Search results for: crop disease detection
Commenced in January 2007
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Edition: International
Paper Count: 7710

Search results for: crop disease detection

450 Factors Influencing Family Resilience and Quality of Life in Pediatric Cancer Patients and Their Caregivers: A Cluster Analysis

Authors: Li Wang, Dan Shu, Shiguang Pang, Lixiu Wang, Bing Xiang Yang, Qian Liu

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Background: Cancer is one of the most severe diseases in childhood; long-term treatment and its side effects significantly impact the patient's physical, psychological, social functioning and quality of life while also placing substantial physical and psychological burdens on caregivers and families. Family resilience is crucial for children with cancer, helping them cope better with the disease and supporting the family in facing challenges together. As a family-level variable, family resilience requires information from multiple family members. However, to our best knowledge, there is currently no research investigating family resilience from both the perspectives of pediatric cancer patients and their caregivers. Therefore, this study aims to investigate the family resilience and quality of life of pediatric cancer patients from a patient–caregiver dyadic perspective. Methods: A total of 149 dyads of patients diagnosed with pediatric cancer patients and their principal caregivers were recruited from oncology departments of 4 tertiary hospitals in Wuhan and Taiyuan, China. All participants completed questionnaires that identified their demographic and clinical characteristics as well as assessed their family resilience and quality of life for both the patients and their caregivers. K-means cluster analysis was used to identify different clusters of family resilience based on the reports from patients and caregivers. Multivariate logistic regression and linear regression are used to analyze the factors influencing family resilience and quality of life, as well as the relationship between the two. Results: Three clusters of family resilience were identified: a cluster of high family resilience (HR), a cluster of low family resilience (LR), and a cluster of discrepant family resilience (DR). Most (67.1%) families fell into the cluster with low resilience. Characteristics such as the types of caregivers perceived social support of the patient were different among the three clusters. Compared to the LR group, families where the mother is the caregiver and where the patient has high social support are more likely to be assigned to the HR. The quality of life for caregivers was consistently highest in the HR cluster and lowest in the LR cluster. The patient's quality of life is not related to family resilience. In the linear regression analysis of the patient's quality of life, patients who are the first-born have higher quality of life, while those living with their parents have lower quality of life. The participants' characteristics were not associated with the quality of life for caregivers. Conclusions: In most families, family resilience was low. Families with maternal caregivers and patients receiving high levels of social support are more inclined to be higher levels of family resilience. Family resilience was linked to the quality of life of caregivers of pediatric cancer patients. The clinical implications of this findings suggest that healthcare and social support organizations should prioritize and support the participation of mothers in caregiving responsibilities. Furthermore, they should assist families in accessing social support to enhance family resilience. This study also emphasizes the importance of promoting family resilience for enhancing family health and happiness, as well as improving the quality of life for caregivers.

Keywords: pediatric cancer, cluster analysis, family resilience, quality of life

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449 Effects of the Natural Compound on SARS-CoV-2 Spike Protein-Mediated Metabolic Alteration in THP-1 Cells Explored by the ¹H-NMR-Based Metabolomics Approach

Authors: Gyaltsen Dakpa, K. J. Senthil Kumar, Nai-Wen Tsao, Sheng-Yang Wang

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Context: Coronavirus disease 2019 (COVID-19) is a severe respiratory illness caused by the SARS-CoV-2 virus. One of the hallmarks of COVID-19 is a change in metabolism, which can lead to increased severity and mortality. The mechanism of SARS-CoV-2-mediated perturbations of metabolic pathways has yet to be fully understood. Research Aim: This study aimed to investigate the metabolic alteration caused by SARS-CoV-2 spike protein in Phorbol 12-myristate 13-acetate (PMA)-induced human monocytes (THP-1) and to examine the regulatory effect of natural compounds like Antcins A on SARS-CoV-2 spike protein-induced metabolic alteration. Methodology: The study used a combination of proton nuclear magnetic resonance (1H-NMR) and MetaboAnalyst 5.0 software. THP-1 cells were treated with SARS-CoV-2 spike protein or control, and the metabolomic profiles of the cells were compared. Antcin A was also added to the cells to assess its regulatory effect on SARS-CoV-2 spike protein-induced metabolic alteration. Findings: The study results showed that treatment with SARS-CoV-2 spike protein significantly altered the metabolomic profiles of THP-1 cells. Eight metabolites, including glycerol-phosphocholine, glycine, canadine, sarcosine, phosphoenolpyruvic acid, glutamine, glutamate, and N, N-dimethylglycine, were significantly different between control and spike-protein treatment groups. Antcin A significantly reversed the changes in these metabolites. In addition, treatment with antacid A significantly inhibited SARS-CoV-2 spike protein-mediated up-regulation of TLR-4 and ACE2 receptors. Theoretical Importance The findings of this study suggest that SARS-CoV-2 spike protein can cause significant metabolic alterations in THP-1 cells. Antcin A, a natural compound, has the potential to reverse these metabolic alterations and may be a potential candidate for developing preventive or therapeutic agents for COVID-19. Data Collection: The data for this study was collected from THP-1 cells that were treated with SARS-CoV-2 spike protein or a control. The metabolomic profiles of the cells were then compared using 1H-NMR and MetaboAnalyst 5.0 software. Analysis Procedures: The metabolomic profiles of the THP-1 cells were analyzed using 1H-NMR and MetaboAnalyst 5.0 software. The software was used to identify and quantify the cells' metabolites and compare the control and spike-protein treatment groups. Questions Addressed: The question addressed by this study was whether SARS-CoV-2 spike protein could cause metabolic alterations in THP-1 cells and whether Antcin A can reverse these alterations. Conclusion: The findings of this study suggest that SARS-CoV-2 spike protein can cause significant metabolic alterations in THP-1 cells. Antcin A, a natural compound, has the potential to reverse these metabolic alterations and may be a potential candidate for developing preventive or therapeutic agents for COVID-19.

Keywords: SARS-CoV-2-spike, ¹H-NMR, metabolomics, antcin-A, taiwanofungus camphoratus

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448 Identifying Protein-Coding and Non-Coding Regions in Transcriptomes

Authors: Angela U. Makolo

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Protein-coding and Non-coding regions determine the biology of a sequenced transcriptome. Research advances have shown that Non-coding regions are important in disease progression and clinical diagnosis. Existing bioinformatics tools have been targeted towards Protein-coding regions alone. Therefore, there are challenges associated with gaining biological insights from transcriptome sequence data. These tools are also limited to computationally intensive sequence alignment, which is inadequate and less accurate to identify both Protein-coding and Non-coding regions. Alignment-free techniques can overcome the limitation of identifying both regions. Therefore, this study was designed to develop an efficient sequence alignment-free model for identifying both Protein-coding and Non-coding regions in sequenced transcriptomes. Feature grouping and randomization procedures were applied to the input transcriptomes (37,503 data points). Successive iterations were carried out to compute the gradient vector that converged the developed Protein-coding and Non-coding Region Identifier (PNRI) model to the approximate coefficient vector. The logistic regression algorithm was used with a sigmoid activation function. A parameter vector was estimated for every sample in 37,503 data points in a bid to reduce the generalization error and cost. Maximum Likelihood Estimation (MLE) was used for parameter estimation by taking the log-likelihood of six features and combining them into a summation function. Dynamic thresholding was used to classify the Protein-coding and Non-coding regions, and the Receiver Operating Characteristic (ROC) curve was determined. The generalization performance of PNRI was determined in terms of F1 score, accuracy, sensitivity, and specificity. The average generalization performance of PNRI was determined using a benchmark of multi-species organisms. The generalization error for identifying Protein-coding and Non-coding regions decreased from 0.514 to 0.508 and to 0.378, respectively, after three iterations. The cost (difference between the predicted and the actual outcome) also decreased from 1.446 to 0.842 and to 0.718, respectively, for the first, second and third iterations. The iterations terminated at the 390th epoch, having an error of 0.036 and a cost of 0.316. The computed elements of the parameter vector that maximized the objective function were 0.043, 0.519, 0.715, 0.878, 1.157, and 2.575. The PNRI gave an ROC of 0.97, indicating an improved predictive ability. The PNRI identified both Protein-coding and Non-coding regions with an F1 score of 0.970, accuracy (0.969), sensitivity (0.966), and specificity of 0.973. Using 13 non-human multi-species model organisms, the average generalization performance of the traditional method was 74.4%, while that of the developed model was 85.2%, thereby making the developed model better in the identification of Protein-coding and Non-coding regions in transcriptomes. The developed Protein-coding and Non-coding region identifier model efficiently identified the Protein-coding and Non-coding transcriptomic regions. It could be used in genome annotation and in the analysis of transcriptomes.

Keywords: sequence alignment-free model, dynamic thresholding classification, input randomization, genome annotation

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447 Nursing Students’ Learning Effects of Online Visits for Mothers Rearing Infants during the COVID-19 Pandemic

Authors: Saori Fujimoto, Hiromi Kawasaki, Mari Murakami, Yoko Ueno

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Background: Coronavirus disease (COVID-19) has been spreading throughout the world. In Japan, many nursing universities have conducted online clinical practices to secure students’ learning opportunities. In the field of women’s health nursing, even after the pandemic ended, it will be worthwhile to utilize online practice in declining birthrate and reducing the burden of mothers. This study examined the learning effects of conducting online visits for mothers with infants during the COVID-19 pandemic by nursing students to enhance the students’ ability to carry out the online practice even in ordinary times effectively. Methods: Students were divided into groups of three, and information on the mothers was assessed, and the visits were planned. After role-play was conducted by the students and teachers, an online visit was conducted. The analysis target was the self-evaluation score of nine students who conducted online visits in June 2020 and had consented to participate. The evaluation contents included three items for assessment, two items for planning, one item for ethical consideration, five items for nursing practice, and two items for evaluation. The self-evaluation score ranged from 4 (‘Can do with a little advice’) to 1 (‘Can’t do with a little advice’). A univariate statistical analysis was performed. This study was approved by the Ethical Committee for Epidemiology of Hiroshima University. Results: The items with the highest mean (standard deviation) scores were ‘advocates for the dignity and the rights of mothers’ (3.89 (0.31)) and ‘communication behavior needed to create a trusting relationship’ (3.89 (0.31)).’ Next were the ‘individual nursing practice tailored to mothers (3.78 (0.42))’ and ‘review own practice and work on own task (3.78 (0.42)).’ The mean (standard deviation) of the items by type were as follows: three assessment items, 3.26 (0.70), two planning items, 3.11 (0.49), one ethical consideration item, 3.89 (0.31), five nursing practice items, 3.56 (0.54), and two evaluation items, 3.67 (0.47). Conclusion: The highest self-evaluations were for ‘advocates for the dignity and the rights of mothers’ and ‘communication behavior needed to create a trusting relationship.’ These findings suggest that the students were able to form good relationships with the mothers by improving their ability to effectively communicate and by presenting a positive attitude, even when conducting health visits online. However, the self-evaluation scores for assessment and planning were lower than those of ethical consideration, nursing practice, and evaluation. This was most likely due to a lack of opportunities and time to gather information and the need to modify and add plans in a short amount of time during one online visit. It is necessary to further consider the methods used in conducting online visits from the following viewpoints: methods of gathering information and the ability to make changes through multiple visits.

Keywords: infants, learning effects, mothers, online visit practice

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446 Evaluation of Antidiabetic Activity of a Combination Extract of Nigella Sativa & Cinnamomum Cassia in Streptozotocin Induced Type-I Diabetic Rats

Authors: Ginpreet Kaur, Mohammad Yasir Usmani, Mohammed Kamil Khan

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Diabetes mellitus is a disease with a high global burden and results in significant morbidity and mortality. In India, the number of people suffering with diabetes is expected to rise from 19 to 57 million in 2025. At present, interest in herbal remedies is growing to reduce the side effects associated with conventional dosage form like oral hypoglycemic agents and insulin for the treatment of diabetes mellitus. Our aim was to investigate the antidiabetic activities of combinatorial extract of N. sativa & C. cassia in Streptozotocin induced type-I Diabetic Rats. Thus, the present study was undertaken to screen postprandial glucose excursion potential through α- glucosidase inhibitory activity (In Vitro) and effect of combinatorial extract of N. sativa & C. cassia in Streptozotocin induced type-I Diabetic Rats (In Vivo). In addition changes in body weight, plasma glucose, lipid profile and kidney profile were also determined. The IC50 values for both extract and Acarbose was calculated by extrapolation method. Combinatorial extract of N. sativa & C. cassia at different dosages (100 and 200 mg/kg orally) and Metformin (50 mg/kg orally) as the standard drug was administered for 28 days and then biochemical estimation, body weights and OGTT (Oral glucose tolerance test) were determined. Histopathological studies were also performed on kidney and pancreatic tissue. In In-Vitro the combinatorial extract shows much more inhibiting effect than the individual extracts. The results reveals that combinatorial extract of N. sativa & C. cassia has shown significant decrease in plasma glucose (p<0.0001), total cholesterol and LDL levels when compared with the STZ group The decreasing level of BUN and creatinine revealed the protection of N. sativa & C. cassia extracts against nephropathy associated with diabetes. Combination of N. sativa & C. cassia significantly improved glucose tolerance to exogenously administered glucose (2 g/kg) after 60, 90 and 120 min interval on OGTT in high dose streptozotocin induced diabetic rats compared with the untreated control group. Histopathological studies shown that treatment with N. sativa & C. cassia extract alone and in combination restored pancreatic tissue integrity and was able to regenerate the STZ damaged pancreatic β cells. Thus, the present study reveals that combination of N. sativa & C. cassia extract has significant α- glucosidase inhibitory activity and thus has great potential as a new source for diabetes treatment.

Keywords: lipid levels, OGTT, diabetes, herbs, glucosidase

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445 Socioeconomic Burden of Life Long Disease: A Case of Diabetes Care in Bangladesh

Authors: Samira Humaira Habib

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Diabetes has profound effects on individuals and their families. If diabetes is not well monitored and managed, then it leads to long-term complications and a large and growing cost to the health care system. Prevalence and socioeconomic burden of diabetes and relative return of investment for the elimination or the reduction of the burden are much more important regarding its cost burden. Various studies regarding the socioeconomic cost burden of diabetes are well explored in developed countries but almost absent in developing countries like Bangladesh. The main objective of the study is to estimate the total socioeconomic burden of diabetes. It is a prospective longitudinal follow up study which is analytical in nature. Primary and secondary data are collected from patients who are undergoing treatment for diabetes at the out-patient department of Bangladesh Institute of Research & Rehabilitation in Diabetes, Endocrine & Metabolic Disorders (BIRDEM). Of the 2115 diabetic subjects, females constitute around 50.35% of the study subject, and the rest are male (49.65%). Among the subjects, 1323 are controlled, and 792 are uncontrolled diabetes. Cost analysis of 2115 diabetic patients shows that the total cost of diabetes management and treatment is US$ 903018 with an average of US$ 426.95 per patient. In direct cost, the investigation and medical treatment at hospital along with investigation constitute most of the cost in diabetes. The average cost of a hospital is US$ 311.79, which indicates an alarming warn for diabetic patients. The indirect cost shows that cost of productivity loss (US$ 51110.1) is higher among the all indirect item. All constitute total indirect cost as US$ 69215.7. The incremental cost of intensive management of uncontrolled diabetes is US$ 101.54 per patient and event-free time gained in this group is 0.55 years and the life years gain is 1.19 years. The incremental cost per event-free year gained is US$ 198.12. The incremental cost of intensive management of the controlled group is US$ 89.54 per patient and event-free time gained is 0.68 years, and the life year gain is 1.12 years. The incremental cost per event-free year gained is US$ 223.34. The EuroQoL difference between the groups is found to be 64.04. The cost-effective ratio is found to be US$ 1.64 cost per effect in case of controlled diabetes and US$ 1.69 cost per effect in case of uncontrolled diabetes. So management of diabetes is much more cost-effective. Cost of young type 1 diabetic patient showed upper socioeconomic class, and with the increase of the duration of diabetes, the cost increased also. The dietary pattern showed macronutrients intake and cost are significantly higher in the uncontrolled group than their counterparts. Proper management and control of diabetes can decrease the cost of care for the long term.

Keywords: cost, cost-effective, chronic diseases, diabetes care, burden, Bangladesh

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444 Aerobic Training Combined with Nutritional Guidance as an Effective Strategy for Improving Aerobic Fitness and Reducing BMI in Inactive Adults

Authors: Leif Inge Tjelta, Gerd Lise Nordbotten, Cathrine Nyhus Hagum, Merete Hagen Helland

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Overweight and obesity can lead to numerous health problems, and inactive people are more often overweight and obese compared to physically active people. Even a moderate weight loss can improve cardiovascular and endocrine disease risk factors. The aim of the study was to examine to what extent overweight and obese adults starting up with two weekly intensive running sessions had an increase in aerobic capacity, reduction in BMI and waist circumference and changes in body composition after 33 weeks of training. An additional aim was to see if there were differences between participants who, in addition to training, also received lifestyle modification education, including practical cooking (nutritional guidance and training group (NTG =32)) compared to those who were not given any nutritional guidance (training group (TG=40)). 72 participants (49 women), mean age of 46.1 ( ± 10.4) were included. Inclusion Criteria: Previous untrained and inactive adults in all age groups, BMI ≥ 25, desire to become fitter and reduce their BMI. The two weekly supervised training sessions consisted of 10 min warm up followed by 20 to 21 min effective interval running where the participants’ heart rate were between 82 and 92% of hearth rate maximum. The sessions were completed with ten minutes whole body strength training. Measures of BMI, waist circumference (WC) and 3000m running time were performed at the start of the project (T1), after 15 weeks (T2) and at the end of the project (T3). Measurements of fat percentage, muscle mass, and visceral fat were performed at T1 and T3. Twelve participants (9 women) from both groups, who all scored around average on the 3000 m pre-test, were chosen to do a VO₂max test at T1 and T3. The NTG were given ten theoretical sessions (80 minutes each) and eight practical cooking sessions (140 minutes each). There was a significant reduction in bout groups for WC and BMI from T1 to T2. There was not found any further reduction from T2 to T3. Although not significant, NTG reduced their WC more than TG. For both groups, the percentage reduction in WC was similar to the reduction in BMI. There was a decrease in fat percentage in both groups from pre-test to post-test, whereas, for muscle mass, a small, but insignificant increase was observed for both groups. There was a decrease in 3000m running time for both groups from T1 to T2 as well as from T2 to T3. The difference between T2 and T3 was not statistically significant. The 12 participants who tested VO₂max had an increase of 2.86 ( ± 3.84) mlkg⁻¹ min⁻¹ in VO₂max and 3:02 min (± 2:01 min) reduction in running time over 3000 m from T1 until T3. There was a strong, negative correlation between the two variables. The study shows that two intensive running session in 33 weeks can increase aerobic fitness and reduce BMI, WC and fat percent in inactive adults. Cost guidance in addition to training will give additional effect.

Keywords: interval training, nutritional guidance, fitness, BMI

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443 Effect of Reminiscence Therapy on the Sleep Quality of the Elderly Living in Nursing Homes

Authors: Güler Duru Aşiret

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Introduction: Poor sleep quality is a common problem among the older people living in nursing homes. Our study aimed at assessing the effect of individual reminiscence therapy on the sleep quality of the elderly living in nursing homes. Methods: The study had 22 people in the intervention group and 24 people in the control group. The intervention group had reminiscence therapy once a week for 12 weeks in the form of individual sessions of 25-30 minutes. In our study, we first determined the dates suitable for the intervention group and researcher and planned the date and time of individual reminiscence therapies, which would take 12 weeks. While preparing this schedule, we considered subjects’ time schedules for their regular visits to health facilities and the arrival of their visitors. At this stage, the researcher informed the participants that their regular attendance in sessions would affect the intervention outcome. One topic was discussed every week. Weekly topics included: introduction in the first week; childhood and family life, school days, starting work and work life (a day at home for housewives), a fun day out of home, marriage (friendship for the singles), plants and animals they loved, babies and children, food and cooking, holidays and travelling, special days and celebrations, assessment and closure, in the following weeks respectively. The control group had no intervention. Study data was collected by using an introductory information form and the Pittsburgh Sleep Quality Index (PSQI). Results: In our study, participants’ average age was 76.02 ± 7.31. 58.7% of them were male and 84.8% were single. All of them had at least one chronic disease. 76.1% did not need help for performing their daily life activities. The length of stay in the institution was 6.32 ± 3.85 years. According to the participants’ descriptive characteristics, there was no difference between groups. While there was no statistically significant difference between the pretest PSQI median scores (p > 0.05) of both groups, PSQI median score had a statistically significant decrease after 12 weeks of reminiscence therapy (p < 0.05). There was no statistically significant change in the median scores of the subcomponents of sleep latency, sleep duration, sleep efficiency, sleep disturbance and use of sleep medication before and after reminiscence therapy. After the 12-weeks reminiscence therapy, there was a statistically significant change in the median scores for the PSQI subcomponents of subjective sleep quality (p<0.05). Conclusion: Our study found that reminiscence therapy increased the sleep quality of the elderly living in nursing homes. Acknowledgment: This study (project no 2017-037) was supported by the Scientific Research Projects Coordination Unit of Aksaray University. We thank the elderly subjects for their kind participation.

Keywords: nursing, older people, reminiscence therapy, sleep

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442 Kidnapping of Migrants by Drug Cartels in Mexico as a New Trend in Contemporary Slavery

Authors: Itze Coronel Salomon

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The rise of organized crime and violence related to drug cartels in Mexico has created serious challenges for the authorities to provide security to those who live within its borders. However, to achieve a significant improvement in security is absolute respect for fundamental human rights by the authorities. Irregular migrants in Mexico are at serious risk of abuse. Research by Amnesty International as well as reports of the NHRC (National Human Rights) in Mexico, have indicated the major humanitarian crisis faced by thousands of migrants traveling in the shadows. However, the true extent of the problem remains invisible to the general population. The fact that federal and state governments leave no proper record of abuse and do not publish reliable data contributes to ignorance and misinformation, often spread by the media that portray migrants as the source of crime rather than their victims. Discrimination and intolerance against irregular migrants can generate greater hostility and exclusion. According to the modus operandi that has been recorded criminal organizations and criminal groups linked to drug trafficking structures deprive migrants of their liberty for forced labor and illegal activities related to drug trafficking, even some have been kidnapped for be trained as murderers . If the victim or their family cannot pay the ransom, the kidnapped person may suffer torture, mutilation and amputation of limbs or death. Migrant women are victims of sexual abuse during her abduction as well. In 2011, at least 177 bodies were identified in the largest mass grave found in Mexico, located in the town of San Fernando, in the border state of Tamaulipas, most of the victims were killed by blunt instruments, and most seemed to be immigrants and travelers passing through the country. With dozens of small graves discovered in northern Mexico, this may suggest a change in tactics between organized crime groups to the different means of obtaining revenue and reduce murder profile methods. Competition and conflict over territorial control drug trafficking can provide strong incentives for organized crime groups send signals of violence to the authorities and rival groups. However, as some Mexican organized crime groups are increasingly looking to take advantage of income and vulnerable groups, such as Central American migrants seem less interested in advertising his work to authorities and others, and more interested in evading detection and confrontation. This paper pretends to analyze the introduction of this new trend of kidnapping migrants for forced labors by drug cartels in Mexico into the forms of contemporary slavery and its implications.

Keywords: international law, migration, transnational organized crime

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441 Direct Assessment of Cellular Immune Responses to Ovalbumin with a Secreted Luciferase Transgenic Reporter Mouse Strain IFNγ-Lucia

Authors: Martyna Chotomska, Aleksandra Studzinska, Marta Lisowska, Justyna Szubert, Aleksandra Tabis, Jacek Bania, Arkadiusz Miazek

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Objectives: Assessing antigen-specific T cell responses is of utmost importance for the pre-clinical testing of prototype vaccines against intracellular pathogens and tumor antigens. Mainly two types of in vitro assays are used for this purpose 1) enzyme-linked immunospot (ELISpot) and 2) intracellular cytokine staining (ICS). Both are time-consuming, relatively expensive, and require manual dexterity. Here, we assess if a straightforward detection of luciferase activity in blood samples of transgenic reporter mice expressing a secreted Lucia luciferase under the transcriptional control of IFN-γ promoter parallels the sensitivity of IFNγ ELISpot assay. Methods: IFN-γ-LUCIA mouse strain carrying multiple copies of Lucia luciferase transgene under the transcriptional control of IFNγ minimal promoter were generated by pronuclear injection of linear DNA. The specificity of transgene expression and mobilization was assessed in vitro using transgenic splenocytes exposed to various mitogens. The IFN-γ-LUCIA mice were immunized with 50mg of ovalbumin (OVA) emulsified in incomplete Freund’s adjuvant three times every two weeks by subcutaneous injections. Blood samples were collected before and five days after each immunization. Luciferase activity was assessed in blood serum. Peripheral blood mononuclear cells were separated and assessed for frequencies of OVA-specific IFNγ-secreting T cells. Results: We show that in vitro cultured splenocytes of IFN-γ-LUCIA mice respond by 2 and 3 fold increase in secreted luciferase activity to T cell mitogens concanavalin A and phorbol myristate acetate, respectively but fail to respond to B cell-stimulating E.coli lipopolysaccharide. Immunization of IFN-γ-LUCIA mice with OVA leads to over 4 fold increase in luciferase activity in blood serum five days post-immunization with a barely detectable increase in OVA-specific, IFNγ-secreting T cells by ELISpot. Second and third immunizations, further increase the luciferase activity and coincidently also increase the frequencies of OVA-specific T cells by ELISpot. Conclusions: We conclude that minimally invasive monitoring of luciferase secretions in blood serum of IFN-γ-LUCIA mice constitutes a sensitive method for evaluating primary and memory Th1 responses to protein antigens. As such, this method may complement existing methods for rapid immunogenicity assessment of prototype vaccines.

Keywords: ELISpot, immunogenicity, interferon-gamma, reporter mice, vaccines

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440 Characterization of Fine Particles Emitted by the Inland and Maritime Shipping

Authors: Malika Souada, Juanita Rausch, Benjamin Guinot, Christine Bugajny

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The increase of global commerce and tourism makes the shipping sector an important contributor of atmospheric pollution. Both, airborne particles and gaseous pollutants have negative impact on health and climate. This is especially the case in port cities, due to the proximity of the exposed population to the shipping emissions in addition to other multiple sources of pollution linked to the surrounding urban activity. The objective of this study is to determine the concentrations of fine particles (immission), specifically PM2.5, PM1, PM0.3, BC and sulphates, in a context where maritime passenger traffic plays an important role (port area of Bordeaux centre). The methodology is based on high temporal resolution measurements of pollutants, correlated with meteorological and ship movements data. Particles and gaseous pollutants from seven maritime passenger ships were sampled and analysed during the docking, manoeuvring and berthing phases. The particle mass measurements were supplemented by measurements of the number concentration of ultrafine particles (<300 nm diameter). The different measurement points were chosen by taking into account the local meteorological conditions and by pre-modelling the dispersion of the smoke plumes. The results of the measurement campaign carried out during the summer of 2021 in the port of Bordeaux show that the detection of concentrations of particles emitted by ships proved to be punctual and stealthy. Punctual peaks of ultrafine particle concentration in number (P#/m3) and BC (ng/m3) were measured during the docking phases of the ships, but the concentrations returned to their background level within minutes. However, it appears that the influence of the docking phases does not significantly affect the air quality of Bordeaux centre in terms of mass concentration. Additionally, no clear differences in PM2.5 concentrations between the periods with and without ships at berth were observed. The urban background pollution seems to be mainly dominated by exhaust and non-exhaust road traffic emissions. However, temporal high-resolution measurements suggest a probable emission of gaseous precursors responsible for the formation of secondary aerosols related to the ship activities. This was evidenced by the high values of the PM1/BC and PN/BC ratios, tracers of non-primary particle formation, during periods of ship berthing vs. periods without ships at berth. The research findings from this study provide robust support for port area air quality assessment and source apportionment.

Keywords: characterization, fine particulate matter, harbour air quality, shipping impacts

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439 Energy Atlas: Geographic Information Systems-Based Energy Analysis and Planning Tool

Authors: Katarina Pogacnik, Ursa Zakrajsek, Nejc Sirk, Ziga Lampret

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Due to an increase in living standards along with global population growth and a trend of urbanization, municipalities and regions are faced with an ever rising energy demand. A challenge has arisen for cities around the world to modify the energy supply chain in order to reduce its consumption and CO₂ emissions. The aim of our work is the development of a computational-analytical platform for dynamic support in decision-making and the determination of economic and technical indicators of energy efficiency in a smart city, named Energy Atlas. Similar products in this field focuse on a narrower approach, whereas in order to achieve its aim, this platform encompasses a wider spectrum of beneficial and important information for energy planning on a local or regional scale. GIS based interactive maps provide an extensive database on the potential, use and supply of energy and renewable energy sources along with climate, transport and spatial data of the selected municipality. Beneficiaries of Energy atlas are local communities, companies, investors, contractors as well as residents. The Energy Atlas platform consists of three modules named E-Planning, E-Indicators and E-Cooperation. The E-Planning module is a comprehensive data service, which represents a support towards optimal decision-making and offers a sum of solutions and feasibility of measures and their effects in the area of efficient use of energy and renewable energy sources. The E-Indicators module identifies, collects and develops optimal data and key performance indicators and develops an analytical application service for dynamic support in managing a smart city in regards to energy use and sustainable environment. In order to support cooperation and direct involvement of citizens of the smart city, the E-cooperation is developed with the purpose of integrating the interdisciplinary and sociological aspects of energy end-users. Interaction of all the above-described modules contributes to regional development because it enables for a precise assessment of the current situation, strategic planning, detection of potential future difficulties and also the possibility of public involvement in decision-making. From the implementation of the technology in Slovenian municipalities of Ljubljana, Piran, and Novo mesto, there is evidence to suggest that the set goals are to be achieved to a great extent. Such thorough urban energy planning tool is viewed as an important piece of the puzzle towards achieving a low-carbon society, circular economy and therefore, sustainable society.

Keywords: circular economy, energy atlas, energy management, energy planning, low-carbon society

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438 Comparative Histological, Immunohistochemical and Biochemical Study on the Effect of Vit. C, Vit. E, Gallic Acid and Silymarin on Carbon Tetrachloride Model of Liver Fibrosis in Rats

Authors: Safaa S. Hassan, Mohammed H. Elbakry, Safwat A. Mangoura, Zainab M. Omar

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Background: Liver fibrosis is the main reason for increased mortality in chronic liver disease. It has no standard treatment. Antioxidants from a variety of sources are capable of slowing or preventing oxidation of other molecules. Aim: to evaluate the hepatoprotective effect of vit. C, vit. E and gallic acid in comparison to silymarin in the rat model of carbon tetrachloride induced liver fibrosis and their possible mechanisms of action. Material& Methods: A total number of 60 adult male albino rats 160-200gm were divided into six equal groups; received subcutaneous (s.c) injection for 8 weeks. Group I: as control. Group II: received 1.5 mL/kg of CCL4 .Group III: CCL4 and co- treatment with silymarin 100mg/kg p.o. daily. Group IV: CCL4 and co-treatment with vit. C 50mg/kg p.o. daily. Group V: CCL4 and co-treatment with vit. E 200mg/kg. p.o. Group VI: CCL4 and co-treatment with Gallic acid 100mg/kg. p.o. daily. Liver was processed for histological and immunohistochemical examination. Levels of AST, ALT, ALP, reduced GSH, MDA, SOD and hydroxyproline concentration were measured and evaluated statistically. Results: Light and electron microscopic examination of liver of group II exhibited foci of altered cells with dense nuclei and vacuolated, granular cytoplasm, mononuclear cell infiltration in portal areas, profuse collagen fiber deposits were found around portal tract, more intense staining α-SMA-positive cells occupied most of the liver fibrosis tissue, electron lucent areas in the cytoplasm of the hepatocytes, margination of nuclear chromatin. Treatment by any of the antioxidants variably reduced the hepatic structural changes induced by CCL4. Biochemical analysis showed that carbon tetrachloride significantly increased the levels of serum AST, ALT, ALP, hepatic malondialdehyde and hydroxyproline content. Moreover, it decreased the activities of superoxide dismutase and glutathione. Treatment with silymarin, gallic acid, vit. C and vit. E decreased significantly the AST, ALT, and ALP levels in plasma, MDA and hydroxyproline and increased the activities of SOD and glutathione in liver tissue. The effect of administration of CCl4 was improved with the used antioxidants in variable degrees. The most efficient antioxidant was silymarin followed by gallic acid and vit. C then vit. E. It is possibly due to their antioxidant effect, free radical scavenging properties and the reduction of oxidant dependent activation and proliferation of HSCs. Conclusion: So these antioxidants can be a promising drugs candidate for ameliorating liver fibrosis better than the use of the drugs and their side effects.

Keywords: antioxidant, ccl4, gallic acid, liver fibrosis

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437 Correlations between Folate, Homocysteine Levels, and Markers of Brain Atrophy in Elderly Male and Female Rats

Authors: Fatimah A. Alhomaid, Nadia H. Mahmoud, Maha A. Al-Qaraawi

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The present study was designed to induce hyperhomocysteinemia (HHcy) in elderly male and female rats. Also,to evaluate, the effect of (HHcy) as a risk factor for cerebrovascular disease and brain atrophy and folate supplementation on serum levels of Hcy, total cholesterol, low density lipoprotein cholesterol (LDLc), high density lipoprotein cholesterol (HDLc), triglycerides, pyridoxal phosphate , folate also, histopathological examination of brain and cerebrovascular vessels In this work 50 male and 50 female elderly albino rats were used and divided into five groups. The first group served as control, the second and third group received two different dose of L-methionine, the fourth and fifth group received fortified diet with folate powder plus L-methionine. Our results showed that homocysteine levels in male and female rats that received low and high dose of methionine were higher than in the control group, while the levels of folate significantly decreased in male rats only. Induced hyperhomocysteinemia in elderly male and female rats led to significant increase in serum level of cholesterol, LDLc and triglycerides but serum level of HDLc were significantly lower in methionine treated male and female rats than in control. Our results showed that a strong positive correlation between all these parameters and homocysteine except HDLc levels which correlate negatively to Hcy levels. Administration of folate to methionine treated male rats led to insignificant changes in the level of cholesterol when compared to control group but this level was found to be significantly decrease in female rats received small dose of methionine. When the level of cholesterol compared to the same dose of methionine treated group we found a significant decrease in both male and female rats. LDLc and triglycerides level significantly decrease in male rats only versus the control rats, while when compared to low and high dose of methionine a significant decreased occurs. A significant increase in serum level of HDLc in male and female rats when compared to both control and methionine treated groups. In male and female rats supplemented with folate we found an increased serum levels of folate when compared to rats received both dose of methionine. The levels of pyridoxal phosphate significantly decreased in all treated rats compared to the control group and its level were increased with supplementation of folate versus the rats received small and large dose of methionine. It can be concluded that hyperhomocysteinemia may be an additional risk factor for cerebrovascular atherosclesosis and brain atrophy in elderly people and diatery supplementation with folate blocking the activity of homocysteine and may be considered as a therapeutic possibility.

Keywords: hyperhomocysteinemia, brain atrophy, cerebrovascular, L-methionine, pyridoxal phosphate

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436 Interdisciplinary Evaluations of Children with Autism Spectrum Disorder in a Telehealth Arena

Authors: Janice Keener, Christine Houlihan

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Over the last several years, there has been an increase in children identified as having Autism Spectrum Disorder (ASD). Specialists across several disciplines: mental health and medical professionals have been tasked with ensuring accurate and timely evaluations for children with suspected ASD. Due to the nature of the ASD symptom presentation, an interdisciplinary assessment and treatment approach best addresses the needs of the whole child. During the unprecedented COVID-19 Pandemic, clinicians were faced with how to continue with interdisciplinary assessments in a telehealth arena. Instruments that were previously used to assess ASD in-person were no longer appropriate measures to use due to the safety restrictions. For example, The Autism Diagnostic Observation Schedule requires examiners and children to be in very close proximity of each other and if masks or face shields are worn, they render the evaluation invalid. Similar issues arose with the various cognitive measures that are used to assess children such as the Weschler Tests of Intelligence and the Differential Ability Scale. Thus the need arose to identify measures that are able to be safely and accurately administered using safety guidelines. The incidence of ASD continues to rise over time. Currently, the Center for Disease Control estimates that 1 in 59 children meet the criteria for a diagnosis of ASD. The reasons for this increase are likely multifold, including changes in diagnostic criteria, public awareness of the condition, and other environmental and genetic factors. The rise in the incidence of ASD has led to a greater need for diagnostic and treatment services across the United States. The uncertainty of the diagnostic process can lead to an increased level of stress for families of children with suspected ASD. Along with this increase, there is a need for diagnostic clarity to avoid both under and over-identification of this condition. Interdisciplinary assessment is ideal for children with suspected ASD, as it allows for an assessment of the whole child over the course of time and across multiple settings. Clinicians such as Psychologists and Developmental Pediatricians play important roles in the initial evaluation of autism spectrum disorder. An ASD assessment may consist of several types of measures such as standardized checklists, structured interviews, and direct assessments such as the ADOS-2 are just a few examples. With the advent of telehealth clinicians were asked to continue to provide meaningful interdisciplinary assessments via an electronic platform and, in a sense, going to the family home and evaluating the clinical symptom presentation remotely and confidently making an accurate diagnosis. This poster presentation will review the benefits, limitations, and interpretation of these various instruments. The role of other medical professionals will also be addressed, including medical providers, speech pathology, and occupational therapy.

Keywords: Autism Spectrum Disorder Assessments, Interdisciplinary Evaluations , Tele-Assessment with Autism Spectrum Disorder, Diagnosis of Autism Spectrum Disorder

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435 Generating a Multiplex Sensing Platform for the Accurate Diagnosis of Sepsis

Authors: N. Demertzis, J. L. Bowen

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Sepsis is a complex and rapidly evolving condition, resulting from uncontrolled prolonged activation of host immune system due to pathogenic insult. The aim of this study is the development of a multiplex electrochemical sensing platform, capable of detecting both pathogen associated and host immune markers to enable the rapid and definitive diagnosis of sepsis. A combination of aptamers and molecular imprinting approaches have been employed to generate sensing systems for lipopolysaccharide (LPS), c-reactive protein (CRP) and procalcitonin (PCT). Gold working electrodes were mechanically polished and electrochemically cleaned with 0.1 M sulphuric acid using cyclic voltammetry (CV). Following activation, a self-assembled monolayer (SAM) was generated, by incubating the electrodes with a thiolated anti-LPS aptamer / dithiodibutiric acid (DTBA) mixture (1:20). 3-aminophenylboronic acid (3-APBA) in combination with the anti-LPS aptamer was used for the development of the hybrid molecularly imprinted sensor (apta-MIP). Aptasensors, targeting PCT and CRP were also fabricated, following the same approach as in the case of LPS, with mercaptohexanol (MCH) replacing DTBA. In the case of the CRP aptasensor, the SAM was formed following incubation of a 1:1 aptamer: MCH mixture. However, in the case of PCT, the SAM was formed with the aptamer itself, with subsequent backfilling with 1 μM MCH. The binding performance of all systems has been evaluated using electrochemical impedance spectroscopy. The apta-MIP’s polymer thickness is controlled by varying the number of electropolymerisation cycles. In the ideal number of polymerisation cycles, the polymer must cover the electrode surface and create a binding pocket around LPS and its aptamer binding site. Less polymerisation cycles will create a hybrid system which resembles an aptasensor, while more cycles will be able to cover the complex and demonstrate a bulk polymer-like behaviour. Both aptasensor and apta-MIP were challenged with LPS and compared to conventional imprinted (absence of aptamer from the binding site, polymer formed in presence of LPS) and non-imprinted polymers (NIPS, absence of LPS whilst hybrid polymer is formed). A stable LPS aptasensor, capable of detecting down to 5 pg/ml of LPS was generated. The apparent Kd of the system was estimated at 17 pM, with a Bmax of approximately 50 pM. The aptasensor demonstrated high specificity to LPS. The apta-MIP demonstrated superior recognition properties with a limit of detection of 1 fg/ml and a Bmax of 100 pg/ml. The CRP and PCT aptasensors were both able to detect down to 5 pg/ml. Whilst full binding performance is currently being evaluated, there is none of the sensors demonstrate cross-reactivity towards LPS, CRP or PCT. In conclusion, stable aptasensors capable of detecting LPS, PCT and CRP at low concentrations have been generated. The realisation of a multiplex panel such as described herein, will effectively contribute to the rapid, personalised diagnosis of sepsis.

Keywords: aptamer, electrochemical impedance spectroscopy, molecularly imprinted polymers, sepsis

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434 Reducing Falls in Memory Care through Implementation of the Stopping Elderly Accidents, Deaths, and Injuries Program

Authors: Cory B. Lord

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Falls among the elderly population has become an area of concern in healthcare today. The negative impacts of falls lead to increased morbidity, mortality, and financial burdens for both patients and healthcare systems. Falls in the United States is reported at an annual rate of 36 million in those aged 65 and older. Each year, one out of four people in this age group will suffer a fall, with 20% of these falls causing injury. The setting for this Doctor of Nursing Practice (DNP) project was a memory care unit in an assisted living community, as these facilities house cognitively impaired older adults. These communities lack fall prevention programs; therefore, the need exists to add to the body of knowledge to positively impact this population. The objective of this project was to reduce fall rates through the implementation of the Center for Disease Control and Prevention (CDC) STEADI (stopping elderly accidents, deaths, and injuries) program. The DNP project performed was a quality improvement pilot study with a pre and post-test design. This program was implemented in the memory care setting over 12 weeks. The project included an educational session for staff and a fall risk assessment with appropriate resident referrals. The three aims of the DNP project were to reduce fall rates among the elderly aged 65 and older who reside in the memory care unit, increase staff knowledge of STEADI fall prevention measures after an educational session, and assess the willingness of memory care unit staff to adopt an evidence-based a fall prevention program. The Donabedian model was used as a guiding conceptual framework for this quality improvement pilot study. The fall rate data for 12 months before the intervention was evaluated and compared to post-intervention fall rates. The educational session comprised of a pre and post-test to assess staff knowledge of the fall prevention program and the willingness of staff to adopt the fall prevention program. The overarching goal was to reduce falls in the elderly population who live in memory care units. The results of the study showed, on average that the fall rate during the implementation period of STEADI (μ=6.79) was significantly lower when compared to the prior 12 months (μ= 9.50) (p=0.02, α = 0.05). The mean staff knowledge scores improved from pretest (μ=77.74%) to post-test (μ=87.42%) (p=0.00, α= 0.05) after the education session. The results of the willingness to adopt a fall prevention program were scored at 100%. In summation, implementing the STEADI fall prevention program can assist in reducing fall rates for residents aged 65 and older who reside in a memory care setting.

Keywords: dementia, elderly, falls, STEADI

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433 Immunomodulatory Role of Heat Killed Mycobacterium indicus pranii against Cervical Cancer

Authors: Priyanka Bhowmik, Subrata Majumdar, Debprasad Chattopadhyay

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Background: Cervical cancer is the third major cause of cancer in women and the second most frequent cause of cancer related deaths causing 300,000 deaths annually worldwide. Evasion of immune response by Human Papilloma Virus (HPV), the key contributing factor behind cancer and pre-cancerous lesions of the uterine cervix, makes immunotherapy a necessity to treat this disease. Objective: A Heat killed fraction of Mycobacterium indicus pranii (MIP), a non-pathogenic Mycobacterium has been shown to exhibit cytotoxic effects on different cancer cells, including human cervical carcinoma cell line HeLa. However, the underlying mechanisms remain unknown. The aim of this study is to decipher the mechanism of MIP induced HeLa cell death. Methods: The cytotoxicity of Mycobacterium indicus pranii against HeLa cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by annexin V and Propidium iodide (PI) staining. The assessment of reactive oxygen species (ROS) generation and cell cycle analysis were measured by flow cytometry. The expression of apoptosis associated genes was analyzed by real time PCR. Result: MIP could inhibit the proliferation of HeLa cell in a time and dose dependent manner but caused minor damage to normal cells. The induction of apoptosis was confirmed by the cell surface presentation of phosphatidyl serine, DNA fragmentation, and mitochondrial damage. MIP caused very early (as early as 30 minutes) transcriptional activation of p53, followed by a higher activation (32 fold) at 24 hours suggesting prime importance of p53 in MIP-induced apoptosis in HeLa cell. The up regulation of p53 dependent pro-apoptotic genes Bax, Bak, PUMA, and Noxa followed a lag phase that was required for the transcriptional p53 program. MIP also caused the transcriptional up regulation of Toll like receptor 2 and 4 after 30 minutes of MIP treatment suggesting recognition of MIP by toll like receptors. Moreover, MIP caused the inhibition of expression of HPV anti apoptotic gene E6, which is known to interfere with p53/PUMA/Bax apoptotic cascade. This inhibition might have played a role in transcriptional up regulation of PUMA and subsequently apoptosis. ROS was generated transiently which was concomitant with the highest transcription activation of p53 suggesting a plausible feedback loop network of p53 and ROS in the apoptosis of HeLa cells. Scavenger of ROS, such as N-acetyl-L-cysteine, decreased apoptosis suggesting ROS is an important effector of MIP induced apoptosis. Conclusion: Taken together, MIP possesses full potential to be a novel therapeutic agent in the clinical treatment of cervical cancer.

Keywords: cancer, mycobacterium, immunity, immunotherapy.

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432 Anti-Apoptotic Effect of Pueraria tuberosa in Rats with Streptozotocin Induced Diabetic Nephropathy

Authors: Rashmi Shukla, Yamini Bhusan Tripathi

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Diabetic nephropathy (DN) is characterized as diabetic kidney disease which involves many pathways e.g. hyperactivated protein kinase c (PKC), polyol pathway, excess production of advanced glycation end product (AGEs) & free radical accumulation etc. All of them results to hypoxia followed by apoptosis of podocytes, glomerulosclerosis, extracellular matrix (ECM) accumulation and fibrosis resulting to irreversible changes in kidney. This is continuously rising worldwide and there are not enough specific drugs, to retard its progress. Due to increasing side effects of allopathic drugs, interest in herbal remedies is growing. Earlier, we have reported that PTY-2 (a phytomedicine, derived from Pueraria tuberosa Linn.) inhibits the accumulation of extracellular matrix (ECM) through activation of MMP-9. Present study exhibited the therapeutic potential of Pueraria tuberosa in the prevention of podocytes apoptosis and modulation of nephrin expression in streptozotocin (STZ) induced DN rats. DN rats were produced by maintaining persistent hyperglycemia for 8 weeks by intra-peritoneal injection of 55 mg/kg streptozotocin (STZ). These rats were randomly divided in 2 groups, i.e. DN control, and DN+ water extract of Pueraria tuberosa (PTW). One group of age-matched normal rats served as non-diabetic control (group-1), The STZ induced DN rats (group-2) and DN+PTW treated rats (group-3). The PTW was orally administered (0.3g/kg) daily to group-2 rats and drug vector (1 ml of 10% tween 20) in control rats. The treatments were continued for 20 days and blood and urine samples were collected. Rats were then sacrificed to investigate the expression Bcl2, Bax and nephroprotective protein i.e. nephrin in kidney glomerulus. The effect of PTW was evaluated, we have found that the PTW significantly(p < .001) reversed the raised serum urea, serum creatinine, urine protein and improved the creatinine clearance in STZ induce diabetic nephropathy in rats and also significantly(p < .001) prevented the rise in urine albumin excretion. The Western blot analysis of kidney tissue homogenate showed increased expression of Bcl2 in PTW treated rats. The RT-PCR showed the increased expression and accumulation of nephrin mRNA. The confocal photomicrographs also supported the reduction of Bax and a simultaneous increase in Bcl2 and nephrin in glomerular podocytes. Hence, our finding suggests that the nephroprotective role of PTW is mediated via restoration of nephrin thus prevents the podocytes apoptosis and ameliorates diabetic nephropathy. The clinical trial of PTW would prove to be a potential food supplement/ drug of alternative medicine for patients with diabetic nephropathy in early stage.

Keywords: Pueraria tuberosa, diabetic nephropathy, anti-apoptosis, nephrin

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431 Basal Cell Carcinoma: Epidemiological Analysis of a 5-Year Period in a Brazilian City with a High Level of Solar Radiation

Authors: Maria E. V. Amarante, Carolina L. Cerdeira, Julia V. Cortes, Fiorita G. L. Mundim

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Basal cell carcinoma (BCC) is the most prevalent type of skin cancer in humans. It arises from the basal cells of the epidermis and cutaneous appendages. The role of sunlight exposure as a risk factor for BCC is very well defined due to its power to influence genetic mutations, in addition to having a suppressor effect on the skin immune system. Despite showing low metastasis and mortality rates, the tumor is locally infiltrative, aggressive, and destructive. Considering the high prevalence rate of this carcinoma and the importance of early detection, a retrospective study was carried out in order to correlate the clinical data available on BBC, characterize it epidemiologically, and thus enable effective prevention measures for the population. Data on the period from January 2015 to December 2019 were collected from the medical records of patients registered at one pathology service located in the southeast region of Brazil, known as SVO, which delivers skin biopsy results. The study was aimed at correlating the variables, sex, age, and subtypes found. Data analysis was performed using the chi-square test at a nominal significance level of 5% in order to verify the independence between the variables of interest. Fisher's exact test was applied in cases where the absolute frequency in the cells of the contingency table was less than or equal to five. The statistical analysis was performed using the R® software. Ninety-three basal cell carcinoma were analyzed, and its frequency in the 31-to 45-year-old age group was 5.8 times higher in men than in women, whereas, from 46 to 59 years, the frequency was found 2.4 times higher in women than in men. Between the ages of 46 to 59 years, it should be noted that the sclerodermiform subtype appears more than the solid one, with a difference of 7.26 percentage points. Reversely, the solid form appears more frequently in individuals aged 60 years or more, with a difference of 8.57 percentage points. Among women, the frequency of the solid subtype was 9.93 percentage points higher than the sclerodermiform frequency. In males, the same percentage difference is observed, but sclerodermiform is the most prevalent subtype. It is concluded in this study that, in general, there is a predominance of basal cell carcinoma in females and in individuals aged 60 years and over, which demonstrates the tendency of this tumor. However, when rarely found in younger individuals, the male gender prevailed. The most prevalent subtype was the solid one. It is worth mentioning that the sclerodermiform subtype, which is more aggressive, was seen more frequently in males and in the 46-to 59-year-old range.

Keywords: basal cell carcinoma, epidemiology, sclerodermiform basal cell carcinoma, skin cancer, solar radiation, solid basal cell carcinoma

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430 Modeling Engagement with Multimodal Multisensor Data: The Continuous Performance Test as an Objective Tool to Track Flow

Authors: Mohammad H. Taheri, David J. Brown, Nasser Sherkat

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Engagement is one of the most important factors in determining successful outcomes and deep learning in students. Existing approaches to detect student engagement involve periodic human observations that are subject to inter-rater reliability. Our solution uses real-time multimodal multisensor data labeled by objective performance outcomes to infer the engagement of students. The study involves four students with a combined diagnosis of cerebral palsy and a learning disability who took part in a 3-month trial over 59 sessions. Multimodal multisensor data were collected while they participated in a continuous performance test. Eye gaze, electroencephalogram, body pose, and interaction data were used to create a model of student engagement through objective labeling from the continuous performance test outcomes. In order to achieve this, a type of continuous performance test is introduced, the Seek-X type. Nine features were extracted including high-level handpicked compound features. Using leave-one-out cross-validation, a series of different machine learning approaches were evaluated. Overall, the random forest classification approach achieved the best classification results. Using random forest, 93.3% classification for engagement and 42.9% accuracy for disengagement were achieved. We compared these results to outcomes from different models: AdaBoost, decision tree, k-Nearest Neighbor, naïve Bayes, neural network, and support vector machine. We showed that using a multisensor approach achieved higher accuracy than using features from any reduced set of sensors. We found that using high-level handpicked features can improve the classification accuracy in every sensor mode. Our approach is robust to both sensor fallout and occlusions. The single most important sensor feature to the classification of engagement and distraction was shown to be eye gaze. It has been shown that we can accurately predict the level of engagement of students with learning disabilities in a real-time approach that is not subject to inter-rater reliability, human observation or reliant on a single mode of sensor input. This will help teachers design interventions for a heterogeneous group of students, where teachers cannot possibly attend to each of their individual needs. Our approach can be used to identify those with the greatest learning challenges so that all students are supported to reach their full potential.

Keywords: affective computing in education, affect detection, continuous performance test, engagement, flow, HCI, interaction, learning disabilities, machine learning, multimodal, multisensor, physiological sensors, student engagement

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429 Scenario of Some Minerals and Impact of Promoter Hypermethylation of DAP-K Gene in Gastric Carcinoma Patients of Kashmir Valley

Authors: Showkat Ahmad Bhat, Iqra Reyaz, Falaque ul Afshan, Ahmad Arif Reshi, Muneeb U. Rehman, Manzoor R. Mir, Sabhiya Majid, Sonallah, Sheikh Bilal, Ishraq Hussain

Abstract:

Background: Gastric cancer is the fourth most common cancer and the second leading cause of worldwide cancer-related deaths, with a wide variation in incidence rates across different geographical areas. The current view of cancer is that a malignancy arises from a transformation of the genetic material of a normal cell, followed by successive mutations and by chain of alterations in genes such as DNA repair genes, oncogenes, Tumor suppressor genes. Minerals are necessary for the functioning of several transcriptional factors, proteins that recognize certain DNA sequences and have been found to play a role in gastric cancer. Material Methods:The present work was a case control study and its aim was to ascertain the role of minerals and promoter hypermethylation of CpG islands of DAP-K gene in Gastric cancer patients among the Kashmiri population. Serum was extracted from all the samples and mineral estimation was done by AAS from serum, DNA was also extracted and was modified using bisulphite modification kit. Methylation-specific PCR was used for the analysis of the promoter hypermethylation status of DAP-K gene. The epigenetic analysis revealed that unlike other high risk regions, Kashmiri population has a different promoter hypermethylation profile of DAP-K gene and has different mineral profile. Results: In our study mean serum copper levels were significantly different for the two genders (p<0.05), while as no significant differences were observed for iron and zinc levels. In Methylation-specific PCR the methylation status of the promoter region of DAP-K gene was as 67.50% (27/40) of the gastric cancer tissues showed methylated DAP-K promoter and 32.50% (13/40) of the cases however showed unmethylated DAP-K promoter. Almost all 85% (17/20) of the histopathologically confirmed normal tissues showed unmethylated DAP-K promoter except only in 3 cases where DAP-K promoter was found to be methylated. The association of promoter hypermethylation with gastric cancer was evaluated by χ2 (Chi square) test and was found to be significant (P=0.0006). Occurrence of DAP-K methylation was found to be unequally distributed in males and females with more frequency in males than in females but the difference was not statistically significant (P =0.7635, Odds ratio=1.368 and 95% C.I=0.4197 to 4.456). When the frequency of DAP-K promoter methylation was compared with clinical staging of the disease, DAP-K promoter methylation was found to be certainly higher in Stage III/IV (85.71%) compared to Stage I/ II (57.69%) but the difference was not statistically significant (P =0.0673). These results suggest that DAP-K aberrant promoter hypermethylation in Kashmiri population contributes to the process of carcinogenesis in Gastric cancer and is reportedly one of the commonest epigenetic changes in the development of Gastric cancer.

Keywords: gastric cancer, minerals, AAS, hypermethylation, CpG islands, DAP-K gene

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428 Lamivudine Continuation/Tenofovir Add-on Adversely Affects Treatment Response among Lamivudine Non-Responder HIV-HBV Co-Infected Patients from Eastern India

Authors: Ananya Pal, Neelakshi Sarkar, Debraj Saha, Dipanwita Das, Subhashish Kamal Guha, Bibhuti Saha, Runu Chakravarty

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Presently, tenofovir disoproxil fumurate (TDF) is the most effective anti-viral agent for the treatment of hepatitis B virus (HBV) in individuals co-infected with HIV and HBV as TDF has activity to suppress both wild-type and lamivudine (3TC)-resistant HBV. However, suboptimal response to TDF was reported in HIV-HBV co-infected individuals with prior 3TC therapy from different countries recently. The incidence of 3TC-resistant HBV strains is quite high in HIV-HBV co-infected patients experiencing long-term anti-retroviral therapy (ART) in eastern India. In spite of this risk, most of the patients with long-term 3TC treatment are continued with the same anti-viral agent in this country. Only a few have received TDF in addition to 3TC in the ART regimen since TDF has been available in India for the treatment of HIV-infected patients in 2012. In this preliminary study, we investigated the virologic and biochemical parameters among HIV-HBV co-infected patients who are non-responders to 3TC treatment during the continuation of 3TC or TDF add-on to 3TC in their ART regimen. Fifteen HIV-HBV co-infected patients who experienced long-term 3TC (mean duration months 36.87 ± 24.08 months) were identified with high HBV viremia ( > 20,000 IU/ml) or harbouring 3TC-resistant HBV. These patients receiving ART from School of Tropical Medicine Kolkata, the main ART centre in eastern India were followed-up semi-annually for next three visits. Different virologic parameters including quantification of plasma HBV load by real-time PCR, detection of hepatitis B e antigen (HBeAg) by commercial ELISA and anti-viral resistant mutations by sequencing were studied. During three follow-up among study subjects, 86%, 47%, and 43% had 3TC-mono-therapy (mean treatment-duration 41.54±18.84, 49.67±11.67, 54.17±12.37 months respectively) whereas 14%, 53%, and 57% experienced TDF in addition to 3TC (mean treatment duration 4.5±2.12, 16.56±11.06, and 23±4.07 months respectively). Mean CD4 cell-count in patients receiving 3TC was tended to be lower during third follow-up as compared to the first and the second [520.67±380.30 (1st), 454.8±196.90 (2nd), and 397.5±189.24 (3rd) cells/mm3) and similar trend was seen in patients experiencing TDF in addition to 3TC [334.5±330.218 (1st), 476.5±194.25 (2nd), and 461.17±269.89 (3rd) cells/mm3]. Serum HBV load was increased during successive follow-up of patients with 3TC-mono-therapy. Initiation of TDF lowered serum HBV-load among 3TC-non-responders at the time of second visit ( < 2,000 IU/ml), interestingly during third follow-up, mean HBV viremia increased >1 log IU/ml (mean 3.56±2.84 log IU/ml). Persistence of 3TC-resistant double and triple mutations was also observed in both the treatment regimens. Mean serum alanine aminotransferase remained elevated in these patients during this follow-up study. Persistence of high HBV viraemia and 3TC-resistant mutation in HBV during the continuation of 3TC might lead to major public health threat in India. The inclusion of TDF in the ART regimen of 3TC non-responder HIV-HBV co-infected patients showed adverse treatment response in terms of virologic and biochemical parameters. Therefore, serious attention is necessary for proper management of long-term 3TC experienced HIV-HBV co-infected patients with high HBV viraemia or 3TC-resistant HBV mutants in India.

Keywords: HBV, HIV, TDF, 3TC-resistant

Procedia PDF Downloads 355
427 Elimination of Mother to Child Transmission of HIV/AIDS: A Study of the Knowledge, Attitudes and Perceptions of Healthcare Workers in Abuja Nigeria

Authors: Ezinne K. Okoro, Takahiko Katoh, Yoko Kawamura, Stanley C. Meribe

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HIV infection in children is largely as a result of vertical transmission (mother to child transmission [MTCT]). Thus, elimination of mother to child transmission of HIV/AIDS is critical in eliminating HIV infection in children. In Nigeria, drawbacks such as; limited pediatric screening, limited human capital, insufficient advocacy and poor understanding of ART guidelines, have impacted efforts at combating the disease, even as treatment services are free. Prevention of Mother to Child Transmission (PMTCT) program relies on health workers who not only counsel pregnant women on first contact but can competently provide HIV-positive pregnant women with accurate information about the PMTCT program such as feeding techniques and drug adherence. In developing regions like Nigeria where health care delivery faces a lot of drawbacks, it becomes paramount to address these issues of poor PMTCT coverage by conducting a baseline assessment of the knowledge, practices and perceptions related to HIV prevention amongst healthcare workers in Nigeria. A descriptive cross-sectional study was conducted amongst 250 health workers currently employed in health facilities in Abuja, Nigeria where PMTCT services were offered with the capacity to carry out early infant diagnosis testing (EID). Data was collected using a self-administered, pretested, structured questionnaire. This study showed that the knowledge of PMTCT of HIV was poor (30%) among healthcare workers who offer this service day-to-day to pregnant women. When PMTCT practices were analyzed in keeping with National PMTCT guidelines, over 61% of the respondents reported observing standard practices and the majority (58%) had good attitudes towards caring for patients with HIV/AIDS. Although 61% of the respondents reported being satisfied with the quality of service being rendered, 63% reported not being satisfied with their level of knowledge. Predictors of good knowledge were job designation and level of educational attainment. Health workers who were more satisfied with their working conditions and those who had worked for a longer time in the PMTCT service were more likely to observe standard PMTCT practices. With over 62% of the healthcare workers suggesting that more training would improve the quality of service being rendered, this is a strong pointer to stakeholders to consider a ‘healthcare worker-oriented approach’ when planning and conducting PMTCT training for healthcare workers. This in turn will increase pediatric ARV coverage, the knowledge and effectiveness of the healthcare workers in carrying out appropriate PMTCT interventions and culminating in the reduction/elimination of HIV transmission to newborns.

Keywords: attitudes, HIV/AIDS, healthcare workers, knowledge, mother to child transmission, Nigeria, perceptions

Procedia PDF Downloads 188
426 Curcumin Nanomedicine: A Breakthrough Approach for Enhanced Lung Cancer Therapy

Authors: Shiva Shakori Poshteh

Abstract:

Lung cancer is a highly prevalent and devastating disease, representing a significant global health concern with profound implications for healthcare systems and society. Its high incidence, mortality rates, and late-stage diagnosis contribute to its formidable nature. To address these challenges, nanoparticle-based drug delivery has emerged as a promising therapeutic strategy. Curcumin (CUR), a natural compound derived from turmeric, has garnered attention as a potential nanomedicine for lung cancer treatment. Nanoparticle formulations of CUR offer several advantages, including improved drug delivery efficiency, enhanced stability, controlled release kinetics, and targeted delivery to lung cancer cells. CUR exhibits a diverse array of effects on cancer cells. It induces apoptosis by upregulating pro-apoptotic proteins, such as Bax and Bak, and downregulating anti-apoptotic proteins, such as Bcl-2. Additionally, CUR inhibits cell proliferation by modulating key signaling pathways involved in cancer progression. It suppresses the PI3K/Akt pathway, crucial for cell survival and growth, and attenuates the mTOR pathway, which regulates protein synthesis and cell proliferation. CUR also interferes with the MAPK pathway, which controls cell proliferation and survival, and modulates the Wnt/β-catenin pathway, which plays a role in cell proliferation and tumor development. Moreover, CUR exhibits potent antioxidant activity, reducing oxidative stress and protecting cells from DNA damage. Utilizing CUR as a standalone treatment is limited by poor bioavailability, lack of targeting, and degradation susceptibility. Nanoparticle-based delivery systems can overcome these challenges. They enhance CUR’s bioavailability, protect it from degradation, and improve absorption. Further, Nanoparticles enable targeted delivery to lung cancer cells through surface modifications or ligand-based targeting, ensuring sustained release of CUR to prolong therapeutic effects, reduce administration frequency, and facilitate penetration through the tumor microenvironment, thereby enhancing CUR’s access to cancer cells. Thus, nanoparticle-based CUR delivery systems promise to improve lung cancer treatment outcomes. This article provides an overview of lung cancer, explores CUR nanoparticles as a treatment approach, discusses the benefits and challenges of nanoparticle-based drug delivery, and highlights prospects for CUR nanoparticles in lung cancer treatment. Future research aims to optimize these delivery systems for improved efficacy and patient prognosis in lung cancer.

Keywords: lung cancer, curcumin, nanomedicine, nanoparticle-based drug delivery

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425 Evaluation of Antimicrobial and Anti-Inflammatory Activity of Doani Sidr Honey and Madecassoside against Propionibacterium Acnes

Authors: Hana Al-Baghaoi, Kumar Shiva Gubbiyappa, Mayuren Candasamy, Kiruthiga Perumal Vijayaraman

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Acne is a chronic inflammatory disease of the sebaceous glands characterized by areas of skin with seborrhea, comedones, papules, pustules, nodules, and possibly scarring. Propionibacterium acnes (P. acnes), plays a key role in the pathogenesis of acne. Their colonization and proliferation trigger the host’s inflammatory response leading to the production of pro-inflammatory cytokines such as interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α). The usage of honey and natural compounds to treat skin ailments has strong support in the current trend of drug discovery. The present study was carried out evaluate antimicrobial and anti-inflammatory potential of Doani Sidr honey and its fractions against P. acnes and to screen madecassoside alone and in combination with fractions of honey. The broth dilution method was used to assess the antibacterial activity. Also, ultra structural changes in cell morphology were studied before and after exposure to Sidr honey using transmission electron microscopy (TEM). The three non-toxic concentrations of the samples were investigated for suppression of cytokines IL 8 and TNF α by testing the cell supernatants in the co-culture of the human peripheral blood mononuclear cells (hPBMCs) heat killed P. acnes using enzyme immunoassay kits (ELISA). Results obtained was evaluated by statistical analysis using Graph Pad Prism 5 software. The Doani Sidr honey and polysaccharide fractions were able to inhibit the growth of P. acnes with a noteworthy minimum inhibitory concentration (MIC) value of 18% (w/v) and 29% (w/v), respectively. The proximity of MIC and MBC values indicates that Doani Sidr honey had bactericidal effect against P. acnes which is confirmed by TEM analysis. TEM images of P. acnes after treatment with Doani Sidr honey showed completely physical membrane damage and lysis of cells; whereas non honey treated cells (control) did not show any damage. In addition, Doani Sidr honey and its fractions significantly inhibited (> 90%) of secretion of pro-inflammatory cytokines like TNF α and IL 8 by hPBMCs pretreated with heat-killed P. acnes. However, no significant inhibition was detected for madecassoside at its highest concentration tested. Our results suggested that Doani Sidr honey possesses both antimicrobial and anti-inflammatory effects against P. acnes and can possibly be used as therapeutic agents for acne. Furthermore, polysaccharide fraction derived from Doani Sidr honey showed potent inhibitory effect toward P. acnes. Hence, we hypothesize that fraction prepared from Sidr honey might be contributing to the antimicrobial and anti-inflammatory activity. Therefore, this polysaccharide fraction of Doani Sidr honey needs to be further explored and characterized for various phytochemicals which are contributing to antimicrobial and anti-inflammatory properties.

Keywords: Doani sidr honey, Propionibacterium acnes, IL-8, TNF alpha

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424 Active Vibration Reduction for a Flexible Structure Bonded with Sensor/Actuator Pairs on Efficient Locations Using a Developed Methodology

Authors: Ali H. Daraji, Jack M. Hale, Ye Jianqiao

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With the extensive use of high specific strength structures to optimise the loading capacity and material cost in aerospace and most engineering applications, much effort has been expended to develop intelligent structures for active vibration reduction and structural health monitoring. These structures are highly flexible, inherently low internal damping and associated with large vibration and long decay time. The modification of such structures by adding lightweight piezoelectric sensors and actuators at efficient locations integrated with an optimal control scheme is considered an effective solution for structural vibration monitoring and controlling. The size and location of sensor and actuator are important research topics to investigate their effects on the level of vibration detection and reduction and the amount of energy provided by a controller. Several methodologies have been presented to determine the optimal location of a limited number of sensors and actuators for small-scale structures. However, these studies have tackled this problem directly, measuring the fitness function based on eigenvalues and eigenvectors achieved with numerous combinations of sensor/actuator pair locations and converging on an optimal set using heuristic optimisation techniques such as the genetic algorithms. This is computationally expensive for small- and large-scale structures subject to optimise a number of s/a pairs to suppress multiple vibration modes. This paper proposes an efficient method to determine optimal locations for a limited number of sensor/actuator pairs for active vibration reduction of a flexible structure based on finite element method and Hamilton’s principle. The current work takes the simplified approach of modelling a structure with sensors at all locations, subjecting it to an external force to excite the various modes of interest and noting the locations of sensors giving the largest average percentage sensors effectiveness measured by dividing all sensor output voltage over the maximum for each mode. The methodology was implemented for a cantilever plate under external force excitation to find the optimal distribution of six sensor/actuator pairs to suppress the first six modes of vibration. It is shown that the results of the optimal sensor locations give good agreement with published optimal locations, but with very much reduced computational effort and higher effectiveness. Furthermore, it is shown that collocated sensor/actuator pairs placed in these locations give very effective active vibration reduction using optimal linear quadratic control scheme.

Keywords: optimisation, plate, sensor effectiveness, vibration control

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423 Severe Infestation of Laspeyresia Koenigana Fab. and Alternaria Leaf Spot on Azadirachta Indica (Neem)

Authors: Shiwani Bhatnagar, K. K. Srivastava, Sangeeta Singh, Ameen Ullah Khan, Bundesh Kumar, Lokendra Singh Rathore

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From the instigation of the world medicinal plants are treated as part and parcel of human society to fight against diseases. Azadirachta indica (Neem) a herbal plant has been used as an Indian traditional medicine since ages and its products are acknowledged to solve agricultural, forestry and public health related problems, owing to its beneficial medicinal properties. Each part of the neem tree is known for its medicinal property. Bark & leaf extracts of neem have been used to control leprosy, respiratory disorders, constipation and also as blood purifier and a general health tonic. Neem is still regarded as ' rural community dispensary' in India or a tree for solving medical problems. Use of Neem as pesticides for the management of insect pest of agriculture crops and forestry has been seen as a shift in the use of synthetic pesticides to ecofriendly botanicals. Neem oil and seed extracts possess germicidal and anti-bacterial properties which when sprayed on the plant helps in protecting them from foliage pests. Azadirachtin, the main active ingredient found in neem tree, acts as an insect repellent and antifeedant. However the young plants are susceptible to many insect pest and foliar diseases. Recently, in the avenue plantation, planted by Arid Forest Research Institute, Jodhpur, around the premises of IIT Jodhpur, two years old neem plants were found to be severely infested with tip borer Laspeyresia koenigana (Family: Eucosmidae). The adult moth of L. koenigana lays eggs on the tender shoots and the young larvae tunnel into the shoot and feed inside. A small pinhole can be seen at the entrance point, from where the larva enters in to the stem. The severely attached apical shoots exhibit profuse gum exudation resulting in development of a callus structure. The internal feeding causes the stem to wilt and the leaves to dry up from the tips resulting in growth retardation. Alternaria Leaf spot and blight symptoms were also recorded on these neem plants. For the management of tip borer and Alternaria Leaf spot, foliar spray of monocrotophos @0.05% and Dithane M-45 @ 0.15% and powermin @ 2ml/lit were found efficient in managing the insect pest and foliar disease problem. No Further incidence of pest/diseases was noticed.

Keywords: azadirachta indica, alternaria leaf spot, laspeyresia koenigana, management

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422 Innovative Technologies Functional Methods of Dental Research

Authors: Sergey N. Ermoliev, Margarita A. Belousova, Aida D. Goncharenko

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Application of the diagnostic complex of highly informative functional methods (electromyography, reodentography, laser Doppler flowmetry, reoperiodontography, vital computer capillaroscopy, optical tissue oximetry, laser fluorescence diagnosis) allows to perform a multifactorial analysis of the dental status and to prescribe complex etiopathogenetic treatment. Introduction. It is necessary to create a complex of innovative highly informative and safe functional diagnostic methods for improvement of the quality of patient treatment by the early detection of stomatologic diseases. The purpose of the present study was to investigate the etiology and pathogenesis of functional disorders identified in the pathology of hard tissue, dental pulp, periodontal, oral mucosa and chewing function, and the creation of new approaches to the diagnosis of dental diseases. Material and methods. 172 patients were examined. Density of hard tissues of the teeth and jaw bone was studied by intraoral ultrasonic densitometry (USD). Electromyographic activity of masticatory muscles was assessed by electromyography (EMG). Functional state of dental pulp vessels assessed by reodentography (RDG) and laser Doppler flowmetry (LDF). Reoperiodontography method (RPG) studied regional blood flow in the periodontal tissues. Microcirculatory vascular periodontal studied by vital computer capillaroscopy (VCC) and laser Doppler flowmetry (LDF). The metabolic level of the mucous membrane was determined by optical tissue oximetry (OTO) and laser fluorescence diagnosis (LFD). Results and discussion. The results obtained revealed changes in mineral density of hard tissues of the teeth and jaw bone, the bioelectric activity of masticatory muscles, regional blood flow and microcirculation in the dental pulp and periodontal tissues. LDF and OTO methods estimated fluctuations of saturation level and oxygen transport in microvasculature of periodontal tissues. With LFD identified changes in the concentration of enzymes (nicotinamide, flavins, lipofuscin, porphyrins) involved in metabolic processes Conclusion. Our preliminary results confirmed feasibility and safety the of intraoral ultrasound densitometry technique in the density of bone tissue of periodontium. Conclusion. Application of the diagnostic complex of above mentioned highly informative functional methods allows to perform a multifactorial analysis of the dental status and to prescribe complex etiopathogenetic treatment.

Keywords: electromyography (EMG), reodentography (RDG), laser Doppler flowmetry (LDF), reoperiodontography method (RPG), vital computer capillaroscopy (VCC), optical tissue oximetry (OTO), laser fluorescence diagnosis (LFD)

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421 High Throughput Virtual Screening against ns3 Helicase of Japanese Encephalitis Virus (JEV)

Authors: Soma Banerjee, Aamen Talukdar, Argha Mandal, Dipankar Chaudhuri

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Japanese Encephalitis is a major infectious disease with nearly half the world’s population living in areas where it is prevalent. Currently, treatment for it involves only supportive care and symptom management through vaccination. Due to the lack of antiviral drugs against Japanese Encephalitis Virus (JEV), the quest for such agents remains a priority. For these reasons, simulation studies of drug targets against JEV are important. Towards this purpose, docking experiments of the kinase inhibitors were done against the chosen target NS3 helicase as it is a nucleoside binding protein. Previous efforts regarding computational drug design against JEV revealed some lead molecules by virtual screening using public domain software. To be more specific and accurate regarding finding leads, in this study a proprietary software Schrödinger-GLIDE has been used. Druggability of the pockets in the NS3 helicase crystal structure was first calculated by SITEMAP. Then the sites were screened according to compatibility with ATP. The site which is most compatible with ATP was selected as target. Virtual screening was performed by acquiring ligands from databases: KinaseSARfari, KinaseKnowledgebase and Published inhibitor Set using GLIDE. The 25 ligands with best docking scores from each database were re-docked in XP mode. Protein structure alignment of NS3 was performed using VAST against MMDB, and similar human proteins were docked to all the best scoring ligands. The low scoring ligands were chosen for further studies and the high scoring ligands were screened. Seventy-three ligands were listed as the best scoring ones after performing HTVS. Protein structure alignment of NS3 revealed 3 human proteins with RMSD values lesser than 2Å. Docking results with these three proteins revealed the inhibitors that can interfere and inhibit human proteins. Those inhibitors were screened. Among the ones left, those with docking scores worse than a threshold value were also removed to get the final hits. Analysis of the docked complexes through 2D interaction diagrams revealed the amino acid residues that are essential for ligand binding within the active site. Interaction analysis will help to find a strongly interacting scaffold among the hits. This experiment yielded 21 hits with the best docking scores which could be investigated further for their drug like properties. Aside from getting suitable leads, specific NS3 helicase-inhibitor interactions were identified. Selection of Target modification strategies complementing docking methodologies which can result in choosing better lead compounds are in progress. Those enhanced leads can lead to better in vitro testing.

Keywords: antivirals, docking, glide, high-throughput virtual screening, Japanese encephalitis, ns3 helicase

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