Search results for: human balance

Authors: Eszter Repasi, Akos Koller

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Our genetic information determines our look, physiology, sports performance and all our features. Maximizing the performances of athletes have adopted a science-based approach to the nutritional support. Nowadays genetics studies have blended with nutritional sciences, and a dynamically evolving, new research field have appeared. Nutritional genomics is needed to be used by nutritional experts. This is a recent field of nutritional science, which can provide a solution to reach the best sport performance using correlations between the athlete’s genome, nutritions, molecules, included human microbiome (links between food, microbiome and epigenetics), nutrigenomics and nutrigenetics. Nutritional genomics has a tremendous potential to change the future of dietary guidelines and personal recommendations. Experts need to use new technology to get information about the athletes, like nutritional genomics profile (included the determination of the oral and gut microbiome and DNA coded reaction for food components), which can modify the preparation term and sports performance. The influence of nutrients on the genes expression is called Nutrigenomics. The heterogeneous response of gene variants to nutrients, dietary components is called Nutrigenetics. The human microbiome plays a critical role in the state of health and well-being, and there are more links between food or nutrition and the human microbiome composition, which can develop diseases and epigenetic changes as well. A nutritional genomics-based profile of athletes can be the best technic for a dietitian to make a unique sports nutrition diet plan. Using functional food and the right food components can be effected on health state, thus sports performance. Scientists need to determine the best response, due to the effect of nutrients on health, through altering genome promote metabolites and result changes in physiology. Nutritional biochemistry explains why polymorphisms in genes for the absorption, circulation, or metabolism of essential nutrients (such as n-3 polyunsaturated fatty acids or epigallocatechin-3-gallate), would affect the efficacy of that nutrient. Controlled nutritional deficiencies and failures, prevented the change of health state or a newly discovered food intolerance are observed by a proper medical team, can support better sports performance. It is important that the dietetics profession informed on gene-diet interactions, that may be leading to optimal health, reduced risk of injury or disease. A special medical application for documentation and monitoring of data of health state and risk factors can uphold and warn the medical team for an early action and help to be able to do a proper health service in time. This model can set up a personalized nutrition advice from the status control, through the recovery, to the monitoring. But more studies are needed to understand the mechanisms and to be able to change the composition of the microbiome, environmental and genetic risk factors in cases of athletes.

Keywords: gene-diet interaction, multidisciplinary team, microbiome, diet plan

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Authors: Catarina Isabel Ramos Pereira, Jorge Machado, Begona Alonso Criado, Maria João Santos

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Introduction: Gait disorders are one of the symptoms that have severe implications on the quality of life in Parkinson's disease (PD). Currently, there is no therapy to reverse or treat this condition. None of the drugs used in conventional medical treatment is entirely efficient, and all have a high incidence of side effects. Acupuncture treatment is believed to improve motor ability, but there is still little scientific evidence in individuals with PD. Aim: The aim of the study is to investigate the acute effect of acupuncture on gait parameters in Parkinson's disease. Methods: This is a randomized and controlled crossover study. The same individual patient was part of both the experimental (real acupuncture) and control group (false acupuncture/sham), and the sequence was randomized. Gait parameters were measured at two different moments, before and after treatment, using four force platforms as well as the collection of 3D markers positions taken by 11 cameras. Images were quantitatively analyzed using Qualisys Track Manager software that let us extract data related to the quality of gait and balance. Seven patients with the diagnosis of Parkinson's disease were included in the study. Results: Statistically significant differences were found in gait speed (p = 0.016), gait cadence (p = 0.006), support base width (p = 0.0001), medio-lateral oscillation (p = 0.017), left-right step length (p = 0.0002), and stride length: right-right (p = 0.0000) and left-left (p = 0.0018), time of left support phase (p = 0.029), right support phase (p = 0.025) and double support phase (p = 0.015), between the initial and final moments for the experimental group. Differences in right-left stride length were found for both groups. Conclusion: Our results show that acupuncture could enhance gait in Parkinson's disease patients. Deep research involving a larger number of volunteers should be accomplished to validate these encouraging findings.

Keywords: acupuncture, traditional Chinese medicine, Parkinson's disease, gait

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Authors: Amy Gooden

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When human genomic data is considered, this is often done through only one dimension of the law, or the interplay between the various dimensions is not considered, thus providing an incomplete picture of the legal framework. This research considers and analyzes the various dimensions in South African law applicable to genomic sequence data – including property rights, personality rights, and intellectual property rights. The effective use of personal genomic sequence data requires the acknowledgement and harmonization of the rights applicable to such data.

Keywords: artificial intelligence, data, law, genomics, rights

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Authors: Jernice S. Y. Tan

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Introduction: Reliability within and between testers is vital to ensure the accuracy of any motor assessment instrument. However, reliability checks of the Movement Assessment Battery for Children-2 (MABC-2) age band 3 using multiple testers assigned to different MABC-2 tasks for the same group of participants are uncommon. Multiple testers were not stated as a choice in the MABC-2 manual. Therefore, the purpose of this study was to determine the inter- and intra-tester reliability for using multiple testers to administer the test protocols of MABC-2 age band 3. Methods: Thirty volunteered adolescents (n = 30; 15 males, 15 females; age range: 13 – 16 years) performed the eight tasks in a randomised sequence at three different test stations for the MABC-2 task components (Manual Dexterity, Aiming and Catching, Balance). Ethics approval and parental consent were obtained. The participants were videotaped while performing the test protocols of MABC-2 age band 3. Five testers were involved in the data collection process. They were Sports Science graduating students doing their final year project and were supervised by experienced motor assessor. Inter- and intra-tester reliability checks using intra-class coefficient (ICC) were carried out using the videotaped data. Results: The inter-tester reliability between the five testers for the eight tasks ranged from rᵢcc = 0.705 to rᵢcc = 0.995. This suggests that the average agreement between them was considered good to excellent. With the exception of one tester who had rᵢcc = 0.687 for one of the eight tasks (i.e. zip-zap hopping), the intra-tester reliability within each tester ranged from rᵢcc = 0.728 to rᵢcc = 1.000, and this also suggested good to excellent consistency within testers. Discussion: The use of multiple testers with good intra-tester reliability for different test stations is feasible. This method allows several participants to be assessed concurrently at different test stations and saves overall data collection time. Therefore, it is recommended that the administering of MABC-2 with multiple testers should be extended to other age bands ensuring the feasibility of such method for other age bands.

Keywords: adolescents, MABC, motor assessment, motor skills, reliability

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Authors: Mohammad Tofayel Ahmed, Seung Kook An

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In contemporary research world, focus is more set on sustainable products and innovative processes. The global textile industries are putting tremendous effort to achieve a balance between economic development and ecological protection concurrently. The conservation of water sources and environment have become immensely significant issue in textile dyeing production. Accordingly, an attempt has been taken in this study to develop a process to dye polyester blend cotton without reduction clearing process and any extra wash off chemical by simple modification aiming at cost reduction and sustainability. A widely used combination of 60/40 cotton/polyester (c/p) single jersey knitted fabric of 30’s, 180 g/m² was considered for study. Traditionally, pretreatment is done followed by polyester part dyeing, reduction clearing and cotton part dyeing for c/p blend dyeing. But in this study, polyester part is dyed right away followed by pretreatment process and cotton part dyeing by skipping the reduction clearing process diametrically. The dyed samples of both traditional and modified samples were scrutinized by various color fastness tests, dyeing parameters and by consumption of water, steam, power, process time and total batch cost. The modified process in this study showed no necessity of reduction clearing process for polyester blend cotton dyeing. The key issue contributing to avoid the reduction clearing after polyester part dyeing has been the multifunctional effect of NaOH and H₂O₂ while pretreatment of cotton after polyester part dyeing. The results also revealed that the modified process could reduce the consumption of water, steam, power, time and cost remarkably. The bulk trial of modified process demonstrated the well exploitability to dye polyester blend cotton substrate ensuring all fastness and dyeing properties regardless of dyes category, blend ratio, color, and shade percentage thus making the process sustainable, eco-friendly and economical. Furthermore, the proposed method could be applicable to any cellulosic blend with polyester.

Keywords: cotton, dyeing, economical, polyester

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Authors: Sandra Cecilia Muhirirwe, Bart Van Der Bruggen, Violet Kisakye

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Economic analysis of Rainwater harvesting (RWH) systems is vital in search of a cost-effective solution to water unreliability, especially in low-income countries. There is little literature focusing on the financial aspects of RWH for dairy farmers. The main purpose was to assess the economic viability of rainwater harvesting for diary framers in the Rwenzori region. The study focused on the use of rainwater harvesting systems from the rooftop and collection in above surface tanks. Daily rainfall time series for 12 years was obtained across nine gauging stations. The daily water balance equation was used for optimal sizing of the tank. Economic analysis of the investment was carried out based on the life cycle costs and the accruing benefits for the period of 15 years. Roof areas were varied from 75m2 as the minimum required area to 500m2 while maintaining the same number of cattle and keeping the daily water demand constant. The results show that the required rainwater tank sizes are very large and may be impractical to install due to the strongly varying terrain and the initial cost of investment. In all districts, there is a significant reduction of the volume of the required tank with an increasing collection area. The results further show that increasing the collection area has a minor effect on reducing the required tank size. Generally, for all rainfall areas, the reliability increases with an increase in the roof area. The results indicate that 100% reliability can only be realized with very large collection areas that are impractical to install. The estimated benefits outweigh the cost of investment. The Present Net Value shows that the investment is economically viable and investment with a short payback of a maximum of 3 years for all the time series in the study area.

Keywords: dairy cattle, optimisation, rainwater harvesting, economic analysis

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Authors: Tong Ming Liu

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Human mesenchymal stem cells (MSCs) represent the most used stem cells for clinical application, which have been used in over 1000 clinical trials to treat over 30 diseases due to multilineage differentiation potential, secretome and immunosuppression. Gene therapies of MSCs hold great promise in the treatment of many diseases due to enhanced MSC-based clinical outcomes. To identify genes for gene therapy of MSCs, by comparing gene expression profile before and after MSC differentiation following by functional screening, we have identified ZNF145 that regulated MSC differentiation. Forced expression of ZNF145 resulted in enhanced in vitro chondrogenesis of MSCs as an upstream factor of SOX9 and improved osteochondral repair upon implant into osteochondral defects in rodents. By comparing gene expression profile during differentiation of iPSCs toward MSCs, we also identified gene HOX regulating MSC stemness, which was much downregulated in late-passaged MSCs. Knockdown of this gene greatly compromised MSC stemness including abolished proliferation, decreased CFU-F, promoted senescence and reduced expression of cell surface antigens linked to the MSC phenotype. In addition, multi-linage differentiation was also greatly impaired. Notably, HOX overexpression resulted in improved multi-lineage differentiation. In the mechanism, HOX expression significantly deceased in late passage of MSCs compared with early passage of MSCs, correlating with MSC important genes. ChIP-seq data shown that HOX binds to genes related to MSC self-renewal and differentiation. Most importantly, most HOX binding sites are lost in late passage of MSCs. HOX exerts its effects by directing binding Twist1, one important gene of MSCs. The identification of the genes regulating MSC differentiation and stemness will provide and promising strategies for gene therapy of MSCs in regenerative medicine.

Keywords: mesenchymal stem cell, novel transcription factor, stemness, gene therapy, cartilage repair, signaling pathway

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Authors: Meenu Joshi, Natalie Naidoo, Farzeen Kader

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Identification of body fluids is an essential step in forensic investigation to aid in crime reconstruction. Tissue-specific differentially methylated regions (tDMRs) of the human genome can be targeted to be used as biomarkers to differentiate between body fluids. The present study was undertaken to establish the methylation status of potential tDMRs in blood, semen, saliva, and vaginal fluid by using methylation-specific PCR (MSP) and bisulfite sequencing (BS). The methylation statuses of 3 potential tDMRS in genes ZNF282, PTPRS, and HPCAL1 were analysed in 10 samples of each body fluid. With MSP analysis, the ZNF282, and PTPRS1 tDMR displayed semen-specific hypomethylation while HPCAL1 tDMR showed saliva-specific hypomethylation. With quantitative analysis by BS, the ZNF282 tDMR showed statistically significant difference in overall methylation between semen and all other body fluids as well as at individual CpG sites (p < 0.05). To evaluate the effect of environmental conditions on the stability of methylation profiles of the ZNF282 tDMR, five samples of each body fluid were subjected to five different forensic simulated conditions (dry at room temperature, wet in an exsiccator, outside on the ground, sprayed with alcohol, and sprayed with bleach) for 50 days. Vaginal fluid showed highest DNA recovery under all conditions while semen had least DNA quantity. Under outside on the ground condition, all body fluids except semen showed a decrease in methylation level; however, a significant decrease in methylation level was observed for saliva. A statistical significant difference was observed for saliva and semen (p < 0.05) for outside on the ground condition. No differences in methylation level were observed for the ZNF282 tDMR under all conditions for vaginal fluid samples. Thus, in the present study ZNF282 tDMR has been identified as a novel and stable semen-specific hypomethylation marker.

Keywords: body fluids, bisulphite sequencing, forensics, tDMRs, MSP

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Authors: Hong Li, Haiyang Yu, Shiqing Cheng, Nai Cao, Zhiliang Shi

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Unconventional resources have gradually become the main direction for oil and gas exploration and development. However, the productivity of gas wells, the level of water production, and the seepage law in tight fractured gas reservoirs are very different. These are the reasons why production prediction is so difficult. Firstly, a three-dimensional multi-scale fracture and multiphase mathematical model based on an embedded discrete fracture model (EDFM) is established. And the material balance method is used to calculate the water body multiple according to the production performance characteristics of water-producing gas well. This will help construct a 'virtual water body'. Based on these, this paper presents a numerical simulation process that can adapt to different production modes of gas wells. The research results show that fractures have a double-sided effect. The positive side is that it can increase the initial production capacity, but the negative side is that it can connect to the water body, which will lead to the gas production drop and the water production rise both rapidly, showing a 'scissor-like' characteristic. It is worth noting that fractures with different angles have different abilities to connect with the water body. The higher the angle of gas well development, the earlier the water maybe break through. When the reservoir is a single layer, there may be a stable production period without water before the fractures connect with the water body. Once connected, a 'scissors shape' will appear. If the reservoir has multiple layers, the gas and water will produce at the same time. The above gas-water relationship can be matched with the gas well production date of the Xujiahe gas reservoir in the Sichuan Basin. This method is used to predict the productivity of a well with hydraulic fractures in this gas reservoir, and the prediction results are in agreement with on-site production data by more than 90%. It shows that this research idea has great potential in the productivity prediction of water-producing gas wells. Early prediction results are of great significance to guide the design of development plans.

Keywords: EDFM, multiphase, multilayer, water body

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Authors: N. Farahin Ali, Naharriah Mohamed, Hafiz Majdi, Fathiyyah, Fadliana Saman

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This paper investigates the imperative for developing Islamic accounting standards tailored to Baitulmal, waqaf, and zakat transactions, with the goal of strengthening accountability and transparency in financial reporting. Current financial reporting frameworks in Malaysia—namely, the Malaysian Financial Reporting Standards (MFRS) and Malaysian Private Entities Reporting Standards (MPERS)—are designed predominantly for conventional financial transactions and fail to fully capture the Shariah-specific nature of these religious funds. The objective of this study is to critically examine the discrepancies between these conventional reporting standards and the requirements of Shariah-compliant financial transactions, specifically for Baitulmal, waqaf, and zakat. This research adopts a qualitative methodology, utilizing case studies from four different State Islamic Religious Councils to explore the current reporting practices. The findings reveal significant gaps between the conventional frameworks and the specific needs of Shariah-compliant accounting, leading to off-balance-sheet reporting of certain transactions and inconsistencies in financial disclosures across different states. These disparities undermine both the comparability and integrity of the financial reports, raising critical concerns regarding transparency and governance. The broader implications of this study underscore the necessity for a unified Islamic accounting standard that would align more closely with Shariah principles. Such a standard would not only enhance the disclosure and presentation of baitulmal, waqaf, and zakat transactions, but also improve decision-making processes, thereby fostering greater accountability and trust in the management of these Islamic funds. This paper advocates for a concerted effort to bridge the existing gap, ensuring that the distinctive characteristics of Islamic charitable funds are appropriately reflected in the financial reporting process.

Keywords: islamic accounting, waqf, zakat, islamic finance

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Authors: Siewchuiang Sia, Gimcheong Tan

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Bacteriophages are the most abundant and genetically diverse living entities on earth; they help in regulating and maintaining microbial diversity and balance in its natural ecosystem. In this study, the infectivity of SFN6B tailed phage was investigated in various water samples. Host bacteria (Shigella flexneri) were spiked in sterilized environmental and domestic water samples, followed by SFN6B treatment. Two incubation conditions were selected for this study, 37 oC and room temperature. S. flexneri and SFN6B viability were monitored hourly for consecutive 7 hours and extended viability study for consecutive 4 days. Absorbance of all bacteria spiked water samples were taken to monitor the bacteria count. Results showed reduction in the absorbance of the SFN6B treated water sample as compared to negative control, indicating reduction in bacterial count either due to negative growth or lysis by the lytic bacteriophage. Consistent with the result, SFN6B titer increases for first two days. However, prolong incubation of these cultures reaches equilibrium, between phage and bacteria. Temperature and water sample source also influence the interaction between S. flexneri and SFN6B. Stronger interaction was observed in 37oC as compared to room temperature, where higher bacteria count and phage titer increase were recorded. Availability of nutrient in water sample also plays a crucial role in the interaction between bacteria and phage. Higher nutrient level, such as lake and river waters were observed to give better infectivity and viability of both bacteria and phage as compared to tab water. It is believed that S. flexneri continue to remain viable and able to grow in the present of SFN6B bacteriophage, but the number was closely regulated by surrounding phages. This allows better understanding of the characteristics of SFN6B that could serve as the basis for future studies and applications.

Keywords: bacteriophage, Shigella flexneri, infection, microbial diversity

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Authors: Anand Malik

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The Himalayas with high tectonic activities poses a great threat to human life and property. Climate change is another reason which triggering extreme events multiple fold effect on high mountain glacial environment, rock falls, landslides, debris flows, flash flood and snow avalanches. One such extreme event of cloud burst along with breach of moraine dammed Chorabri Lake occurred from June 14 to June 17, 2013, triggered flooding of Saraswati and Mandakini rivers in the Kedarnath Valley of Rudraprayag district of Uttrakhand state of India. As a result, huge volume of water with its high velocity created a catastrophe of the century, which resulted into loss of large number of human/animals, pilgrimage, tourism, agriculture and property. Thus a comprehensive assessment of debris flow hazards requires GIS-based modeling using numerical methods. The aim of present study is to focus on analysis and mapping of debris flow movements using geospatial data with flow-r (developed by team at IGAR, University of Lausanne). The model is based on combined probabilistic and energetic algorithms for the assessment of spreading of flow with maximum run out distances. Aster Digital Elevation Model (DEM) with 30m x 30m cell size (resolution) is used as main geospatial data for preparing the run out assessment, while Landsat data is used to analyze land use land cover change in the study area. The results of the study area show that model can be applied with great accuracy as the model is very useful in determining debris flow areas. The results are compared with existing available landslides/debris flow maps. ArcGIS software is used in preparing run out susceptibility maps which can be used in debris flow mitigation and future land use planning.

Keywords: debris flow, geospatial data, GIS based modeling, flow-R

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Authors: Zhila Hemati, Seyed Sajjad Hosseni, Sohrab Zamzami

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In nature, forests serve a multitude of functions. They stabilize and nourish soil, store carbon, clean the air and water, and support biodiverse ecosystems. A natural disaster that can affect forests and ecosystems locally or globally is wildfires. Iran experiences annual forest fires that affect roughly 6000 hectares, with the Arasbaran forest being the most affected. These fires may be generated unnaturally by human activity in the forests, or they could occur naturally as a result of climate change. These days, wildfires pose a major natural risk. Wildfires significantly reduce the amount of property and human life in ecosystems globally. Concerns regarding the immediate and longterm effects have been raised by the rise in fire activity in various Iranian regions in recent decades. Natural ecosystem abundance, quality, and health will all be impacted by pasture and forest fires. Monitoring is the first line of defense against and control for forest fires. To determine the spatial-temporal variations of these occurrences in the vegetation regions of Arasbaran, this study was carried out to estimate the areas affected by fires. The findings indicated that July through September, which spans over 130000 hectares, is when fires in Arasbaran's vegetation areas occur to their greatest extent. A significant portion of the nation's forests caught fire in 2024, particularly in the northwest of the Arasbaran vegetation area. On the other hand, January through March sees the least number of fire locations in the Arasbaran vegetation areas. The Arasbaran forest experiences its greatest number of forest fires during the hot, dry months of the year. As a result, the linear association between the burned and active fire regions in the Arasbaran forest indicates a substantial relationship between species abundance and plant species. This link demonstrates that some of the active forest fire centers are the burned regions in Arasbaran's vegetation areas.

Keywords: wildfire, vegetation, plant species, forest

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Authors: Tajudeen Ojo Ibraheem

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In a world characterized by greed and the lust for power and its attendant trappings, abuse of legal power is nothing new to most of us. Legal abuses of power abound in all fields of human endeavour. Accounts of such abuses dominate the mass media and for the average individual, no single day goes by without his getting to hear about at least one such occurrence. This paper briefly looks at the meaning of legal power, what legal abuse is all about, its causes, and some of its manifestations in the society. Its consequences will also be discussed and some suggestions for reform will be made. In the course of the paper, references will be made to various jurisdictions around the world.

Keywords: abuse, legal, power, society

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Authors: K. C. Sharda

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Introduction: In the world, almost half of the population are lacking proper access to improved sanitation services. In Nepal, large number of people are living without access to any sanitation facility. Ecological sanitation toilet which is defined as water conserving and nutrient recycling system for use of human urine and excreta in agriculture would count a lot to utilize locally available resources, to regenerate soil fertility, to save national currency and to achieve the goal of elimination open defecation in country like Nepal. The objectives of the research were to test the efficacy of human urine for improving crop performance and to evaluate the feasibility of ecological sanitation in rural area of Central Nepal. Materials and Methods: The field investigation was carried out at Palung Village Development Committee (VDC) of Makawanpur District, Nepal from March – August, 2016. Five eco-san toilets in two villages (Angare and Bhot Khoriya) were constructed and questionnaire survey was carried out. During the questionnaire survey, respondents were asked about socio-economic parameters, farming practices, awareness of ecological sanitation and fertilizer value of human urine and excreta in agriculture. In prior to a field experiment, soil was sampled for analysis of basic characteristics. In the field experiment, cauliflower was cultivated for a month in the two sites to compare the fertilizer value of urine with chemical fertilizer and no fertilizer with three replications. The harvested plant samples were analyzed to understand the nutrient content in plant with different treatments. Results and Discussion: Eighty three percent respondents were engaged in agriculture growing mainly vegetables, which may raise the feasibility of ecological sanitation. In the study area, water deficiencies in dry season, high demand of chemical fertilizer, lack of sanitation awareness were found to be solved. The soil at Angare has sandier texture and lower nitrogen content compared to that in Bhot Khoriya. While the field experiment in Angare showed that the aboveground biomass of cauliflower in the urine fertilized plot were similar with that in the chemically fertilized plot and higher than those in the non-fertilized plots, no significant difference among the treatments were found in Bhot Khoriya. The more distinctive response of crop growth to the three treatments in the former might be attributed to the poorer soil productivity, which in turn could be caused by the poorer inherent soil fertility and the poorer past management by the farmer in Angare. Thus, use of urine as fertilizer could help poor farmers with low quality soil. The significantly different content of nitrogen and potassium in the plant samples among three treatments in Bhot Khoriya would require further investigation. When urine is utilized as a fertilizer, the productivity could be increased and the money to buy chemical fertilizer would be utilized in other livelihood activities. Ecological sanitation is feasible in the area with similar socio-economic parameter.

Keywords: cauliflower, chemical fertilizer, ecological sanitation, Nepal, urine

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Authors: Andrew R. Beatty

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The exploitation of Australia’s vast mineral wealth is regulated by a matrix of planning, environment and heritage legislation, and despite the desire for a ‘balance’ between economic, environmental and heritage values, Aboriginal objects and places are often detrimentally impacted by mining approvals. The Australian experience is not novel. There are other cases of clashes between the rights of traditional landowners and businesses seeking to exploit mineral or other resources on or beneath those lands, including in the United States, Canada, and Brazil. How one reconciles the rights of traditional owners with those of resource companies is an ongoing legal problem of general interest. In Australia, planning and environmental approvals for resource projects are ordinarily issued by State or Territory governments. Federal legislation such as the Aboriginal and Torres Strait Islander Heritage Protection Act 1984 (Cth) is intended to act as a safety net when State or Territory legislation is incapable of protecting Indigenous objects or places in the context of approvals for resource projects. This paper will analyse the context and effectiveness of legislation enacted to protect Indigenous heritage in the planning process. In particular, the paper will analyse how the statutory objects of such legislation need to be weighed against the statutory objects of competing legislation designed to facilitate and control resource exploitation. Using a current claim in the Federal Court of Australia for the protection of a culturally significant landscape as a case study, this paper will examine the challenges faced in ascribing value to cultural heritage within the wider context of environmental and planning laws. Our findings will reveal that there is an inherent difficulty in defining and weighing competing economic, environmental and heritage considerations. An alternative framework will be proposed to guide regulators towards making decisions that result in better protection of Indigenous heritage in the context of resource management.

Keywords: environmental law, heritage law, indigenous rights, mining

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Authors: G. Vishnu, T. V. Bharat

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Rainfall plays a major role in the stability of natural slopes in tropical and subtropical regions. These slopes usually have high slope angles and are stable during the dry season. The critical rainfall intensity that might trigger a landslide may not be the highest rainfall. In addition to geological discontinuities and anthropogenic factors, water content, suction, and hydraulic conductivity also play a role. A thorough geotechnical investigation with the principles of unsaturated soil mechanics is required to predict the failures in these cases. The study discusses three landslide events that had occurred in residual hills of Guwahati, India. Rainfall data analysis, history image analysis, land use, and slope maps of the region were analyzed and discussed. The landslide occurred on June (24, 26, and 28) 2020, on the respective sites, but the highest rainfall was on June (6 and 17) 2020. The factors that lead to the landslide occurrence is the combination of critical events initiated with rainfall, causing a reduction in suction. The sites consist of a mixture of rocks and soil. The slope failure occurs due to the saturation of the soil layer leading to loss of soil strength resulting in the flow of the entire soil rock mass. The land-use change, construction activities, other human and natural activities that lead to faster disintegration of rock mass may accelerate the landslide events. Landslides in these slopes are inevitable, and the development of an early warning system (EWS) to save human lives and resources is a feasible way. The actual time of failure of a slope can be better predicted by considering all these factors rather than depending solely on the rainfall intensities. An effective EWS is required with less false alarms in these regions by proper instrumentation of slope and appropriate climatic downscaling.

Keywords: early warning system, historic image analysis, slope instrumentation, unsaturated soil mechanics

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Authors: Harshita Raj, Joydeep Ghosh, Rakesh L. Tanna, Prabal K. Chattopadhyay, K. A. Jadeja, Sharvil Patel, Kaushal M. Patel, Narendra C. Patel, S. B. Bhatt, V. K. Panchal, Chhaya Chavda, C. N. Gupta, D. Raju, S. K. Jha, J. Raval, S. Joisa, S. Purohit, C. V. S. Rao, P. K. Atrey, Umesh Nagora, R. Manchanda, M. B. Chowdhuri, Nilam Ramaiya, S. Banerjee, Y. C. Saxena

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Efficient gas fueling is a critical aspect that needs to be mastered in order to maintain plasma density, to carry out fusion. This requires a fair understanding of fuel recycling in order to optimize the gas fueling. In Aditya tokamak, multiple gas puffs are used in a precise and controlled manner, for hydrogen fueling during the flat top of plasma discharge which has been instrumental in achieving discharges with enhanced density as well as energy confinement time. Following each gas puff, we observe peaks in temporal profile of Hα emission, Soft X-ray (SXR) and chord averaged electron density in a number of discharges, indicating efficient gas fueling. Interestingly, Hα temporal profile exhibited an additional peak following the peak corresponding to each gas puff. These additional peak Hα appeared in between the two gas puffs, indicating the presence of a secondary hydrogen source apart from the gas puffs. A thorough investigation revealed that these secondary Hα peaks coincide with Hard X- ray bursts which come from the interaction of runaway electrons with vessel limiters. This leads to consider that the runaway electrons (REs), which hit the wall, in turn, bring out the absorbed hydrogen and oxygen from the wall and makes the interaction of REs with limiter a secondary hydrogen source. These observations suggest that runaway electron induced recycling should also be included in recycling particle source in the particle balance calculations in tokamaks. Observation of two Hα peaks associated with one gas puff and their roles in enhancing and maintaining plasma density in Aditya tokamak will be discussed in this paper.

Keywords: fusion, gas fueling, recycling, Tokamak, Aditya

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Authors: Saima Murtaza

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Ethics and aesthetics have invariably remained the two closely integrated artistic appurtenances for the production of any work of art. These artistic devices configure themselves into a complex synthesis in our contemporary literature. The labyrinthine integration of ethics and aesthetics, operating in the lives of human characters, to the extent of transcending all limits has resulted in an artistic puzzle for the readers. Art, no doubt, is an extrinsic expression of the intrinsic life of man. The use of aesthetics in literature pertaining to human existence; aesthetic solipsism, has resulted in the artistic objectification of these characters. The practice of the like aestheticism deprives the characters of their souls, rendering them as mere objects of aesthetic gaze at the hands of their artists-creators. Artists orchestrate their lives founding it on a plot which deviates from normal social and ethical standards. Their perverse attitude can be seen in dealing with characters, their feelings and the incidents of their lives. Morality is made to appear not as a religious construct but as an individual’s private affair. Furthermore, the idea of beauty incarnated, in other words hedonistic aesthetic does not placate a true aesthete. Ethics and aesthetics are the two most recurring motifs of our contemporary literature, especially of Nabokov’s world. The purpose of this study is to peruse these aforementioned motifs in Nabokov’s most enigmatic novel Lolita, a story of pedophilia, which is in fact reflective of our complex individual psychic and societal patterns. The narrative subverts all the traditional and hitherto known notions of aesthetics and ethics. When applied to literature, aesthetic does not simply mean ‘beautiful’ in the text. It refers to an intricate relationship between feelings and perception and also incorporates within its range wide-ranging emotional reactions to text. The term aesthetics in literature is connected with the readers whose critical responses to the text determine the merit of any work to be really a piece of art. Aestheticism is the child of ethics. Morality sets the grounds for the production of any work and the idea of aesthetics gives it transcendence.

Keywords: ethics, aesthetics and hedonistic aesthetic, nymphet syndrome, pedophilia

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Authors: Federica Verna, Alessandra Pautasso, Maria Caramelli, Cristiana Maurella, Walter Mignone, Cristina Casalone

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Mosquito-Borne Diseases (MBDs) are dangerously increasing in prevalence, geographical distribution and severity, representing an emerging threat for both humans and animals. Interaction between multiple disciplines is needed for an effective early warning, surveillance and control of MBDs, according to the One Health concept. This work reports the integrated surveillance system enforced by IZSPLV in Piedmont, Liguria and Valle d’Aosta regions (Northwestern Italy) in order to control MDBs spread. Veterinary services and local human health authority are involved in an information network, to connect the surveillance of human clinical cases with entomological surveillance and veterinary monitoring in order to implement control measures in case of outbreak. A systematic entomological surveillance is carried out during the vector season using mosquitoes traps located in sites selected according to risk factors. Collected mosquitoes are counted, identified to species level by morphological standard classification keys and pooled by collection site, date and species with a maximum of 100 individuals. Pools are analyzed, after RNA extraction, by Real Time RT-PCR distinctive for West Nile Virus (WNV) Lineage 1 and Lineage 2, Real Time RT-PCR USUTU virus (USUV) and a traditional flavivirus End-point RT-PCR. Positive pools are sequenced and the related sequences employed to perform a basic local alignment search tool (BLAST) in the GenBank library. Positive samples are sent to the National Reference Centre for Animal Exotic Diseases (CESME, Teramo) for confirmation. With particular reference to WNV, after the confirmation, as provided by national legislation, control measures involving both local veterinary and human health services are activated: equine sera are randomly sampled within a 4 km radius from the positive collection sites and tested with ELISA kit and WNV NAT screening of blood donors is introduced. This surveillance network allowed to detect since 2011 USUV circulation in this area of Italy. WNV was detected in Piedmont and Liguria for the first time in 2014 in mosquitoes. During the 2015 vector season, we observed the expansion of its activity in Piedmont. The virus was detected in almost all Provinces both in mosquitoes (6 pools) and animals (19 equine sera, 4 birds). No blood bag tested resulted infected. The first neuroinvasive human case occurred too. Competent authorities should be aware of a potentially increased risk of MBDs activity during the 2016 vector season. This work shows that this surveillance network allowed to early detect the presence of MBDs in humans and animals, and provided useful information to public authorities, in order to apply control measures. Finally, an additional value of our diagnostic protocol is the ability to detect all viruses belonging to the Flaviviridae family, considering the emergence caused by other Flaviviruses in humans such as the recent Zika virus infection in South America. Italy has climatic and environmental features conducive to Zika virus transmission, the competent vector and many travellers from Brazil reported every year.

Keywords: integrated surveillance, mosquito borne disease, West Nile virus, Zika virus

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Authors: Eda Arat Maden, Ceyhan Altun, Bilal Ozmen, Feridun Basak

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Purpose: The purpose of this study was to compare the antimicrobial effect of toothpastes containing fluoride, xylitol or xylitol-probiotic in vivo, Streptococcus mutans and Lactobacillus in 13-15 years old children. Method: The study consisted of 60 pediatric patients were randomly divided into 3 groups of 20 each. Group 1 received fluoride toothpaste (Colgate Max Fresh), group 2 used xylitol toothpaste (Xyliwhite) and group 3 used xylitol-probiotic toothpaste (PerioBiotic). Subjects were asked to use the allocated dentifrice two times a day, for 6 weeks. We performed tests on the samples of saliva in the beginning of the study and after 6 weeks’ duration following the use of toothpaste. Result and Conclusion: All of the participants of the study stated that they brushed their teeth well twice a day by using the toothpastes given to them for 6 weeks. Majority of the subjects had high counts of salivary mutans streptococci and Lactobacillus at baseline. When the number of cariogenic bacteria (S. mutans and Lactobacillus) at the start of the PerioBiotic Probiotic toothpaste usage are compared with the results measured after 6 weeks, an important decrease is observed in the S. mutans and Lactobacillus bacteria according to the CRT Tests. After the 6-week use of Probiotic toothpaste, the S. mutans (≥105) decreased to 20% from 75% in the group with S. mutans and Lactobacillus (≥105) decreased to 30% from 60% in the group with Lactobacillus. In addition, an important decrease was recorded in the participants with the S. mutans percentage (80% - 45%) and Lactobacillus (70% - 55%) after using the Colgate Max Fresh toothpaste for six weeks. On the other hand, it was determined with the Chi-square that there were not important changes between the Xyliwhite toothpaste group and the other groups with S. mutans (80% - 75%) and Lactobacillus (75% -65%). It was also determined after the comparison of the groups that the decrease in the S. mutans was higher than the group using PerioBiotic Probiotic toothpaste at a significant level, when compared with the Colgate Max Fresh toothpaste and Xyliwhite toothpaste. S. mutans were more sensitive to the antimicrobial activity of the PerioBiotic Probiotic toothpaste and to the Colgate Max Fresh toothpaste when compared with the Lactobacillus. In the light of the data obtained in this in vivo study, the use of probiotics ensure the balance between the bacterial flora in the oral cavity.

Keywords: lactobacillus, probiotic, Streptococcus mutans, toothpaste

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Authors: P. Jayashree, S. Rajkumar

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With the trend of virtual and augmented reality environments booming to provide a life like experience, gaming is a major tool in supporting such learning environments. In this work, a variant of Voronoi heuristics, employing supervised learning for the TRON game is proposed. The paper discusses the features that would be really useful when a machine learning bot is to be used as an opponent against a human player. Various game scenarios, nature of the bot and the experimental results are provided for the proposed variant to prove that the approach is better than those that are currently followed.

Keywords: artificial Intelligence, automation, machine learning, TRON game, Voronoi heuristics

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Authors: Agoston Restas

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Introduction: This paper describes many initiatives and shows also practical examples which happened recently using Unmanned Aerial Systems (UAS) to support disaster management. Since the operation of manned aircraft at disasters is usually not only expensive but often impossible to use as well, in many cases managers fail to use the aerial activity. UAS can be an alternative moreover cost-effective solution for supporting disaster management. Methods: This article uses thematic division of UAS applications; it is based on two key elements, one of them is the time flow of managing disasters, other is its tactical requirements. Logically UAS can be used like pre-disaster activity, activity immediately after the occurrence of a disaster and the activity after the primary disaster elimination. Paper faces different disasters, like dangerous material releases, floods, earthquakes, forest fires and human-induced disasters. Research used function analysis, practical experiments, mathematical formulas, economic analysis and also expert estimation. Author gathered international examples and used own experiences in this field as well. Results and discussion: An earthquake is a rapid escalating disaster, where, many times, there is no other way for a rapid damage assessment than aerial reconnaissance. For special rescue teams, the UAS application can help much in a rapid location selection, where enough place remained to survive for victims. Floods are typical for a slow onset disaster. In contrast, managing floods is a very complex and difficult task. It requires continuous monitoring of dykes, flooded and threatened areas. UAS can help managers largely keeping an area under observation. Forest fires are disasters, where the tactical application of UAS is already well developed. It can be used for fire detection, intervention monitoring and also for post-fire monitoring. In case of nuclear accident or hazardous material leakage, UAS is also a very effective or can be the only one tool for supporting disaster management. Paper shows some efforts using UAS to avoid human-induced disasters in low-income countries as part of health cooperation.

Keywords: disaster management, floods, forest fires, Unmanned Aerial Systems

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Authors: Ghalia Shamlan, M. Denise Robertson, Adam Collins

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Appetite control (i.e. control of energy intake) is important for weight maintenance. Exercise contributes to the most variable component of energy expenditure (EE) but its impact is beyond the energy cost of exercise including physiological, behavioural, and appetite effects. Exercise is known to acutely influence effect appetite but evidence as to the independent effect of intensity is lacking. This study investigated the role of exercise intensity on appetite, energy intake (EI), appetite related hormone, fat utilisation and subjective measures of appetite. One hour after a standardised breakfast, 10 sedentary overweight volunteers. Subjects undertook either 8 repeated 60 second bouts of cycling at 95% VO2max (high intensity) or 30 minutes of continuous cycling, at a fixed cadence, equivalent to 50% of the participant’s VO2max (low intensity) in a randomised crossover design. Glucose, NEFA, glucagon-like peptide-1 (GLP-1) were measured fasted, postprandial, and pre and post-exercise. Satiety was assessed subjectively throughout the study using visual analogue scales (VAS). Ad libitum intake of a pasta meal was measured at the end (3-h post-breakfast). Interestingly, there was not significant difference in EE fat oxidation between HI and LI post-exercise. Also, no significant effect of high intensity (HI) was observed on the ad libitum meal, 24h and 48h EI post-exercise. However the mean 24h EI was 3000 KJ lower following HI than low intensity (LI). Despite, no significant differences in hunger score, glucose, NEFA and GLP-1 between both intensities were observed. However, NEFA and GLP-1 plasma level were higher until 30 min post LI. In conclusion, the similarity of EE and oxidation outcomes could give overweight individuals an option to choose between intensities. However, HI could help to reduce EI. There are mechanisms and consequences of exercise in short and long-term appetite control; however, these mechanisms warrant further explanation. These results support the need for future research in to the role of in regulation energy balance, especially for obese people.

Keywords: appetite, exercise, food intake, energy expenditure

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Authors: Kevin Moustapha

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Psychopathy is perceived today as being «the most important concept in the criminal justice system» and as «the most important legal notion of the early 21 th century». The explosion of research related to psychopathy seems to perfectly illustrate this trend. Traditionally, many studies tend to focus on links between insanity defense and psychopathy. That is why our purpose in this article is to analyze psychopathic disorders in the scope of judges sentencing in Canada. Indeed, in every Canadian case related to dangerous offenders, judges must balance between fairness and protection of the individuals rights of the accused and protection of society from dangerous predators who may commit future acts of physical or sexual violence. Increasingly, psychopathic disorders are taking an important part in judge sentencing, especially in Canada. This phenomenon can be illustrated by the high proportion of psychopath offenders incarcerated in North American prisons. Many decisions in Canadians courtrooms seem to point out that psychopathy is often used as a strong argument by the judges to preserve public safety. The fact that psychopathy is often associated with violence, recklessness and recidivism, it could explain why many judges consider psychopathic disorders as an aggravating factor. Generally, the judge reasoning is based on article 753 of Canadian Criminal Code related to dangerous offenders, which is used for individuals who show a pattern of repetitive and persistent aggressive behaviour. However, with cognitive neurosciences, the psychopath’s situation in courtrooms would probably change. Cerebral imaging and news data provided by the neurosciences show that emotional and volitional functions in psychopath’s brains are impaired. Understanding these new issues could enable some judges to recognize psychopathic disorders as a mitigating factor. Two important questions ought to be raised in this article: can exploring psychopaths ‘brains really change the judge sentencing in Canadian courtrooms? If yes, can judges consider psychopathy more as a mitigating factor than an aggravating factor?

Keywords: criminal law, judges sentencing, neurosciences, psychopathy

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Authors: Rai Friedman

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The recent migrant crisis has revealed an unmet demand for increased international protection and promotion of migrant rights. Europe has found itself at the centre of the migration crisis, being the recipient to the largest number of asylum-seekers since the conclusion of the second World War. Rather than impart a unified humanitarian lens of offering legal protections, the Schengen territory is devising new, preventative measures to confront the influx of asylum-seekers. This paper will focus on the refugee crisis in Europe as it relates to the Central Mediterranean route. To do so, it will outline the increased need for international protection for migrant rights through analyzing historic human rights treaties and conventions; the formation of the current composition of the Schengen area; the evolutionary changes in policies and legal landscapes throughout Europe and the Central Mediterranean route; the vernacular transformation surrounding refugees, migrants, and asylum-seekers; and expose the gaps in international protection. It will also discuss Europe’s critical position, both geographically and conceptually, critiquing the notion of European victimization. Lastly, it will discuss the increased harm of preventative border measures and argue for tangible sustainability solutions through economic programming models in highly vulnerable countries. To do so, this paper will observe a case study in Algeria that has conceded to an economic programming model for forced migrants. In 2017 amid worker shortages, Algeria announced it would grant African migrants’ legal status to become agriculturalists and construction workers. Algeria is one of the few countries along the Central Mediterranean route that has adopted a law to govern foreign nationals’ conditions of entry, stay and circulation. Thereafter, it will provide recommendations for solutions for forced migration along the Central Mediterranean route and advocate for strengthened protections under international law.

Keywords: refugees, migrants, human rights, middle east, Africa, mediterranean, international humanitarian law, policy

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Authors: Soumaya Mrabet, Imen Akkari, Amira Atig, Elhem Ben Jazia

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Introduction: Celiac disease (CD) is a chronic autoimmune inflammatory enteropathy caused by gluten. The clinical presentation is very variable. Malabsorption in the MC is responsible for an alteration of the bone metabolism. Our purpose is to study the osteoarticular manifestations related to this condition. Material and methods: It is a retrospective study of 41 cases of CD diagnosed on clinical, immunological, endoscopic and histological arguments, in the Internal Medicine and Gastroenterology Department of Farhat Hached Hospital between September 2005 and January 2016. Results: Osteoarticular manifestations were found in 9 patients (22%) among 41 patients presenting CD. These were 7 women and 2 men with an average age of 35.7 years (25 to 67 years). These manifestations were revelatory of CD in 3 cases. Abdominal pain and diarrhea were present in 6 cases. Inflammatory polyarthralgia of wrists and knees has been reported in 7 patients. Mechanical mono arthralgia was noted in 2 patients. Biological tests revealed microcytic anemia by iron deficiency in 7 cases, hypocalcemia in 5 cases, Hypophosphatemia in 3 cases and elevated alkaline phosphatases in 3 cases. Upper gastrointestinal endoscopy with duodenal biopsy found villous atrophy in all cases. In immunology, Anti-transglutaminase antibodies were positive in all patients, Anti-endomysium in 7 cases. Measurement of bone mineral density (BMD) by biphotonic X-ray absorptiometer with evaluation of the T-score and the Z-score was performed in Twenty patients (48.8%). It was normal in 7 cases (33%) and showed osteopenia in 5 patients (25%) and osteoporosis in 2 patients (10%). All patients were treated with a Gluten-free diet associated with vitamin D and calcium substitution in 5 cases. The evolution was favorable in all cases with reduction of bone pain and normalization of the phosphocalcic balance. Conclusion: The bone impact of CD is frequent but often asymptomatic. Patients with CD should be evaluated by the measurement of bone mineral density and monitored for calcium and vitamin D deficiencies.

Keywords: bone mineral density, celiac disease, osteoarticular manifestations, vitamin D and calcium

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Authors: Rahaba Marima, Clement Penny

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The Health-related quality of life (HRQoL) for HIV positive patients has improved since the introduction of the highly active antiretroviral treatment (HAART). However, in the present HAART era, HIV co-morbidities such as lung cancer, a non-AIDS (NAIDS) defining cancer have been documented to be on the rise. Under normal physiological conditions, cells grow, repair and proliferate through the cell-cycle as cellular homeostasis is important in the maintenance and proper regulation of tissues and organs. Contrarily, the deregulation of the cell-cycle is a hallmark of cancer, including lung cancer. The association between lung cancer and the use of HAART components such as Efavirenz (EFV) is poorly understood. This study aimed at elucidating the effects of EFV on the cell-cycle genes’ expression in lung cancer. For this purpose, the human cell-cycle gene array composed of 84 genes was evaluated on both normal lung fibroblasts (MRC-5) cells and adenocarcinoma (A549) lung cells, in response to 13µM EFV or 0.01% vehicle. The ±2 up or down fold change was used as a basis of target selection, with p < 0.05. Additionally, RT-qPCR was done to validate the gene array results. Next, In-silico bio-informatics tools, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Reactome, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Ingenuity Pathway Analysis (IPA) were used for gene/gene interaction studies as well as to map the molecular and biological pathways influenced by the identified targets. Interestingly, the DNA damage response (DDR) pathway genes such as p53, Ataxia telangiectasia mutated and Rad3 related (ATR), Growth arrest and DNA damage inducible alpha (GADD45A), HUS1 checkpoint homolog (HUS1) and Role of radiation (RAD) genes were shown to be upregulated following EFV treatment, as revealed by STRING analysis. Additionally, functional enrichment analysis by the KEGG pathway revealed that most of the differentially expressed gene targets function at the cell-cycle checkpoint such as p21, Aurora kinase B (AURKB) and Mitotic Arrest Deficient-Like 2 (MAD2L2). Core analysis by IPA revealed that p53 downstream targets such as survivin, Bcl2, and cyclin/cyclin dependent kinases (CDKs) complexes are down-regulated, following exposure to EFV. Furthermore, Reactome analysis showed a significant increase in cellular response to stress genes, DNA repair genes, and apoptosis genes, as observed in both normal and cancerous cells. These findings implicate the genotoxic effects of EFV on lung cells, provoking the DDR pathway. Notably, the constitutive expression of this pathway (DDR) often leads to uncontrolled cell proliferation and eventually tumourigenesis, which could be the attribute of HAART components’ (such as EFV) effect on human cancers. Targeting the cell-cycle and its regulation holds a promising therapeutic intervention to the potential HAART associated carcinogenesis, particularly lung cancer.

Keywords: cell-cycle, DNA damage response, Efavirenz, lung cancer

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Authors: Tunde Puskas, Anita Andersson

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In Swedish early childhood education research, the issues related to religious identifications and practices have often been marginalized or relegated either to the realm of diversity and multiculturalism or to the realm of national traditions. This paper is part of a research project about whether religion is considered as part of Swedish cultural heritage in Swedish preschools. Our aim in this paper is to explore how a Swedish preschool balance between keeping the education non-confessional and at the same time introducing the traditions associated with advent and Christmas. Christmas was chosen because of the religious background of the holiday and because it is a tradition widely celebrated in Swedish preschools. In Swedish education system, the concept of freedom of religion is understood in the sense that education is declared to be non-confessional. Nevertheless, as the major state holidays in Sweden are tied to Lutheran Christian traditions, and according to the curriculum preschool educators, are given the task to pass on a cultural heritage, defined in terms of values, traditions, history, language, and knowledge, it is the preschool teams or individual preschool teachers who determine whether and to what extent religious considerations are/ought to be seen as part of the cultural heritage the preschool passes on. The data consists of ten video taped observations from two preschools. The video data was transcribed and the transcripts were thereafter analysed through content analysis. In the analysis, we draw on the concept of banal religiosity that has helped us to draw attention to the workings of religious considerations that are so familiar that they rarely are noticed as religious and on Ninian Smart’s theory on the dimensions of religion. The analysis shows that what the adults actually do with religion fulfils six of seven dimensions common to religious traditions as outlined by Smart. At the same time, Christmas is performed as a lived tradition within which the commercial and religious rituals intersect and result in a banal, national religiosity.

Keywords: secular advent, banal religiosity, dimensions of religion, rites

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Authors: Ji-Young Choi, Jungjin Kim, Sang-Sun Yun, Sangmee Ahn Jo

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Intracellular adhesion molecule1 (ICAM1) is a mediator of inflammation and involved in adhesion and transmigration of leukocytes to endothelial cells, resulting in enhancement of brain inflammation. We hypothesized that increase of ICAM1 expression in endothelial cells is an early step in the pathogenesis of brain diseases such as Alzheimer’s disease. Here, we report that ICAM1 expression is regulated by pro-inflammatory cytokine TNFa in human microvascular endothelial cell (HBMVEC). TNFa significantly increased ICAM1 mRNA and protein levels at the concentrations showing no cell toxicity. This increase was also shown in micro vessels of mouse brain 24 hours after treatment with TNFa (8 mg/kg, i.v). We then investigated the epigenetic mechanism involved in the induction of ICAM1 expression. Chromatin immunoprecipitation assay revealed that TNFa reduced methylation of histone3K9 (H3K9-2me) and histone3K27 (H3K27-3me), well-known modification as gene suppression, with in the ICAM1 promoter region. However, acetylation of H3K9 and H3K14, well-known modification as gene activation, was not changed by TNFa. Treatment of BIX01294, a specific inhibitor of histone methyltransferase G9a responsible for H3K9-2me, dramatically increased in ICAM1 mRNA and protein levels and overexpression of G9a gene suppressed TNFa-induced ICAM1 expression. In contrast, GSK126, an inhibitor of histone methyltransferase EZH2 responsible for H3K27-3me and valproic acid, an inhibitor of histone deacetylase (HDAC) did not affect ICAM1 expression. These results suggested that histone3 methylation is involved in ICAM1 repression. Moreover, TNFa or BIX01294-induced ICAM induction resulted in both enhancements in adhesion and transmigration of leukocyte on endothelial cell. This study demonstrates that TNFa upregulates ICAM1 expression through H3K9-2me and H3K27-3me within the ICAM1 promoter region, in which G9a is likely to play a pivotal role in ICAM1 transcription. Our study provides a novel mechanism for ICAM1 transcription regulation in HBMVEC.

Keywords: ICAM1, TNFa, HBMVEC, H3K9-2me

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