Search results for: regulatory diet
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1688

Search results for: regulatory diet

1358 Detecting Memory-Related Gene Modules in sc/snRNA-seq Data by Deep-Learning

Authors: Yong Chen

Abstract:

To understand the detailed molecular mechanisms of memory formation in engram cells is one of the most fundamental questions in neuroscience. Recent single-cell RNA-seq (scRNA-seq) and single-nucleus RNA-seq (snRNA-seq) techniques have allowed us to explore the sparsely activated engram ensembles, enabling access to the molecular mechanisms that underlie experience-dependent memory formation and consolidation. However, the absence of specific and powerful computational methods to detect memory-related genes (modules) and their regulatory relationships in the sc/snRNA-seq datasets has strictly limited the analysis of underlying mechanisms and memory coding principles in mammalian brains. Here, we present a deep-learning method named SCENTBOX, to detect memory-related gene modules and causal regulatory relationships among themfromsc/snRNA-seq datasets. SCENTBOX first constructs codifferential expression gene network (CEGN) from case versus control sc/snRNA-seq datasets. It then detects the highly correlated modules of differential expression genes (DEGs) in CEGN. The deep network embedding and attention-based convolutional neural network strategies are employed to precisely detect regulatory relationships among DEG genes in a module. We applied them on scRNA-seq datasets of TRAP; Ai14 mouse neurons with fear memory and detected not only known memory-related genes, but also the modules and potential causal regulations. Our results provided novel regulations within an interesting module, including Arc, Bdnf, Creb, Dusp1, Rgs4, and Btg2. Overall, our methods provide a general computational tool for processing sc/snRNA-seq data from case versus control studie and a systematic investigation of fear-memory-related gene modules.

Keywords: sc/snRNA-seq, memory formation, deep learning, gene module, causal inference

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1357 Heamatological and Biochemical Changes in Cockerels Fed Graded Levels of Wild Sunflower Leaf Meal

Authors: Siyanbola Mojisola Funmilayo, Amao Emmanuel Ayodele

Abstract:

The poultry industry in Nigeria has been played by a variety of problems, which include the search for feed ingredients that are not competed for by man. This has resulted in a reduced interest of farmers in the industry leading to a reduction in animal protein availability for human consumption as a consequence of a high cost of production. The incorporation of wild sunflower meal (Tithonia diversfolia, Hemsl A. Gray) (WSF Meal) and some others in poultry diets have been reported to result in compounded feed with nutrient profiles that compare favourable with feeds of conventional feedstuff and reduce feed cost as they reduce competition with humans. A 98-day feeding trial was used to evaluate the effect of Wild sunflower leaf (WSL) at varying levels on the hematology and biochemistry of cockerels. A total of one hundred and twenty(120) cockerel birds were randomly allotted into four experimental diets with three replicates per experimental diet (ten birds per replicate). Wild sunflower leaf was included in four graded levels ; 0, 5, 10, and 15%. Packed cell volume, Red blood cell count, White blood cell count, Hemoglobin count, Lymphocyte count, Neutrophil count, Platelets, Mean Corpuscular Hemoglobin Concentration (MCHC), Mean Corpuscular Hemoglobin (MCH), Aspartate aminotransferase (AST), Glucose, Urea, Chloride, Sodium, and Potassium ion values were significantly different (p<0.05) among the treatments. Mean values obtained for Creatinine, Total Protein, Alanine aminotransferase (ALT), Albumin, and Mean Corpuscular Volume (MCV) were not significantly different (p>0.05) in all the treatment. WSL could be included up to 15% in the diet of cockerel without any deleterious effect on the birds. Based on the results, up to 15% Wild sunflower meal (WSL) can be included in the diet of cockerel without any adverse effect on the hematology and biochemical indices of birds.

Keywords: biochemical changes, cockerels, hematology, wild sunflower leaf

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1356 Effects of Ensiled Mulberry Leaves and Sun-Dried Mulberry Fruit Pomace on the Composition of Bacteria in Feces of Finishing Steers

Authors: Yan Li, Qingxiang Meng, Bo Zhou, Zhenming Zhou

Abstract:

The objective of this study was to compare the effects of ensiled mulberry leaves (EML), and sun-dried mulberry fruit pomace (SMFP) on fecal bacterial communities in Simmental crossbred finishing steers fed the following 3 diets: a standard TMR diet, standard diet containing EML and standard diet containing SMFP, and the diets had similar protein and energy levels. Bacterial communities in the fecal content were analyzed using Illumina Miseq sequencing of the V4 region of the 16S rRNA gene amplification. Quantitative real-time PCR was used to detect the selected bacterial species in the feces. Most of the sequences were assigned to phyla Firmicutes (56.67%) and Bacteroidetes(35.90%), followed by Proteobacteria(1.86%), Verrucomicrobia(1.80%) and Tenericutes(1.37%). And the predominant genera included the 5-7N15 (5.91%), CF231 (2.49%), Oscillospira (2.33%), Paludibacter (1.23%) and Akkermansia(1.11%). As for the treatments, no significant differences were observed in Firmicutes (p = 0.28), Bacteroidetes (p = 0.63), Proteobacteria (p = 0.46), Verrucomicrobia (p = 0.17) and Tenericutes (p = 0.75). On the genus level, classified genera with high abundance (more than 0.1%) mainly came from two phyla: Bacteroidetes and Firmicutes. Also no differences were observed in most genera level, 5-7N15 (p = 0.21), CF231 (p = 0.62), Oscillospira (p = 0.9), Paludibacter (p = 0.33) and Akkermansia (p = 0.37), except that rc4-4 were lower in the CON and SMFP groups compared to the EML animals (p = 0.02). Additionally, there were no differences in richness estimate and diversity indices (p > 0.16), and treatments had no significant effect on most selected bacterial species in the fecal (p > 0.06), except that Ruminococcus albus were higher in the EML group (p < 0.01) and Streptococcus bovis were lower in the CON group (p < 0.01). In conclusion, diets supplemented with EML and SMFP have little influence on fecal bacterial community composition in finishing steers.

Keywords: fecal bacteria community composition, sequencing, ensiled mulberry leaves (EML), sun-dried mulberry fruit pomace (SMFP)

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1355 Target and Biomarker Identification Platform to Design New Drugs against Aging and Age-Related Diseases

Authors: Peter Fedichev

Abstract:

We studied fundamental aspects of aging to develop a mathematical model of gene regulatory network. We show that aging manifests itself as an inherent instability of gene network leading to exponential accumulation of regulatory errors with age. To validate our approach we studied age-dependent omic data such as transcriptomes, metabolomes etc. of different model organisms and humans. We build a computational platform based on our model to identify the targets and biomarkers of aging to design new drugs against aging and age-related diseases. As biomarkers of aging, we choose the rate of aging and the biological age since they completely determine the state of the organism. Since rate of aging rapidly changes in response to an external stress, this kind of biomarker can be useful as a tool for quantitative efficacy assessment of drugs, their combinations, dose optimization, chronic toxicity estimate, personalized therapies selection, clinical endpoints achievement (within clinical research), and death risk assessments. According to our model, we propose a method for targets identification for further interventions against aging and age-related diseases. Being a biotech company, we offer a complete pipeline to develop an anti-aging drug-candidate.

Keywords: aging, longevity, biomarkers, senescence

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1354 Social Licence to Operate Methodology to Secure Commercial, Community and Regulatory Approval for Small and Large Scale Fisheries

Authors: Kelly S. Parkinson, Katherine Y. Teh-White

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Futureye has a bespoke social licence to operate methodology which has successfully secured community approval and commercial return for fisheries which have faced regulatory and financial risk. This unique approach to fisheries management focuses on delivering improved social and environmental outcomes to support the fishing industry make steps towards achieving the United Nations SDGs. An SLO is the community’s implicit consent for a business or project to exist. An SLO must be earned and maintained alongside regulatory licences. In current and new operations, it helps you to anticipate and measure community concerns around your operations – leading to more predictable and sensible policy outcomes that will not jeopardise your commercial returns. Rising societal expectations and increasing activist sophistication mean the international fishing industry needs to resolve community concerns at each stage their supply chain. Futureye applied our tested social licence to operate (SLO) methodology to help Austral Fisheries who was being attacked by activists concerned about the sustainability of Patagonian Toothfish. Austral was Marine Stewardship Council certified, but pirates were making the overall catch unsustainable. Austral wanted to be carbon neutral. SLO provides a lens on the risk that helps industries and companies act before regulatory and political risk escalates. To do this assessment, we have a methodology that assesses the risk that we can then translate into a process to create a strategy. 1) Audience: we understand the drivers of change and the transmission of those drivers across all audience segments. 2) Expectation: we understand the level of social norming of changing expectations. 3) Outrage: we understand the technical and perceptual aspects of risk and the opportunities to mitigate these. 4) Inter-relationships: we understand the political, regulatory, and reputation system so that we can understand the levers of change. 5) Strategy: we understand whether the strategy will achieve a social licence through bringing the internal and external stakeholders on the journey. Futureye’s SLO methodologies helped Austral to understand risks and opportunities to enhance its resilience. Futureye reviewed the issues, assessed outrage and materiality and mapped SLO threats to the company. Austral was introduced to a new way that it could manage activism, climate action, and responsible consumption. As a result of Futureye’s work, Austral worked closely with Sea Shepherd who was campaigning against pirates illegally fishing Patagonian Toothfish as well as international governments. In 2016 Austral launched the world’s first carbon neutral fish which won Austral a thirteen percent premium for tender on the open market. In 2017, Austral received the prestigious Banksia Foundation Sustainability Leadership Award for seafood that is sustainable, healthy and carbon neutral. Austral’s position as a leader in sustainable development has opened doors for retailers all over the world. Futureye’s SLO methodology can identify the societal, political and regulatory risks facing fisheries and position them to proactively address the issues and become an industry leader in sustainability.

Keywords: carbon neutral, fisheries management, risk communication, social licence to operate, sustainable development

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1353 Probiotics as an Alternative to Antibiotic Use in Pig Production

Authors: Z. C. Dlamini, R. L. S. Langa, A. I. Okoh, O. A. Aiyegoro

Abstract:

The indiscriminate usage of antibiotics in swine production have consequential outcomes; such as development of bacterial resistance to prophylactic antibiotics and possibility of antibiotic residues in animal products. The use of probiotics appears to be the most effective procedure with positive metabolic nutritional implications. The aim of this study was to investigate the efficacy of probiotic bacteria (Lactobacillus reuteri ZJ625, Lactobacillus reuteri VB4, Lactobacillus salivarius ZJ614 and Streptococcus salivarius NBRC13956) administered as direct-fed microorganisms in weaned piglets. 45 weaned piglets blocked by weight were dived into 5 treatments groups: diet with antibiotic, diet with no-antibiotic and no probiotic, and diet with probiotic and diet with combination of probiotics. Piglets performance was monitored during the trials. Faecal and Ileum samples were collected for microbial count analysis. Blood samples were collected from pigs at the end of the trial, for analysis of haematological, biochemical and IgG stimulation. The data was analysed by Split-Plot ANOVA using SAS statistically software (SAS 9.3) (2003). The difference was observed between treatments for daily weight and feed conversion ratio. No difference was observed in analysis of faecal samples in regards with bacterial counts, difference was observed in ileums samples with enteric bacteria colony forming unit being lower in P2 treatment group as compared with lactic acid and total bacteria. With exception of globulin and albumin, biochemistry blood parameters were not affected, likewise for haematology, only basophils and segmented neutrophils were differed by having higher concentration in NC treatment group as compared with other treatment groups. Moreover, in IgG stimulation analysis, difference was also observed, with P2 treatment group having high concentration of IgG in P2 treatment group as compared to other groups. The results of this study suggest that probiotics have a beneficial effect on growth performances, blood parameters and IgG stimulation of pigs, most effective when they are administered in synergy form. This means that it is most likely that these probiotics will offer a significant benefit in pig farming by reducing risk of morbidity and mortality and produce quality meat that is more affordable to poorer communities, and thereby enhance South African pig industry’s economy. In addition, these results indicate that there is still more research need to be done on probiotics in regards with, i.e. dosage, shelf life and mechanism of action.

Keywords: antibiotics, biochemistry, haematology, IgG-stimulation, microbial count, probiotics

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1352 In vivo Alterations in Ruminal Parameters by Megasphaera Elsdenii Inoculation on Subacute Ruminal Acidosis (SARA)

Authors: M. S. Alatas, H. D. Umucalilar

Abstract:

SARA is a common and serious metabolic disorder in early lactation in dairy cattle and in finishing beef cattle, caused by diets with high inclusion of cereal grain. This experiment was performed to determine the efficacy of Megasphaera elsdenii, a major lactate-utilizing bacterium in prevention/treatment of SARA in vivo. In vivo experimentation, it was used eight ruminally cannulated rams and it was applied the rapid adaptation with the mixture of grain based on wheat (%80 wheat, %20 barley) and barley (%80 barley, %20 wheat). During the systematic adaptation, it was followed the probability of SARA formation by being measured the rumen pH with two hours intervals after and before feeding. After being evaluated the data, it was determined the ruminal pH ranged from 5,2-5,6 on the condition of feeding with 60 percentage of grain mixture based on barley and wheat, that assured the definite form of subacute acidosis. In four days SARA period, M. elsdenii (1010 cfu ml-1) was inoculated during the first two days. During the SARA period, it was observed the decrease of feed intake with M. elsdenii inoculation. Inoculation of M. elsdenii was caused to differentiation of rumen pH (P < 0,0001), while it was found the pH level approximately 5,55 in animals applied the inoculation, it was 5,63 pH in other animals. It was observed that total VFA with the bacterium inoculation tended to change in terms of grain feed (P < 0,07). It increased with the effect of total VFA inoculation in barley based diet, but it was more stabilized in wheat based diet. Bacterium inoculation increased the ratio of propionic acid (18,33%-21,38%) but it caused to decrease the butyric acid, and acetic/propionic acid. During the rapid adaptation, the concentration of lactic acid in the rumen liquid increased depending upon grain level (P<0,0001). On the other hand bacterium inoculation did not have an effect on concentration of lactic acid. M. elsdenii inoculation did not affect ruminal ammonia concentration. In the group that did not apply inoculation, the level of ruminal ammonia concentration was higher than the others applied inoculation. M. elsdenii inoculation did not changed protozoa count in barley-based diet whereas it decreased in wheat-based diet. In the period of SARA, it was observed that the level of blood glucose, lactate and hematocrit increased greatly after inoculation (P < 0,0001). When it is generally evaluated, it is seen that M. elsdenii inoculation has not a positive impact on rumen parameters. Therefore, to reveal the full impact of the inoculation with different strains, feedstuffs and animal groups, further research is required.

Keywords: In vivo, Subactute ruminal acidosis, Megasphaera elsdenii, Rumen fermentation

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1351 The Effects of Acupoint Catgut Embedding for Weight Control in Mice Model

Authors: Chanya Inprasit, Ching-Liang Hsieh, Yi-Wen Lin

Abstract:

Obesity (OB) is a hazardous global health problem that has been increasing in prevalence, more severely in last decade. It is the mainly resultant from the imbalance between food consumption and energy expenditure, which is concordant with a modern lifestyle, implying an increase in calories with poorer quality of food intake accompanied by a decrease in physical activities. Obesity does not concern the appearance only but is also a major factor contributing to poor physiology, psychology, society and economic issues. Moreover, OB induces low-grade inflammation in the body through the regulatory effect it enacts on the adipocyte function. Various alternative treatments were investigated for body weight control, including Acupoint Catgut Embedding (ACE). ACE is the implantation of absorbable catgut sutures at specific acupoints, displaying durable and potent stimulation and thereby reducing the treatment frequency. Our study utilized a mouse model to exclude any psychological factors of OB and ACE treatment. High-fat diet and body weight were measured once a week before subjects in ACE and Sham group received the ACE treatment or placebo treatment. We hypothesized that ACE can control body weight through the interaction of the TRPV1 pathways, as TRPV1 accordingly responds to inflammatory factors. The results of body weight variation show a significant decrease in body weight in ACE group compared with the baseline of control and Sham group. Meanwhile, converse results were explored in TRPV1 knockout mice, where a significant maintenance of normal body weight throughout the experiment period was observed. There was no significant difference in food consumption of each group. These finding indicated that TRPV1 pathways and its associated pathways may be involved in the maintenance of body weight, which can be controlled by ACE treatment of genetic manipulation.

Keywords: acupoint catgut embedding, obesity, hypothalamus, TRPV1

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1350 Privatization of Pakistan Gas Sector: Role of Regulator

Authors: Lala Rukh, Muhammad Abbas Choudhary, Saddam Akber Abbasi

Abstract:

In Pakistan, the privatization of major sector of the national economy i.e. power, telecom, and gas is very strongly advocated since 80s. With varying degree of progress made in these sectors, it has been the government’s approach that the privatization accelerates the sectorial growth, increases operational efficiency and attracts the foreign investment and is of special significance for developing economies. The gas sector was not an exception and the privatization in this sector has moved through various stages during this time within the realms of socio-political agenda. This paper presents the overview of the gas sector in the country. The Oil and Gas Regulatory Authority (OGRA) Ordinance and privatization commission policy position as depicted in the press briefings provides philosophical foundations to the privatization and sectorial restructuring in this paper. The role of the major players from privatization perspective is discussed with special reference to the importance of natural gas sector. The case study further discusses the economic regulations that are being adopted by utility regulators in Pakistan and elsewhere in the world and some issues that the Regulatory Authority will be concerned are outlined. Major operators in the gas sector including Oil & Gas Development Corporation (OGDC), Sui Northern Gas Pipelines Limited (SNGPL), Sui Southern Gas Pipelines Limited (SSGPL) is also presented.

Keywords: privatization, economic regulation, OGDCL, SSGCL, SNGPL

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1349 A Review: Role of Chromium in Broiler

Authors: Naveed Zahra, Zahid Kamran, Shakeel Ahmad

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Heat stress is one of the most important environmental stressors challenging poultry production worldwide. The detrimental effect of heat stress results in reduction in the productive performance of poultry with high incidences of mortality. Researchers have made efforts to prevent such damage to poultry production through dietary manipulation. Supplementation with Chromium (Cr) might have some positive effects on some aspect of blood parameters and broilers performance. Chromium (Cr) the element whose trivalent Cr (III) organic state is present in trace amounts in animal feed and water is found to be a key element in evading heat stress and thus cutting down the heavy expenditure on air conditioning in broiler sheds. Chromium, along with other essential minerals is lost due to increased excretion during heat stress and thus its inclusion in broiler diet is kind of mandatory in areas of hot climate. Chromium picolinate in broiler diet has shown a hike in growth rate including muscle gain with body fat reduction under environmental stress. Fat reduction is probably linked to the ability of chromium to increase the sensitivity of the insulin receptors on tissues and thus the uptake of sugar from blood increases which decreases the amount of glucose to be converted to amino acids and stored in adipose tissue as triglycerides. Organic chromium has also shown to increase lymphocyte proliferation rate and antioxidant levels. So, the immune competency, muscle gain and fat reduction along with evasion of heat stress are good enough signs that indicate the fruitful inclusion of dietary chromium for broiler. This promising element may bring the much needed break in the local poultry industry. The task is now to set the exact dose of the element in the diet that would be useful enough and still not toxic to broiler. In conclusion there is a growing body of evidence which suggest that chromium may be an essential trace element for livestock and poultry. The nutritional requirement for chromium may vary with different species and physiological state within a species.

Keywords: broiler, chromium, heat stress, performance

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1348 Functional Food Industry in Thailand: Perspectives from Government, Education, and Private Sector

Authors: Charintorn Suwannawong, Tananpon Yavilas, Sopida Boonaneksap, Chotika Viriyarattanasak, Chairath Tangduangdee

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With increasing aging population and health conscious consumers, the demand for health promoting products such as functional foods, dietary supplements, and nutraceutical products has continuously increased in Thailand. Nevertheless, the strategic framework for regulatory functional food developments in Thailand is still unclear. The objective of this study was to survey stakeholders’ perspectives on three scopes, consisting of 1) the current status 2) obstacles, and 3) future trend for the development and production of functional foods in Thailand. A survey was conducted by interviewing ten experts from governmental organization, industrial sector and academic institute. The obtained results show that there is no established definition for functional foods in Thailand. There is a variety of raw materials that are capable to be potential ingredients for functional food production in Thailand and exported to global market. However, the scaling up technology into a commercial production is limited. Moreover, there is a need to establish the infrastructures, such as testing laboratory, and regulatory standards for quality control and ensuring product safety. This information is useful for government in the development of the strategic framework and policy statement on improvement of functional food industry in Thailand.

Keywords: functional foods, interview, perspective, Thailand

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1347 Management of Autoimmune Diseases with Ayurveda

Authors: Simmi Chopra

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In the last few years, there has been a surge of Autoimmune diseases that have become more like an epidemic all over the world. The reasons vary from stress, insufficient sleep, smoking, genetics, environmental pollution, adulterated foods, and a diet full of “the deadly white,” which is white sugar and white flour. Most of the people diagnosed with these diseases are given steroids, opioids, supplements, or elimination diets to manage their lives, but most of them continue suffering to varying degrees. On the other hand, Ayurveda can help manage autoimmune problems effectively. Ayurveda is a 5000 years old holistic medical system from India that has an individualistic approach where health problems are looked at from the lens of balancing body and mind and by targeting the root cause of the problem. A combination of diet and lifestyle according to Ayurvedic principles, Ayurvedic herbal formulations and Ayurvedic therapies can help in the management of autoimmune and other chronic diseases. Panchkarma, which is an intense six weeks detox method, helps balance our body and mind, and has been very effective in managing autoimmune problems. The paper will introduce the basic concepts of Ayurveda and describe the terminologies- doshas, agni and ama. The paper will discuss the importance of diet and lifestyle according to the individual’s imbalance in the three functional parameters - doshas, which govern every aspect of our body and mind, our cells and tissues. The significance of agni, which can be correlated to digestive strength and ama, which can be correlated to toxins that are formed in our body leading to health problems, will be outlined. The Ayurvedic pathophysiology of autoimmune diseases will be discussed with emphasis on Rheumatoid arthritis, Multiple sclerosis and Psoriasis. Ayurvedic management will be discussed for these autoimmune conditions. As Ayurveda is an individualistic system, one protocol will not work for everyone. Therefore, case studies with Ayurvedic protocols for the above autoimmune disease will be presented. Conclusion: Ayurveda can help in managing as well as arresting the progression of autoimmune problems. Ayurveda is an ancient medical system, is much more needed today than ever. It is a tried and tested holistic system which has been practiced for the past many generations in India.

Keywords: ayurveda, autoimmune, diseases, nutrition

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1346 Long-Term Outcomes of Dysphagia in Children with Severe Cerebral Palsy Using Videofluoroscopic Evaluation

Authors: Eun Jae Ko, In Young Sung, Eui Soo Joeng

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Oropharyngeal dysphagia is prevalent in children with cerebral palsy (CP). There are many studies concerning this problem, however, studies examining long term outcomes of dysphagia using videofluoroscopic study (VFSS) are very rare. The Aim of this study is to investigate long-term outcomes of dysphagia in children with severe CP using initial VFSS. It was a retrospective study and chart review was done from January 2000 to December 2013. Thirty one patients under 18 years who have been diagnosed as CP in outpatient clinic of Rehabilitation Medicine, and who did VFSS were included. Long-term outcomes such as feeding method, height percentile, weight percentile, and body mass index (BMI) were tracked up for at least 3 years by medical records. Significant differences between initial and follow-up datas were investigated. The patients consisted of 18 males and 13 females, and the mean age was 31.0±18.0 months old. 64.5% of patients were doing oral diet, and 25.8% of patients were doing non-oral diet. When comparing VFSS findings among oral feeding patients, oral and non-oral feeding patients, and non-oral feeding patients at initial period, dysphagia severity, supraglottic penetration, and subglottic aspiration showed significant differences. Most of the patients who could feed orally at initial period were found to have the same feeding method at follow-up. But among eight patients who required non-oral feeding initially, three patients became possible to feed orally, and one patient was doing oral and non-oral feeding method together at follow-up. Follow up feeding method showed correlation with dysphagia severity by initial VFSS. Weight percentile was decreased in patients with GMFCS level V at follow up, which may represent poor nutritional status due to severe dysphagia compared to other patients. Initial VFSS severity would play a significant role in making an assumption about future diet in children with severe CP. Patients with GMFCS level V seem to have serious dysphagia at follow up and have nutritional deficiency over time, therefore, more careful nutritional support is needed in children with severe CP are suggested.

Keywords: cerebral palsy, child, dysphagia, videofluoroscopic study

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1345 Ordinary Differentiation Equations (ODE) Reconstruction of High-Dimensional Genetic Networks through Game Theory with Application to Dissecting Tree Salt Tolerance

Authors: Libo Jiang, Huan Li, Rongling Wu

Abstract:

Ordinary differentiation equations (ODE) have proven to be powerful for reconstructing precise and informative gene regulatory networks (GRNs) from dynamic gene expression data. However, joint modeling and analysis of all genes, essential for the systematical characterization of genetic interactions, are challenging due to high dimensionality and a complex pattern of genetic regulation including activation, repression, and antitermination. Here, we address these challenges by unifying variable selection and game theory through ODE. Each gene within a GRN is co-expressed with its partner genes in a way like a game of multiple players, each of which tends to choose an optimal strategy to maximize its “fitness” across the whole network. Based on this unifying theory, we designed and conducted a real experiment to infer salt tolerance-related GRNs for Euphrates poplar, a hero tree that can grow in the saline desert. The pattern and magnitude of interactions between several hub genes within these GRNs were found to determine the capacity of Euphrates poplar to resist to saline stress.

Keywords: gene regulatory network, ordinary differential equation, game theory, LASSO, saline resistance

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1344 Calculational-Experimental Approach of Radiation Damage Parameters on VVER Equipment Evaluation

Authors: Pavel Borodkin, Nikolay Khrennikov, Azamat Gazetdinov

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The problem of ensuring of VVER type reactor equipment integrity is now most actual in connection with justification of safety of the NPP Units and extension of their service life to 60 years and more. First of all, it concerns old units with VVER-440 and VVER-1000. The justification of the VVER equipment integrity depends on the reliability of estimation of the degree of the equipment damage. One of the mandatory requirements, providing the reliability of such estimation, and also evaluation of VVER equipment lifetime, is the monitoring of equipment radiation loading parameters. In this connection, there is a problem of justification of such normative parameters, used for an estimation of the pressure vessel metal embrittlement, as the fluence and fluence rate (FR) of fast neutrons above 0.5 MeV. From the point of view of regulatory practice, a comparison of displacement per atom (DPA) and fast neutron fluence (FNF) above 0.5 MeV has a practical concern. In accordance with the Russian regulatory rules, neutron fluence F(E > 0.5 MeV) is a radiation exposure parameter used in steel embrittlement prediction under neutron irradiation. However, the DPA parameter is a more physically legitimate quantity of neutron damage of Fe based materials. If DPA distribution in reactor structures is more conservative as neutron fluence, this case should attract the attention of the regulatory authority. The purpose of this work was to show what radiation load parameters (fluence, DPA) on all VVER equipment should be under control, and give the reasonable estimations of such parameters in the volume of all equipment. The second task is to give the conservative estimation of each parameter including its uncertainty. Results of recently received investigations allow to test the conservatism of calculational predictions, and, as it has been shown in the paper, combination of ex-vessel measured data with calculated ones allows to assess unpredicted uncertainties which are results of specific unique features of individual equipment for VVER reactor. Some results of calculational-experimental investigations are presented in this paper.

Keywords: equipment integrity, fluence, displacement per atom, nuclear power plant, neutron activation measurements, neutron transport calculations

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1343 Determination of Aflatoxins in Edible-Medicinal Plant Samples by HPLC with Fluorescence Detector and KOBRA-Cell

Authors: Isil Gazioglu, Abdulselam Ertas

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Aflatoxins (AFs) are secondary toxic metabolites of Aspergillus flavus and A. parasiticus. AFs can be absorbed through the skin. Potent carcinogens like AFs should be completely absent from cosmetics, this can be achieved by careful quality control of the raw plant materials. Regulatory limits for aflatoxins have been established in many countries, and reliable testing methodology is needed to implement and enforce the regulatory limits. In this study, ten medicinal plant samples (Bundelia tournefortti, Capsella bursa-pastoris, Carduus tenuiflorus, Cardaria draba, Malva neglecta, Malvella sharardiana, Melissa officinalis, Sideritis libanotica, Stakys thirkei, Thymus nummularius) were investigated for aflatoxin (AF) contaminations by employing an HPLC assay for the determination of AFB1, B2, G1 and G2. The samples were extracted with 70% (v/v) methanol in water before further cleaned up with an immunoaffinity column and followed by the detection of AFs by using an electrochemically post-column derivatization with Kobra-Cell and fluorescence detector. The extraction procedure was optimized in order to obtain the best recovery. The method was successfully carried out with all medicinal plant samples. The results revealed that five (50%) of samples were contaminated with AFs. The association between particular samples and the AF contaminated could not be determined due to the low frequency of positive samples.

Keywords: aflatoxin B1, HPLC-FLD, KOBRA-Cell, mycotoxin

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1342 Diet-Induced Epigenetic Transgenerational Inheritance

Authors: Gaby Fahmy

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The last decades have seen a rise in metabolic disorders like diabetes, obesity, and fatty liver disease around the world. Environmental factors, especially nutrition, have contributed to this increase. Additionally, pre-conceptional parental nutritional choices have been shown to result in epigenetic modifications affecting gene expression during the developmental process in-utero. These epigenetic modifications have also been seen to extend to the following offspring in a trans-generational effect. This further highlights the significance and relevance of epigenetics and epigenetic tags, which were previously thought to be stripped in newly formed embryos. Suitable prenatal nutrition may partially counteract adverse outcomes caused by exposures to environmental contaminants, ultimately resulting in improved metabolic profiles like body weight and glucose homeostasis. This was seen in patients who were given dietary interventions like restrictive caloric intake, intermittent fasting, and time-restricted feeding. Changes in nutrition are pivotal in the regulation of epigenetic modifications that are transgenerational. For example, dietary choices such as fatty foods vs. vegetables and nuts in fathers were shown to significantly affect sperm motility and volume. This was pivotal in understanding the importance of paternal inheritance. Further research in the field is needed as it remains unclear how many generations are affected by these changes.

Keywords: epigenetics, transgenerational, diet, fasting

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1341 Phytochemical Screening, Antioxidant Activity, Lipid Profile Effect of Citrus reticulata Fruit Peel, Zingiber officinale Rhizome, and Sesamum indicum Seed Extracts

Authors: Samar Saadeldin Abdelmotalab Omer, Ikram Mohammed Eltayeb Elsiddig, Amna Beshir Medani Ahmed, Saad Mohammed Hussein Ayoub

Abstract:

Many herbal medicinal products are considered as potential hypocholesterolemic agents with encouraging safety profiles, however, only a limited amount of clinical research exists to support their efficacy. The present study was designed to compare the antihypercholesterolaemic and antioxidant activities of the crude ethanolic extracts of Citrus reticulata peel, Zingiber officinale rhizome, and Sesamum indicum seeds. Forty-five rats were used throughout the experiment, which were divided into nine groups, five rats in each as follows; normal control group (normal rats fed with standard normal diet), rats fed hypercholesterolemic diet consisting of 1% cholesterol and 10% saturated animal fat, which were further divided into eight groups; hypercholesterolemic control group (rats only fed hypercholesterolemic diet), groups 3,4,5,6,7, and 8 were given Citrus reticulata, Zingiber officinale, and Sesamum indicum ethanolic extracts at doses of (250mg/kg and 500mg/kg, respectively) orally; and group 9 rats were given atorvastatin (0.18mg/kg) orally as a reference antihypercholesterolaemic drug. Blood samples were obtained four weeks following treatment from the retro-orbital venous plexus after fasting overnight from all groups and the lipid profile (serum total cholesterol (TC), high-density-lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and triglycerides levels) was measured and the risk ratio (TC/HDL-C) was assessed. The antioxidant activity of the three plant extracts was determined using DPPH free-radical assay. Results of in vivo and in vitro antihypercholesterolaemic and antioxidant assay, respectively, revealed that the three extracts possess comparable antioxidant and anti-hypercholesterolaemic activities.

Keywords: anti hypercholesterolemic effects, antioxidant activity, HDL, LDL, TC, TGs, citrus reticulata, sesamum indicum, zingiber officinale

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1340 Intensive Crosstalk between Autophagy and Intracellular Signaling Regulates Osteosarcoma Cell Survival Response under Cisplatin Stress

Authors: Jyothi Nagraj, Sudeshna Mukherjee, Rajdeep Chowdhury

Abstract:

Autophagy has recently been linked with cancer cell survival post drug insult contributing to acquisition of resistance. However, the molecular signaling governing autophagic survival response is poorly explored. In our study, in osteosarcoma (OS) cells cisplatin shock was found to activate both MAPK and autophagy signaling. An activation of JNK and autophagy acted as pro-survival strategy, while ERK1/2 triggered apoptotic signals upon cisplatin stress. An increased sensitivity of the cells to cisplatin was obtained with simultaneous inhibition of both autophagy and JNK pathway. Furthermore, we observed that the autophagic stimulation upon drug stress regulates other developmentally active signaling pathways like the Hippo pathway in OS cells. Cisplatin resistant cells were thereafter developed by repetitive drug exposure followed by clonal selection. Basal levels of autophagy were found to be high in resistant cells to. However, the signaling mechanism leading to autophagic up-regulation and its regulatory effect differed in OS cells upon attaining drug resistance. Our results provide valuable clues to regulatory dynamics of autophagy that can be considered for development of improved therapeutic strategy against resistant type cancers.

Keywords: JNK, autophagy, drug resistance, cancer

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1339 Variation in pH Values and Tenderness of Meat of Cattle Fed Different Levels of Lipids

Authors: Erico Da Silva Lima, Tiago Neves Pereira Valente, Roberto De Oliveira Roça

Abstract:

Introduction: Over the last few years the market has increased its demand for high quality meat. Based on this premise some producers have continuously improved their efficiency in breeding beef cattle with the purpose to support this demand. It is well recognized that final quality of beef is intimately linked to animal’s diet. The key objective of this study is to evaluate the influence of feeding animals with cottonseed and its lipids and the final results in terms of pH and shear forces of the meat. Materials and Methods: The study was carried out in the Chapéu de Couro Farm in Aguaí/SP, Brazil. A group of 39 uncastrated Nellore cattle. Mean age of the animals was 36 months and initial mean live weight was 494.1 ± 10.1. Animals were randomly assigned to one of three treatments, based on dry matter: feed with control diet 2.50% cottonseed, feed with 11.50% cottonseed, and feed with 3.13% cottonseed added of 1.77% protected lipid. Forage:concentrate ratio was 50:50 on a dry matter basis. Sugar cane chopped was used as forage. After slaughter, carcasses were identified and divided into two halves that were kept in a cold chamber for 24 h at 2°C. Using pH meter was determined post-mortem pH in Longissimus thoracis muscle between the 12th and 13th rib of the left half carcass. After, part of each animal was removed, and divided in three samples (steaks). Steaks were 2.5 cm thick and were identified and stored individually in plastic bags under vacuum. Samples were frozen in a freezer at -18°C. The same samples cooked were refrigerated by 12 h the 4°C, and then cut into cylinders 1.10 Øcm with the support of a drill press avoiding fats and nerves. Shear force was calculated in these samples cut into cylinders through the Brookfield texture CT3 Texture Analyzer 25 k equipped with a set of blade Warner-Bratzler. Results and Discussion: No differences (P > 0.05) in pH 24 h after slaughter were observed in the meat of Nellore cattle fed different sources of fat, and mean value for this variable was 5.59. However, for the shear force differences (P < 0.05) were founded. For diet with 2,50% cottonseed the lowest value found 5.10 (kg) while for the treatment with 11.50% cottonseed the great value found was 6.30 (kg). High shear force values mean greater texture of meat that indicates less tenderness. The texture of the meat can be influenced by age, weight to the slaughter of animals. For cattle breed Nellore Bos taurus indicus more high value of shear force. Conclusions: The add the cottonseed or protected lipid in diet is not affected pH values in meat. The whole cottonseed does not contribute to the improvement of tenderness of the meat. Acknowledgments: IFGoiano, FAPEG and CNPq (Brazil).

Keywords: beef quality, cottonseed, protected fat, shear force

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1338 Effects of Raw Bee Propolis and Water or Ethanol Extract of Propolis on Performance, Immune System and Some Blood Parameters on Broiler Bredeers

Authors: Hasan Alp Sahin, Ergin Ozturk

Abstract:

The effects of raw bee propolis (RP) and water (WEP) or ethanol (EEP) extract of propolis on growth performance, selected immune parameters (IgA, IgY and IgM) and some blood parameters such as aspartate aminotransferase, alanine aminotransferase, trygliceride, total protein, albumin, calcium, phosphorus, total antioxidant status and total oxidant status were determined. The study was conducted between 15th and 20th weeks (6 weeks) and used a total of 48 broiler breeder pullets (Ross-308). The broiler breeder in control group was fed diet without propolis whereas the birds in RP, WEP and EEP groups were fed diets with RP, WEP and EEP at the level of 1200, 400 and 400 ppm, respectively. All pullets were fed mash form diet with 15% crude protein and 2800 ME kcal/kg. All propolis forms had not a beneficial effect on any studied parameters compared to control group (P > 0.05). The results of the study indicated that both the level of the active matters supplied from the bee propolis has no enough beneficial effect on performance, some immune and blood parameters on broiler breeders or they did not have such a level that would cause a beneficial effect on these variables.

Keywords: antioxidant, bee product , poultry breeders, growth performance, immune parameters, blood chemistry

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1337 Using Virtual Reality to Convey the Information of Food Supply Chain

Authors: Xinrong Li, Jiawei Dai

Abstract:

Food production, food safety, and the food supply chain are causing a great challenge to human health and the environment. Different kinds of food have different environmental costs. Therefore, a healthy diet can alleviate this problem to a certain extent. In this project, an online questionnaire was conducted to understand the purchase behaviour of consumers and their attitudes towards basic food information. However, the data shows that the public's current consumption habits and ideology do not meet the long-term development of sustainable social needs. In order to solve the environmental problems caused by the unbalanced diet of the public and the social problems of unequal food distribution, the purpose of this paper is to explore how to use the emerging media of VR to visualize food supply chain information so as to attract users' attention to the environmental cost of food. In this project, the food supply chain of imported and local cheese was compared side-by-side in the virtual reality environment, including the origin, transportation, sales, and other processes, which can effectively help users understand the difference between the two processes and environmental costs. Besides, the experimental data demonstrated that the participant would like to choose low environmental cost food after experiencing the whole process.

Keywords: virtual reality, information design, food supply chain, environmental cost

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1336 Functional Beverage to Boosting Immune System in Elderly

Authors: Adineh Tajmousavilangerudi, Ali Zein Alabiden Tlais, Raffaella Di Cagno

Abstract:

The SARS-Cov-2 pandemic has exposed our vulnerability to new illnesses and novel viruses that attack our immune systems, particularly in the elderly. The vaccine is being gradually introduced over the world, but new strains of the virus and COVID-19 will emerge and continue to cause illness. Aging is associated with significant changes in intestinal physiology, which increases the production of inflammatory products, alters the gut microbiota, and consequently establish inadequate immune response to minimize symptoms and disease development. In this context, older people who followed a Mediterranean-style diet, rich in polyphenols and dietary fiber, performed better physically and mentally (1,2). This demonstrates the importance of the human gut microbiome in transforming complex dietary macromolecules into the most biologically available and active nutrients, which in turn help to regulate metabolism and both intestinal and systemic immune function (3,4). The role of lactic acid fermentation is prominent also as a powerful tool for improving the nutritional quality of the human diet by releasing nutrients and boosting the complex bioactive compounds and vitamin content. the PhD project aims to design fermented and functional foods/beverages capable of modulating human immune function via the gut microbiome.

Keywords: functional bevarage, fermented beverage, gut microbiota functionality, immun system

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1335 Possibilities of Building Regional Migration Governance due to the Venezuelan Diaspora in Ibero-America (2015-2018)

Authors: Jonathan Palatz Cedeño

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The paper will seek to examine the scope and limitations of the process of construction of ordinary and extraordinary migration regulatory tools of the countries of Latin America, due to the Venezuelan diaspora in Ibero-America (2015-2018). The analysis methodology will be based on a systematic presentation of the existing advances in the subject under a qualitative approach, in which the results are detailed. We hold that an important part of the Latin American countries that used to be the emitters of migrants have had to generate, with greater or lesser success both nationally and regionally, ordinary and extraordinary migration regulatory tools to respond to the rapid intensification of the current Venezuelan migratory flows. This fact beyond implementing policies for the reception and integration of this population marks a new moment that represents a huge challenge both for the receiving States and for the young Ibero-American institutional migration system. Therefore, we can say that measures to adopt reception and solidarity policies, despite being supported by organs of the multilateral system such as UNHCR and IOM, are not found as guidelines for national and regional action, at the expense of the reactions of the respective public opinions and the influence of what to do of the neighboring countries in the face of the problem.

Keywords: Venezuela, migration, migration policies and governance, Venezuelan diaspora

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1334 The Contribution of Diet and Lifestyle Factors in the Prevalence of Irritable Bowel Syndrome

Authors: Alexander Dao, Oscar Wambuguh

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Irritable Bowel Syndrome (IBS) is a heterogeneous functional bowel disease that is characterized by chronic visceral abdominal pain and abnormal bowel function and habits. Its multifactorial pathophysiology and mechanisms are still largely a mystery to the contemporary biomedical community, although there are many hypotheses to try to explain IBS’s presumed physiological, psychosocial, genetic, and environmental etiologies. IBS’s symptomatic presentation is varied and divided into four major subtypes: IBS-C, IBS-D, IBS-M, and IBS-U. Given its diverse presentation and unclear mechanisms, diagnosis is done through a combination of positive identification utilizing the “Rome IV Irritable Bowel Syndrome Criteria'' (Rome IV) diagnostic criteria while also excluding other potential conditions with similar symptoms. Treatment of IBS is focused on the management of symptoms using an assortment of pharmaceuticals, lifestyle changes, and dietary changes, with future potential in microbial treatment and psychotherapy as other therapy methods. Its chronic, heterogeneous nature and disruptive gastrointestinal (GI) symptoms are negatively impactful on patients’ daily lives, health systems, and society. However, with a better understanding of the gaps in knowledge and technological advances in IBS’s pathophysiology, management, and treatment options, there is optimism for the millions of people worldwide who are suffering from the debilitating effects of IBS.

Keywords: irritable bowel syndrome, lifestyle, diet, functional gastrointestinal disorder

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1333 Kluyveromyces marxianus ABB S8 as Yeast-Based Technology to Manufacture Low FODMAP Baking Good

Authors: Jordi Cuñé, Carlos de Lecea, Laia Marti

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Small molecules known as fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) are quickly fermented in the large intestine after being poorly absorbed in the small intestine. There is proof that individuals suffering from functional gastrointestinal disorders, like irritable bowel syndrome (IBS), observe an improvement while following a diet low in FODMAPs. Because wheat has a relatively high fructan content, it is a key source of FODMAPs in our diet. A yeast-based method was created in this study to lower the amounts of FODMAP in (whole wheat) bread. In contrast to fermentation by regular baker yeast, the combination of Kluyveromyces marxianus ABB S7 with Saccharomyces cerevisiae allowed a reduction of fructan content by 60% without implying the appearance of other substrates categorized as FODMAP (excess fructose or polyols). The final FODMAP content in the developed whole wheat bread would allow its classification as a safe product for sensitive people, according to international consensus. Cocultures of S. cerevisiae and K. marxianus were established in order to ensure sufficient CO₂ generation; larger quantities of gas were produced due to the strains' synergistic relationship. Thus, this method works well for lowering the levels of FODMAPs in bread.

Keywords: Kluyveromyces marxianus, bakery, bread, FODMAP, IBS, functional gastro intestinal disorders

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1332 Effect of Antioxidant-Rich Nutraceutical on Serum Glucose, Lipid Profile and Oxidative Stress Markers of Salt-Induced Metabolic Syndrome in Rats

Authors: Nura Lawal, Lawal Suleiman Bilbis, Rabiu Aliyu Umar, Anas A. Sabir

Abstract:

Metabolic syndrome (MS) a high-risk condition involving obesity, dyslipidemia, hypertension, and diabetes mellitus is prevalent in Nigeria. The study aims to formulate an antioxidant-rich nutraceutical from locally available foodstuff (onion, garlic, ginger, tomato, lemon, palm oil, watermelon seeds) and investigate their effects on blood pressure, body weight, serum glucose, lipid profile, insulin and oxidative stress markers in salt-induced rats. The rats were placed on 8% salt diet for 6 weeks and then supplementation and treatment with nutraceutical and nifedipine in the presence of salt diet for additional 4 weeks. Feeding rats with salt diet for 6 weeks increased blood pressure and body weight of the salt-loaded rats relative to control. Significant (P < 0.001) increase in serum blood glucose and lipid profile, and the decrease in high-density lipoprotein-cholesterol (HDL-C) was observed in salt-loaded rats as compared with control. Both supplementation and treatment (nifedipine) lowered the blood pressure but the only supplementation lowered the body weight. Supplementation with nutraceutical resulted in significant (P < 0.001) decrease in the serum blood glucose, lipid profile, malonyldialdehyde (MDA), insulin levels, insulin resistance, and increased HDL-C and antioxidant indices. The percentage protection against atherogenesis was 76.5±2.13%. There is strong positive correlation between blood pressure, body weight and serum blood glucose, lipid profile, markers of oxidative stress and strong negative correlation with HDL-C and antioxidant status. The results suggest that the nutraceuticals are useful in reversing most of the component of metabolic syndrome and might be beneficial in the treatment of patients with metabolic syndrome.

Keywords: metabolic syndrome, hypertension, diabetes mallitus, obesity

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1331 Evaluation of Chemoprotective Effect of NBRIQU16 against N-Methyl-N-Nitro-N-Nitrosoguanidine and NaCl-Induced Gastric Carcinomas in Wistar Rats

Authors: Lubna Azmi, Ila Shukla, Shyam Sundar Gupta, Padam Kant, C. V. Rao

Abstract:

To investigate the chemoprotective potential of NBRIQU16 chemotype isolated from Argyreia speciosa (Family: Convolvulaceae) on N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and NaCl-induced gastric carcinomas in Wistar rats. Forty-six male 6-week-old Wistar rats were divided into two groups. Thirty rats in group A were fed with a diet supplemented with 8 % NaCl for 20 weeks and simultaneously given N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) in drinking water at a concentration of 100 ug/ml for the first 17 weeks. After administration of the carcinogen, 200 and 400 mg/kg of NBRIQU16 were administered orally once a day throughout the study. From week 18, these rats were given normal water. From week 21, these rats were fed with a normal diet for 15 weeks. Group B containing 16 rats was fed standard diet for thirty-five days. It served as control. Ten rats from group A were sacrificed after 20 weeks. Scarification of remaining animals was conducted after 35 weeks. Entire stomach and some part of the duodenum were incised parallel to the greater curvature, and the samples were collected. After opening the stomach location and size of tumors were recorded. The number of tumors with their locations and sizes were recorded. Expression of survivin was examined by recording the Immunohistochemistry of the specimens. The treatment with NBRIQU16 significantly reduced the nodule incidence and nodule multiplicity in the rats after MNNG administration. Surviving expression in glandular stomachs of normal rats, of rats in middle induction period, in adenocarcinomas and NBRIQU16 treated tissues adjacent to tumor were 0, 42.0 %, 79.3%, and 36.4 %, respectively. Expression of survivin was significantly different as compared to the normal rats. Histological observations of stomach tissues too correlated with the biochemical observations.These finding powerfully supports that NBRIQU16 chemopreventive effect by suppressing the tumor burden and restoring the activities of gastric cancer marker enzymes on MNNG and NaCl-induced gastric carcinomas in Wistar rats.

Keywords: Argyreia speciosa, gastric carcinoma, immunochemistry, NBRIQU16

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1330 Accountants and Anti-Money Laundering Compliance in the Real Estate Sector

Authors: Mark E. Lokanan, Liz Lee

Abstract:

This paper aims to examine the role of accountants as gatekeepers in anti-money laundering compliance in real estate transactions. The paper seeks to answer questions on ways in which accountants are involved in real estate transactions and mandatory compliance with regulatory authorities in Canada. The data for the study came from semi-structured interviews with accountants, lawyers, and government officials. Preliminary results reveal that there is a conflict between accountants’ obligation to disclose and loyalty to their clients. Accountants often do not see why they are obligated to disclose their clients' information to government agencies. The importance of the client in terms of the amount of revenue contributed to the accounting firm also plays a significant role in accountants' reporting decision-making process. Although the involvement of accountants in real estate purchase and sale transactions is limited to lawyers or notaries, they are often involved in designing financing schemes, which may involve money laundering activities. The paper is of wider public policy interests to both accountants and regulators. It is hard not to see Chartered Professional Accountant (CPA) Canada and government regulators using the findings to better understand the decision-making processes of accountants in their reporting practices to regulatory authorities.

Keywords: money laundering, real estate, disclosure, legislation, compliance

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1329 Scientific and Regulatory Challenges of Advanced Therapy Medicinal Products

Authors: Alaa Abdellatif, Gabrièle Breda

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Background. Advanced therapy medicinal products (ATMPs) are innovative therapies that mainly target orphan diseases and high unmet medical needs. ATMP includes gene therapy medicinal products (GTMP), somatic cell therapy medicinal products (CTMP), and tissue-engineered therapies (TEP). Since legislation opened the way in 2007, 25 ATMPs have been approved in the EU, which is about the same amount as the U.S. Food and Drug Administration. However, not all of the ATMPs that have been approved have successfully reached the market and retained their approval. Objectives. We aim to understand all the factors limiting the market access to very promising therapies in a systemic approach, to be able to overcome these problems, in the future, with scientific, regulatory and commercial innovations. Further to recent reviews that focus either on specific countries, products, or dimensions, we will address all the challenges faced by ATMP development today. Methodology. We used mixed methods and a multi-level approach for data collection. First, we performed an updated academic literature review on ATMP development and their scientific and market access challenges (papers published between 2018 and April 2023). Second, we analyzed industry feedback from cell and gene therapy webinars and white papers published by providers and pharmaceutical industries. Finally, we established a comparative analysis of the regulatory guidelines published by EMA and the FDA for ATMP approval. Results: The main challenges in bringing these therapies to market are the high development costs. Developing ATMPs is expensive due to the need for specialized manufacturing processes. Furthermore, the regulatory pathways for ATMPs are often complex and can vary between countries, making it challenging to obtain approval and ensure compliance with different regulations. As a result of the high costs associated with ATMPs, challenges in obtaining reimbursement from healthcare payers lead to limited patient access to these treatments. ATMPs are often developed for orphan diseases, which means that the patient population is limited for clinical trials which can make it challenging to demonstrate their safety and efficacy. In addition, the complex manufacturing processes required for ATMPs can make it challenging to scale up production to meet demand, which can limit their availability and increase costs. Finally, ATMPs face safety and efficacy challenges: dangerous adverse events of these therapies like toxicity related to the use of viral vectors or cell therapy, starting material and donor-related aspects. Conclusion. As a result of our mixed method analysis, we found that ATMPs face a number of challenges in their development, regulatory approval, and commercialization and that addressing these challenges requires collaboration between industry, regulators, healthcare providers, and patient groups. This first analysis will help us to address, for each challenge, proper and innovative solution(s) in order to increase the number of ATMPs approved and reach the patients

Keywords: advanced therapy medicinal products (ATMPs), product development, market access, innovation

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