Search results for: MICE tourism in Georgia
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1713

Search results for: MICE tourism in Georgia

693 Development of NO-Ergic Synaptic Transmission in Sympathetic Neurons of Mammals: Immunohistochemical Study

Authors: Konstantin Yu. Moiseev, Antonina F. Budnik, Andrey I. Emanuilov, Petr M. Masliukov

Abstract:

The vast majority of sympathetic ganglionic neurons are catecholaminergic. Some sympathetic neurons lack catecholamines and mostly use acetylcholine as their main neurotransmitter. Some cholinergic postganglionic neurons also express neuronal nitric oxide synthase (nNOS). Preganglionic sympathetic neurons are cholinergic and most of them are also nNOS-immunoreactive (IR). The purpose of this study was to gain further insight into the neuroplasticity of sympathetic neurons during postnatal ontogenesis by comparing the development of pre- and postganglionic neurons expressing nNOS in different mammals. nNOS was investigated by immunohistochemistry in the sympathetic superior cervical ganglion (SCG), stellate ganglion (SG), celiac ganglion (CG) and spinal cord from rats, mice and cats of different ages (newborn, 10-day-old, 20-day-old, 30-day-old, 2-month-old and 2-year-old). In rats and mice, nNOS-positive neurons were not found in sympathetic ganglia from birth onwards. In cats, non-catecholaminergic nNOS-IR sympathetic ganglionic neurons are present from the moment of birth. In all studied age groups, substantial populations of nNOS-IR cells (up to 8.3%) was found in the SG, with a much smaller population found in the SCG (<1%) and only few cells observed in the CG. The percentage of nNOS-IR neurons in the CG and SCG did not significantly change during development. The proportion of nNOS-IR neuron profiles in the SG increased in first 20 days of life from 2.3±0.15% to 8.3±0.56%. In the SG, percentages of nNOS-IR sympathetic neurons colocalizing vasoactive intestinal peptide increased in the first 20 days of life. Choline acetyltransferase (ChAT)-IR and calcitonin gene-related peptide-IR neurons were not observed in the sympathetic ganglia of newborn animals and did not appear until 10 days after birth. In the SG of newborn and 10-day-old kittens, the majority of NOS-IR neurons were calbindin (CB)-IR, whereas in the SCG and CG of cats of all age groups and in the SG of 30-day-old and older kittens, the vast majority of NOS-IR neurons lacked CB. In newborn mammals, the most of sympathetic preganglionic neurons in the nucleus intermediolateralis thoracolumbalis pars principalis (nucl.ILp) were nNOS-IR. The percentage of nNOS-IR neurons decreased and the same parameter of ChAT-IR neurons increased during the development. We conclude that the development of nNOS-IR preganglionic and ganglionic sympathetic neurons in different mammals has time and species differences.

Keywords: sympathetic neuron, nitric oxide synthase, immunohistochemistry, development

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692 A Review of the Environmental Impact of Physical Expansion of Shandiz City

Authors: Foruzan Taheri, Seyedeh Negar Hosseinian, Katayoon Alizadeh

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The small countryside city of Shandiz, with a population of about 13.297 is located 35 km to the west of the Mashhad metropolitan. Due to Shandiz’s natural beauty, suitable climate, and its close proximity to Mashhad which is the largest city in the eastern half of the country, many people own second houses in this area. In addition to this, Shandiz hosts millions of visitors annually. Its economic role, which is parallel and complementary to Mashhad, has caused population growth, the increase of activities, and physical expansion, all of which exceed the city’s capacity. The aim of this descriptive and analytical study was to evaluate the impact of city expansion on the environment and aid in preventing further harm to the natural environment of this perimeter. Data were collected from population and housing statistics during a different period of time-based on GIS. Results show that the existence of an integrated environmental management system in order to coordinate development projects and the expansion of tourism programs that meet environmental conditions are necessary and achieving sustainable development with quality of life in this area without considering environmental limitations and capabilities cannot be sustained.

Keywords: population growth, tourism, physical development, environmental impact, Shandiz City

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691 Autophagy Suppresses Bladder Tumor Formation in a Mouse Orthotopic Bladder Tumor Formation Model

Authors: Wan-Ting Kuo, Yi-Wen Liu, Hsiao-Sheng Liu

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Annual incidence of bladder cancer increases in the world and occurs frequently in the male. Most common type is transitional cell carcinoma (TCC) which is treated by transurethral resection followed by intravesical administration of agents. In clinical treatment of bladder cancer, chemotherapeutic drugs-induced apoptosis is always used in patients. However, cancers usually develop resistance to chemotherapeutic drugs and often lead to aggressive tumors with worse clinical outcomes. Approximate 70% TCC recurs and 30% recurrent tumors progress to high-grade invasive tumors, indicating that new therapeutic agents are urgently needed to improve the successful rate of overall treatment. Nonapoptotic program cell death may assist to overcome worse clinical outcomes. Autophagy which is one of the nonapoptotic pathways provides another option for bladder cancer patients. Autophagy is reported as a potent anticancer therapy in some cancers. First of all, we established a mouse orthotopic bladder tumor formation model in order to create a similar tumor microenvironment. IVIS system and micro-ultrasound were utilized to noninvasively monitor tumor formation. In addition, we carried out intravesical treatment in our animal model to be consistent with human clinical treatment. In our study, we carried out intravesical instillation of the autophagy inducer in mouse orthotopic bladder tumor to observe tumor formation by noninvasive IVIS system and micro-ultrasound. Our results showed that bladder tumor formation is suppressed by the autophagy inducer, and there are no significant side effects in the physiology of mice. Furthermore, the autophagy inducer upregulated autophagy in bladder tissues of the treated mice was confirmed by Western blot, immunohistochemistry, and immunofluorescence. In conclusion, we reveal that a novel autophagy inducer with low side effects suppresses bladder tumor formation in our mouse orthotopic bladder tumor model, and it provides another therapeutic approach in bladder cancer patients.

Keywords: bladder cancer, transitional cell carcinoma, orthotopic bladder tumor formation model, autophagy

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690 Evaluating the Economic Impact of Community Sports Facilities on Residents in Ghana

Authors: Samuel Richard Marcourt

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The economic impact of community sports facilities can be examined through various dimensions, such as job creation, tourism, local business development, and property values. The aim of the study is to evaluate the economic impacts of community sports facilities on residents who lived within 500m radii of 4 Astro Turf soccer facilities in Ghana. The results of the study were based on the responses from in-depth semi-structured interviews with 16 purposively selected participants aged between 25 and 55 years. Participants’ responses revealed that community sports facilities create direct and indirect benefits for residents. Further, the direct benefits include job creation and employment among residents in the locality. Again, the promotion of local entrepreneurship and small business development, as well promotion of tourism, were indirect benefits. Consequently, the study provides useful data for stakeholders, including The Ministry of Sports, Ghana Football Association (GFA), and Government and non-governmental organizations, to construct more community sports facilities to assist in reducing the level of unemployment in Ghanaian communities.

Keywords: economic impact, community sports facilities, Astro turf, residents

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689 Effect of Collection Technique of Blood on Clinical Pathology

Authors: Marwa Elkalla, E. Ali Abdelfadil, Ali. Mohamed. M. Sami, Ali M. Abdel-Monem

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To assess the impact of the blood collection technique on clinical pathology markers and to establish reference intervals, a study was performed using normal, healthy C57BL/6 mice. Both sexes were employed, and they were randomly assigned to different groups depending on the phlebotomy technique used. The blood was drawn in one of four ways: intracardiac (IC), caudal vena cava (VC), caudal vena cava (VC) plus a peritoneal collection of any extravasated blood, or retroorbital phlebotomy (RO). Several serum biochemistries, such as a liver function test, a complete blood count with differentials, and a platelet count, were analysed from the blood and serum samples analysed. Red blood cell count, haemoglobin (p >0.002), hematocrit, alkaline phosphatase, albumin, total protein, and creatinine were all significantly greater in female mice. Platelet counts, specific white blood cell numbers (total, neutrophil, lymphocyte, and eosinophil counts), globulin, amylase, and the BUN/creatinine ratio were all greater in males. The VC approach seemed marginally superior to the IC approach for the characteristics under consideration and was linked to the least variation among both sexes. Transaminase levels showed the greatest variation between study groups. The aspartate aminotransferase (AST) values were linked with decreased fluctuation for the VC approach, but the alanine aminotransferase (ALT) values were similar between the IC and VC groups. There was a lot of diversity and range in transaminase levels between the MC and RO groups. We found that the RO approach, the only one tested that allowed for repeated sample collection, yielded acceptable ALT readings. The findings show that the test results are significantly affected by the phlebotomy technique and that the VC or IC techniques provide the most reliable data. When organising a study and comparing data to reference ranges, the ranges supplied here by collection method and sex can be utilised to determine the best approach to data collection. The authors suggest establishing norms based on the procedures used by each individual researcher in his or her own lab.

Keywords: clinical, pathology, blood, effect

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688 Food Safety and Quality Assurance and Skills Development among Farmers in Georgia

Authors: Kakha Nadiardze, Nana Phirosmanashvili

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The goal of this paper is to present the problems of lack of information among farmers in food safety. Global food supply chains are becoming more and more diverse, making traceability systems much harder to implement across different food markets. In this abstract, we will present our work for analyzing the key developments in Georgian food market from regulatory controls to administrative procedures to traceability technologies. Food safety and quality assurance are most problematic issues in Georgia as food trade networks become more and more complex, food businesses are under more and more pressure to ensure that their products are safe and authentic. The theme follow-up principles from farm to table must be top-of-mind for all food manufacturers, farmers and retailers. Following the E. coli breakout last year, as well as more recent cases of food mislabeling, developments in food traceability systems is essential to food businesses if they are to present a credible brand image. Alongside this are the ever-developing technologies in food traceability networks, technologies that manufacturers and retailers need to be aware of if they are to keep up with food safety regulations and avoid recall. How to examine best practice in food management is the main question in order to protect company brand through safe and authenticated food. We are working with our farmers to work with our food safety experts and technology developers throughout the food supply chain. We provide time by time food analyses on heavy metals, pesticide residues and different pollutants. We are disseminating information among farmers how the latest food safety regulations will impact the methods to use to identify risks within their products.

Keywords: food safety, GMO, LMO, E. coli, quality

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687 Capability of a Single Antigen to Induce Both Protective and Disease Enhancing Antibody: An Obstacle in the Creation of Vaccines and Passive Immunotherapies

Authors: Parul Kulshreshtha, Subrata Sinha, Rakesh Bhatnagar

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This study was conducted by taking B. anthracis as a model pathogen. On infecting a host, B. anthracis secretes three proteins, namely, protective antigen (PA, 83kDa), edema factor (EF, 89 kDa) and lethal factor (LF, 90 kDa). These three proteins are the components of two anthrax toxins. PA binds to the cell surface receptors, namely, tumor endothelial marker (TEM) 8 and capillary morphogenesis protein (CMG) 2. TEM8 and CMG2 interact with LDL-receptor related protein (LRP) 6 for endocytosis of EF and LF. On entering the cell, EF acts as a calmodulin-dependent adenylate cyclase that causes a prolonged increase of cytosolic cyclic adenosine monophosphate (cAMP). LF is a metalloprotease that cleaves most isoforms of mitogen-activated protein kinase kinases (MAPKK/MEK) close to their N-terminus. By secreting these two toxins, B.anthracis ascertains death of the host. Once the systemic levels of the toxins rise, antibiotics alone cannot save the host. Therefore, toxin-specific inhibitors have to be developed. In this wake, monoclonal antibodies have been developed for the neutralization of toxic effects of anthrax toxins. We created hybridomas by using spleen of mice that were actively immunized with rLFn (recombinant N-terminal domain of lethal factor of B. anthracis) to obtain anti-toxin antibodies. Later on, separate group of mice were immunized with rLFn to obtain a polyclonal control for passive immunization studies of monoclonal antibodies. This led to the identification of one cohort of rLFn-immunized mice that harboured disease-enhancing polyclonal antibodies. At the same time, the monoclonal antibodies from all the hybridomas were being tested. Two hybridomas secreted monoclonal antibodies (H8 and H10) that were cross-reactive with EF (edema factor) and LF (lethal factor), while the other two hybridomas secreted LF-specific antibodies (H7 and H11). The protective efficacy of H7, H8, H10 and H11 was investigated. H7, H8 and H10 were found to be protective. H11 was found to have disease enhancing characteristics in-vitro and in mouse model of challenge with B. anthracis. In this study the disease enhancing character of H11 monoclonal antibody and anti-rLFn polyclonal sera was investigated. Combination of H11 with protective monoclonal antibodies (H8 and H10) reduced its disease enhancing nature both in-vitro and in-vivo. But combination of H11 with LETscFv (an scFv with VH and VL identical to H10 but lacking Fc region) could not abrogate the disease-enhancing character of H11 mAb. Therefore it was concluded that for suppression of disease enhancement, Fc portion was absolutely essential for interaction of H10 with H11. Our study indicates that the protective potential of an antibody depends equally on its idiotype/ antigen specificity and its isotype. A number of monoclonal and engineered antibodies are being explored as immunotherapeutics but it is absolutely essential to characterize each one for their individual and combined protective potential. Although new in the sphere of toxin-based diseases, it is extremely important to characterize the disease-enhancing nature of polyclonal as well as monoclonal antibodies. This is because several anti-viral therapeutics and vaccines have failed in the face of this phenomenon. The passive –immunotherapy thus needs to be well formulated to avoid any contraindications.

Keywords: immunotherapy, polyclonal, monoclonal, antibody-dependent disease enhancement

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686 Region Coastal Land Management and Tracking Changes in Ownership Status

Authors: Tayfun Cay, Fazil Nacar

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Energy investments have increased in North Mediterranean Ceyhan and Yumurtalık districts of Turkey in the last years because of the treaties which are signed between Turkey and other countries for petroleum and natural gas transmission. Authority of land use has passed to district and metropolitan municipalities from town municipalities because of changes in coast legislation and local management legislation. Also Ministry of Environment and Urban Planning and Ministry of Industry and Commerce have had a right to comment on planning unofficially. Public investments increase in area and related planning and expropriation services continue. On the other hand, a lot of private sectors invest in organised industrial sites and industrial areas and it causes a rapid change in ownership status. Also Ceyhan-yumurtalık region is the tourism centre of North Mediterranean. Tourism investments continue in this district. Especially construction sector gain speed and a lot of country sites and apartments are built. In these studies, changes in planning activities in management of different administrative organisations and changes in ownership status and changes in private properties will be presented.

Keywords: coast management, land management, land use, property, public interest

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685 Amifostine Analogue, Drde-30, Attenuates Radiation-Induced Lung Injury in Mice

Authors: Aastha Arora, Vikas Bhuria, Saurabh Singh, Uma Pathak, Shweta Mathur, Puja P. Hazari, Rajat Sandhir, Ravi Soni, Anant N. Bhatt, Bilikere S. Dwarakanath

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Radiotherapy is an effective curative and palliative option for patients with thoracic malignancies. However, lung injury, comprising of pneumonitis and fibrosis, remains a significant clin¬ical complication of thoracic radiation, thus making it a dose-limiting factor. Also, injury to the lung is often reported as part of multi-organ failure in victims of accidental radiation exposures. Radiation induced inflammatory response in the lung, characterized by leukocyte infiltration and vascular changes, is an important contributing factor for the injury. Therefore, countermeasure agents to attenuate radiation induced inflammatory response are considered as an important approach to prevent chronic lung damage. Although Amifostine, the widely used, FDA approved radio-protector, has been found to reduce the radiation induced pneumonitis during radiation therapy of non-small cell lung carcinoma, its application during mass and field exposure is limited due to associated toxicity and ineffectiveness with the oral administration. The amifostine analogue (DRDE-30) overcomes this limitation as it is orally effective in reducing the mortality of whole body irradiated mice. The current study was undertaken to investigate the potential of DRDE-30 to ameliorate radiation induced lung damage. DRDE-30 was administered intra-peritoneally, 30 minutes prior to 13.5 Gy thoracic (60Co-gamma) radiation in C57BL/6 mice. Broncheo- alveolar lavage fluid (BALF) and lung tissues were harvested at 12 and 24 weeks post irradiation for studying inflammatory and fibrotic markers. Lactate dehydrogenase (LDH) leakage, leukocyte count and protein content in BALF were used as parameters to evaluate lung vascular permeability. Inflammatory cell signaling (p38 phosphorylation) and anti-oxidant status (MnSOD and Catalase level) was assessed by Western blot, while X-ray CT scan, H & E staining and trichrome staining were done to study the lung architecture and collagen deposition. Irradiation of the lung increased the total protein content, LDH leakage and total leukocyte count in the BALF, reflecting endothelial barrier dysfunction. These disruptive effects were significantly abolished by DRDE-30, which appear to be linked to the DRDE-30 mediated abrogation of activation of the redox-sensitive pro- inflammatory signaling cascade, the MAPK pathway. Concurrent administration of DRDE-30 with radiation inhibited radiation-induced oxidative stress by strengthening the anti-oxidant defense system and abrogated p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and macrophage recruitment to the lungs. Histopathological examination (by H & E staining) of the lung showed radiation-induced inflammation of the lungs, characterized by cellular infiltration, interstitial oedema, alveolar wall thickening, perivascular fibrosis and obstruction of alveolar spaces, which were all reduced by pre-administration of DRDE-30. Structural analysis with X-ray CT indicated lung architecture (linked to the degree of opacity) comparable to un-irradiated mice that correlated well with the lung morphology and reduced collagen deposition. Reduction in the radiation-induced inflammation and fibrosis brought about by DRDE-30 resulted in a profound increase in animal survival (72 % in the combination vs 24% with radiation) observed at the end of 24 weeks following irradiation. These findings establish the potential of the Amifostine analogue, DRDE-30, in reducing radiation induced pulmonary injury by attenuating the inflammatory and fibrotic responses.

Keywords: amifostine, fibrosis, inflammation, lung injury radiation

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684 Stimulating Policy for Attracting Foreign Direct Investment in Georgia

Authors: G. Erkomaishvili, M. Kobalava, T. Lazariashvili, N. Damenia

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Current state of foreign direct investment (FDI) in Georgia is analyzed and evaluated in the paper, the existing legislative background for regulating investments and stimulating policies to attract investments are shown. It is noted that in developing countries encouragement of investment activity, support and implementation are of the most important tasks, implying a consistent investment policy, investor-friendly tax regime and the legal system, reducing administrative barriers and restrictions, fare competitive conditions and business development infrastructure. The work deals with the determining factor of FDIs and the main directions of stimulation, as well as prospective industries where new investments are needed. Contributing and hindering factors and stimulating measures are analyzed. As a result of the research, the direct and indirect factors attracting FDI have been identified. Facilitating factors to FDI inflow are as follows: simplicity of starting business, geopolitical location, low taxes, access to credit, ease of ownership registration, natural resources, low burden of regulations, low level of corruption and low crime rates. Hindering factors to FDI inflow are as follows: small market, lack of policy for attracting investments, low qualification of the workforce (despite the large number of unemployed people it is difficult to find workers with necessary special skills and qualifications), high interest rates, instability of national currency exchange rate, presence of conflict zones within the country and so forth.

Keywords: foreign direct investment, investor, investment attracting marketing policies, reinvestment

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683 Role of Autophagic Lysosome Reformation for Cell Viability in an in vitro Infection Model

Authors: Muhammad Awais Afzal, Lorena Tuchscherr De Hauschopp, Christian Hübner

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Introduction: Autophagy is an evolutionarily conserved lysosome-dependent degradation pathway, which can be induced by extrinsic and intrinsic stressors in living systems to adapt to fluctuating environmental conditions. In the context of inflammatory stress, autophagy contributes to the elimination of invading pathogens, the regulation of innate and adaptive immune mechanisms, and regulation of inflammasome activity as well as tissue damage repair. Lysosomes can be recycled from autolysosomes by the process of autophagic lysosome reformation (ALR), which depends on the presence of several proteins including Spatacsin. Thus ALR contributes to the replenishment of lysosomes that are available for fusion with autophagosomes in situations of increased autophagic turnover, e.g., during bacterial infections, inflammatory stress or sepsis. Objectives: We aimed to assess whether ALR plays a role for cell survival in an in-vitro bacterial infection model. Methods: Mouse embryonic fibroblasts (MEFs) were isolated from wild-type mice and Spatacsin (Spg11-/-) knockout mice. Wild-type MEFs and Spg11-/- MEFs were infected with Staphylococcus aureus (multiplication of infection (MOI) used was 10). After 8 and 16 hours of infection, cell viability was assessed on BD flow cytometer through propidium iodide intake. Bacterial intake by cells was also calculated by plating cell lysates on blood agar plates. Results: in-vitro infection of MEFs with Staphylococcus aureus showed a marked decrease of cell viability in ALR deficient Spatacsin knockout (Spg11-/-) MEFs after 16 hours of infection as compared to wild-type MEFs (n=3 independent experiments; p < 0.0001) although no difference was observed for bacterial intake by both genotypes. Conclusion: Suggesting that ALR is important for the defense of invading pathogens e.g. S. aureus, we observed a marked increase of cell death in an in-vitro infection model in cells with compromised ALR.

Keywords: autophagy, autophagic lysosome reformation, bacterial infections, Staphylococcus aureus

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682 Festival Gamification: Conceptualization and Scale Development

Authors: Liu Chyong-Ru, Wang Yao-Chin, Huang Wen-Shiung, Tang Wan-Ching

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Although gamification has been concerned and applied in the tourism industry, limited literature could be found in tourism academy. Therefore, to contribute knowledge in festival gamification, it becomes essential to start by establishing a Festival Gamification Scale (FGS). This study defines festival gamification as the extent of a festival to involve game elements and game mechanisms. Based on self-determination theory, this study developed an FGS. Through the multi-study method, in study one, five FGS dimensions were sorted through literature review, followed by twelve in-depth interviews. A total of 296 statements were extracted from interviews and were later narrowed down to 33 items under six dimensions. In study two, 226 survey responses were collected from a cycling festival for exploratory factor analysis, resulting in twenty items under five dimensions. In study three, 253 survey responses were obtained from a marathon festival for confirmatory factor analysis, resulting in the final sixteen items under five dimensions. Then, results of criterion-related validity confirmed the positive effects of these five dimensions on flow experience. In study four, for examining the model extension of the developed five-dimensional 16-item FGS, which includes dimensions of relatedness, mastery, competence, fun, and narratives, cross-validation analysis was performed using 219 survey responses from a religious festival. For the tourism academy, the FGS could further be applied in other sub-fields such as destinations, theme parks, cruise trips, or resorts. The FGS serves as a starting point for examining the mechanism of festival gamification in changing tourists’ attitudes and behaviors. Future studies could work on follow-up studies of FGS by testing outcomes of festival gamification or examining moderating effects of enhancing outcomes of festival gamification. On the other hand, although the FGS has been tested in cycling, marathon, and religious festivals, the research settings are all in Taiwan. Cultural differences of FGS is another further direction for contributing knowledge in festival gamification. This study also contributes to several valuable practical implications. First, this FGS could be utilized in tourist surveys for evaluating the extent of gamification of a festival. Based on the results of the performance assessment by FGS, festival management organizations and festival planners could learn the relative scores among dimensions of FGS, and plan for future improvement of gamifying the festival. Second, the FGS could be applied in positioning a gamified festival. Festival management organizations and festival planners could firstly consider the features and types of their festival, and then gamify their festival based on investing resources in key FGS dimensions.

Keywords: festival gamification, festival tourism, scale development, self-determination theory

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681 The Analgesic Effect of Electroacupuncture in a Murine Fibromyalgia Model

Authors: Bernice Jeanne Lottering, Yi-Wen Lin

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Introduction: Chronic pain has a definitive lack of objective parameters in the measurement and treatment efficacy of diseases such as Fibromyalgia (FM). Persistent widespread pain and generalized tenderness are the characteristic symptoms affecting a large majority of the global population, particularly females. This disease has indicated a refractory tendency to conventional treatment ventures, largely resultant from a lack of etiological and pathogenic understanding of the disease development. Emerging evidence indicates that the central nervous system (CNS) plays a critical role in the amplification of pain signals and the neurotransmitters associated therewith. Various stimuli have been found to activate the channels existent on nociceptor terminals, thereby actuating nociceptive impulses along the pain pathways. The transient receptor potential vanalloid 1 (TRPV1) channel functions as a molecular integrator for numerous sensory inputs, such as nociception, and was explored in the current study. Current intervention approaches face a multitude challenges, ranging from effective therapeutic interventions to the limitation of pathognomonic criteria resultant from incomplete understanding and partial evidence on the mechanisms of action of FM. It remains unclear whether electroacupuncture (EA) plays an integral role in the functioning of the TRPV1 pathway, and whether or not it can reduce the chronic pain induced by FM. Aims: The aim of this study was to explore the mechanisms underlying the activation and modulation of the TRPV1 channel pathway in a cold stress model of FM applied to a murine model. Furthermore, the effect of EA in the treatment of mechanical and thermal pain, as expressed in FM was also to be investigated. Methods: 18 C57BL/6 wild type and 6 TRPV1 knockout (KO) mice, aged 8-12 weeks, were exposed to an intermittent cold stress-induced fibromyalgia-like pain model, with or without EA treatment at ZusanLi ST36 (2Hz/20min) on day 3 to 5. Von Frey and Hargreaves behaviour tests were implemented in order to analyze the mechanical and thermal pain thresholds on day 0, 3 and 5 in control group (C), FM group (FM), FM mice with EA treated group (FM + EA) and FM in KO group. Results: An increase in mechanical and thermal hyperalgesia was observed in the FM, EA and KO groups when compared to the control group. This initial increase was reduced in the EA group, which directs focus at the treatment efficacy of EA in nociceptive sensitization, and the analgesic effect EA has attenuating FM associated pain. Discussion: An increase in the nociceptive sensitization was observed through higher withdrawal thresholds in the von Frey mechanical test and the Hargreaves thermal test. TRPV1 function in mice has been scientifically associated with these nociceptive conduits, and the increased behaviour test results suggest that TRPV1 upregulation is central to the FM induced hyperalgesia. This data was supported by the decrease in sensitivity observed in results of the TRPV1 KO group. Moreover, the treatment of EA showed a decrease in this FM induced nociceptive sensitization, suggesting TRPV1 upregulation and overexpression can be attenuated by EA at bilateral ST36. This evidence compellingly implies that the analgesic effect of EA is associated with TRPV1 downregulation.

Keywords: fibromyalgia, electroacupuncture, TRPV1, nociception

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680 Hepatoprotective Effect of Ethyl Acetate Fraction of Ficus carica L. Leaves against Carbon Tetrachloride-Induced Toxicity in vitro and in vivo

Authors: Syeda Hira, Muhammad Gulfraz

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Background: Liver diseases cause serious health issues. Plants contain active compounds that significantly help in the treatment of various diseases. Ficus carica is traditionally used for the treatment of liver diseases. The purpose of the present study was the isolation and identification of active components from F.carica leaves which are responsible for hepatoprotective activity. Methods: The study was designed to identify the most active hepatoprotective sub-fraction from ethyl acetate fraction of Ficus carica by in vitro study and evaluation of its in vivo hepatoprotective effect in animal models. Ethyl acetate fraction was subjected to column, and a total of eight sub-fractions were obtained. In vitro, the hepatoprotective effect of all sub-fractions was determined on HepG2 cell lines. Toxicity was induced by CCl₄ (Carbon tetrachloride), and silymarin was used as a positive control. On the basis of the results, the most active sub-fraction was subjected to LC-MS and FT-IR analysis for the identification of bioactive compounds. In vivo, the hepatoprotective effect was determined in mice. Toxicity was induced by CCl₄; at the end of the experiment, biochemical parameters such as ALT, AST, ALP, bilirubin, and total protein were estimated in serum. Histopathology of liver tissues was also done. Results: Sub-fraction FVI exhibited significant (P<0.05) hepatoprotective activity as compared to other sub-fractions, which was almost similar to the standard drug silymarin. Six known bioactive compounds were identified from this sub-fraction after LC-MS analysis. In vivo, the hepatoprotective activity of sub-fraction FVI was evaluated in CCl₄-induced toxicated mice. Administration of CCl₄ significantly increased level of ALT (Alanine transaminase), AST (Aspartate aminotransferase), ALP (Alkaline phosphatase), and bilirubin and decreased the total protein. Treatment with sub-fraction FVI significantly (p<0.05) reversed the level of these biomarkers toward normal at both doses of 25 mg/kg and 50 mg/kg. Conclusion: Our findings confirmed the hepatoprotective effect of ethyl acetate fraction of F.carica. It could be a good candidate for the development of a natural hepatoprotective drug; pre-clinical investigation on ethyl acetate fraction is recommended.

Keywords: Ficus carica, hepatoprotective, CCl₄, bioactive compounds, liver markers

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679 Evaluation of the Effectiveness of Barriers for the Control of Rats in Rice Plantation Field

Authors: Melina, Jumardi Jumardi, Erwin Erwin, Sri Nuraminah, Andi Nasruddin

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The rice field rat (Rattus argentiventer Robinson and Kloss) is a pest causing the greatest yield loss of rice plants, especially in lowland agroecosystems with intensive cropping patterns (2-3 plantings per year). Field mice damage rice plants at all stages of growth, from seedling to harvest, even in storage warehouses. Severe damage with yield loss of up to 100% occurs if rats attack rice at the generative stage because the plants are no longer able to recover by forming new tillers. Farmers mainly use rodenticides in the form of poisoned baits or as fumigants, which are applied to rat burrow holes. This practice is generally less effective because mice are able to avoid the poison or become resistant after several exposures to it. In addition, excessive use of rodenticides can have negative impacts on the environment and non-target organisms. For this reason, this research was conducted to evaluate the effectiveness of fences as an environmentally friendly mechanical control method in reducing rice yield losses due to rat attacks. This study used a factorial randomized block design. The first factor was the fence material, namely galvanized zinc plate and plastic. The second factor was the height of the fence, namely 25, 50, 75, and 100 cm from the ground level. Each treatment combination was repeated five times. Data shows that zinc fences with a height of 75 and 100 cm are able to provide full protection to plants from rat infestations throughout the planting season. However, zinc fences with a height of 25 and 50 cm failed to prevent rat attacks. Plastic fences with a height of 25 and 50 cm failed to prevent rat attacks during the planting season, whereas 75 and 100 cm were able to prevent rat attacks until all the crops outside of the fence had been eaten by rats. The rat managed to get into the fence by biting the plastic fence close to the ground. Thus, the research results show that fences made of zinc plate with a height of at least 75 cm from the ground surface are effective in preventing plant damage caused by rats. To our knowledge, this research is the first to quantify the effectiveness of fences as a control of field rodents.

Keywords: rice field rat, Rattus argentiventer, fence, rice

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678 Assessment Proposal to Establish the First Geo-Park in Egypt at Abu-Roash Area, Cairo

Authors: Kholoud Abdelmaksoud, Mahmoud Emam, Wael Al-Metwaly

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Egypt is known as cradle of civilization due to its ancient history and archeological sites, but Egypt possess also a cradle of Geo-sites, which qualify it to be listed as one of the most important Geo-heritage sites all over the country. Geology and landscape in Abu-Roash area is considered as one of the most important geological places (geo-sites) inside Cairo which help us to know and understand geology and geologic processes, so the area is used mainly for geological education purposes, also the area contain an archeological sites; pyramid complex, tombs, and Coptic monastery which give the area unique importance. Abu-Roash area is located inside Cairo 9 km north of the Giza Pyramids, which make the accessibility to the area easy and safe, the geology of Abu-Roash constitutes a complex Cretaceous sedimentary succession mass with showing outstanding tectonic features (Syrian Arc system event), these features are considered as a Geo-heritage, which will be the main designation of ‘Geo-parks’ establishing. The research is dealing with the numerous geo-sites found in the area, and its geologic and archeological importance, the relation between geo-sites and archeology, also the research proposed a detailed maps for these sites depicting Geo-routes and the hazardous places surrounding Abu-Roash area. The research is proposing a new proposal not applied in Egypt before, establishing a Geo-park, to promote this unique geo-heritage from hazardous factors and anthropogenic effects, also it will offer geo-educational opportunities to the general public and to the scientific community, enhancement of Geo-tourism which will be linked easily with the Ancient Egyptian tourism, it will also provide a significant economic benefit to Abu-Roash residential area. Finally, the research recommends that The United Nations Educational, Scientific and Cultural Organizations promote conservation of geological and geo-morphological heritage to list this area for its importance under the umbrella of geo-parks.

Keywords: geo-park, geo-sites, Abu-roash, archaeological sites, geo-tourism

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677 Hypoglycaemic and Hypolipidemic Activity of Cassia occidentalis Linn. Stem Bark Extract in Streptozotocin Induced Diabetes

Authors: Manjusha Choudhary

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Objective: Cassia occidentalis Linn. belongs to Family Caesalpiniaceae is a common weed scattered from the foothills of Himalayas to West Bengal, South India, Burma, and Sri Lanka. It is used widely in folklore medicine in India as laxative, expectorant, analgesic, anti-malarial, hepatoprotective, relaxant, anti-inflammatory and antidiabetic. The present study was carried out to investigate the hypoglycaemic and hypolipidemic activities of ethanolic extract of Cassia occidentalis stem bark. Methods: Stem bark extract of Cassia occidentalis (SBCO) was administered orally at 250 and 500 mg/kg doses to normal and streptozotocin (STZ) induced type-2 diabetic mice. Various parameters like fasting blood glucose (FBG) level, serum cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides (TG), total protein, urea, creatinine, serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) levels and physical parameters like change in body weight, food intake, water intake were performed for the evaluation of antidiabetic effects. Results: Both the doses of extract caused a marked decrease in FBG levels in STZ induced type 2 diabetic mice. Administration of SBCO led to the decrease in the blood glucose, food intake, water intake, organ weight, SGOT, SGPT levels with significant value and increased the levels of TG, HDL cholesterol, creatinine, cholesterol, total protein with a significant value (p < 0.05-0.01). The decrease in body weight induced by STZ was restored to normal with a significant value (p < 0.01) at both doses. Conclusion: Present study reveals that SBCO possess potent hypoglycaemic and hypolipidemic activities and supports the folklore use of the stem bark of plant as antidiabetic agent.

Keywords: Cassia occidentalis, diabetes, folklore, herbs, hypoglycemia, streptozotocin

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676 The Changes of Functions of Leishan Miao New-Year in Southeast Guizhou

Authors: Lanyan Peng, Ling Chen

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Leishan Miao New-Year is one of the grandest festivals in the southeastern of Guizhou Province in China. It was officially listed in the National Intangible Cultural Heritage List in 2008, as a traditional folk cultural activity organized by the local Miao people. With the rise of cultural tourism, after 19 years of exploration, the local government has successfully built Miao New-Year into a cultural card that is well-known at home and abroad. During the Miao New-Year period, it has attracted 3.8 million tourists and achieves a win-win situation in the economy and culture. However, tourism development has changed the living environment and living state of the local people. And it is accompanied by changes in the form of the festival, the content of the festival, and the local people’s needs and attitudes to the festival. This paper uses the field investigation method to achieve 410 questionnaires and 35 interviews, exploring the process and the reasons for changes of Leishan Miao New-Year’s cultural function. Among all the functions, the economic function, identity function, and entertainment function have been enhanced, and the marriage and love function has been extended. In the meanwhile, sacrificial function has been weakened. There are some trends in functions. The function of commemorating ancestor and self-entertainment has been changed to entertaining people and economic pursuit.

Keywords: Miao New-Year, Miao nationality, festival function, changes

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675 Therapeutic Effects of Guar Gum Nanoparticles in Oxazolone-Induced Atopic Dermatitis

Authors: Nandita Ghosh, Shinjini Mitra, Ena Ray Banerjee

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Atopic dermatitis (AD) is a chronic disease of the skin, involving itchy, reddish, and scaly lesions. It mainly affects children and has a high prevalence in developing countries. The AD may occur due to environmental or genetic factors. There is no permanent cure for the AD. Currently, all therapeutic strategies involve methods to simply alleviate the symptoms, and include lotions and corticosteroids, which have adverse effects. Use of phytochemicals and natural products has not yet been exploited fully. The particle used in this study is derived from Cyamopsis tetragonoloba, an edible polysaccharide with a galactomannan component. The mannose component mainly increases its specificity towards cellular uptake by mannose receptors, highly expressed by the macrophage. The aim of this study was to determine the therapeutic effect of guar gum nanoparticles (GN) in vitro and in vivo in the AD. To assess the wound healing capacity of the guar gum nanoparticle (GN), we first treated adherent NIH3T3 cells, with a scratch injury, with GN. GN successfully healed the wound caused by the scratch. In the in vivo experiment, Balb/c mice ear were topically treated with oxazolone (oxa) to induce AD and then were topically treated with GN. The ear thickness was increased significantly till day 28 on the treatment of Oxa. The GN application showed a significant decrease in the thickness as assessed on day 28. The total cell count of skin cells showed fold increase when treated with oxa, was again decreased on topical application of GN on the affected skin. The eosinophil count, as assessed by Giemsa staining was also increased when treated with oxa, GN application led to a significant decrease. The IgE level was assessed in the serum samples which showed that GN helped in restoring the alleviated IgE level. The T helper cells and the macrophage population showed increased percentage when treated with oxa, the GN application. This was examined by flow cytometry. The H&E staining of the ear tissue showed epidermal thickness in the oxa treated mice, GN application showed reduced cellular filtration followed by epidermal thickness. Thus our assays showed that GN was successful in alleviating the disease caused by Oxa when administered topically.

Keywords: allergen, inflammation, nanodrug, wound

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674 Factors Relating to Travel Behavior at the Floating Market of Thai Tourists

Authors: Siri-orn Champatong

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The purpose of this research was to study factors that were related with travel behaviors of Thai tourists at the Ayothaya Floating Market, Phra Nakhon Sri Ayutthaya. The quantitative research was conducted with 400 samples of Thai tourists traveling to the Ayothaya Floating Market. The Questionnaire was a tool used to collect data, and the statistics used for data analysis were mean and Pearson product moment correlation coefficient. The results found that Thai tourists focused on attraction, easy access and facilities of the tourist spot at a high level. In addition, they gave priority to the marketing mix in the dimension of products, price, and distribution channels at a high level as well. For marketing promotion, it was at the moderate level. The results of hypothesis testing revealed that factors related to the attractions of the tourist destination, easy access to the tourist destination, the facilities of the tourist spot, and product and price of the marketing mix were associated with travel behaviors in the aspect of the number of visits used and the budget on tourism.

Keywords: floating market, marketing mix, tourism attractions, travelling behavior

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673 Understanding the Influence of Cross-National Distances on Tourist Expenditure

Authors: Wei-Ting Hung

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Inbound tourist expenditure might not only have influenced by individual tourist characteristics but may also be affected by nationality characteristics. The cross national distance effects on tourist consumption behavior should be incorporated in the analytical framework. Additionally, the often used factor analysis, cluster analysis and regression analysis overlook the hierarchical tourist consumption data structure and may lead to misleading results. The objectives of the present study were twofold. First, we propose a multilevel model that takes individual and cross-national differences into account under a hierarchical framework. Second, we further sought to determine the types of cross-national differences affecting tourist expenditure. Thus, this study incorporates the individual tourist effects and cross national distance effects simultaneously, uses the data of 2010 Annual Survey Report on Visitors’ Expenditure and Trends in Taiwan to investigate the determinants of inbound tourist expenditure. Multilevel analysis was used to investigate the influence of individual tourist effects and cross national distance effects on inbound tourist expenditure. The empirical results show that cross national distance plays a crucial role in tourist consumption behavior. Our findings also indicate age and income have positive influence on tourism expenditure., whereas education and gender do not have significant impact. Regarding macro-level factors, geographic and cultural differences exhibited significant positive relationships on tourism expenditure, while economic differences did not. Based on the above empirical results, it is suggested that tour operators should take tourists’ individual attributes, particularly their income and age, into consideration when arranging tours. In addition, nationality holds sway over tourists’ consumption behavior, of which geographic and cultural differences are the two major factors at play. The empirical results of this study serve as practical suggestions for tourism marketing strategies and policy implications for government policies.

Keywords: cross national distance, inbound tourist, multilevel analysis, tourist expenditure

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672 Managing the Baltic Sea Region Resilience: Prevention, Treatment Actions and Circular Economy

Authors: J. Burlakovs, Y. Jani, L. Grinberga, M. Kriipsalu, O. Anne, I. Grinfelde, W. Hogland

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The worldwide future sustainable economies are oriented towards the sea: the maritime economy is becoming one of the strongest driving forces in many regions as population growth is the highest in coastal areas. For hundreds of years sea resources were depleted unsustainably by fishing, mining, transportation, tourism, and waste. European Sustainable Development Strategy is identifying and developing actions to enable the EU to achieve a continuous, long-term improvement of the quality of life through the creation of sustainable communities. The aim of this paper is to provide insight in Baltic Sea Region case studies on implemented actions on tourism industry waste and beach wrack management in coastal areas, hazardous contaminants and plastic flow treatment from waste, wastewaters and stormwaters. These projects mentioned in study promote successful prevention of contaminant flows to the sea environments and provide perspectives for creation of valuable new products from residuals for future circular economy are the step forward to green innovation winning streak.

Keywords: resilience, hazardous waste, phytoremediation, water management, circular economy

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671 Cell-Cell Interactions in Diseased Conditions Revealed by Three Dimensional and Intravital Two Photon Microscope: From Visualization to Quantification

Authors: Satoshi Nishimura

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Although much information has been garnered from the genomes of humans and mice, it remains difficult to extend that information to explain physiological and pathological phenomena. This is because the processes underlying life are by nature stochastic and fluctuate with time. Thus, we developed novel "in vivo molecular imaging" method based on single and two-photon microscopy. We visualized and analyzed many life phenomena, including common adult diseases. We integrated the knowledge obtained, and established new models that will serve as the basis for new minimally invasive therapeutic approaches.

Keywords: two photon microscope, intravital visualization, thrombus, artery

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670 Study on the Use of Manganese-Containing Materials as a Micro Fertilizer Based on the Local Mineral Resources and Industrial Wastes in Hydroponic Systems

Authors: Marine Shavlakadze

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Hydroponic greenhouses systems (production of the artificial substrate without soil) are becoming popular in the world. Mostly the system is used to grow vegetables and berries. Different countries are taking action to participate in the development of hydroponic technology and solutions such as EU members, Turkey, Australia, New Zealand, Israel, Scandinavian countries, etc. Many vegetables and berries are grown by hydroponics in Europe. As a result of our research, we have obtained material containing manganese and nitrogen. It became possible to produce this fertilizer by means of one-stage thermal processing, using industrial waste containing manganese (ores and sludges) and mineral substance (ammonium nitrate) that exist in Georgia. The received material is usable as a micro-fertilizer with economic efficiency. It became possible to turn practically water-insoluble manganese dioxide substance into the soluble condition from industrial waste in an indirect way. The ability to use the material as a fertilizer is predetermined by its chemical and phase composition, as the amount of the active component of the material in relation to manganese is 30%. At the same time, the active component elements presented non-ballast sustained action compounds. The studies implemented in Poland and in Georgia by us have shown that the manganese-containing micro-fertilizer- Mn(NO3)2 can provide the plant with nitrate nitrogen, which is a form that can be used for plants, providing the economy and simplicity of the application of fertilizers. Given the fact that the application of the manganese-containing micro-fertilizers significantly increases the productivity and improves the quality of the big number of agricultural products, it is necessary to mention that it is recommended to introduce the manganese containing fertilizers into the following cultures: sugar beet, corn, potato, vegetables, vine grape, fruit, berries, and other cultures. Also, as a result of the study, it was established that the material obtained is the predominant fertilizer for vegetable cultures in the soil. Based on the positive results of the research, we consider it expedient to conduct research in hydroponic systems, which will enable us to provide plants the required amount of manganese; we also introduce nitrogen in solution and regulate the solution of pH, which is one of the main problems in hydroponic production. The findings of our research will be used in hydroponic greenhouse farms to increase the fertility of vegetable crops and, consequently, to get bountiful and high-quality harvests, which will promote the development of hydroponic greenhouses in Georgia as well as abroad.

Keywords: hydroponics, micro-fertilizers, manganese-containing materials, industrial wastes

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669 Examining the Acceptability of Destination Local Food by Domestic Tourist Visiting Northern Nigeria

Authors: Eldah Ephraim Buba, Jamila Mohammed Waziri

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There are challenges faced by tourist in respect of choosing food while in tourism destination. Food is very important in the choice of holiday of tourist. Many tourists choose a destination not only because of physical attraction but they choose destination where they will not encounter challenges in respect to food. The study is aimed at examining the acceptability of northern delicacies by tourists from other parts of Nigeria. Six delicacies were produced and presented to 50 tourists who are randomly picked from the south-east, south-west, south-south and the middle belt of Nigeria. The study found out that Danwake, Masa, and Kwadon zogale were generally accepted by majority of the respondents. Although, the respondents were not comfortable with the appearance of danwake, other aspect of the checklist was accepted. Tuwon shinkafa miyan taushe was accepted in terms of appearance but rejected in terms of taste and texture. ‘Yar Tsame and dindikolo were generally rejected. The study recommended that caterers, attraction owners and hoteliers should include such meals in their menu so that tourist will enjoy the gastronomy of the northern part of Nigeria.

Keywords: acceptability, examination, food, tourism

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668 Oak Gall Wasps (Hymenoptera, Cynipidae, Cynipini) and Galls Form Recorded from Georgia

Authors: Marine Nozadze, George Japoshvili, George Melika

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In 2020-2021 we studied oaks gall wasps of different oak species in Georgia at 7 locations of their natural distribution: 1. Quercuse petrea subsp. iberica - Mtskheta municipality, village. Mukhattskaro; 2. Quercus subsp. pendunculifloria - Kvareli municipality, village. Gramy;3. Quercus robur subsp. imeretina -Baghdati Municipality, Ajameti Reserve; 4. Quercus pontica -Chokhatauri municipality, village. Tskhratskaro; 5. Quercus macranthera -Tetritskaro Municipality, Algeti National Park; 6. Quercuse petrea subsp. iberica - Shuakhevi municipality, village. Uchamba 7. Quercus hartwissiana - Baghdatis municipality, village. Dimi. Samples were collected from early spring to late autumn. As a result, 7 forms of galls were collected and described wich caused by different species of oak gall wasps: 1. Neuroterus numismalis asexual gall 2. Neuroterus quercusbaccarum asexual galls 3. Cynips korsakovi asexual gall 4. Biorhiza pallida sexual gall 5. Neuroterus quercusbaccarum asexual galls 6. Neuroterus numismalis sexual gall 7. Cynips quercusfolii. Neuroterus quercusbaccarum asexual galls form the most represented of them: In Algeti National Park; In Mtskheta municipality; In Shuakhevi municipality and Ajameti reserve. The most damaged locations by oak gall wasps were Algeti National Park and Mtskheta Municipality, whereas the most biodiversity according to galls form was represented In Algeti National Park.

Keywords: gall wasps, oak, cynipidae, species

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667 CSR Practices in Bali: An Exploratory Study on the Environmental Aspect

Authors: Trianasari, Gede Adi Yuniarta

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The tourism industry has been widely recognized as one of the world’s largest industries and is expected to have continuous growth. While it has positive impacts especially on the job markets and economic aspect, this industry also brings serious environmental impacts that may not be neglected. As such, the tourism industry is faced with increasing demands and challenges to deal with the environmental issues. Corporate Social Responsibility (CSR) is a way to show the firms’ concern on the societal and environmental aspects. In line with the increasing pressure on such responsibilities, a growing number of firms have involved in CSR activities. In Bali, the majority of both chained and locally owned hotels have shown their efforts on CSR practices. However, little is known about what and how they perform or implement such program especially within the environmental aspect. The importance of understanding what they focus on lays in the identification of areas that have received sufficient treatment and those that require more attention. Furthermore, also, it is especially essential considering that Bali is one of the worldly known destinations that have been facing numerous crucial issues on environment that may threaten the sustainability of the island and its people. This paper reports on the results of a study exploring the practices of CSR in hotels in Bali. Data were collected from 49 hotel managers and human resource managers in Bali across four major tourist areas, using semi structured interview method. The analysis was conducted qualitatively. The results showed that all hotels under study have implemented CSR activities in which environment was found to be the second key aspect, following the activities directly related to community aspect. Moreover, there were five major types of environmental action identified: beach cleaning, replantation, marine conservation, turtle conservation, mangrove, and garbage management. These findings suggest that hotels in Bali under study have shown their concern on the environment, however, less attention was given on attempt to reduce the environmental impacts of their operations. Mapping the types of environmental related CSR activities enhances the knowledge of and gives lights into the CSR literature especially from the perspective of Eastern practice.

Keywords: CSR, exploratory study, sustainable tourism, tourist object

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666 Superiority of Bone Marrow Derived-Osteoblastic Cells (ALLOB®) over Bone Marrow Derived-Mesenchymal Stem Cells

Authors: Sandra Pietri, Helene Dubout, Sabrina Ena, Candice Hoste, Enrico Bastianelli

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Bone Therapeutics is a bone cell therapy company addressing high unmet medical needs in the field of bone fracture repair, more specifically in non-union and delayed-union fractures where the bone repair process is impaired. The company has developed a unique allogeneic osteoblastic cell product (ALLOB®) derived from bone marrow which is currently tested in humans in the indication of delayed-union fractures. The purpose of our study was to directly compare ALLOB® vs. non-differentiated mesenchymal stem cells (MSC) for their in vitro osteogenic characteristics and their in vivo osteogenic potential in order to determine which cellular type would be the most adapted for bone fracture repair. Methods: Healthy volunteers’ bone marrow aspirates (n=6) were expended (i) into BM-MSCs using a complete MSC culture medium or (ii) into ALLOB® cells according to its manufacturing process. Cells were characterized in vitro by morphology, immunophenotype, gene expression and differentiation potential. Additionally, their osteogenic potential was assessed in vivo in the subperiosteal calvaria bone formation model in nude mice. Results: The in vitro side-by-side comparison studies showed that although ALLOB® and BM-MSC shared some common general characteristics such as the 3 minimal MSC criteria, ALLOB® expressed significantly higher levels of chondro/osteoblastic genes such as BMP2 (fold change (FC) > 100), ALPL (FC > 12), CBFA1 (FC > 3) and differentiated significantly earlier than BM-MSC toward the osteogenic lineage. Moreover the bone formation model in nude mice demonstrated that used at the same cellular concentration, ALLOB® was able to induce significantly more (160% vs.107% for control animals) bone formation than BM-MSC (118% vs. 107 % for control animals) two weeks after administration. Conclusion: Our side-by-side comparison studies demonstrated that in vitro and in vivo, ALLOB® displays superior osteogenic capacity to BM-MScs and is therefore a better candidate for the treatment of bone fractures.

Keywords: gene expression, histomorphometry, mesenchymal stem cells, osteogenic differentiation potential, preclinical

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665 Down Regulation of Smad-2 Transcription and TGF-B1 Signaling in Nano Sized Titanium Dioxide-Induced Liver Injury in Mice by Potent Antioxidants

Authors: Maha Z. Rizk, Sami A. Fattah, Heba M. Darwish, Sanaa A. Ali, Mai O. Kadry

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Although it is known that nano-TiO2 and other nanoparticles can induce liver toxicity, the mechanisms and the molecular pathogenesis are still unclear. The present study investigated some biochemical indices of nano-sized Titanium dioxide (TiO2 NPS) toxicity in mice liver and the ameliorative efficacy of individual and combined doses of idebenone, carnosine and vitamin E. Nano-anatase TiO2 (21 nm) was administered as a total oral dose of 2.2 gm/Kg daily for 2 weeks followed by the afore-mentioned antioxidants daily either individually or in combination for 1month. TiO2-NPS induced a significant elevation in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatic oxidative stress biomarkers [lipid peroxides (LP), and nitric oxide levels (NOX), while it significantly reduced glutathione reductase (GR), reduced glutathione (GSH) and glutathione peroxidase(GPX) levels. Moreover the quantitative RT-PCR analysis showed that nano-anatase TiO2 can significantly alter the mRNA and protein expressions of the fibrotic factors TGF-B1, VEGFand Smad-2. Histopathological examination of hepatic tissue reinforced the previous biochemical results. Our results also implied that inflammatory responses and liver injury may be involved in nano-anatase TiO2-induced liver toxicity Tumor necrosis factor-α (TNF-α) and Interleukin -6 (IL-6) and increased the percent of DNA damage which was assessed by COMET assay in addition to the apoptotic marker Caspase-3. Moreover mRNA gene expression observed by RT-PCR showed a significant overexpression in nuclear factor relation -2 (Nrf2), nuclear factor kappa beta (NF-Kβ) and the apoptotic factor (bax), and a significant down regulation in the antiapoptotic factor (bcl2) level. In conclusion idebenone, carnosine and vitamin E ameliorated the deviated previously mentioned parameters with variable degrees with the most pronounced role in alleviating the hazardous effect of TiO2 NPS toxicity following the combination regimen.

Keywords: Nano-anatase TiO2, TGF-B1, SMAD-2

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664 Analysis of Anti-Tuberculosis Immune Response Induced in Lungs by Intranasal Immunization with Mycobacterium indicus pranii

Authors: Ananya Gupta, Sangeeta Bhaskar

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Mycobacterium indicus pranii (MIP) is a saprophytic mycobacterium. It is a predecessor of M. avium complex (MAC). Whole genome analysis and growth kinetics studies have placed MIP in between pathogenic and non-pathogenic species. It shares significant antigenic repertoire with M. tuberculosis and have unique immunomodulatory properties. MIP provides better protection than BCG against pulmonary tuberculosis in animal models. Immunization with MIP by aerosol route provides significantly higher protection as compared to immunization by subcutaneous (s.c.) route. However, mechanism behind differential protection has not been studied. In this study, using mice model we have evaluated and compared the M.tb specific immune response in lung compartments (airway lumen / lung interstitium) as well as spleen following MIP immunization via nasal (i.n.) and s.c. route. MIP i.n. vaccination resulted in increased seeding of memory T cells (CD4+ and CD8+ T-cells) in the airway lumen. Frequency of CD4+ T cells expressing Th1 migratory marker (CXCR3) and activation marker (CD69) were also high in airway lumen of MIP i.n. group. Significantly high ex vivo secretion of cytokines- IFN-, IL-12, IL-17 and TNF- from cells of airway luminal spaces provides evidence of antigen-specific lung immune response, besides generating systemic immunity comparable to MIP s.c. group. Analysis of T cell response on per cell basis revealed that antigen specific T-cells of MIP i.n. group were functionally superior as higher percentage of these cells simultaneously secreted IFN-gamma, IL-2 and TNF-alpha cytokines as compared to MIP s.c. group. T-cells secreting more than one of the cytokines simultaneously are believed to have robust effector response and crucial for protection, compared with single cytokine secreting T-cells. Adoptive transfer of airway luminal T-cells from MIP i.n. group into trachea of naive B6 mice revealed that MIP induced CD8 T-cells play crucial role in providing long term protection. Thus the study demonstrates that MIP intranasal vaccination induces M.tb specific memory T-cells in the airway lumen that results in an early and robust recall response against M.tb infection.

Keywords: airway lumen, Mycobacterium indicus pranii, Th1 migratory markers, vaccination

Procedia PDF Downloads 172