Search results for: drug target
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4435

Search results for: drug target

3355 Pharmacogenetics of Uridine Diphosphate Glucuronosyltransferase (UGT1A9) Genetic Polymorphism on Sodium Valproate Pharmacokinetics in Epilepsy

Authors: Murali Munisamy, Gauthaman Karunakaran, Mubarak Al-Gahtany, Vivekanandhan Subbiah, M. Manjari Tripati

Abstract:

Background: Sodium valproate is a widely prescribed broad-spectrum anti-epileptic drug. It shows high inter-individual variability in pharmacokinetics and pharmacodynamics and has a narrow therapeutic range. We evaluated the effects of polymorphic uridine diphosphate glucuronosyltransferase (UGT1A9) metabolizing enzyme on the pharmacokinetics of sodium valproate in the patients with epilepsy who showed toxicity to therapy. Methods: Genotype analysis of the patients was made with polymerase chain–restriction fragment length polymorphism (RFLP) with sequencing. Plasma drug concentrations were measured with reversed phase high-performance liquid chromatography (HPLC) and concentration–time data were analyzed by using a non-compartmental approach. Results: The results of this study suggested a significant genotypic as well as allelic association with valproic acid toxicity for UGT1A9 polymorphic enzymes. The elimination half-life (t 1/2=40.2 h) of valproic acid was longer and the clearance rate (CL=937 ml/h) was lower in the poor metabolizers group of UGT1A9 polymorphism who showed toxicity than in the intermediate metabolizers group (t1/2=35.5 h, CL=1042 ml/h) or the extensive metabolizers group (t1/2=26. h, CL=1,302 ml/h). Conclusion: Our findings suggest that the UGT1A9 genetic polymorphism plays a significant role in the steady state concentration of sodium valproate, and it thereby has an impact on the toxicity of the sodium valproate used in the patients with epilepsy.

Keywords: UGT1A9, sodium valporate, pharmacogenetics, polymorphism

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3354 Higher Education Institution Students’ Perception on Educational Technology

Authors: Kuek Teik Sheng, Leaw Zee Guan, Lim Wah Kien, Ting Tin Tin

Abstract:

Educational technology such as YouTube and Kahoot have arisen as an alternative to effective learning among higher education institutions. There are many researches done in carrying out experiments to test different educational technologies and received positive feedback from students. Yet, similar study is hardly found in Malaysia especially study that includes the latest educational technologies. As a developing country, it is crucial to ensure that these emerging technologies are assisting students in learning process before it is widely adopted in institutions. This paper conducted a study to explore the perception of higher education institution students on the current educational technologies in Malaysia which include online educational games, online videos/course, social media, presentation tools and resource management tool. Some of these technologies have not been looked into its potential in effective learning process. An online survey using questionnaire is conducted among a target of 300 university/college. In the survey, the result shows that majority of the target students in Malaysia agree that the current educational technologies help them in learning, understanding and manage their studies. It is necessary to discover students’ perceptions on the educational technologies in order to provide guidelines for the educators/institutions in selecting appropriate technology to conduct the lecture/tutorial efficiently and effectively.

Keywords: education, educational technology, Facebook, PowerPoint, YouTube

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3353 Phenolic Acids of Plant Origin as Promising Compounds for Elaboration of Antiviral Drugs against Influenza

Authors: Vladimir Berezin, Aizhan Turmagambetova, Andrey Bogoyavlenskiy, Pavel Alexyuk, Madina Alexyuk, Irina Zaitceva, Nadezhda Sokolova

Abstract:

Introduction: Influenza viruses could infect approximately 5% to 10% of the global human population annually, resulting in serious social and economic damage. Vaccination and etiotropic antiviral drugs are used for the prevention and treatment of influenza. Vaccination is important; however, antiviral drugs represent the second line of defense against new emerging influenza virus strains for which vaccines may be unsuccessful. However, the significant drawback of commercial synthetic anti-flu drugs is the appearance of drug-resistant influenza virus strains. Therefore, the search and development of new anti-flu drugs efficient against drug-resistant strains is an important medical problem for today. The aim of this work was a study of four phenolic acids of plant origin (Gallic, Syringic, Vanillic, and Protocatechuic acids) as a possible tool for treatment against influenza virus. Methods: Phenolic acids; gallic, syringic, vanillic, and protocatechuic have been prepared by extraction from plant tissues and purified using high-performance liquid chromatography fractionation. Avian influenza virus, strain A/Tern/South Africa/1/1961 (H5N3) and human epidemic influenza virus, strain A/Almaty/8/98 (H3N2) resistant to commercial anti-flu drugs (Rimantadine, Oseltamivir) were used for testing antiviral activity. Viruses were grown in the allantoic cavity of 10 days old chicken embryos. The chemotherapeutic index (CTI), determined as the ratio of an average toxic concentration of the tested compound (TC₅₀) to the average effective virus-inhibition concentration (EC₅₀), has been used as a criteria of specific antiviral action. Results: The results of study have shown that the structure of phenolic acids significantly affected their ability to suppress the reproduction of tested influenza virus strains. The highest antiviral activity among tested phenolic acids was detected for gallic acid, which contains three hydroxyl groups in the molecule at C3, C4, and C5 positions. Antiviral activity of gallic acid against A/H5N3 and A/H3N2 influenza virus strains was higher than antiviral activity of Oseltamivir and Rimantadine. gallic acid inhibited almost 100% of the infection activity of both tested viruses. Protocatechuic acid, which possesses 2 hydroxyl groups (C3 and C4) have shown weaker antiviral activity in comparison with gallic acid and inhibited less than 10% of virus infection activity. Syringic acid, which contains two hydroxyl groups (C3 and C5), was able to suppress up to 12% of infection activity. Substitution of two hydroxyl groups by methoxy groups resulted in the complete loss of antiviral activity. Vanillic acid, which is different from protocatechuic acid by replacing of C3 hydroxyl group to methoxy group, was able to suppress about 30% of infection activity of tested influenza viruses. Conclusion: For pronounced antiviral activity, the molecular of phenolic acid must have at least two hydroxyl groups. Replacement of hydroxyl groups to methoxy group leads to a reduction of antiviral properties. Gallic acid demonstrated high antiviral activity against influenza viruses, including Rimantadine and Oseltamivir resistant strains, and could be used as a potential candidate for the development of antiviral drug against influenza virus.

Keywords: antiviral activity, influenza virus, drug resistance, phenolic acids

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3352 Virulence Phenotypes among Multi Drug Resistant Uropathogenic E. Coli and Klebsiella SPP

Authors: V. V. Lakshmi, Y. V. S. Annapurna

Abstract:

Urinary tract infection (UTI) is one of the most common infectious diseases seen in the community. Susceptible individuals experience multiple episodes, and progress to acute pyelonephritis or uro-sepsis or develop asymptomatic bacteriuria (ABU). Ability to cause extraintestinal infections depends on several virulence factors required for survival at extraintestinal sites. Presence of virulence phenotypes enhances the pathogenicity of these otherwise commensal organisms and thus augments its ability to cause extraintestinal infections, the most frequent in urinary tract infections(UTI). The present study focuses on detection of the virulence characters exhibited by the uropathogenic organism and most common factors exhibited in the local pathogens. A total of 700 isolates of E.coli and Klebsiella spp were included in the study.These were isolated from patients from local hospitals reported to be suffering with UTI over a period of three years. Isolation and identification was done based on Gram character and IMVIC reactions. Antibiotic sensitivity profile was carried out by disc diffusion method and multi drug resistant strains with MAR index of 0.7 were further selected. Virulence features examined included their ability to produce exopolysaccharides, protease- gelatinase production, hemolysin production, haemagglutination and hydrophobicity test. Exopolysaccharide production was most predominant virulence feature among the isolates when checked by congo red method. The biofilms production examined by microtitre plates using ELISA reader confirmed that this is the major factor contributing to virulencity of the pathogens followed by hemolysin production.

Keywords: Escherichia coli, Klebsiella spp, Uropathogens, virulence features

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3351 Patterns and Extent of Self-Medication Practice among Adolescents in Selected Public Secondary Schools in IFE Central Local Government Area of Osun State, Nigeria

Authors: Olajumoke A. Ojeleye

Abstract:

The study assessed the patterns and extent of self-medication practice among adolescents in selected public senior secondary schools in Ife Central Local Government Area of Osun State. The objectives of the study were to find out the patterns of self-medication among adolescents, to elucidate whether age or gender has any effect on the self-medication patterns of adolescent, to ascertain to what extent adolescents indulge in self-medication, to examine the sources of drug information of these adolescents and also to examine the sources of these drugs. A cross-sectional design was employed for the study. A self-administered questionnaire tested for validity was used to collect data. Multistage sampling technique was used and 238 adolescents participated in the study. Data collection took two weeks and was analysed using Statistical Package for Social Sciences version 17. Results were presented using descriptive (e.g. frequency counts) and inferential statistics (e.g. chi-square). Results showed that more females (55.9%) than males (44.1%) practiced self-medication. Although the results showed that there is a low prevalence rate (33.6%) of self-medication among adolescents, chemists served as both the source of information on how to use the drug as well as the source of the drugs. Also, adolescents under study will only self-medicate in medical conditions such as malaria or wound/injuries but will prefer to see a doctor for conditions such as abdominal pain, infections or allergic reactions. It was recommended that government officials responsible for regulating and controlling of drugs should be more active in ensuring that safe drugs are made available over the counter and the consumer be given adequate information about the use of drugs and when to consult the doctor.

Keywords: adolescents, drugs, patterns, self-medication

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3350 Deep Reinforcement Learning Model Using Parameterised Quantum Circuits

Authors: Lokes Parvatha Kumaran S., Sakthi Jay Mahenthar C., Sathyaprakash P., Jayakumar V., Shobanadevi A.

Abstract:

With the evolution of technology, the need to solve complex computational problems like machine learning and deep learning has shot up. But even the most powerful classical supercomputers find it difficult to execute these tasks. With the recent development of quantum computing, researchers and tech-giants strive for new quantum circuits for machine learning tasks, as present works on Quantum Machine Learning (QML) ensure less memory consumption and reduced model parameters. But it is strenuous to simulate classical deep learning models on existing quantum computing platforms due to the inflexibility of deep quantum circuits. As a consequence, it is essential to design viable quantum algorithms for QML for noisy intermediate-scale quantum (NISQ) devices. The proposed work aims to explore Variational Quantum Circuits (VQC) for Deep Reinforcement Learning by remodeling the experience replay and target network into a representation of VQC. In addition, to reduce the number of model parameters, quantum information encoding schemes are used to achieve better results than the classical neural networks. VQCs are employed to approximate the deep Q-value function for decision-making and policy-selection reinforcement learning with experience replay and the target network.

Keywords: quantum computing, quantum machine learning, variational quantum circuit, deep reinforcement learning, quantum information encoding scheme

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3349 Visualization of Corrosion at Plate-Like Structures Based on Ultrasonic Wave Propagation Images

Authors: Aoqi Zhang, Changgil Lee Lee, Seunghee Park

Abstract:

A non-contact nondestructive technique using laser-induced ultrasonic wave generation method was applied to visualize corrosion damage at aluminum alloy plate structures. The ultrasonic waves were generated by a Nd:YAG pulse laser, and a galvanometer-based laser scanner was used to scan specific area at a target structure. At the same time, wave responses were measured at a piezoelectric sensor which was attached on the target structure. The visualization of structural damage was achieved by calculating logarithmic values of root mean square (RMS). Damage-sensitive feature was defined as the scattering characteristics of the waves that encounter corrosion damage. The corroded damage was artificially formed by hydrochloric acid. To observe the effect of the location where the corrosion was formed, the both sides of the plate were scanned with same scanning area. Also, the effect on the depth of the corrosion was considered as well as the effect on the size of the corrosion. The results indicated that the damages were successfully visualized for almost cases, whether the damages were formed at the front or back side. However, the damage could not be clearly detected because the depth of the corrosion was shallow. In the future works, it needs to develop signal processing algorithm to more clearly visualize the damage by improving signal-to-noise ratio.

Keywords: non-destructive testing, corrosion, pulsed laser scanning, ultrasonic waves, plate structure

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3348 Evaluation of Gingival Hyperplasia Caused by Medications

Authors: Ilma Robo, Saimir Heta, Greta Plaka, Vera Ostreni

Abstract:

Purpose: Drug gingival hyperplasia is an uncommon pathology encountered during routine work in dental units. The purpose of this paper is to present the clinical appearance of gingival hyperplasia caused by medications. There are already three classes of medications that cause hyperplasia and based on data from the literature, the clinical cases encountered and included in this study have been compared. Materials and Methods: The study was conducted in a total of 311 patients, out of which 182 patients were included in our study, meeting the inclusion criteria. After each patient's history was recorded and it was found that patients were in their knowledge of chronic illness, undergoing treatment of gingivitis hypertrophic drugs was performed with a clinical examination of oral cavity and assessment by vertical and horizontal evaluation according to the periodontal indexes. Results: Of the data collected during the study, it was observed that 97% of patients with gingival hyperplasia are treated with nifedipine. 84% of patients treated with selected medicines and gingival hyperplasia in the oral cavity has been exposed at time period for more than 1 year and 1 month. According to the GOI, in the first rank of this index are about 21% of patients, in the second rank are 52%, in the third rank are 24% and in the fourth grade are 3%. According to the horizontal growth index of gingival hyperplasia, grade 1 included about 61% of patients and grade 2 included about 39% of patients with gingival hyperplasia. Bacterial index divides patients by degrees: grading 0 - 8.2%, grading 1 - 32.4%, grading 2 - 14% and grading 3 - 45.1%. Conclusions: The highest percentage of gingival hyperplasia caused by drugs is due to dosing of nifedipine for a duration of dosing and application for systemic healing for more than 1 year.

Keywords: drug gingival hyperplasia, horizontal growth index, vertical growth index

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3347 Comparative Study on the Evaluation of Patient Safety in Malaysian Retail Pharmacy Setup

Authors: Palanisamy Sivanandy, Tan Tyng Wei, Tan Wee Loon, Lim Chong Yee

Abstract:

Background: Patient safety has become a major concern over recent years with elevated medication errors; particularly prescribing and dispensing errors. Meticulous prescription screening and diligent drug dispensing is therefore important to prevent drug-related adverse events from inflicting harm to patients. Hence, pharmacists play a significant role in this scenario. The evaluation of patient safety in a pharmacy setup is crucial to contemplate current practices, attitude and perception of pharmacists towards patient safety. Method: The questionnaire for Pharmacy Survey on Patient Safety Culture developed by the Agency for Healthcare and Research Quality (AHRQ) was used to assess patient safety. Main objectives of the study was to evaluate the attitude and perception of pharmacists towards patient safety in retail pharmacies setup in Malaysia. Results: 417 questionnaire were distributed via convenience sampling in three different states of Malaysia, where 390 participants were responded and the response rate was 93.52%. The overall positive response rate (PRR) was ranged from 31.20% to 87.43% and the average PRR was found to be 67%. The overall patient safety grade for our pharmacies was appreciable and it ranges from good to very good. The study found a significant difference in the perception of senior and junior pharmacists towards patient safety. The internal consistency of the questionnaire contents /dimensions was satisfactory (Cronbach’s alpha - 0.92). Conclusion: Our results reflect that there was positive attitude and perception of retail pharmacists towards patient safety. Despite this, various efforts can be implemented in the future to amplify patient safety in retail pharmacies setup.

Keywords: patient safety, attitude, perception, positive response rate, medication errors

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3346 Investigating the Effect of the Psychoactive Substances Act 2016 on the Incidence of Adverse Medical Events in Her Majesty’s Prison (HMP) Leeds

Authors: Hayley Boal, Chloe Bromley, John Fairfield

Abstract:

Novel Psychoactive Substances (NPS) are synthetic compounds designed to reproduce effects of illicit drugs. Cheap, potent, and readily available on UK highstreets from so-called ‘head shops’, in recent years their use has surged and with it have emerged side effects including seizures, aggression, palpitations, coma, and death. Rapid development of new substances has vastly outpaced pre-existing drug legislation but the Psychoactive Substances Act 2016 rendered all but tobacco, alcohol, and amyl nitrates, illegal. Drug use has long been rife within prisons, but the absence of a reliable screening tool alongside the availability of NPS makes them ideal for prison use. Here we examine the occurrence of NPS-related adverse side effects within HMP Leeds, comparing May-September of 2015 and 2017 using daily reports distributed amongst prison staff summarising medical and behavioural incidents of the previous day. There was a statistically-significant rise of over 200% in the use of NPS between 2015 and 2017: 0.562 and 1.149 incidents per day respectively. In 2017, 38.46% incidents required ambulances, fallen from 51.02% in 2015. Although the most common descriptions in both years were ‘seizure’ and ‘unresponsive’, by 2017 ‘inhalation by staff’ had emerged. Patterns of NPS consumption mirrored the prison regime, peaking when cell doors opened, and prisoners could socialise. Despite limited data, the Psychoactive Substances Act has clearly been an insufficient deterrent to the prison population; more must be done to understand and address substance misuse in prison. NPS remains a significant risk to prisoners’ health and wellbeing.

Keywords: legislation, novel psychoactive substances, prison, spice

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3345 Non-Time and Non-Sense: Temporalities of Addiction for Heroin Users in Scotland

Authors: Laura Roe

Abstract:

This study draws on twelve months of ethnographic fieldwork conducted in 2017 with heroin and poly-substance users in Scotland and explores experiences of time and temporality as factors in continuing drug use. The research largely took place over the year in which drug-related deaths in Scotland reached a record high, and were statistically recorded as the highest in Europe. This qualitative research is therefore significant in understanding both evolving patterns of drug use and the experiential lifeworlds of those who use heroin and other substances in high doses. Methodologies included participant observation, structured and semi-structured interviews, and unstructured conversations with twenty-two regular participants. The fieldwork was conducted in two needle exchanges, a community recovery group and in the community. The initial aim of the study was to assess evolving patterns of drug preferences in order to explore a clinical and user-reported rise in the use of novel psychoactive substances (NPS), which are typically considered to be highly potent, synthetic substances, often available at a low cost. It was found, however, that while most research participants had experimented with NPS with varying intensity, those who used every day regularly consumed heroin, methadone, and alcohol with benzodiazepines such as diazepam or anticonvulsants such as gabapentin. The research found that many participants deliberately pursued the non-fatal effects of overdose, aiming to induce states of dissociation, detachment and uneven consciousness, and did so by both mixing substances and experimenting with novel modes of consumption. Temporality was significant in the decision to consume cocktails of substances, as users described wishing to sever themselves from time; entering into states of ‘non-time’ and insensibility through specific modes of intoxication. Time and temporality similarly impacted other aspects of addicted life. Periods of attempted abstinence witnessed a slowing of time’s passage that was tied to affective states of boredom and melancholy, in addition to a disruptive return of distressing and difficult memories. Abject past memories frequently dominated and disrupted the present, which otherwise could be highly immersive due to the time and energy-consuming nature of seeking drugs while in financial difficulty. There was furthermore a discordance between individual user temporalities and the strict time-based regimes of recovery services and institutional bodies, and the study aims to highlight the impact of such a disjuncture on the efficacy of treatment programs. Many participants had difficulty in adhering to set appointments or temporal frameworks due to their specific temporal situatedness. Overall, exploring increasing tendencies of heroin users in Scotland towards poly-substance use, this study draws on experiences and perceptions of time, analysing how temporality comes to bear on the ways drugs are sought and consumed, and how recovery is imagined and enacted. The study attempts to outline the experiential, intimate and subjective worlds of heroin and poly-substance users while explicating the structural and historical factors that shape them.

Keywords: addiction, poly-substance use, temporality, timelessness

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3344 Dual Drug Piperine-Paclitaxel Nanoparticles Inhibit Migration and Invasion in Human Breast Cancer Cells

Authors: Monika Verma, Renuka Sharma, B. R. Gulati, Namita Singh

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In combination therapy, two chemotherapeutic agents work together in a collaborative action. It has appeared as one of the promising approaches to improve anti-cancer treatment efficacy. In the present investigation, piperine (P-NPS), paclitaxel (PTX NPS), and a combination of both, piperine-paclitaxel nanoparticle (Pip-PTX NPS), were made by the nanoprecipitation method and later characterized by PSA, DSC, SEM, TEM, and FTIR. All nanoparticles exhibited a monodispersed size distribution with a size of below 200 nm, zeta potential ranges from (-30-40mV) and a narrow polydispersity index (>0.3) of the drugs. The average encapsulation efficiency was found to be between 80 and 90%. In vitro release of drugs for nanoparticles was done spectrophotometrically. FTIR and DSC results confirmed the presence of the drug. The Pip-PTX NPS significantly inhibit cell proliferation as compared to the native drugs nanoparticles in the breast cancer cell line MCF-7. In addition, Pip-PTX NPS suppresses cells in colony formation and soft gel agar assay. Scratch migration and Transwell chamber invasion assays revealed that combined nanoparticles reduce the migration and invasion of breast cancer cells. Morphological studies showed that Pip-PTX NPS penetrates the cells and induces apoptosis, which was further confirmed by DNA fragmentation, SEM, and western blot analysis. Taken together, Pip-PTX NPS inhibits cell proliferation, anchorage dependent and anchorage independent cell growth, reduces migration and invasion, and induces apoptosis in cells. These findings support that combination therapy using Pip-PTX NPS represents a potential approach and could be helpful in the future for breast cancer therapy.

Keywords: piperine, paclitaxel, breast cancer, apoptosis

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3343 Effect of Miconazole Nitrate on Immunological Response and Its Preventive Efficacy in Labeo rohita Fingerlings against Oomycetes Saprolegnia parasitica

Authors: Mukta Singh, Ratan Kumar Saha, Himadri Saha, Paramveer Singh

Abstract:

The present study evaluated the effect of sub-lethal doses of antifungal drug miconazole nitrate (MCZ) on immunological responses including immune-related gene expression and its role as a prophylactic drug against S. parasitica in Labeo rohita fingerlings. Fish were fed with sub lethal doses of MCZ i.e., T1- 6.30 mg MCZ kgBW⁻¹, T2- 12.61 mg MCZ kgBW⁻¹ and T3- 25.22 mg MCZ kgBW⁻¹ and sampling was done at different time intervals for 240 h. Immunological parameters viz. lysozyme activity, oxygen radical production and plasma anti-protease activity showed significant enhancement (p < 0.05) in fish fed with T2 and T3 doses. Significant reduction in plasma protein content was observed in all the dietary groups as compared to control. Expression of immune-relevant genes like TLR-22 and β2-M showed significantly higher expression at six h and 24 h of sampling in both liver and head-kidney. However, these genes showed a down-regulation after 120 h of sampling in both the tissues. Preventive efficacy study showed that single dose of MCZ provides protection against oomycetes up to the fourth day of infection. Significantly higher mortality was observed in control diet-fed fish as compared to fish fed with MCZ medicated diet. Thus, from the study, it can be concluded that the MCZ can act as a potent antifungal agent for preventing oomycetes infection as well as to enhance the immune response.

Keywords: antifungal, immune gene, immunological, miconazole nitrate, prophylactic

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3342 Unveiling the Self-Assembly Behavior and Salt-Induced Morphological Transition of Double PEG-Tailed Unconventional Amphiphiles

Authors: Rita Ghosh, Joykrishna Dey

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PEG-based amphiphiles are of tremendous importance for its widespread applications in pharmaceutics, household purposes, and drug delivery. Previously, a number of single PEG-tailed amphiphiles having significant applications have been reported from our group. Therefore, it was of immense interest to explore the properties and application potential of PEG-based double tailed amphiphiles. Herein, for the first time, two novel double PEG-tailed amphiphiles having different PEG chain lengths have been developed. The self-assembly behavior of the newly developed amphiphiles in aqueous buffer (pH 7.0) was thoroughly investigated at 25 oC by a number of techniques including, 1H-NMR, and steady-state and time-dependent fluorescence spectroscopy, dynamic light scattering, transmission electron microscopy, atomic force microscopy, and isothermal titration calorimetry. Despite having two polar PEG chains both molecules were found to have strong tendency to self-assemble in aqueous buffered solution above a very low concentration. Surprisingly, the amphiphiles were shown to form stable vesicles spontaneously at room temperature without any external stimuli. The results of calorimetric measurements showed that the vesicle formation is driven by the hydrophobic effect (positive entropy change) of the system, which is associated with the helix-to-random coil transition of the PEG chain. The spectroscopic data confirmed that the bilayer membrane of the vesicles is constituted by the PEG chains of the amphiphilic molecule. Interestingly, the vesicles were also found to exhibit structural transitions upon addition of salts in solution. These properties of the vesicles enable them as potential candidate for drug delivery.

Keywords: double-tailed amphiphiles, fluorescence, microscopy, PEG, vesicles

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3341 Self-Supervised Learning for Hate-Speech Identification

Authors: Shrabani Ghosh

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Automatic offensive language detection in social media has become a stirring task in today's NLP. Manual Offensive language detection is tedious and laborious work where automatic methods based on machine learning are only alternatives. Previous works have done sentiment analysis over social media in different ways such as supervised, semi-supervised, and unsupervised manner. Domain adaptation in a semi-supervised way has also been explored in NLP, where the source domain and the target domain are different. In domain adaptation, the source domain usually has a large amount of labeled data, while only a limited amount of labeled data is available in the target domain. Pretrained transformers like BERT, RoBERTa models are fine-tuned to perform text classification in an unsupervised manner to perform further pre-train masked language modeling (MLM) tasks. In previous work, hate speech detection has been explored in Gab.ai, which is a free speech platform described as a platform of extremist in varying degrees in online social media. In domain adaptation process, Twitter data is used as the source domain, and Gab data is used as the target domain. The performance of domain adaptation also depends on the cross-domain similarity. Different distance measure methods such as L2 distance, cosine distance, Maximum Mean Discrepancy (MMD), Fisher Linear Discriminant (FLD), and CORAL have been used to estimate domain similarity. Certainly, in-domain distances are small, and between-domain distances are expected to be large. The previous work finding shows that pretrain masked language model (MLM) fine-tuned with a mixture of posts of source and target domain gives higher accuracy. However, in-domain performance of the hate classifier on Twitter data accuracy is 71.78%, and out-of-domain performance of the hate classifier on Gab data goes down to 56.53%. Recently self-supervised learning got a lot of attention as it is more applicable when labeled data are scarce. Few works have already been explored to apply self-supervised learning on NLP tasks such as sentiment classification. Self-supervised language representation model ALBERTA focuses on modeling inter-sentence coherence and helps downstream tasks with multi-sentence inputs. Self-supervised attention learning approach shows better performance as it exploits extracted context word in the training process. In this work, a self-supervised attention mechanism has been proposed to detect hate speech on Gab.ai. This framework initially classifies the Gab dataset in an attention-based self-supervised manner. On the next step, a semi-supervised classifier trained on the combination of labeled data from the first step and unlabeled data. The performance of the proposed framework will be compared with the results described earlier and also with optimized outcomes obtained from different optimization techniques.

Keywords: attention learning, language model, offensive language detection, self-supervised learning

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3340 The Lytic Bacteriophage VbɸAB-1 Against Drug-Resistant Acinetobacter Baumannii Isolated from Hospitalized Pressure Ulcers Patients

Authors: M. Doudi, M. H. Pazandeh, L. Rahimzadeh Torabi

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Bedsores are pressure ulcers that occur on the skin or tissue due to being immobile and lying in bed for extended periods. Bedsores have the potential to progress into open ulcers, increasing the possibility of a variety of bacterial infections. Acinetobacter baumannii, a pathogen of considerable clinical importance, exhibited a significant correlation with Bedsores (pressure ulcers) infections, thereby manifesting a wide spectrum of antibiotic resistance. The emergence of drug resistance has led researchers to focus on alternative methods, particularly phage therapy, for tackling bacterial infections. Phage therapy has emerged as a novel therapeutic approach to regulate the activity of these agents. The management of bacterial infections greatly benefits from the clinical utilization of bacteriophages as a valuable antimicrobial intervention. The primary objective of this investigation consisted of isolating and discerning potent bacteriophage capable of targeting multi-drug-resistant (MDR) and extensively drug-resistant (XDR) bacteria obtained from pressure ulcers. The present study analyzed and isolated A. baumannii strains obtained from a cohort of patients suffering from pressure ulcers at Taleghani Hospital in Ahvaz, Iran. An approach that included biochemical and molecular identification techniques was used to determine the taxonomic classification of bacterial isolates at the genus and species levels. The molecular identification process was facilitated by using the 16S rRNA gene in combination with universal primers 27 F and 1492 R. Bacteriophage was obtained through the isolation process conducted on treatment plant sewage located in Isfahan, Iran. The main goal of this study was to evaluate different characteristics of phage, such as their appearance, the range of hosts they can infect, how quickly they can enter a host, their stability at varying temperatures and pH levels, their effectiveness in killing bacteria, the growth pattern of a single phage stage, mapping of enzymatic digestion, and identification of proteomics patterns. The findings demonstrated that an examination was conducted on a sample of 50 specimens, wherein 15 instances of A. baumannii were identified. These microorganisms are the predominant Gram-negative agents known to cause wound infections in individuals suffering from bedsores. The study's findings indicated a high prevalence of antibiotic resistance in the strains isolated from pressure ulcers, excluding the clinical strains that exhibited responsiveness to colistin. According to the findings obtained from assessments of host range and morphological characteristics of bacteriophage VbɸAB-1, it can be concluded that this phage possesses specificity towards A. Baumannii BAH_Glau1001 was classified as a member of the Podoviridae family. The bacteriophage mentioned earlier showed the strongest antibacterial effect at a temperature of 18 °C and a pH of 6.5. Through the utilization of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis on protein fragments, it was established that the bacteriophage VbɸAB-1 exhibited a size range between 50 and 75 kilodaltons (KDa). The numerous research findings on the effectiveness of phages and the safety studies conducted suggest that the phages studied in this research can be considered as a practical solution and recommended approach for controlling and treating stubborn pathogens in burn wounds among hospitalized patients. The findings of our research indicated that isolated phages could be an effective antimicrobial and an appreciate candidate for prophylaxis against pressure ulcers.

Keywords: acinetobacter baumannii, extremely drug-resistant, phage therapy, surgery wound

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3339 Occurrence of Foreign Matter in Food: Applied Identification Method - Association of Official Agricultural Chemists (AOAC) and Food and Drug Administration (FDA)

Authors: E. C. Mattos, V. S. M. G. Daros, R. Dal Col, A. L. Nascimento

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The aim of this study is to present the results of a retrospective survey on the foreign matter found in foods analyzed at the Adolfo Lutz Institute, from July 2001 to July 2015. All the analyses were conducted according to the official methods described on Association of Official Agricultural Chemists (AOAC) for the micro analytical procedures and Food and Drug Administration (FDA) for the macro analytical procedures. The results showed flours, cereals and derivatives such as baking and pasta products were the types of food where foreign matters were found more frequently followed by condiments and teas. Fragments of stored grains insects, its larvae, nets, excrement, dead mites and rodent excrement were the most foreign matter found in food. Besides, foreign matters that can cause a physical risk to the consumer’s health such as metal, stones, glass, wood were found but rarely. Miscellaneous (shell, sand, dirt and seeds) were also reported. There are a lot of extraneous materials that are considered unavoidable since are something inherent to the product itself, such as insect fragments in grains. In contrast, there are avoidable extraneous materials that are less tolerated because it is preventable with the Good Manufacturing Practice. The conclusion of this work is that although most extraneous materials found in food are considered unavoidable it is necessary to keep the Good Manufacturing Practice throughout the food processing as well as maintaining a constant surveillance of the production process in order to avoid accidents that may lead to occurrence of these extraneous materials in food.

Keywords: extraneous materials, food contamination, foreign matter, surveillance

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3338 Analysis of Thermal Damage Characteristics of High Pressure Turbine Blade According to Off-Design Operating Conditions

Authors: Seon Ho Kim, Minho Bang, Seok Min Choi, Young Moon Lee, Dong Kwan Kim, Hyung Hee Cho

Abstract:

Gas turbines are heat engines that convert chemical energy into electrical energy through mechanical energy. Since their high energy density per unit volume and low pollutant emissions, gas turbines are classified as clean energy. In order to obtain better performance, the turbine inlet temperature of the current gas turbine is operated at about 1600℃, and thermal damage is a very serious problem. Especially, these thermal damages are more prominent in off-design conditions than in design conditions. In this study, the thermal damage characteristics of high temperature components of a gas turbine made of a single crystal material are studied numerically for the off-design operating conditions. The target gas turbine is configured as a reheat cycle and is operated in peak load operation mode, not normal operation. In particular, the target gas turbine features a lot of low-load operation. In this study, a commercial code, ANSYS 18.2, was used for analyzing the thermal-flow coupling problems. As a result, the flow separation phenomenon on the pressure side due to the flow reduction was remarkable at the off-design condition, and the high heat transfer coefficient at the upper end of the suction surface due to the tip leakage flow was appeared.

Keywords: gas turbine, single crystal blade, off-design, thermal analysis

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3337 Antioxidant Activity of Avocado Puree on Blood Urea Nitrogen and Creatinine Level in White Rats (Rattus norvegicus) Induced with Toxic Doses of Meloxicam

Authors: Amelia R. Anshar, Dini Kurnia, Muh A. Bahar

Abstract:

Nowadays, there are so many incidences had been reported in pet animals regarding drug overdose caused by incorrect doses of a non-steroidal anti-inflammatory drug (NSAID), for instance, meloxicam. As supporting treatment, the avocado is used in traditional medicine to treat or prevent some health cases. The study was aimed at providing the basis for the antioxidant activity of avocado puree in animal medicine. Experimental animals used in this study were 24 male rats that were randomly divided into 4 groups (n=6). Control Group I got 1 ml CMC 1% and control II got meloxicam 30 mg/kgBB and 1 ml CMC 1%. Treatment group I got meloxicam 30 mg/kgBB and avocado 5 g/kgBB/day and treatment II got meloxicam 30 mg/kgBB and avocado 10 g/kgBB/day. The study was conducted over 8 days, then the level of Blood Urea Nitrogen and creatinine of the white rats were examined in 1st day and 8th day. The results were analyzed by ANOVA Two Way With Replication, then followed by T-test (α = 0,05) if there were a difference. Comparison test among the four groups after treatment with avocado using Anova Two Way With Replication test showed that there were significant differences between the mean of the four groups either decreased levels of Blood Urea Nitrogen and creatinine with p < 0,05. Treatment group I and II received treatment showed remarkable (p < 0,05) decreases ini Blood Urea Nitrogen level by 27,17 mg/dl and 17,83 mg/dl respectively. There was also significant decrease in the values of creatinine in Treatment group I and treatment group II by 0,983 mg/dl and 0,713 mg/dl respectively. The conclusion of this study was that avocado decreases level of Blood Urea Nitrogen and creatinine in white rats which are exposed to toxic doses of meloxicam.

Keywords: avocado, blood urea nitrogen, creatinine, meloxicam

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3336 Convolution Neural Network Based on Hypnogram of Sleep Stages to Predict Dosages and Types of Hypnotic Drugs for Insomnia

Authors: Chi Wu, Dean Wu, Wen-Te Liu, Cheng-Yu Tsai, Shin-Mei Hsu, Yin-Tzu Lin, Ru-Yin Yang

Abstract:

Background: The results of previous studies compared the benefits and risks of receiving insomnia medication. However, the effects between hypnotic drugs used and enhancement of sleep quality were still unclear. Objective: The aim of this study is to establish a prediction model for hypnotic drugs' dosage used for insomnia subjects and associated the relationship between sleep stage ratio change and drug types. Methodologies: According to American Academy of Sleep Medicine (AASM) guideline, sleep stages were classified and transformed to hypnogram via the polysomnography (PSG) in a hospital in New Taipei City (Taiwan). The subjects with diagnosis for insomnia without receiving hypnotic drugs treatment were be set as the comparison group. Conversely, hypnotic drugs dosage within the past three months was obtained from the clinical registration for each subject. Furthermore, the collecting subjects were divided into two groups for training and testing. After training convolution neuron network (CNN) to predict types of hypnotics used and dosages are taken, the test group was used to evaluate the accuracy of classification. Results: We recruited 76 subjects in this study, who had been done PSG for transforming hypnogram from their sleep stages. The accuracy of dosages obtained from confusion matrix on the test group by CNN is 81.94%, and accuracy of hypnotic drug types used is 74.22%. Moreover, the subjects with high ratio of wake stage were correctly classified as requiring medical treatment. Conclusion: CNN with hypnogram was potentially used for adjusting the dosage of hypnotic drugs and providing subjects to pre-screening the types of hypnotic drugs taken.

Keywords: convolution neuron network, hypnotic drugs, insomnia, polysomnography

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3335 The Effect of Education on Nurses' Knowledge Level for Ventrogluteal Site Injection: Pilot Study

Authors: Emel Bayraktar, Gulengun Turk

Abstract:

Introduction and Objective: Safe administration of medicines is one of the main responsibilities of nurses. Intramuscular drug administration is among the most common methods used by nurses among all drug applications. This study was carried out in order to determine determine the effect of education given on injection in ventrogluteal area on the level of knowledge of nurses on this subject. Methods: The sample of the study consisted of 20 nurses who agreed to participate in the study between 01 October and 31 December 2019. The research is a pretest-posttest comparative, quasi-experimental type pilot study. The nurses were given a 4-hour training prepared on injection into the ventrogluteal area. The training consisted of two hours of theoretical and two hours of laboratory practice. Before the training and 4 weeks after the training, a questionnaire form containing questions about their knowledge and practices regarding the injection of the ventrogluteal region was applied to the nurses. Results: The average age of the nurses is 26.55 ± 7.60, 35% (n = 7) of them are undergraduate and 30% (n = 6) of them work in intensive care units. Before the training, 35% (n = 7) of the nurses stated that the most frequently used intramuscular injection site was the ventrogluteal area, and 75% (n = 15) stated that the safest area was the rectus femoris muscle. After the training, 55% (n = 11) of the nurses stated that they most frequently used the ventrogluteal area and 100% (n = 20) of them stated that the ventrogluteal area was the safest area. The average score the nurses got from the premises before the training is 14.15 ± 6.63 (min = 0, max = 20), the total score is 184. The average score obtained after the training was determined as 18.69 ± 2.35 (min = 12, max = 20), and the total score was 243. Conclusion: As a result of the research, it was determined that the training given on the injection of ventrogluteal area increased the knowledge level of the nurses. It is recommended to organize in-service trainings for all nurses on the injection of ventrogluteal area.

Keywords: safe injection, knowledge level, nurse, intramuscular injection, ventrogluteal area

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3334 DPAGT1 Inhibitors: Discovery of Anti-Metastatic Drugs

Authors: Michio Kurosu

Abstract:

Alterations in glycosylation not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Identification of cell type-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems for certain cancers via immunodetection reagents. N- and O-linked glycans are the most abundant forms of glycoproteins. Recent studies of cancer immunotherapy are based on the immunogenicity of truncated O-glycan chains (e.g., Tn, sTn, T, and sLea/x). The prevalence of N-linked glycan changes in the development of tumor cells is known; however, therapeutic antibodies against N-glycans have not yet been developed. This is due to the lack of specificity of N-linked glycans between normal/healthy and cancer cells. Abnormal branching of N-linked glycans has been observed, particularly in solid cancer cells. While the discovery of drug-like glycosyltransferase inhibitors that block the biosynthesis of specific branching has a very low likelihood of success, altered glycosylation levels can be exploited by suppressing N-glycan biosynthesis through the inhibition of dolichyl-phosphate N-acetylglucosaminephosphotransferase1 (DPAGT1) activity. Inhibition of DPAGT1 function leads to changes of O-glycosylation on proteins associated with mitochondria and zinc finger binding proteins (indirect effects). On the basis of dynamic crosstalk between DPAGT1 and Snail/Slung/ZEB1 (a family of transcription factors that promote the repression of the adhesion molecules), we have developed pharmacologically acceptable selective DPAGT1 inhibitors. Tunicamycin kills a wide range of cancer and healthy cells in a non-selective manner. In sharp contrast, our DPAGT1 inhibitors display strong cytostatic effects against 16 solid cancers, which require the overexpression of DPAGT1 in their progression but do not affect the cell viability of healthy cells. The identified DPAGT1 inhibitors possess impressive anti-metastatic ability in various solid cancer cell lines and induce their mitochondrial structural changes, resulting in apoptosis. A prototype DPAGT1 inhibitor, APPB has already been proven to shrink solid tumors (e.g., pancreatic cancers, triple-negative breast cancers) in vivo while suppressing metastases and has strong synergistic effects when combined with current cytotoxic drugs (e.g., paclitaxel). At this conference, our discovery of selective DPAGT1 inhibitors with drug-like properties and proof-of-pharmaceutical concept studies of a novel DPAGT1 inhibitor are presented.

Keywords: DPAGT1 inhibitors, anti-metastatic drugs, natural product based drug designs, cytostatic effects

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3333 Diselenide-Linked Redox Stimuli-Responsive Methoxy Poly(Ethylene Glycol)-b-Poly(Lactide-Co-Glycolide) Micelles for the Delivery of Doxorubicin in Cancer Cells

Authors: Yihenew Simegniew Birhan, Hsieh Chih Tsai

Abstract:

The recent advancements in synthetic chemistry and nanotechnology fostered the development of different nanocarriers for enhanced intracellular delivery of pharmaceutical agents to tumor cells. Polymeric micelles (PMs), characterized by small size, appreciable drug loading capacity (DLC), better accumulation in tumor tissue via enhanced permeability and retention (EPR) effect, and the ability to avoid detection and subsequent clearance by the mononuclear phagocyte (MNP) system, are convenient to improve the poor solubility, slow absorption and non-selective biodistribution of payloads embedded in their hydrophobic cores and hence, enhance the therapeutic efficacy of chemotherapeutic agents. Recently, redox-responsive polymeric micelles have gained significant attention for the delivery and controlled release of anticancer drugs in tumor cells. In this study, we synthesized redox-responsive diselenide bond containing amphiphilic polymer, Bi(mPEG-PLGA)-Se₂ from mPEG-PLGA, and 3,3'-diselanediyldipropanoic acid (DSeDPA) using DCC/DMAP as coupling agents. The successful synthesis of the copolymers was verified by different spectroscopic techniques. Above the critical micelle concentration, the amphiphilic copolymer, Bi(mPEG-PLGA)-Se₂, self-assembled into stable micelles. The DLS data indicated that the hydrodynamic diameter of the micelles (123.9 ± 0.85 nm) was suitable for extravasation into the tumor cells through the EPR effect. The drug loading content (DLC) and encapsulation efficiency (EE) of DOX-loaded micelles were found to be 6.61 wt% and 54.9%, respectively. The DOX-loaded micelles showed initial burst release accompanied by sustained release trend where 73.94% and 69.54% of encapsulated DOX was released upon treatment with 6mM GSH and 0.1% H₂O₂, respectively. The biocompatible nature of Bi(mPEG-PLGA)-Se₂ copolymer was confirmed by the cell viability study. In addition, the DOX-loaded micelles exhibited significant inhibition against HeLa cells (44.46%), at a maximum dose of 7.5 µg/mL. The fluorescent microscope images of HeLa cells treated with 3 µg/mL (equivalent DOX concentration) revealed efficient internalization and accumulation of DOX-loaded Bi(mPEG-PLGA)-Se₂ micelles in the cytosol of cancer cells. In conclusion, the intelligent, biocompatible, and the redox stimuli-responsive behavior of Bi(mPEG-PLGA)-Se₂ copolymer marked the potential applications of diselenide-linked mPEG-PLGA micelles for the delivery and on-demand release of chemotherapeutic agents in cancer cells.

Keywords: anticancer drug delivery, diselenide bond, polymeric micelles, redox-responsive

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3332 Insight into the Binding Theme of CA-074Me to Cathepsin B: Molecular Dynamics Simulations and Scaffold Hopping to Identify Potential Analogues as Anti-Neurodegenerative Diseases

Authors: Tivani Phosa Mashamba-Thompson, Mahmoud E. S. Soliman

Abstract:

To date, the cause of neurodegeneration is not well understood and diseases that stem from neurodegeneration currently have no known cures. Cathepsin B (CB) enzyme is known to be involved in the production of peptide neurotransmitters and toxic peptides in neurodegenerative diseases (NDs). CA-074Me is a membrane-permeable irreversible selective cathepsin B (CB) inhibitor as confirmed by in vivo studies. Due to the lack of the crystal structure, the binding mode of CA-074Me with the human CB at molecular level has not been previously reported. The main aim of this study is to gain an insight into the binding mode of CB CA-074Me to human CB using various computational tools. Herein, molecular dynamics simulations, binding free energy calculations and per-residue energy decomposition analysis were employed to accomplish the aim of the study. Another objective was to identify novel CB inhibitors based on the structure of CA-074Me using fragment based drug design using scaffold hoping drug design approach. Results showed that two of the designed ligands (hit 1 and hit 2) were found to have better binding affinities than the prototype inhibitor, CA-074Me, by ~2-3 kcal/mol. Per-residue energy decomposition showed that amino acid residues Cys29, Gly196, His197 and Val174 contributed the most towards the binding. The Van der Waals binding forces were found to be the major component of the binding interactions. The findings of this study should assist medicinal chemist towards the design of potential irreversible CB inhibitors.

Keywords: cathepsin B, scaffold hopping, docking, molecular dynamics, binding-free energy, neurodegerative diseases

Procedia PDF Downloads 359
3331 Stability Indicating RP – HPLC Method Development, Validation and Kinetic Study for Amiloride Hydrochloride and Furosemide in Pharmaceutical Dosage Form

Authors: Jignasha Derasari, Patel Krishna M, Modi Jignasa G.

Abstract:

Chemical stability of pharmaceutical molecules is a matter of great concern as it affects the safety and efficacy of the drug product.Stability testing data provides the basis to understand how the quality of a drug substance and drug product changes with time under the influence of various environmental factors. Besides this, it also helps in selecting proper formulation and package as well as providing proper storage conditions and shelf life, which is essential for regulatory documentation. The ICH guideline states that stress testing is intended to identify the likely degradation products which further help in determination of the intrinsic stability of the molecule and establishing degradation pathways, and to validate the stability indicating procedures. A simple, accurate and precise stability indicating RP- HPLC method was developed and validated for simultaneous estimation of Amiloride Hydrochloride and Furosemide in tablet dosage form. Separation was achieved on an Phenomenexluna ODS C18 (250 mm × 4.6 mm i.d., 5 µm particle size) by using a mobile phase consisting of Ortho phosphoric acid: Acetonitrile (50:50 %v/v) at a flow rate of 1.0 ml/min (pH 3.5 adjusted with 0.1 % TEA in Water) isocratic pump mode, Injection volume 20 µl and wavelength of detection was kept at 283 nm. Retention time for Amiloride Hydrochloride and Furosemide was 1.810 min and 4.269 min respectively. Linearity of the proposed method was obtained in the range of 40-60 µg/ml and 320-480 µg/ml and Correlation coefficient was 0.999 and 0.998 for Amiloride hydrochloride and Furosemide, respectively. Forced degradation study was carried out on combined dosage form with various stress conditions like hydrolysis (acid and base hydrolysis), oxidative and thermal conditions as per ICH guideline Q2 (R1). The RP- HPLC method has shown an adequate separation for Amiloride hydrochloride and Furosemide from its degradation products. Proposed method was validated as per ICH guidelines for specificity, linearity, accuracy; precision and robustness for estimation of Amiloride hydrochloride and Furosemide in commercially available tablet dosage form and results were found to be satisfactory and significant. The developed and validated stability indicating RP-HPLC method can be used successfully for marketed formulations. Forced degradation studies help in generating degradants in much shorter span of time, mostly a few weeks can be used to develop the stability indicating method which can be applied later for the analysis of samples generated from accelerated and long term stability studies. Further, kinetic study was also performed for different forced degradation parameters of the same combination, which help in determining order of reaction.

Keywords: amiloride hydrochloride, furosemide, kinetic study, stability indicating RP-HPLC method validation

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3330 Molecular Characterisation and Expression of Glutathione S-Transferase of Fasciola Gigantica

Authors: J. Adeppa, S. Samanta, O. K. Raina

Abstract:

Fasciolosis is a widespread economically important parasitic infection throughout the world caused by Fasciola hepatica and F. gigantica. In order to identify novel immunogen conferring significant protection against fasciolosis, currently, research has been focused on the defined antigens viz. glutathione S-transferase, fatty acid binding protein, cathepsin-L, fluke hemoglobin, paramyosin, myosin and F. hepatica- Kunitz Type Molecule. Among various antigens, GST which plays a crucial role in detoxification processes, i.e. phase II defense mechanism of this parasite, has a unique position as a novel vaccine candidate and a drug target in the control of this disease. For producing the antigens in large quantities and their purification to complete homogeneity, the recombinant DNA technology has become an important tool to achieve this milestone. RT- PCR was carried out using F. gigantica total RNA as template, and an amplicon of 657 bp GST gene was obtained. TA cloning vector was used for cloning of this gene, and the presence of insert was confirmed by blue-white selection for recombinant colonies. Sequence analysis of the present isolate showed 99.1% sequence homology with the published sequence of the F. gigantica GST gene of cattle origin (accession no. AF112657), with six nucleotide changes at 72, 74, 423, 513, 549 and 627th bp found in the present isolate, causing an overall change of 4 amino acids. The 657 bp GST gene was cloned at BamH1 and HindIII restriction sites of the prokaryotic expression vector pPROEXHTb in frame with six histidine residues and expressed in E. coli DH5α. Recombinant protein was purified from the bacterial lysate under non-denaturing conditions by the process of sonication after lysozyme treatment and subjecting the soluble fraction of the bacterial lysate to Ni-NTA affinity chromatography. Western blotting with rabbit hyper-immune serum showed immuno-reactivity with 25 kDa recombinant GST. Recombinant protein detected F. gigantica experimental as well as field infection in buffaloes by dot-ELISA. However, cross-reactivity studies on Fasciola gigantica GST antigen are needed to evaluate the utility of this protein in the serodiagnosis of fasciolosis.

Keywords: fasciola gigantic, fasciola hepatica, GST, RT- PCR

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3329 Drug Reaction with Eosinophilia and Systemic Symptoms (Dress) Syndrome Presenting as Multi-Organ Failure

Authors: Keshari Shrestha, Philip Vatterott

Abstract:

Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal drug-related syndrome. DRESS classically presents with a diffuse maculopapular rash, fevers, and eosinophilia more than three weeks after drug exposure. DRESS can present with multi-organ involvement, with liver damage being the most common and severe. Pulmonary involvement is a less common manifestation and is associated with poor clinical outcomes. Chest imaging is often nonspecific, and symptoms can range from mild cough to acute respiratory distress syndrome (ARDS) . This is a case of a 49-year-old female with a history of recent clostridium difficile colitis status post treatment with oral vancomycin who presented with rash, acute liver and kidney failure, as well as diffuse nodular alveolar lung opacities concerning for DRESS syndrome with multi-organ involvement. Clinical Course: This patient initially presented to an outside hospital with clostridium difficile colitis, acute liver injury, and acute kidney injury. She developed a desquamating maculopapular rash in the setting of recent oral vancomycin, meloxicam, and furosemide initiation. She was hospitalized on two additional occasions with worsening altered mental status, liver injury, and acute kidney injury and was initiated on intermittent hemodialysis. Notably, she was found to have systemic eosinophilia (4100 cells/microliter) several weeks prior. She was transferred to this institution for further management where she was found to have encephalopathy, jaundice, lower extremity edema, and diffuse bilateral rhonchorous breath sounds on pulmonary examination. The patient was started on methylprednisolone for suspected DRESS syndrome. She underwent an evaluation for alternative causes of her organ failure. Her workup included a negative infectious, autoimmune, metabolic, toxic, and malignant work-up. Abdominal computed tomography (CT) and ultrasound were remarkable for evidence of hepatic steatosis and possible cirrhotic morphology. Additionally, a chest CT demonstrated diffuse and symmetric nodular alveolar lung opacities with peripheral sparing not consistent with acute respiratory distress syndrome or edema. Ultimately, her condition continued to decline, and she required intubation on several occasions. On hospital day 25 she succumbed to distributive shock in the setting of probable sepsis and multi-organ failure. Discussion: DRESS syndrome occurs in 1 in 1,000 to 10,000 patients with a mortality rate of around 10%. Anti-convulsant, anti-bacterial, anti-viral, and sulfonamide drugs are the most common drugs implicated in the development of DRESS syndrome; however, the list of offending agents is extensive . The diagnosis of DRESS syndrome is made after excluding other causes of disease such as infectious and autoimmune etiologies. The RegiSCAR scoring system is used to diagnose DRESS syndrome with 2-3 points indicating possible disease, 4-5 probable disease, and >5 definite disease. This patient scored a 7 on the RegiSCAR scale for eosinophilia, rash, organ involvement, and exclusion of other causes (infectious and autoimmune). While the pharmacologic trigger in this case is unknown, it is speculated to be caused by vancomycin, meloxicam, or furosemide due to the favorable timeline of initiation. Despite aggressive treatment, DRESS syndrome can often be fatal. Because of this, early diagnosis and treatment of patients with suspected DRESS syndrome is imperative.

Keywords: drug reaction with eosinophilia and systemic symptoms, multi-organ failure, pulmonary involvement, renal failure

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3328 The Saying of Conceptual Metaphors about Law, Righteousness, and Justice in the Old Testament: Cardinal Tendencies

Authors: Ivana Prochazkova

Abstract:

Cognitive linguistics offers biblical scholarship a specific methodological tool for analysis and interpretation of metaphorical expressions. Its methodology makes it possible to study processes involved in constructing the meaning of individual metaphorical expressions and whole conceptual metaphors; to analyze their function in the text; to follow the semantic development of concepts and conceptual domains, and to trace semantic changes and their motivation. The legal language in the Hebrew canon is extremely specific and formalized. Especially in the preambles to the collections of laws in the Pentateuch, more general considerations of the motif of keeping and breaking the law are encountered. This is also true in the psalms and wisdom literature. Legal theory and the philosophy of law deal with these motifs today. Metaphors play an important role in texts that reflect on more general issues. The purpose of this conference contribution is to write all over the central metaphorical concept, conceptual metaphor ךרד תורה (TORAH/LAW IS A JOURNEY), its function in the Torah and principal trends of the further development in the Prophets and the Writings. The conceptual metaphor תורה ךרד (TORAH/LAW IS A JOURNEY) constitutes a coherent system in conjunction with other metaphors that include e.g., conceptual metaphors נחה תורה (TORAH/LAW LEADS); its variant רעה תורה (TORAH IS A SHEPHERD/GUIDE); מקור תורה (TORAH/LAW IS A FOUNTAIN/A SOURCE OF LIFE). Some conceptual metaphors are well known, and their using are conventional (עשׁר תורה TORAH/LAW IS RICHES, שׂשׂון תורה TORAH/LAW IS DELIGHT, דבשׁ תורה TORAH/LAW IS HONEY, שׁמשׁ תורה TORAH/LAW IS SUN ). But some conceptual metaphors are by its occurrence innovative and unique (e.g., שׁריון תורה TORAH /LAW IS BODY ARMOR, כובע תורה TORAH /LAW IS A HELMET, בגד תורה TORAH/LAW IS A GARMENT, etc.). There will be given examples. Conceptual metaphors will be described by means of some 'metaphorical vehicles,' which are Hebrew expressions in the source domain that are repeatedly used in metaphorical conceptualizations of the target domain(s). Conceptual metaphors will be further described by means of 'generic narrative structures,' which are the particular aspects of a conceptual metaphor that emerge during the metaphorical structuring of concepts. They are the units of the metaphorical vehicles – the Hebrew expressions in the source domain – that structure concepts in much the same way that the conceptual metaphor in the target domain does. And finally, they will be described by means of the network of correspondences that exist between metaphorical vehicles – or generic metaphorical structures – and the Hebrew expressions in the target domain.

Keywords: cognitive theology, conceptual metaphor in the Old Testament, conceptual metaphors of the Torah, conceptual domain of law, righteousness, and justice

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3327 Gene Expression Profile Reveals Breast Cancer Proliferation and Metastasis

Authors: Nandhana Vivek, Bhaskar Gogoi, Ayyavu Mahesh

Abstract:

Breast cancer metastasis plays a key role in cancer progression and fatality. The present study examines the potential causes of metastasis in breast cancer by investigating the novel interactions between genes and their pathways. The gene expression profile of GSE99394, GSE1246464, and GSE103865 was downloaded from the GEO data repository to analyze the differentially expressed genes (DEGs). Protein-protein interactions, target factor interactions, pathways and gene relationships, and functional enrichment networks were investigated. The proliferation pathway was shown to be highly expressed in breast cancer progression and metastasis in all three datasets. Gene Ontology analysis revealed 11 DEGs as gene targets to control breast cancer metastasis: LYN, DLGAP5, CXCR4, CDC6, NANOG, IFI30, TXP2, AGTR1, MKI67, and FTH1. Upon studying the function, genomic and proteomic data, and pathway involvement of the target genes, DLGAP5 proved to be a promising candidate due to it being highly differentially expressed in all datasets. The study takes a unique perspective on the avenues through which DLGAP5 promotes metastasis. The current investigation helps pave the way in understanding the role DLGAP5 plays in metastasis, which leads to an increased incidence of death among breast cancer patients.

Keywords: genomics, metastasis, microarray, cancer

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3326 Measuring the Height of a Person in Closed Circuit Television Video Footage Using 3D Human Body Model

Authors: Dojoon Jung, Kiwoong Moon, Joong Lee

Abstract:

The height of criminals is one of the important clues that can determine the scope of the suspect's search or exclude the suspect from the search target. Although measuring the height of criminals by video alone is limited by various reasons, the 3D data of the scene and the Closed Circuit Television (CCTV) footage are matched, the height of the criminal can be measured. However, it is still difficult to measure the height of CCTV footage in the non-contact type measurement method because of variables such as position, posture, and head shape of criminals. In this paper, we propose a method of matching the CCTV footage with the 3D data on the crime scene and measuring the height of the person using the 3D human body model in the matched data. In the proposed method, the height is measured by using 3D human model in various scenes of the person in the CCTV footage, and the measurement value of the target person is corrected by the measurement error of the replay CCTV footage of the reference person. We tested for 20 people's walking CCTV footage captured from an indoor and an outdoor and corrected the measurement values with 5 reference persons. Experimental results show that the measurement error (true value-measured value) average is 0.45 cm, and this method is effective for the measurement of the person's height in CCTV footage.

Keywords: human height, CCTV footage, 2D/3D matching, 3D human body model

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