Vitamin E, Solutol HS 15 and Transcutol P were selected as oil phase, surfactant and co-surfactant respectively. Optimization of SNEDDS formulations was done by a three-factor, three-level (33)BBD. The independent factors were Sefsol+ Vitamin E, Solutol HS15, and Transcutol P. The dependent variables were globule size, self emulsification time (SEF), % transmittance and cumulative percentage drug released. Various response surface graphs and contour plots were constructed to understand the effect of different factor, their levels and combinations on the responses. The optimized Rutin SNEDDS formulation was characterized for various parameters such as globule size, zeta potential, viscosity, refractive index , % Transmittance and in vitro drug release. Ex vivo permeation studies and pharmacokinetic studies were performed for optimized formulation. Antioxidant activity was determined by DPPH and reducing power assays. Anti-inflammatory activity was determined by using carrageenan induced rat paw oedema method. Permeation of rutin across small intestine was assessed using confocal laser scanning microscopy (CLSM). Major findings:The optimized SNEDDS formulation consisting of Sefsol+ Vitamin E - Solutol HS15 -Transcutol HP at proportions of 25:35:17.5 (w/w) was prepared and a comparison of the predicted values and experimental values were found to be in close agreement. The globule size and PDI of optimized SNEDDS formulation was found to be 16.08 ± 0.02 nm and 0.124±0.01 respectively. Significant (p˂0.05) increase in percentage drug release was achieved in the case of optimized SNEDDS formulation (98.8 %) as compared to rutin suspension. Furthermore, pharmacokinetic study showed a 2.3-fold increase in relative oral bioavailability compared with that of the suspension. Antioxidant assay results indicated better efficacy of the developed formulation than the pure drug and it was found to be comparable with ascorbic acid. The results of anti-inflammatory studies showed 72.93 % inhibition for the SNEDDS formulation which was significantly higher than the drug suspension 46.56%. The results of CLSM indicated that the absorption of SNEDDS formulation was considerably higher than that from rutin suspension. Conclusion: Rutin SNEDDS have been successfully prepared and they can serve as an effective tool in enhancing oral bioavailability and efficacy of Rutin.

Keywords: rutin, oral bioavilability, pharamacokinetics, pharmacodynamics

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234 Identification of the Target Genes to Increase the Immunotherapy Response in Bladder Cancer Patients using Computational and Experimental Approach

Authors: Sahar Nasr, Lin Li, Edwin Wang

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Bladder cancer (BLCA) is known as the 13th cause of death among cancer patients worldwide, and ~575,000 new BLCA cases are diagnosed each year. Urothelial carcinoma (UC) is the most prevalent subtype among BLCA patients, which can be categorized into muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Currently, various therapeutic options are available for UC patients, including (1) transurethral resection followed by intravesical instillation of chemotherapeutics or Bacillus Calmette-Guérin for NMIBC patients, (2) neoadjuvant platinum-based chemotherapy (NAC) plus radical cystectomy is the standard of care for localized MIBC patients, and (3) systematic chemotherapy for metastatic UC. However, conventional treatments may lead to several challenges for treating patients. As an illustration, some patients may suffer from recurrence of the disease after the first line of treatment. Recently, immune checkpoint therapy (ICT) has been introduced as an alternative treatment strategy for the first or second line of treatment in advanced or metastatic BLCA patients. Although ICT showed lucrative results for a fraction of BLCA patients, ~80% of patients were not responsive to it. Therefore, novel treatment methods are required to augment the ICI response rate within BLCA patients. It has been shown that the infiltration of T-cells into the tumor microenvironment (TME) is positively correlated with the response to ICT within cancerous patients. Therefore, the goal of this study is to enhance the infiltration of cytotoxic T-cells into TME through the identification of target genes within the tumor that are responsible for the non-T-cell inflamed TME and their inhibition. BLCA bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) and immune score for TCGA samples were used to determine the Pearson correlation score between the expression of different genes and immune score for each sample. The genes with strong negative correlations were selected (r < -0.2). Thereafter, the correlation between the expression of each gene and survival in BLCA patients was calculated using the TCGA data and Cox regression method. The genes that are common in both selected gene lists were chosen for further analysis. Afterward, BLCA bulk and single-cell RNA-sequencing data were ranked based on the expression of each selected gene and the top and bottom 25% samples were used for pathway enrichment analysis. If the pathways related to the T-cell infiltration (e.g., antigen presentation, interferon, or chemokine pathways) were enriched within the low-expression group, the gene was included for downstream analysis. Finally, the selected genes will be used to calculate the correlation between their expression and the infiltration rate of the activated CD+8 T-cells, natural killer cells and the activated dendric cells. A list of potential target genes has been identified and ranked based on the above-mentioned analysis and criteria. SUN-1 got the highest score within the gene list and other identified genes in the literature as benchmarks. In conclusion, inhibition of SUN1 may increase the tumor-infiltrating lymphocytes and the efficacy of ICI in BLCA patients. BLCA tumor cells with and without SUN-1 CRISPR/Cas9 knockout will be injected into the syngeneic mouse model to validate the predicted SUN-1 effect on increasing tumor-infiltrating lymphocytes.

Keywords: data analysis, gene expression analysis, gene identification, immunoinformatic, functional genomics, transcriptomics

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233 Biodegradation Effects onto Source Identification of Diesel Fuel Contaminated Soils

Authors: Colin S. Chen, Chien-Jung Tien, Hsin-Jan Huang

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For weathering studies, the change of chemical constituents by biodegradation effect in diesel-contaminated soils are important factors to be considered, especially when there is a prolonged period of weathering processes. The objective was to evaluate biodegradation effects onto hydrocarbon fingerprinting and distribution patterns of diesel fuels, fuel source screening and differentiation, source-specific marker compounds, and diagnostic ratios of diesel fuel constituents by laboratory and field studies. Biodegradation processes of diesel contaminated soils were evaluated by experiments lasting for 15 and 12 months, respectively. The degradation of diesel fuel in top soils was affected by organic carbon content and biomass of microorganisms in soils. Higher depletion of total petroleum hydrocarbon (TPH), n-alkanes, and polynuclear aromatic hydrocarbons (PAHs) and their alkyl homologues was observed in soils containing higher organic carbon content and biomass. Decreased ratio of selected isoprenoids (i.e., pristane (Pr) and phytane (Ph)) including n-C17/pristane and n-C18/phytane was observed. The ratio of pristane/phytane was remained consistent for a longer period of time. At the end of the experimental period, a decrease of pristane/phytane was observed. Biomarker compounds of bicyclic sesquiterpanes (BS) were less susceptible to the effects of biodegradation. The ratios of characteristic factors such as C15 sesquiterpane/ 8β(H)-drimane (BS3/BS5), C15 sesquiterpane/ 8β(H)-drimane (BS4/BS5), 8β(H)-drimane/8β(H)-homodrimane (BS5/BS10), and C15 sesquiterpane/8β(H)-homodrimane (BS3/BS10) could be adopted for source identification of diesel fuels in top soil. However, for biodegradation processes lasted for six months but shorter than nine months, only BS3/BS5 and BS3/BS10 could be distinguished in two diesel fuels. In subsoil experiments (contaminated soil located 50 cm below), the ratios of characteristic factors including BS3/BS5, BS4/BS5, and BS5/BS10 were valid for source identification of two diesel fuels for nine month biodegradation. At the early stage of contamination, biomass of soil decreased significantly. However, 6 and 7 dominant species were found in soils in top soil experiments, respectively. With less oxygen and nutrients in subsoil, less biomass of microorganisms was observed in subsoils. Only 2 and 4 diesel-degrading species of microorganisms were identified in two soils, respectively. Parameters of double ratio such as fluorene/C1-fluorene: C2-phenanthrene/C3-phenanthrene (C0F/C1F:C2P/C3P) in both top and subsoil, C2-naphthalene/C2-phenanthrene: C1-phenanthrene/C3-phenanthrene (C2N/C2P:C1P/C3P), and C1-phenanthrene/C1-fluorene: C3-naphthalene/C3-phenanthrene (C1P/C1F:C3N/C3P) in subsoil could serve as forensic indicators in diesel contaminated sites. BS3/BS10:BS4/BS5 could be used in 6 to 9 months of biodegradation processes. Results of principal component analysis (PCA) indicated that source identification of diesel fuels in top soil could only be perofrmed for weathering process less than 6 months. For subsoil, identification can be conducted for weathering process less than 9 months. Ratio of isoprenoids (pristane and phytane) and PAHs might be affected by biodegradation in spilled sites. The ratios of bicyclic sesquiterpanes could serve as forensic indicators in diesel-contaminated soils. Finally, source identification was attemped for samples collected from different fuel contaminated sites by using the unique pattern of sesquiterpanes. It was anticipated that the information generated from this study would be adopted by decision makers to evaluate the liability of cleanup in diesel contaminated sites.

Keywords: biodegradation, diagnostic ratio, diesel fuel, environmental forensics

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232 Nano-Enabling Technical Carbon Fabrics to Achieve Improved Through Thickness Electrical Conductivity in Carbon Fiber Reinforced Composites

Authors: Angelos Evangelou, Katerina Loizou, Loukas Koutsokeras, Orestes Marangos, Giorgos Constantinides, Stylianos Yiatros, Katerina Sofocleous, Vasileios Drakonakis

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Owing to their outstanding strength to weight properties, carbon fiber reinforced polymer (CFRPs) composites have attracted significant attention finding use in various fields (sports, automotive, transportation, etc.). The current momentum indicates that there is an increasing demand for their employment in high value bespoke applications such as avionics and electronic casings, damage sensing structures, EMI (electromagnetic interference) structures that dictate the use of materials with increased electrical conductivity both in-plane and through the thickness. Several efforts by research groups have focused on enhancing the through-thickness electrical conductivity of FRPs, in an attempt to combine the intrinsically high relative strengths exhibited with improved z-axis electrical response as well. However, only a limited number of studies deal with printing of nano-enhanced polymer inks to produce a pattern on dry fabric level that could be used to fabricate CFRPs with improved through thickness electrical conductivity. The present study investigates the employment of screen-printing process on technical dry fabrics using nano-reinforced polymer-based inks to achieve the required through thickness conductivity, opening new pathways for the application of fiber reinforced composites in niche products. Commercially available inks and in-house prepared inks reinforced with electrically conductive nanoparticles are employed, printed in different patterns. The aim of the present study is to investigate both the effect of the nanoparticle concentration as well as the droplet patterns (diameter, inter-droplet distance and coverage) to optimize printing for the desired level of conductivity enhancement in the lamina level. The electrical conductivity is measured initially at ink level to pinpoint the optimum concentrations to be employed using a “four-probe” configuration. Upon printing of the different patterns, the coverage of the dry fabric area is assessed along with the permeability of the resulting dry fabrics, in alignment with the fabrication of CFRPs that requires adequate wetting by the epoxy matrix. Results demonstrated increased electrical conductivities of the printed droplets, with increase of the conductivity from the benchmark value of 0.1 S/M to between 8 and 10 S/m. Printability of dense and dispersed patterns has exhibited promising results in terms of increasing the z-axis conductivity without inhibiting the penetration of the epoxy matrix at the processing stage of fiber reinforced composites. The high value and niche prospect of the resulting applications that can stem from CFRPs with increased through thickness electrical conductivities highlights the potential of the presented endeavor, signifying screen printing as the process to to nano-enable z-axis electrical conductivity in composite laminas. This work was co-funded by the European Regional Development Fund and the Republic of Cyprus through the Research and Innovation Foundation (Project: ENTERPRISES/0618/0013).

Keywords: CFRPs, conductivity, nano-reinforcement, screen-printing

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231 Improved Approach to the Treatment of Resistant Breast Cancer

Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

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Background: Breast cancer (BC) is still one of the urgent oncology problems. The essential obstacle to the full anti-tumor therapy implementation is drug resistance development. Taking into account the fact that chemotherapy is main antitumor treatment in BC patients, the important task is to improve treatment results. Certain success in overcoming this situation has been associated with the use of methods of extracorporeal blood treatment (ECBT), plasmapheresis. Materials and Methods: We examined 129 women with resistant BC stages 3-4, aged between 56 to 62 years who had previously received 2 courses of CAF chemotherapy. All patients additionally underwent 2 courses of CAF chemotherapy but against the background ECBT with ultrasonic exposure. We studied the following parameters: 1. The highlights of peripheral blood before and after therapy. 2. The state of cellular immunity and identification of activation markers CD23 +, CD25 +, CD38 +, CD95 + on lymphocytes was performed using monoclonal antibodies. Evaluation of humoral immunity was determined by the level of main classes of immunoglobulins IgG, IgA, IgM in serum. 3. The degree of tumor regression was assessed by WHO recommended 4 gradations. (complete - 100%, partial - more than 50% of initial size, process stabilization–regression is less than 50% of initial size and tumor advance progressing). 4. Medical pathomorphism in the tumor was determined by Lavnikova. 5. The study of immediate and remote results, up to 3 years and more. Results and Discussion: After performing extracorporeal blood treatment anemia occurred in 38.9%, leukopenia in 36.8%, thrombocytopenia in 34.6%, hypolymphemia in 26.8%. Studies of immunoglobulin fractions in blood serum were able to establish a certain relationship between the classes of immunoglobulin A, G, M and their functions. The results showed that after treatment the values of main immunoglobulins in patients’ serum approximated to normal. Analysis of expression of activation markers CD25 + cells bearing receptors for IL-2 (IL-2Rα chain) and CD95 + lymphocytes that were mediated physiological apoptosis showed the tendency to increase, which apparently was due to activation of cellular immunity cytokines allocated by ultrasonic treatment. To carry out ECBT on the background of ultrasonic treatment improved the parameters of the immune system, which were expressed in stimulation of cellular immunity and correcting imbalances in humoral immunity. The key indicator of conducted treatment efficiency is the immediate result measured by the degree of tumor regression. After ECBT performance the complete regression was 10.3%, partial response - 55.5%, process stabilization - 34.5%, tumor advance progressing no observed. Morphological investigations of tumor determined therapeutic pathomorphism grade 2 in 15%, in 25% - grade 3 and therapeutic pathomorphism grade 4 in 60% of patients. One of the main criteria for the effect of conducted treatment is to study the remission terms in the postoperative period (up to 3 years or more). The remission terms up to 3 years with ECBT was 34.5%, 5-year survival was 54%. Carried out research suggests that a comprehensive study of immunological and clinical course of breast cancer allows the differentiated approach to the choice of methods for effective treatment.

Keywords: breast cancer, immunoglobulins, extracorporeal blood treatment, chemotherapy

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230 Evaluation of Toxicity of Cerium Oxide on Zebrafish Developmental Stages

Authors: Roberta Pecoraro, Elena Maria Scalisi

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Engineered Nanoparticles (ENPs) and Nanomaterials (ENMs) concern an active research area and a sector in full expansion. They have physical-chemical characteristics and small size that improve their performance compared to common materials. Due to the increase in their production and their subsequent release into the environment, new strategies are emerging to assess risk of nanomaterials. NPs can be released into the environment through aquatic systems by human activities and exert toxicity on living organisms. We evaluated the potential toxic effect of cerium oxide (CeO2) nanoparticles because it’s used in different fields due to its peculiar properties. In order to assess nanoparticles toxicity, Fish Embryo Toxicity (FET) test was performed. Powders of CeO2 NPs supplied by the CNR-IMM of Catania are indicated as CeO2 type 1 (as-prepared) and CeO2 type 2 (modified), while CeO2 type 3 (commercial) is supplied by Sigma-Aldrich. Starting from a stock solution (0.001g/10 ml dilution water) of each type of CeO2 NPs, the other concentration solutions were obtained adding 1 ml of the stock solution to 9 ml of dilution water, leading to three different solutions of concentration (10-4, 10-5, 10-6 g/ml). All the solutions have been sonicated to avoid natural tendency of NPs to aggregate and sediment. FET test was performed according to the OECD guidelines for testing chemicals using our internal protocol procedure. A number of eight selected fertilized eggs were placed in each becher filled with 5 ml of each concentration of the three types of CeO2 NPs; control samples were incubated only with dilution water. Replication was performed for each concentration. During the exposure period, we observed four endpoints (embryo coagulation, lack of formation of somites, failure to lift the yolk bag, no heartbeat) by a stereomicroscope every 24 hours. Immunohistochemical analysis on treated larvae was performed to evaluate the expression of metallothioneins (MTs), Heat Shock Proteins 70 (HSP70) and 7-ethoxyresorufin-O-diethylase (EROD). Our results have not shown evident alterations on embryonic development because all embryos completed the development and the hatching of the eggs, started around the 48th hour after exposure, took place within the last observation at 72 hours. A good reactivity, both in the embryos and in the newly hatched larvae, was found. The presence of heartbeat has also been observed in embryos with reduced mobility confirming their viability. A higher expression of EROD biomarker was observed in the larvae exposed to the three types of CeO2, showing a clear difference with the control. A weak positivity was found for MTs biomarker in treated larvae as well as in the control. HSP70 are expressed homogeneously in all the type of nanoparticles tested but not too much greater than control. Our results are in agreement with other studies in the literature, in which the exposure of Danio rerio larvae to other metal oxide nanoparticles does not show adverse effects on survival and hatching time. Further studies are necessary to clarify the role of these NPs and also to solve conflicting opinions.

Keywords: Danio rerio, endpoints, fish embryo toxicity test, metallic nanoparticles

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229 On-Farm Biopurification Systems: Fungal Bioaugmentation of Biomixtures For Carbofuran Removal

Authors: Carlos E. Rodríguez-Rodríguez, Karla Ruiz-Hidalgo, Kattia Madrigal-Zúñiga, Juan Salvador Chin-Pampillo, Mario Masís-Mora, Elizabeth Carazo-Rojas

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One of the main causes of contamination linked to agricultural activities is the spillage and disposal of pesticides, especially during the loading, mixing or cleaning of agricultural spraying equipment. One improvement in the handling of pesticides is the use of biopurification systems (BPS), simple and cheap degradation devices where the pesticides are biologically degraded at accelerated rates. The biologically active core of BPS is the biomixture, which is constituted by soil pre-exposed to the target pesticide, a lignocellulosic substrate to promote the activity of ligninolitic fungi and a humic component (peat or compost), mixed at a volumetric proportion of 50:25:25. Considering the known ability of lignocellulosic fungi to degrade a wide range of organic pollutants, and the high amount of lignocellulosic waste used in biomixture preparation, the bioaugmentation of biomixtures with these fungi represents an interesting approach for improving biomixtures. The present work aimed at evaluating the effect of the bioaugmentation of rice husk based biomixtures with the fungus Trametes versicolor in the removal of the insectice/nematicide carbofuran (CFN) and to optimize the composition of the biomixture to obtain the best performance in terms of CFN removal and mineralization, reduction in formation of transformation products and decrease in residual toxicity of the matrix. The evaluation of several lignocellulosic residues (rice husk, wood chips, coconut fiber, sugarcane bagasse or newspaper print) revealed the best colonization by T. versicolor in rice husk. Pre-colonized rice husk was then used in the bioaugmentation of biomixtures also containing soil pre-exposed to CFN and either peat (GTS biomixture) or compost (GCS biomixture). After spiking with 10 mg/kg CBF, the efficiency of the biomixture was evaluated through a multi-component approach that included: monitoring of CBF removal and production of CBF transformation products, mineralization of radioisotopically labeled carbofuran (14C-CBF) and changes in the toxicity of the matrix after the treatment (Daphnia magna acute immobilization test). Estimated half-lives of CBF in the biomixtures were 3.4 d and 8.1 d in GTS and GCS, respectively. The transformation products 3-hydroxycarbofuran and 3-ketocarbofuran were detected at the moment of CFN application, however their concentration continuously disappeared. Mineralization of 14C-CFN was also faster in GTS than GCS. The toxicological evaluation showed a complete toxicity removal in the biomixtures after 48 d of treatment. The composition of the GCS biomixture was optimized using a central composite design and response surface methodology. The design variables were the volumetric content of fungally pre-colonized rice husk and the volumetric ratio compost/soil. According to the response models, maximization of CFN removal and mineralization rate, and minimization in the accumulation of transformation products were obtained with an optimized biomixture of composition 30:43:27 (pre-colonized rice husk:compost:soil), which differs from the 50:25:25 composition commonly employed in BPS. Results suggest that fungal bioaugmentation may enhance the performance of biomixtures in CFN removal. Optimization reveals the importance of assessing new biomixture formulations in order to maximize their performance.

Keywords: bioaugmentation, biopurification systems, degradation, fungi, pesticides, toxicity

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228 Assessment of Antioxidant and Cholinergic Systems, and Liver Histopathologies in Lithobates catesbeianus Exposed to the Waters of an Urban Stream

Authors: Diego R. Boiarski, Camila M. Toigo, Thais M. Sobjak, Andrey F. P. Santos, Silvia Romao, Ana T. B. Guimaraes

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Anthropogenic activities promote changes in the community’s structures and decrease the species abundance of amphibians. Biological communities of fluvial systems are assemblies of organisms that have adapted to regional conditions, including the physical environment and food resources, and are further refined through interactions with other species. The aim of this study was to assess neurotoxic alterations and in the antioxidant system on tadpoles of Lithobates catesbeianus exposed to waters from Cascavel River, in the south of Brazil. A total of 420 L of water was collected from the Cascavel River, 140 L from each of the three different locations: Site 1 – headwater; Site 2 – stretch of the stream that runs through an urbanized area; Site 3 – a stretch from the rural area. Twelve tadpoles were acclimated in each aquarium (100 L of water) for seven days. The water from each aquarium was replaced with the ones sampled from the river, except the one from the control aquarium. After seven days, a portion of the liver was removed and conditioned for ChE, SOD, CAT and LPO analysis; other part of the tissue was conditioned for histological analysis. The statistical analysis performed was one-way ANOVA, followed by post-hoc Tukey-HSD test, and the multivariate principal components analysis. It was not observed any neurotoxic effect, but a slight increase in SOD activity and elevation of CAT activity in both urban and rural environment. A decrease in LPO reaction was detected, mainly among the tadpoles exposed to the waters from the rural area. The results of the present study demonstrate the alteration of the antioxidant system, as well as liver histopathologies in tadpoles exposed mainly to waters collected in urban and rural environments. These alterations may cause the reduction in the velocity of the metamorphosis process from the tadpoles. Further, were observed histological alterations, highlighting necrotic areas mainly among the animals exposed to urban waters. Those damages can lead to metabolic dysfunction, interfering with survival capacity, diminishing not only individual fitness but for the whole population. In the interpretation synthesis of all biomarkers, the cellular damage gradient is perceptible, characterized by the variables related to the antioxidant system, due to the flow direction of the stream. This result is indicative that along the course of the creek occurs dumping of organic material, which promoted an acute response upon tadpoles of L. catesbeianus. and it was also observed the difference in tissue damage between the experimental groups and the control group, the latter presenting histological alterations, but to a lesser degree than the animals exposed to the waters of the Cascavel river. These damages, caused by reactive oxygen species possibly resulting from the contamination by organic compounds, can lead the animals to a series of metabolic dysfunctions, interfering with its metamorphosis capacity. Interruption of metamorphosis may affect survival, which may impair its growth, development and reproduction, diminishing not only the fitness of each individual but in a long-term, to the entire population.

Keywords: American bullfrog, histopathology, oxidative stress, urban creeks pollution

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227 A Nutrient Formulation Affects Brain Myelination in Infants: An Investigative Randomized Controlled Trial

Authors: N. Schneider, M. Bruchhage, M. Hartweg, G. Mutungi, J. O Regan, S. Deoni

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Observational neuroimaging studies suggest differences between breast-fed and formula-fed infants in developmental myelination, a key brain process for learning and cognitive development. However, the possible effects of a nutrient formulation on myelin development in healthy term infants in an intervention study have not been investigated. Objective was, therefore, to investigate the efficacy of a nutrient formulation with higher levels of myelin-relevant nutrients as compared to a control formulation with lower levels of the same nutrients on brain myelination and cognitive development in the first 6 months of life. The study is an ongoing randomized, controlled, double-blind, two-center, parallel-group clinical trial with a nonrandomized, non-blinded arm of exclusively breastfed infants. The current findings result from a staged statistical analysis at 6 months; the recruitment and intervention period has been completed for all participants. Follow-up visits at 12, 18 and 24 months are still ongoing. N= 81 enrolled full term, neurotypical infants of both sexes were randomized into either the investigational (N= 42) or the control group (N= 39), and N= 108 children in the breast-fed arm served as a natural reference group. The effect of a blend of docosahexaenoic acid, arachidonic acid, iron, vitamin B12, folic acid as well as sphingomyelin from a uniquely proceed whey protein concentrate enriched in alpha-lactalbumin and phospholipids in an infant nutrition product matrix was investigated. The main outcomes for the staged statistical analyses at 6 months included brain myelination measures derived from MRI. Additional outcomes were brain volume, cognitive development and safety. The full analyses set at 6 months comprised N= 66 infants. Higher levels of myelin-relevant nutrients compared to lower levels resulted in significant differences in myelin structure, volume, and rate of myelination as early as 3 and 6 months of life. The cross-sectional change of means between groups for whole-brain myelin volume was 8.4% for investigational versus control formulation (3.5% versus the breastfeeding reference) group at 3 months and increased to 36.4% for investigational versus control formulation (14.1% versus breastfeeding reference) at 6 months. No statistically significant differences were detected for early cognition scores. Safety findings were largely similar across groups. This is the first pediatric nutritional neuroimaging study demonstrating the efficacy of a myelin nutrient blend on developmental myelination in well-nourished term infants. Myelination is a critical process in learning and development. The effects were demonstrated across the brain, particularly in temporal and parietal regions, known to be functionally involved in sensory, motor and language skills. These first results add to the field of nutritional neuroscience by demonstrating early life nutrition benefits for brain architecture which may be foundational for later cognitive and behavioral outcomes. ClinicalTrials.gov Identifier: NCT03111927 (Infant Nutrition and Brain Development - Full-Text View - ClinicalTrials.gov).

Keywords: brain development, infant nutrition, MRI, myelination

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226 Malaria Menace in Pregnancy; Hard to Ignore

Authors: Nautiyal Ruchira, Nautiyal Hemant, Chaudhury Devnanda, Bhargava Surbhi, Chauhan Nidhi

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Introduction: South East Asian region contributes 2.5 million cases of malaria each year to the global burden of 300 to 500 million of which 76% is reported from India. Government of India launched a national program almost half a century ago, still malaria remains a major public health challenge. Pregnant women are more susceptible to severe malaria and its fetomaternal complications. Inadequate surveillance and under-reporting underestimates the problem. Aim: Present study aimed to analyze the clinical course and pattern of malaria during pregnancy and to study the feto-maternal outcome. Methodology: This is a prospective observational study carried out at Himalayan Institute of Medical Sciences – a tertiary care center in the sub-Himalayan state of Uttarakhand, Northern India. All the pregnant women with malaria and its complications were recruited in the study during 2009 to 2014 which included referred cases from the state of western Uttar Pradesh. A thorough history and clinical examination were carried out to assess maternal and fetal condition. Relevant investigations including haemogram, platelet count, LFT, RFT, and USG was done. Blood slides and rapid diagnostic tests were done to diagnose the type of malaria.The primary outcomes measured were the type of malaria infection, maternal complications associated with malaria, outcome of pregnancy and effect on the fetus. Results: 67 antenatal cases with malaria infection were studied. 71% patients were diagnosed with plasmodium vivax infection, 25% cases were plasmodium falciparum positive and in 3% cases mixed infection was found. 38(56%) patients were primigravida and 29(43%) were multiparous. Most of the patients had already received some treatment from their local doctors and presented with severe malaria with the complications. Thrombocytopenia was the commonest manifestation seen in 35(52%) patients, jaundice in 28%, severe anemia in 18%, and severe oligohydramnios in 10% and renal failure in 6% cases. Regarding pregnancy outcome there were 44 % preterm deliveries, 22% had IUFD and abortions in 6% cases.20% of newborn were low birth weight and 6% were IUGR. There was only one maternal death which occurred due to ARDS in falciparum malaria. Although Plasmodium vivax was the main parasite considering the severity of clinical presentation, all the patients received intensive care. As most of the patients had received chloroquine therapy hence they were treated with IV artesunate followed by oral artemesinin combination therapy. Other therapies in the form of packed RBC’s and platelet transfusions, dialysis and ventilator support were provided when required. Conclusion: Even in areas with annual parasite index (API) less than 2 like ours, malaria in pregnancy could be an alarming problem. Vivax malaria cannot be considered benign in pregnancy because of high incidence of morbidity. Prompt diagnosis and aggressive treatment can reduce morbidity and mortality significantly. Increased community level research, integrating ANC checkups with the distribution of insecticide-treated nets in areas of high endemicity, imparting education and awareness will strengthen the existing control strategies.

Keywords: severe malaria, pregnancy, plasmodium vivax, plasmodium falciparum

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225 Feasibility of Applying a Hydrodynamic Cavitation Generator as a Method for Intensification of Methane Fermentation Process of Virginia Fanpetals (Sida hermaphrodita) Biomass

Authors: Marcin Zieliński, Marcin Dębowski, Mirosław Krzemieniewski

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The anaerobic degradation of substrates is limited especially by the rate and effectiveness of the first (hydrolytic) stage of fermentation. This stage may be intensified through pre-treatment of substrate aimed at disintegration of the solid phase and destruction of substrate tissues and cells. The most frequently applied criterion of disintegration outcomes evaluation is the increase in biogas recovery owing to the possibility of its use for energetic purposes and, simultaneously, recovery of input energy consumed for the pre-treatment of substrate before fermentation. Hydrodynamic cavitation is one of the methods for organic substrate disintegration that has a high implementation potential. Cavitation is explained as the phenomenon of the formation of discontinuity cavities filled with vapor or gas in a liquid induced by pressure drop to the critical value. It is induced by a varying field of pressures. A void needs to occur in the flow in which the pressure first drops to the value close to the pressure of saturated vapor and then increases. The process of cavitation conducted under controlled conditions was found to significantly improve the effectiveness of anaerobic conversion of organic substrates having various characteristics. This phenomenon allows effective damage and disintegration of cellular and tissue structures. Disintegration of structures and release of organic compounds to the dissolved phase has a direct effect on the intensification of biogas production in the process of anaerobic fermentation, on reduced dry matter content in the post-fermentation sludge as well as a high degree of its hygienization and its increased susceptibility to dehydration. A device the efficiency of which was confirmed both in laboratory conditions and in systems operating in the technical scale is a hydrodynamic generator of cavitation. Cavitators, agitators and emulsifiers constructed and tested worldwide so far have been characterized by low efficiency and high energy demand. Many of them proved effective under laboratory conditions but failed under industrial ones. The only task successfully realized by these appliances and utilized on a wider scale is the heating of liquids. For this reason, their usability was limited to the function of heating installations. Design of the presented cavitation generator allows achieving satisfactory energy efficiency and enables its use under industrial conditions in depolymerization processes of biomass with various characteristics. Investigations conducted on the laboratory and industrial scale confirmed the effectiveness of applying cavitation in the process of biomass destruction. The use of the cavitation generator in laboratory studies for disintegration of sewage sludge allowed increasing biogas production by ca. 30% and shortening the treatment process by ca. 20 - 25%. The shortening of the technological process and increase of wastewater treatment plant effectiveness may delay investments aimed at increasing system output. The use of a mechanical cavitator and application of repeated cavitation process (4-6 times) enables significant acceleration of the biogassing process. In addition, mechanical cavitation accelerates increases in COD and VFA levels.

Keywords: hydrodynamic cavitation, pretreatment, biomass, methane fermentation, Virginia fanpetals

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224 Decreasing the Oxidative Stress in Autistic Children: A Randomized Double-Blind Controlled Study With Palm Dates Fruit

Authors: Ammal Mokhtar Metwally, Amal Elsaied, Ghada A. Abdel-Latef, Ebtissam M. Salah El-Din, Hanaa R. M. Attia

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The link between various diet therapies and autism is controversial and limited. Nutritional interventions aim to increase antioxidant levels suggesting a positive effect on the improvement of autism severity. In this study, the effectiveness of a 90-day Dates fruits consumption fruits (a non-pharmacological and risk-free option) on alleviating autism severity symptoms in individuals with ASD was investigated. The study examined also whether the baseline or improvements of some of the clinical and laboratory characteristics of the subjects affected their response to dates fruits intake on the severity of ASD symptoms. Methodology: This study involved a randomized controlled, double-blind 3-month dates fruits intake. 131 Egyptian children aged 3-12 years with confirmed ASD were enrolled in the study. cases were randomized in one of the three groups as follows; 1st regimen: Group I on 3 dates’ fruits/day (47 cases), 2nd regimen: Group II on 5 dates’ fruits/day (42 cases), and 3rd regimen: group III; nondates group (42 cases). ASD severity was assessed using both the Diagnostic and statistical manual of mental disorders, 5th ed. (DSM-V) criteria and the Childhood Autism Rating Scale (CARS) analysis. The following measures were assessed before and after the regimens: blood levels of three oxidative markers; Malondialdehyde (MDA), glutathione peroxidase (GPX1), and superoxide dismutase (SOD), nutritional, dietary assessment & anthropometric measurements Results: A significant reduction in the mean score of autism was detected based on CARS scores for those on dates’ regimens compared to those on non-dates (p < 0.01). Participants on 5 dates’ fruits/day for three months showed the highest improvement for autism severity based on both CARS and DSM5 compared to those in 3 dates’ fruits/day and non-dates groups. Responders to dates fruits intake as reflected on the Improvement of autism severity based on CARS diagnosis was detected among 78.7 % and 62.9 % based on CARS and DSM5 diagnosis, respectively. Responders had significant improvement in BMI z score and in the ratio levels of both MDA/SOD and MDA/GPX. Conclusion: The positive results of this study suggest that palm dates fruits could be recommended for children with ASD as adjuvant therapy on a daily regular basis to achieve consistent improvement of autism symptoms Objective: Investigate the effectiveness of a 90-day Dates fruits consumption fruits on alleviating autism severity symptoms in individuals with ASD and explore the clinical and laboratory characteristics of the subjects affected their response to dates fruits intake. Methodology: The study was a randomized controlled, double-blind for 3-month. 131 autistic Egyptian children aged 3-12 years were enrolled in one of the three groups; 1st: on 3 dates’ fruits/day (47 cases), 2nd: Group II on 5 dates’ fruits/day (42 cases), and 3rd: group III; nondates group (42 cases). Conclusion: The positive results of this study suggest that palm dates fruit (a non-pharmacological and risk-free option) could be recommended for children with ASD as adjuvant therapy on a daily regular basis to achieve consistent improvement of autism symptoms.

Keywords: autism spectrum disorders, palm dates fruits, CARS, DSM5, oxidative markers

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223 Oat Bran Associated with Nutritional Counseling in Treating Obesity and Other Risk Factors for Cardiovascular Disease

Authors: Simone Raimondi De Souza, Glaucia Maria Moraes De Oliveira, Ronir Raggio Luiz, Glorimar Rosa

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Introduction: Obesity is among the main risk factors for cardiovascular disease (CVD). Genesis is multifactorial, including genetic, hormonal and environmental factors disorders, among which inadequate feeding pattern, for which nutritional counseling strategies have proven effective. The consumption of beta-glucans (soluble fibers that reportedly promote satiety) present in oat bran can be an effective strategy for preventing and treating obesity. Other benefits have been observed with oat bran consumption, such as reduction of hypercholesterolemia and hyperglycemia, two other risk factors for CVD. Objectives: To analyze the effect of oat bran consumption associated with nutritional counseling in reducing body mass index (BMI), blood cholesterol, glucose profile, waist and neck circumference in obese individuals, and to evaluate the change in eating pattern. Methods: clinical trial, randomized, double-blind, placebo-controlled, lasting 90 days with adults of both genders, with BMI ≥30kg/m2. The study was approved by the Ethics in Research involving human beings in a public institute of cardiology, in Rio de Janeiro, Brazil. Individuals were invited to participate and accepted formally by signing the Terms of Consent. Participants were randomized into oat bran group (gOB) or placebo group (gPCB) and received, respectively: morning prepared consisting of 40g oat bran, 30g of skimmed milk powder and 1g sweetener sucralose; refined flour 40g rice, 30g of milk powder and 1g sweetener sucralose. The Ten Steps to Healthy Eating, of Brazilian Ministry of Health were used to support the nutritional counseling. Variables analyzed: gender; age; BMI, waist circumference (WC) neck circumference (NC); systolic blood pressure (SBP); diastolic blood pressure (DBP); food consumption, total cholesterol (TC), LDL-cholesterol (LDL-c), HDL-cholesterol (HDL-c), non-HDL cholesterol (nHDLc), triglycerides (TG), fasting glucose (FG), fasting insulin (FI) and HOMA-IR. Dietary intake was assessed by 24-hour dietary recall. The Diet Quality Index revised for the Brazilian population (IQD-R) assessed quality of feeding pattern. Statistical analyzes were performed using SPSS version 21, considering statistically significant p-value less than 0.05. Results: A total of 38 participants were included, age = 50 ± 7,6years, 63% women. 19 subjects were placed in gOB and 19 in gPCB. After intervention, statistically significant reductions were observed in the following parameters: in gOB: IQD-R, TC, LDL-c, nHDL-c, FI, SBP, DBP, BMI, WC, NC; in gPCB: IQD-R, LDL-c, SBP, DBP, BMI, WC, NC. No statistically significant differences were observed in the results between groups. Conclusion: Our results reinforce nutritional counseling as important strategy for prevention and treatment of obesity and suggest that inclusion of oat bran in daily diet can bring additional benefits controlling risk factors for CVD. More studies are needed to establish all benefits of oat bran to human health as well as the ideal daily dose for consumption.

Keywords: oat bran, cardiovascular disease, nutritional counseling, obesity

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222 An Aptasensor Based on Magnetic Relaxation Switch and Controlled Magnetic Separation for the Sensitive Detection of Pseudomonas aeruginosa

Authors: Fei Jia, Xingjian Bai, Xiaowei Zhang, Wenjie Yan, Ruitong Dai, Xingmin Li, Jozef Kokini

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Pseudomonas aeruginosa is a Gram-negative, aerobic, opportunistic human pathogen that is present in the soil, water, and food. This microbe has been recognized as a representative food-borne spoilage bacterium that can lead to many types of infections. Considering the casualties and property loss caused by P. aeruginosa, the development of a rapid and reliable technique for the detection of P. aeruginosa is crucial. The whole-cell aptasensor, an emerging biosensor using aptamer as a capture probe to bind to the whole cell, for food-borne pathogens detection has attracted much attention due to its convenience and high sensitivity. Here, a low-field magnetic resonance imaging (LF-MRI) aptasensor for the rapid detection of P. aeruginosa was developed. The basic detection principle of the magnetic relaxation switch (MRSw) nanosensor lies on the ‘T₂-shortening’ effect of magnetic nanoparticles in NMR measurements. Briefly speaking, the transverse relaxation time (T₂) of neighboring water protons get shortened when magnetic nanoparticles are clustered due to the cross-linking upon the recognition and binding of biological targets, or simply when the concentration of the magnetic nanoparticles increased. Such shortening is related to both the state change (aggregation or dissociation) and the concentration change of magnetic nanoparticles and can be detected using NMR relaxometry or MRI scanners. In this work, two different sizes of magnetic nanoparticles, which are 10 nm (MN₁₀) and 400 nm (MN₄₀₀) in diameter, were first immobilized with anti- P. aeruginosa aptamer through 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS) chemistry separately, to capture and enrich the P. aeruginosa cells. When incubating with the target, a ‘sandwich’ (MN₁₀-bacteria-MN₄₀₀) complex are formed driven by the bonding of MN400 with P. aeruginosa through aptamer recognition, as well as the conjugate aggregation of MN₁₀ on the surface of P. aeruginosa. Due to the different magnetic performance of the MN₁₀ and MN₄₀₀ in the magnetic field caused by their different saturation magnetization, the MN₁₀-bacteria-MN₄₀₀ complex, as well as the unreacted MN₄₀₀ in the solution, can be quickly removed by magnetic separation, and as a result, only unreacted MN₁₀ remain in the solution. The remaining MN₁₀, which are superparamagnetic and stable in low field magnetic field, work as a signal readout for T₂ measurement. Under the optimum condition, the LF-MRI platform provides both image analysis and quantitative detection of P. aeruginosa, with the detection limit as low as 100 cfu/mL. The feasibility and specificity of the aptasensor are demonstrated in detecting real food samples and validated by using plate counting methods. Only two steps and less than 2 hours needed for the detection procedure, this robust aptasensor can detect P. aeruginosa with a wide linear range from 3.1 ×10² cfu/mL to 3.1 ×10⁷ cfu/mL, which is superior to conventional plate counting method and other molecular biology testing assay. Moreover, the aptasensor has a potential to detect other bacteria or toxins by changing suitable aptamers. Considering the excellent accuracy, feasibility, and practicality, the whole-cell aptasensor provides a promising platform for a quick, direct and accurate determination of food-borne pathogens at cell-level.

Keywords: magnetic resonance imaging, meat spoilage, P. aeruginosa, transverse relaxation time

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221 Healing (in) Relationship: The Theory and Practice of Inner-Outer Peacebuilding in North-Western India

Authors: Josie Gardner

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The overall intention of this research is to reimagine peacebuilding in both in theory and practical application in light of the shortcomings and unsustainability of the current peacebuilding paradigm. These limitations are identified here as an overly rational-material approach to peacebuilding that neglects the inner dimension of peace for a fragmented rather than holistic model, and that espouses a conflict and violence-centric approach to peacebuilding. In counter, this presentation is purposed to investigate the dynamics of inner and outer peace as a holistic, complex system towards ‘inner-outer’ peacebuilding. This paper draws from primary research in the protracted conflict context of north-western India (Jammu, Kashmir & Ladakh) as a case study. This presentation has two central aims. First, to introduce the process of inner (psycho-spiritual) peacebuilding, which has thus far been neglected by mainstream and orthodox literature. Second, to examine why inner peacebuilding is essential for realising sustainable peace on a broader scale as outer (socio-political) peace and to better understand how the inner and outer dynamics of peace relate and affect one another. To these ends, Josephine (the researcher/author/presenter) partnered with Yakjah Reconciliation and Development Network to implement a series of action-oriented workshops and retreats centred around healing, reconciliation, leadership, and personal development for the dual purpose of collaboratively generating data, theory, and insights, as well as providing the youth leaders with an experiential, transformative experience. The research team created and used a novel methodological approach called Mapping Ritual Ecologies, which draws from Participatory Action Research and Digital Ethnography to form a collaborative research model with a group of 20 youth co-researchers who are emerging youth peace leaders in Kashmir, Jammu, and Ladakh. This research found significant intra- and inter-personal shifts towards an experience of inner peace through inner peacebuilding activities. Moreover, this process of inner peacebuilding affected their families and communities through interpersonal healing and peace leadership in an inside-out process of change. These insights have generated rich insights and have supported emerging theories about the dynamics between inner and outer peace, power, justice, and collective healing. This presentation argues that the largely neglected dimension of inner (psycho-spiritual) peacebuilding is imperative for broader socio-political (outer) change. Changing structures of oppression, injustice, and violence—i.e. structures of separation—requires individual, interpersonal, and collective healing. While this presentation primarily examines and advocates for inside-out peacebuilding and social justice, it will also touch upon the effect of systems of separation on the inner condition and human experience. This research reimagines peacebuilding as a holistic inner-outer approach. This offers an alternative path forward those weaves together self-actualisation and social justice. While contextualised within north-western India with a small case study population, the findings speak also to other conflict contexts as well as our global peacebuilding and social justice milieu.

Keywords: holistic, inner peacebuilding, psycho-spiritual, systems youth

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220 Hygrothermal Interactions and Energy Consumption in Cold Climate Hospitals: Integrating Numerical Analysis and Case Studies to Investigate and Analyze the Impact of Air Leakage and Vapor Retarding

Authors: Amir E. Amirzadeh, Richard K. Strand

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Moisture-induced problems are a significant concern for building owners, architects, construction managers, and building engineers, as they can have substantial impacts on building enclosures' durability and performance. Computational analyses, such as hygrothermal and thermal analysis, can provide valuable information and demonstrate the expected relative performance of building enclosure systems but are not grounded in absolute certainty. This paper evaluates the hygrothermal performance of common enclosure systems in hospitals in cold climates. The study aims to investigate the impact of exterior wall systems on hospitals, focusing on factors such as durability, construction deficiencies, and energy performance. The study primarily examines the impact of air leakage and vapor retarding layers relative to energy consumption. While these factors have been studied in residential and commercial buildings, there is a lack of information on their impact on hospitals in a holistic context. The study integrates various research studies and professional experience in hospital building design to achieve its objective. The methodology involves surveying and observing exterior wall assemblies, reviewing common exterior wall assemblies and details used in hospital construction, performing simulations and numerical analyses of various variables, validating the model and mechanism using available data from industry and academia, visualizing the outcomes of the analysis, and developing a mechanism to demonstrate the relative performance of exterior wall systems for hospitals under specific conditions. The data sources include case studies from real-world projects and peer-reviewed articles, industry standards, and practices. This research intends to integrate and analyze the in-situ and as-designed performance and durability of building enclosure assemblies with numerical analysis. The study's primary objective is to provide a clear and precise roadmap to better visualize and comprehend the correlation between the durability and performance of common exterior wall systems used in the construction of hospitals and the energy consumption of these buildings under certain static and dynamic conditions. As the construction of new hospitals and renovation of existing ones have grown over the last few years, it is crucial to understand the effect of poor detailing or construction deficiencies on building enclosure systems' performance and durability in healthcare buildings. This study aims to assist stakeholders involved in hospital design, construction, and maintenance in selecting durable and high-performing wall systems. It highlights the importance of early design evaluation, regular quality control during the construction of hospitals, and understanding the potential impacts of improper and inconsistent maintenance and operation practices on occupants, owner, building enclosure systems, and Heating, Ventilation, and Air Conditioning (HVAC) systems, even if they are designed to meet the project requirements.

Keywords: hygrothermal analysis, building enclosure, hospitals, energy efficiency, optimization and visualization, uncertainty and decision making

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219 ARGO: An Open Designed Unmanned Surface Vehicle Mapping Autonomous Platform

Authors: Papakonstantinou Apostolos, Argyrios Moustakas, Panagiotis Zervos, Dimitrios Stefanakis, Manolis Tsapakis, Nektarios Spyridakis, Mary Paspaliari, Christos Kontos, Antonis Legakis, Sarantis Houzouris, Konstantinos Topouzelis

Abstract:

For years unmanned and remotely operated robots have been used as tools in industry research and education. The rapid development and miniaturization of sensors that can be attached to remotely operated vehicles in recent years allowed industry leaders and researchers to utilize them as an affordable means for data acquisition in air, land, and sea. Despite the recent developments in the ground and unmanned airborne vehicles, a small number of Unmanned Surface Vehicle (USV) platforms are targeted for mapping and monitoring environmental parameters for research and industry purposes. The ARGO project is developed an open-design USV equipped with multi-level control hardware architecture and state-of-the-art sensors and payloads for the autonomous monitoring of environmental parameters in large sea areas. The proposed USV is a catamaran-type USV controlled over a wireless radio link (5G) for long-range mapping capabilities and control for a ground-based control station. The ARGO USV has a propulsion control using 2x fully redundant electric trolling motors with active vector thrust for omnidirectional movement, navigation with opensource autopilot system with high accuracy GNSS device, and communication with the 2.4Ghz digital link able to provide 20km of Line of Sight (Los) range distance. The 3-meter dual hull design and composite structure offer well above 80kg of usable payload capacity. Furthermore, sun and friction energy harvesting methods provide clean energy to the propulsion system. The design is highly modular, where each component or payload can be replaced or modified according to the desired task (industrial or research). The system can be equipped with Multiparameter Sonde, measuring up to 20 water parameters simultaneously, such as conductivity, salinity, turbidity, dissolved oxygen, etc. Furthermore, a high-end multibeam echo sounder can be installed in a specific boat datum for shallow water high-resolution seabed mapping. The system is designed to operate in the Aegean Sea. The developed USV is planned to be utilized as a system for autonomous data acquisition, mapping, and monitoring bathymetry and various environmental parameters. ARGO USV can operate in small or large ports with high maneuverability and endurance to map large geographical extends at sea. The system presents state of the art solutions in the following areas i) the on-board/real-time data processing/analysis capabilities, ii) the energy-independent and environmentally friendly platform entirely made using the latest aeronautical and marine materials, iii) the integration of advanced technology sensors, all in one system (photogrammetric and radiometric footprint, as well as its connection with various environmental and inertial sensors) and iv) the information management application. The ARGO web-based application enables the system to depict the results of the data acquisition process in near real-time. All the recorded environmental variables and indices are presented, allowing users to remotely access all the raw and processed information using the implemented web-based GIS application.

Keywords: monitor marine environment, unmanned surface vehicle, mapping bythometry, sea environmental monitoring

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218 Characteristics of Plasma Synthetic Jet Actuator in Repetitive Working Mode

Authors: Haohua Zong, Marios Kotsonis

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Plasma synthetic jet actuator (PSJA) is a new concept of zero net mass flow actuator which utilizes pulsed arc/spark discharge to rapidly pressurize gas in a small cavity under constant-volume conditions. The unique combination of high exit jet velocity (>400 m/s) and high actuation frequency (>5 kHz) provides a promising solution for high-speed high-Reynolds-number flow control. This paper focuses on the performance of PSJA in repetitive working mode which is more relevant to future flow control applications. A two-electrodes PSJA (cavity volume: 424 mm3, orifice diameter: 2 mm) together with a capacitive discharge circuit (discharge energy: 50 mJ-110 mJ) is designed to enable repetitive operation. Time-Resolved Particle Imaging Velocimetry (TR-PIV) system working at 10 kHz is exploited to investigate the influence of discharge frequency on performance of PSJA. In total, seven cases are tested, covering a wide range of discharge frequencies (20 Hz-560 Hz). The pertinent flow features (shock wave, vortex ring and jet) remain the same for single shot mode and repetitive working mode. Shock wave is issued prior to jet eruption. Two distinct vortex rings are formed in one cycle. The first one is produced by the starting jet whereas the second one is related with the shock wave reflection in cavity. A sudden pressure rise is induced at the throat inlet by the reflection of primary shock wave, promoting the shedding of second vortex ring. In one cycle, jet exit velocity first increases sharply, then decreases almost linearly. Afterwards, an alternate occurrence of multiple jet stages and refresh stages is observed. By monitoring the dynamic evolution of exit velocity in one cycle, some integral performance parameters of PSJA can be deduced. As frequency increases, the jet intensity in steady phase decreases monotonically. In the investigated frequency range, jet duration time drops from 250 µs to 210 µs and peak jet velocity decreases from 53 m/s to approximately 39 m/s. The jet impulse and the expelled gas mass (0.69 µN∙s and 0.027 mg at 20 Hz) decline by 48% and 40%, respectively. However, the electro-mechanical efficiency of PSJA defined by the ratio of jet mechanical energy to capacitor energy doesn’t show significant difference (o(0.01%)). Fourier transformation of the temporal exit velocity signal indicates two dominant frequencies. One corresponds to the discharge frequency, while the other accounts for the alternation frequency of jet stage and refresh stage in one cycle. The alternation period (300 µs approximately) is independent of discharge frequency, and possibly determined intrinsically by the actuator geometry. A simple analytical model is established to interpret the alternation of jet stage and refresh stage. Results show that the dynamic response of exit velocity to a small-scale disturbance (jump in cavity pressure) can be treated as a second-order under-damping system. Oscillation frequency of the exit velocity, namely alternation frequency, is positively proportional to exit area, but inversely proportional to cavity volume and throat length. Theoretical value of alternation period (305 µs) agrees well with the experimental value.

Keywords: plasma, synthetic jet, actuator, frequency effect

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217 A Multi-Scale Approach to Space Use: Habitat Disturbance Alters Behavior, Movement and Energy Budgets in Sloths (Bradypus variegatus)

Authors: Heather E. Ewart, Keith Jensen, Rebecca N. Cliffe

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Fragmentation and changes in the structural composition of tropical forests – as a result of intensifying anthropogenic disturbance – are increasing pressures on local biodiversity. Species with low dispersal abilities have some of the highest extinction risks in response to environmental change, as even small-scale environmental variation can substantially impact their space use and energetic balance. Understanding the implications of forest disturbance is therefore essential, ultimately allowing for more effective and targeted conservation initiatives. Here, the impact of different levels of forest disturbance on the space use, energetics, movement and behavior of 18 brown-throated sloths (Bradypus variegatus) were assessed in the South Caribbean of Costa Rica. A multi-scale framework was used to measure forest disturbance, including large-scale (landscape-level classifications) and fine-scale (within and surrounding individual home ranges) forest composition. Three landscape-level classifications were identified: primary forests (undisturbed), secondary forests (some disturbance, regenerating) and urban forests (high levels of disturbance and fragmentation). Finer-scale forest composition was determined using measurements of habitat structure and quality within and surrounding individual home ranges for each sloth (home range estimates were calculated using autocorrelated kernel density estimation [AKDE]). Measurements of forest quality included tree connectivity, density, diameter and height, species richness, and percentage of canopy cover. To determine space use, energetics, movement and behavior, six sloths in urban forests, seven sloths in secondary forests and five sloths in primary forests were tracked using a combination of Very High Frequency (VHF) radio transmitters and Global Positioning System (GPS) technology over an average period of 120 days. All sloths were also fitted with micro data-loggers (containing tri-axial accelerometers and pressure loggers) for an average of 30 days to allow for behavior-specific movement analyses (data analysis ongoing for data-loggers and primary forest sloths). Data-loggers included determination of activity budgets, circadian rhythms of activity and energy expenditure (using the vector of the dynamic body acceleration [VeDBA] as a proxy). Analyses to date indicate that home range size significantly increased with the level of forest disturbance. Female sloths inhabiting secondary forests averaged 0.67-hectare home ranges, while female sloths inhabiting urban forests averaged 1.93-hectare home ranges (estimates are represented by median values to account for the individual variation in home range size in sloths). Likewise, home range estimates for male sloths were 2.35 hectares in secondary forests and 4.83 in urban forests. Sloths in urban forests also used nearly double (median = 22.5) the number of trees as sloths in the secondary forest (median = 12). These preliminary data indicate that forest disturbance likely heightens the energetic requirements of sloths, a species already critically limited by low dispersal ability and rates of energy acquisition. Energetic and behavioral analyses from the data-loggers will be considered in the context of fine-scale forest composition measurements (i.e., habitat quality and structure) and are expected to reflect the observed home range and movement constraints. The implications of these results are far-reaching, presenting an opportunity to define a critical index of habitat connectivity for low dispersal species such as sloths.

Keywords: biodiversity conservation, forest disturbance, movement ecology, sloths

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216 Pregnancy Outcomes in Patients With Inflammatory Bowel Disease: Retrospective Data From a Greek National Registry

Authors: Evgenia Papathanasiou, Georgios Kokkotis, Georgios Axiaris, Theodoros Argyropoulos, Nikos Viazis, Olga Giouleme, Konstantinos Gkoumas, Αnthia Gatopoulou, Αggelos Theodoulou, Georgios Theocharis, Αngeliki Theodoropoulou, Μaria Κalogirou, Pantelis Karatzas, Κonstantinos Κatsanos, Theodora Kafetzi, Κonstantinos Κarmiris, Αnastasia Κourikou, Ιoannis E Κoutroubakis, Christos Liatsos, Gerassimos J. Mantzaris, Νicoletta Μathou, Georgia Bellou, George Michalopoulos Αikaterini Μantaka, Penelope Nikolaou, Μichael Oikonomou, Dimitrios Polymeros, George Papatheodoridis, Εvdoxia Stergiou, Κonstantinos Soufleris, Εpameinondas Skouloudis, Μaria Tzouvala, Georgia Tsiolakidou, Εftychia Tsironi, Styliani Tsafaraki, Kalliopi Foteinogiannopoulou, Konstantina Chalakatevaki, Αngeliki Christidou, Dimitrios K. Christodoulou, Giorgos Bamias, Spyridon Michopoulos, Εvanthia Zampeli

Abstract:

Background: Inflammatory bowel disease (IBD) commonly affects female patients of reproductive age, making the interaction between fertility, pregnancy and IBD an important issue in disease management. The effect of disease activity on the outcome of pregnancy and its impact on neonatal growth is a field of intense research. Close follow-up of pregnant IBD patients by a multidisciplinary team improves maternal and neonatal outcomes. Aim – Methods: Α national retrospective study of pregnancies in women with IBD between 2010-2020 was carried out in 22 IBD reference centers in Greece. Patient characteristics such as disease profile, type of treatment, and disease activity during gestation were analyzed in correlation to the method of delivery, pregnancy outcomes, as well as breastfeeding and offspring health. Results: Two-hundred and twenty-three pregnancies in 175 IBD patients were registered in the study. 122 with Crohn’s disease (CD). Median age during diagnosis was 25.6 years (12-44), with median disease duration of 7.4 years (0-23). One-hundred and twenty-nine patients (58%) were recorded during their first pregnancy. Early pregnancy termination was reported by 48 patients (22%). Pregnancy as a result of in vitro fertilization (IVF) occurred in 15 cases (6.7%). At the beginning of gestation, 165 patients (74%) were under treatment: 48 with anti-TNF agents (29%), 43 with azathioprine (26%), 101 with 5-aminosalicylic acid formulations (61%) and 12 with steroids (7%). We recorded 49 cases of IBD flares (22%) during pregnancy. Two-thirds of them (n=30) were in remission at the onset of the pregnancy. Almost half of them (n=22) required corticosteroid treatment. Patients with ulcerative colitis (UC) were in greater risk of disease flare during pregnancy (p<0.001). All but 3 pregnancies (99.1%) resulted in uncomplicated delivery. In 147 cases (67.1%), cesarean delivery was performed. Two late fetal deaths (0.9%) were reported, both in patients with continuously active disease since the beginning of pregnancy. After delivery, 75 patients (34%) presented with a disease flare, which was associated with active disease at the beginning of pregnancy (p <0.001). Conclusion: The majority of female, Greek IBD patients, had a favorable pregnancy outcome. Active inflammation during gestation and UC diagnosis were associated with a negative impact on pregnancy outcomes. The results of this study are in favor of the continuation of IBD treatment during pregnancy.

Keywords: pregnancy, ulcerative colitis, Crohn disease, flare

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215 Plasma Collagen XVIII in Response to Intensive Aerobic Running and Aqueous Extraction of Black Crataegus Elbursensis in Male Rats

Authors: A. Abdi, A. Abbasi Daloee, A. Barari

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Aim: The adaptations that occur in human body after doing exercises training are a factor to help healthy people stay away from certain diseases. One of the main adaptations is a change in blood circulation, especially in vessels. The increase of capillary density is dependent on the balance between angiogenic and angiostatic factors. Most studies show that the changes made to angiogenic developmental factors resulted from physical exercises indicate the low level of stimulators compared with inhibitors. It is believed that the plasma level of VEGF-A, the important angiogenic factor, is reduced after physical exercise. Findings indicate that the extract of crataegus plant reduces the platelet-derived growth factor receptor (PDGFR) autophosphorylation in human's fibroblast. More importantly, crataegus (1 to 100 mg in liter) clearly leads to the inhibition of PDGFR autophosphorylation in vascular smooth muscle cells (VSMCs). Angiogenesis is a process that can be classified into physiological and pathophysiological forms. collagen XVIII is a part of extracellular protein and heparan sulfate proteoglycans in vascular epithelial and endothelial basement membrane cause the release of endostatin from noncollagenous collagen XVIII. Endostatin inhibits the growth of endothelial cells, inhibits angiogenesis, weakens different types of cancer, and the growth of tumors. The purpose of the current study was to investigate the effect of intensive aerobic running with or without aqueous extraction of black Crataegus elbursensis on Collagen XVIII in male rats. Design: Thirty-two Wistar male rats (4-6 weeks old, 125-135 gr weight) were acquired from the Pasteur's Institute (Amol, Mazandaran), and randomly assigned into control (n = 16) and training (n = 16) groups. Rats were further divided into saline-control (SC) (n=8), saline-training (ST) (n=8), crataegus pentaegyna extraction -control (CPEC) (n=8), and crataegus pentaegyna extraction - training (CPET) (n=8). The control (SC and CPEC) groups remained sedentary; whereas the training groups underwent a high running exercise program. plasma were excised and immediately frozen in liquid nitrogen. Statistical analysis was performed using a one way analysis of variance and Tukey test. Significance was accepted at P = 0.05. Results: The results show that aerobic exercise group had the highest concentration collagen XVIII compared to other groups and then respectively black crataegus, training-crataegus and control groups. Conclusion: In general, researchers in this study concluded that the increase of collagen XVIII (albeit insignificant) as a result of physical activity and consumption of black crataegus extract could possibly serve as a regional inhibitor of angiogenesis and another evidence for the anti-cancer effects of physical activities. Since the research has not managed in this study to measure the amount of plasma endostatin, it is suggested that both indices are measured with important angiogenic factors so that we can have a more accurate interpretation of changes to angiogenic and angiostatic factors resulted from physical exercises.

Keywords: aerobic running, Crataegus elbursensis, Collagen XVIII

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214 Breast Cancer Therapy-Related Cardiac Dysfunction Identifying in Kazakhstan: Preliminary Findings of the Cohort Study

Authors: Saule Balmagambetova, Zhenisgul Tlegenova, Saule Madinova

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Cardiotoxicity associated with anticancer treatment, now defined as cancer therapy-related cardiac dysfunction (CTRCD), accompanies cancer patients and negatively impacts their survivorship. Currently, a cardio-oncological service is being created in Kazakhstan based on the provisions of the European Society of Cardio-oncology (ESC) Guidelines. In the frames of a pilot project, a cohort study on CTRCD conditions was initiated at the Aktobe Cancer center. One hundred twenty-eight newly diagnosed breast cancer patients started on doxorubicin and/or trastuzumab were recruited. Echocardiography with global longitudinal strain (GLS) assessment, biomarkers panel (cardiac troponin (cTnI), brain natriuretic peptide (BNP), myeloperoxidase (MPO), galectin-3 (Gal-3), D-dimers, C-reactive protein (CRP)), and other tests were performed at baseline and every three months. Patients were stratified by the cardiovascular risks according to the ESC recommendations and allocated into the risk groups during the pre-treatment visit. Of them, 10 (7.8%) patients were assigned to the high-risk group, 48 (37.5%) to the medium-risk group, and 70 (54.7%) to the low-risk group, respectively. High-risk patients have been receiving their cardioprotective treatment from the outset. Patients were also divided by treatment - in the anthracycline-based 83 (64.8%), in trastuzumab- only 13 (10.2%), and in the mixed anthracycline/trastuzumab group 32 individuals (25%), respectively. Mild symptomatic CTRCD was revealed and treated in 2 (1.6%) participants, and a mild asymptomatic variant in 26 (20.5%). Mild asymptomatic conditions are defined as left ventricular ejection fraction (LVEF) ≥50% and further relative reduction in GLS by >15% from baseline and/or a further rise in cardiac biomarkers. The listed biomarkers were assessed longitudinally in repeated-measures linear regression models during 12 months of observation. The associations between changes in biomarkers and CTRCD and between changes in biomarkers and LVEF were evaluated. Analysis by risk groups revealed statistically significant differences in baseline LVEF scores (p 0.001), BNP (p 0.0075), and Gal-3 (p 0.0073). Treatment groups found no statistically significant differences at baseline. After 12 months of follow-up, only LVEF values showed a statistically significant difference by risk groups (p 0.0011). When assessing the temporal changes in the studied parameters for all treatment groups, there were statistically significant changes from visit to visit for LVEF (p 0.003); GLS (p 0.0001); BNP (p<0.00001); MPO (p<0.0001); and Gal-3 (p<0.0001). No moderate or strong correlations were found between the biomarkers values and LVEF, between biomarkers and GLS. Between the biomarkers themselves, a moderate, close to strong correlation was established between cTnI and D-dimer (r 0.65, p<0.05). The dose-dependent effect of anthracyclines has been confirmed: the summary dose has a moderate negative impact on GLS values: -r 0.31 for all treatment groups (p<0.05). The present study found myeloperoxidase as a promising biomarker of cardiac dysfunction in the mixed anthracycline/trastuzumab treatment group. The hazard of CTRCD increased by 24% (HR 1.21; 95% CI 1.01;1.73) per doubling in baseline MPO value (p 0.041). Increases in BNP were also associated with CTRCD (HR per doubling, 1.22; 95% CI 1.12;1.69). No cases of chemotherapy discontinuation due to cardiotoxic complications have been recorded. Further observations are needed to gain insight into the ability of biomarkers to predict CTRCD onset.

Keywords: breast cancer, chemotherapy, cardiotoxicity, Kazakhstan

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213 Benefits of High Power Impulse Magnetron Sputtering (HiPIMS) Method for Preparation of Transparent Indium Gallium Zinc Oxide (IGZO) Thin Films

Authors: Pavel Baroch, Jiri Rezek, Michal Prochazka, Tomas Kozak, Jiri Houska

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Transparent semiconducting amorphous IGZO films have attracted great attention due to their excellent electrical properties and possible utilization in thin film transistors or in photovoltaic applications as they show 20-50 times higher mobility than that of amorphous silicon. It is also known that the properties of IGZO films are highly sensitive to process parameters, especially to oxygen partial pressure. In this study we have focused on the comparison of properties of transparent semiconducting amorphous indium gallium zinc oxide (IGZO) thin films prepared by conventional sputtering methods and those prepared by high power impulse magnetron sputtering (HiPIMS) method. Furthermore we tried to optimize electrical and optical properties of the IGZO thin films and to investigate possibility to apply these coatings on thermally sensitive flexible substrates. We employed dc, pulsed dc, mid frequency sine wave and HiPIMS power supplies for magnetron deposition. Magnetrons were equipped with sintered ceramic InGaZnO targets. As oxygen vacancies are considered to be the main source of the carriers in IGZO films, it is expected that with the increase of oxygen partial pressure number of oxygen vacancies decreases which results in the increase of film resistivity. Therefore in all experiments we focused on the effect of oxygen partial pressure, discharge power and pulsed power mode on the electrical, optical and mechanical properties of IGZO thin films and also on the thermal load deposited to the substrate. As expected, we have observed a very fast transition between low- and high-resistivity films depending on oxygen partial pressure when deposition using conventional sputtering methods/power supplies have been utilized. Therefore we established and utilized HiPIMS sputtering system for enlargement of operation window for better control of IGZO thin film properties. It is shown that with this system we are able to effectively eliminate steep transition between low and high resistivity films exhibited by DC mode of sputtering and the electrical resistivity can be effectively controlled in the wide resistivity range of 10-² to 10⁵ Ω.cm. The highest mobility of charge carriers (up to 50 cm2/V.s) was obtained at very low oxygen partial pressures. Utilization of HiPIMS also led to significant decrease in thermal load deposited to the substrate which is beneficial for deposition on the thermally sensitive and flexible polymer substrates. Deposition rate as a function of discharge power and oxygen partial pressure was also systematically investigated and the results from optical, electrical and structure analysis will be discussed in detail. Most important result which we have obtained demonstrates almost linear control of IGZO thin films resistivity with increasing of oxygen partial pressure utilizing HiPIMS mode of sputtering and highly transparent films with low resistivity were prepared already at low pO2. It was also found that utilization of HiPIMS technique resulted in significant improvement of surface smoothness in reactive mode of sputtering (with increasing of oxygen partial pressure).

Keywords: charge carrier mobility, HiPIMS, IGZO, resistivity

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212 PARP1 Links Transcription of a Subset of RBL2-Dependent Genes with Cell Cycle Progression

Authors: Ewelina Wisnik, Zsolt Regdon, Kinga Chmielewska, Laszlo Virag, Agnieszka Robaszkiewicz

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Apart from protecting genome, PARP1 has been documented to regulate many intracellular processes inter alia gene transcription by physically interacting with chromatin bound proteins and by their ADP-ribosylation. Our recent findings indicate that expression of PARP1 decreases during the differentiation of human CD34+ hematopoietic stem cells to monocytes as a consequence of differentiation-associated cell growth arrest and formation of E2F4-RBL2-HDAC1-SWI/SNF repressive complex at the promoter of this gene. Since the RBL2 complexes repress genes in a E2F-dependent manner and are widespread in the genome in G0 arrested cells, we asked (a) if RBL2 directly contributes to defining monocyte phenotype and function by targeting gene promoters and (b) if RBL2 controls gene transcription indirectly by repressing PARP1. For identification of genes controlled by RBL2 and/or PARP1,we used primer libraries for surface receptors and TLR signaling mediators, genes were silenced by siRNA or shRNA, analysis of gene promoter occupation by selected proteins was carried out by ChIP-qPCR, while statistical analysis in GraphPad Prism 5 and STATISTICA, ChIP-Seq data were analysed in Galaxy 2.5.0.0. On the list of 28 genes regulated by RBL2, we identified only four solely repressed by RBL2-E2F4-HDAC1-BRM complex. Surprisingly, 24 out of 28 emerged genes controlled by RBL2 were co-regulated by PARP1 in six different manners. In one mode of RBL2/PARP1 co-operation, represented by MAP2K6 and MAPK3, PARP1 was found to associate with gene promoters upon RBL2 silencing, which was previously shown to restore PARP1 expression in monocytes. PARP1 effect on gene transcription was observed only in the presence of active EP300, which acetylated gene promoters and activated transcription. Further analysis revealed that PARP1 binding to MA2K6 and MAPK3 promoters enabled recruitment of EP300 in monocytes, while in proliferating cancer cell lines, which actively transcribe PARP1, this protein maintained EP300 at the promoters of MA2K6 and MAPK3. Genome-wide analysis revealed a similar distribution of PARP1 and EP300 around transcription start sites and the co-occupancy of some gene promoters by PARP1 and EP300 in cancer cells. Here, we described a new RBL2/PARP1/EP300 axis which controls gene transcription regardless of the cell type. In this model cell, cycle-dependent transcription of PARP1 regulates expression of some genes repressed by RBL2 upon cell cycle limitation. Thus, RBL2 may indirectly regulate transcription of some genes by controlling the expression of EP300-recruiting PARP1. Acknowledgement: This work was financed by Polish National Science Centre grants nr DEC-2013/11/D/NZ2/00033 and DEC-2015/19/N/NZ2/01735. L.V. is funded by the National Research, Development and Innovation Office grants GINOP-2.3.2-15-2016-00020 TUMORDNS, GINOP-2.3.2-15-2016-00048-STAYALIVE and OTKA K112336. AR is supported by Polish Ministry of Science and Higher Education 776/STYP/11/2016.

Keywords: retinoblastoma transcriptional co-repressor like 2 (RBL2), poly(ADP-ribose) polymerase 1 (PARP1), E1A binding protein p300 (EP300), monocytes

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211 Songwriting in the Postdigital Age: Using TikTok and Instagram as Online Informal Learning Technologies

Authors: Matthias Haenisch, Marc Godau, Julia Barreiro, Dominik Maxelon

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In times of ubiquitous digitalization and the increasing entanglement of humans and technologies in musical practices in the 21st century, it is to be asked, how popular musicians learn in the (post)digital Age. Against the backdrop of the increasing interest in transferring informal learning practices into formal settings of music education the interdisciplinary research association »MusCoDA – Musical Communities in the (Post)Digital Age« (University of Erfurt/University of Applied Sciences Clara Hoffbauer Potsdam, funded by the German Ministry of Education and Research, pursues the goal to derive an empirical model of collective songwriting practices from the study of informal lelearningf songwriters and bands that can be translated into pedagogical concepts for music education in schools. Drawing on concepts from Community of Musical Practice and Actor Network Theory, lelearnings considered not only as social practice and as participation in online and offline communities, but also as an effect of heterogeneous networks composed of human and non-human actors. Learning is not seen as an individual, cognitive process, but as the formation and transformation of actor networks, i.e., as a practice of assembling and mediating humans and technologies. Based on video stimulated recall interviews and videography of online and offline activities, songwriting practices are followed from the initial idea to different forms of performance and distribution. The data evaluation combines coding and mapping methods of Grounded Theory Methodology and Situational Analysis. This results in network maps in which both the temporality of creative practices and the material and spatial relations of human and technological actors are reconstructed. In addition, positional analyses document the power relations between the participants that structure the learning process of the field. In the area of online informal lelearninginitial key research findings reveal a transformation of the learning subject through the specific technological affordances of TikTok and Instagram and the accompanying changes in the learning practices of the corresponding online communities. Learning is explicitly shaped by the material agency of online tools and features and the social practices entangled with these technologies. Thus, any human online community member can be invited to directly intervene in creative decisions that contribute to the further compositional and structural development of songs. At the same time, participants can provide each other with intimate insights into songwriting processes in progress and have the opportunity to perform together with strangers and idols. Online Lelearnings characterized by an increase in social proximity, distribution of creative agency and informational exchange between participants. While it seems obvious that traditional notions not only of lelearningut also of the learning subject cannot be maintained, the question arises, how exactly the observed informal learning practices and the subject that emerges from the use of social media as online learning technologies can be transferred into contexts of formal learning

Keywords: informal learning, postdigitality, songwriting, actor-network theory, community of musical practice, social media, TikTok, Instagram, apps

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210 Health Risk Assessment from Potable Water Containing Tritium and Heavy Metals

Authors: Olga A. Momot, Boris I. Synzynys, Alla A. Oudalova

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Obninsk is situated in the Kaluga region 100 km southwest of Moscow on the left bank of the Protva River. Several enterprises utilizing nuclear energy are operating in the town. A special attention in the region where radiation-hazardous facilities are located has traditionally been paid to radioactive gas and aerosol releases into the atmosphere; liquid waste discharges into the Protva river and groundwater pollution. Municipal intakes involve 34 wells arranged 15 km apart in a sequence north-south along the foot of the left slope of the Protva river valley. Northern and southern water intakes are upstream and downstream of the town, respectively. They belong to river valley intakes with mixed feeding, i.e. precipitation infiltration is responsible for a smaller part of groundwater, and a greater amount is being formed by overflowing from Protva. Water intakes are maintained by the Protva river runoff, the volume of which depends on the precipitation fallen out and watershed area. Groundwater contamination with tritium was first detected in a sanitary-protective zone of the Institute of Physics and Power Engineering (SRC-IPPE) by Roshydromet researchers when realizing the “Program of radiological monitoring in the territory of nuclear industry enterprises”. A comprehensive survey of the SRC-IPPE’s industrial site and adjacent territories has revealed that research nuclear reactors and accelerators where tritium targets are applied as well as radioactive waste storages could be considered as potential sources of technogenic tritium. All the above sources are located within the sanitary controlled area of intakes. Tritium activity in water of springs and wells near the SRC-IPPE is about 17.4 – 3200 Bq/l. The observed values of tritium activity are below the intervention levels (7600 Bq/l for inorganic compounds and 3300 Bq/l for organically bound tritium). The risk has being assessed to estimate possible effect of considered tritium concentrations on human health. Data on tritium concentrations in pipe-line drinking water were used for calculations. The activity of 3H amounted to 10.6 Bq/l and corresponded to the risk of such water consumption of ~ 3·10-7 year-1. The risk value given in magnitude is close to the individual annual death risk for population living near a NPP – 1.6·10-8 year-1 and at the same time corresponds to the level of tolerable risk (10-6) and falls within “risk optimization”, i.e. in the sphere for planning the economically sound measures on exposure risk reduction. To estimate the chemical risk, physical and chemical analysis was made of waters from all springs and wells near the SRC-IPPE. Chemical risk from groundwater contamination was estimated according to the EPA US guidance. The risk of carcinogenic diseases at a drinking water consumption amounts to 5·10-5. According to the classification accepted the health risk in case of spring water consumption is inadmissible. The compared assessments of risk associated with tritium exposure, on the one hand, and the dangerous chemical (e.g. heavy metals) contamination of Obninsk drinking water, on the other hand, have confirmed that just these chemical pollutants are responsible for health risk.

Keywords: radiation-hazardous facilities, water intakes, tritium, heavy metal, health risk

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