Search results for: generic drugs

Authors: Philippa Saunders, Claire Fletcher

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INTRODUCTION: Prostate cancer is the most prevalent malignancy affecting Western males. It is initially an androgen-dependent disease: androgens bind to the androgen receptor and drive the expression of genes that promote proliferation and evasion of apoptosis. Despite reduced androgen dependence in advanced prostate cancer, androgen receptor signaling remains a key driver of growth. Androgen deprivation therapy (ADT) is, therefore, a first-line treatment approach and works well initially, but resistance inevitably develops. Abiraterone and Enzalutamide are drugs widely used in ADT and are androgen synthesis and androgen receptor signaling inhibitors, respectively. The shortage of other treatment options means acquired resistance to these drugs is a major clinical problem. MicroRNAs (miRs) are important mediators of post-transcriptional gene regulation and show altered expression in cancer. Several have been linked to the development of resistance to ADT. Manipulation of such miRs may be a pathway to breakthrough treatments for advanced prostate cancer. This study aimed to validate ADT resistance-implicated miRs and their clinically relevant targets. MATERIAL AND METHOD: Small RNA-sequencing of Abiraterone- and Enzalutamide-resistant C42 prostate cancer cells identified subsets of miRs dysregulated as compared to parental cells. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to validate altered expression of candidate ADT resistance-implicated miRs 195-5p, 497-5p and 29a-5p in ADT-resistant and -responsive prostate cancer cell lines, patient-derived xenografts (PDXs) and primary prostate cancer explants. RESULTS AND DISCUSSION: This study suggests a possible role for miR-497-5p in the development of ADT resistance in prostate cancer. MiR-497-5p expression was increased in ADT-resistant versus ADT-responsive prostate cancer cells. Importantly, miR-497-5p expression was also increased in Enzalutamide-treated, castrated (ADT-mimicking) PDXs versus intact PDXs. MiR-195-5p was also elevated in ADT-resistant versus -responsive prostate cancer cells, while there was a drop in miR-29a-5p expression. Candidate clinically relevant targets of miR-497-5p in prostate cancer were identified by mining AGO-PAR-CLIP-seq data sets and may include AVL9 and FZD6. CONCLUSION: In summary, this study identified microRNAs that are implicated in prostate cancer resistance to androgen deprivation therapy and could represent novel therapeutic targets for advanced disease.

Keywords: microRNA, androgen deprivation therapy, Enzalutamide, abiraterone, patient-derived xenograft

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Authors: Zafar Mahmood, Surayya Naz, Nazir Shah Khattak

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The degree of freedom relates to our capability to observe or model the energy paths within the system. Higher the number of energy paths being modeled leaves to us a higher degree of freedom, but increasing the time and modeling complexity rendering it useless for today’s world’s need for minimum time to market. Since the number of residuals that can be uniquely isolated are dependent on the number of independent outputs of the system, increasing the number of sensors required. The examples of discrete position sensors that may be used to form an array include limit switches, Hall effect sensors, optical sensors, magnetic sensors, etc. Their mechanical design can usually be tailored to fit in the transitional path of an STME in a variety of mechanical configurations. The case studies into multi-sensor system were carried out and actual data from sensors is used to test this generic framework. It is being investigated, how the proper modeling of limit switches as timing sensors, could lead to unified and neutral residual space while keeping the implementation cost reasonably low.

Keywords: low-cost limit sensors, fault diagnostics, Single Throw Mechanical Equipment (STME), parameter estimation, parity-space

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Authors: Anton Hristozov, Eric Matson, Eric Dietz, Marcus Rogers

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Components are heavily used in many software systems, including robotics systems. The growth of sophistication and diversity of new capabilities for robotic systems presents new challenges to their architectures. Their complexity is growing exponentially with the advent of AI, smart sensors, and the complex tasks they have to accomplish. Such complexity requires a more rigorous approach to the creation, use, and interoperability of software components. The issue is exacerbated because robotic systems are becoming more and more reliant on third-party components for certain functions. In order to achieve this kind of interoperability, including dynamic component replacement, we need a way to standardize their interfaces. A formal approach is desperately needed to specify what an interface of a robotic software component should contain. This study performs an analysis of the issue and presents a universal and generic approach to standardizing component interfaces for robotic systems. Our approach is inspired by well-established robotic architectures such as ROS, PX4, and Ardupilot. The study is also applicable to other software systems that share similar characteristics with robotic systems. We consider the use of JSON or Domain Specific Languages (DSL) development with tools such as Antlr and automatic code and configuration file generation for frameworks such as ROS and PX4. A case study with ROS2 is presented as a proof of concept for the proposed methodology.

Keywords: CPS, robots, software architecture, interface, ROS, autopilot

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Authors: Turban Kar, Maitree Bhattacharyya

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Curcumin, a dietary antioxidant has been identified as a wonder molecule to possess therapeutic properties protecting the cellular macromolecules from oxidative damage. In our experimental study, we have explored the effectiveness of curcumin in protecting the structural paradigm of Human Serum Albumin (HSA) when exposed to gamma irradiation. HSA, being an important transport protein of the circulatory system, is involved in binding of variety of metabolites, drugs, dyes and fatty acids due to the presence of hydrophobic pockets inside the structure. HSA is also actively involved in the transportation of drugs and metabolites to their targets, because of its long half-life and regulation of osmotic blood pressure. Gamma rays, in its increasing concentration, results in structural alteration of the protein and superoxide radical generation. Curcumin, on the other hand, mitigates the damage, which has been evidenced in the following experiments. Our study explores the possibility for protection by curcumin during the molecular and conformational changes of HSA when exposed to gamma irradiation. We used a combination of spectroscopic methods to probe the conformational ensemble of the irradiated HSA and finally evaluated the extent of restoration by curcumin. SDS - PAGE indicated the formation of cross linked aggregates as a consequence of increasing exposure of gamma radiation. CD and FTIR spectroscopy inferred significant decrease in alpha helix content of HSA from 57% to 15% with increasing radiation doses. Steady state and time resolved fluorescence studies complemented the spectroscopic measurements when lifetime decay was significantly reduced from 6.35 ns to 0.37 ns. Hydrophobic and bityrosine study showed the effectiveness of curcumin for protection against radiation induced free radical generation. Moreover, bityrosine and hydrophobic profiling of gamma irradiated HSA in presence and absence of curcumin provided light on the formation of ROS species generation and the protective (magical) role of curcumin. The molecular mechanism of curcumin protection to HSA from gamma irradiation is yet unknown, though a possible explanation has been proposed in this work using Thioflavin T assay. It was elucidated, that when HSA is irradiated at low dose of gamma radiation in presence of curcumin, it is capable of retaining the native characteristic properties to a greater extent indicating stabilization of molecular structure. Thus, curcumin may be utilized as a therapeutic strategy to protect cellular proteins.

Keywords: Bityrosine content, conformational change, curcumin, gamma radiation, human serum albumin

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Authors: Cleto J. Sauer Jr., Rita C. Sauer, Chaider G. Andrade, Doris F. Rabelo

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Introduction: Endotracheal Intubation (ETI) is a procedure for clinical management of patients with severe clinical presentation of COVID-19 disease. Realistic simulation (RS) is an active learning methodology utilized for clinical skill's improvement. To improve ETI skills of public health network's physicians from Recôncavo da Bahia region in Brazil, during COVID-19 outbreak, RS training was planned and carried out. Training scenario included the Nasco Lifeform realistic simulator, and three actions were simulated: ETI procedure, sedative drugs management, and bougie guide utilization. Training intervention occurred between May and June 2020, as an interinstitutional cooperation between the Health's Department of Bahia State and the Federal University from Recôncavo da Bahia. Objective: The main objective is to report the effects on participants' self-confidence perception for ETI procedure after RS based training. Methods: This is a descriptive study, with secondary data extracted from questionnaires applied throughout RS training. Priority workplace, time from last intubation, and knowledge about bougie were reported on a preparticipation questionnaire. Additionally, participants completed pre- and post-training qualitative self-assessment (10-point Likert scale) regarding self-confidence perception in performing each of simulated actions. Distribution analysis for qualitative data was performed with Wilcoxon Signed Rank Test, and self-confidence increase analysis in frequency contingency tables with Fisher's Exact Test. Results: 36 physicians participated of training, 25 (69%) from primary care setting, 25 (69%) performed ETI over a year ago, and only 4 (11%) had previous knowledge about the bougie guide utilization. There was an increase in self-confidence medians for all three simulated actions. Medians (variation) for self-confidence before and after training, for each simulated action were as follows: ETI [5 (1-9) vs. 8 (6-10) (p < 0.0001)]; Sedative drug management [5 (1-9) vs. 8 (4-10) (p < 0.0001)]; Bougie guide utilization [2.5 (1-7) vs. 8 (4-10) (p < 0.0001)]. Among those who performed ETI over a year ago (n = 25), an increase in self-confidence greater than 3 points for ETI was reported by 23 vs. 2 physicians (p = 0.0002), and by 21 vs. 4 (p = 0.03) for sedative drugs management. Conclusions: RS training contributed to self-confidence increase in performing ETI. Among participants who performed ETI over a year, there was a significant association between RS training and increase of more than 3 points in self-confidence, both for ETI and sedative drug management. Training with RS methodology is suitable for ETI confidence enhancement during COVID-19 outbreak.

Keywords: confidence, COVID-19, endotracheal intubation, realistic simulation

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Authors: Imran Muhammad

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The main cause of infectious disease in the modern world is Mycobacterium Tuberculosis (MT). To combat tuberculosis, new and efficient drugs are an urgent need in the modern world. Schif bases are potent for their biological pharmacophore activity. Thus we selected different Vanillin-based Schiff bases for their binding activity against target enzymes of Mycobacterium tuberculosis that is (DprE1 (decaprenyl phosphoryl-β-D-ribose 2′-epimerase), and DNA gyrase subunit-A), using molecular docking. We evaluate the inhibition potential, interaction, and binding mode of these compounds with the target enzymes.

Keywords: schiff bases, tuberculosis, DNA gyrase, DprE1, docking

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Authors: José Ramón López-Mínguez, Estrella Suárez-Corchuelo, Sergio López-Tejero, Luis Nombela-Franco, Xavier Freixa-Rofastes, Guillermo Bastos-Fernández, Xavier Millán-Álvarez, Raúl Moreno-Gómez, José Antonio Fernández-Díaz, Ignacio Amat-Santos, Tomás Benito-González, Fernando Alfonso-Manterola, Pablo Salinas-Sanguino, Pedro Cepas-Guillén, Dabit Arzamendi, Ignacio Cruz-González, Juan Manuel Nogales-Asensio

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Background and objectives: The treatment of patients with non-valvular atrial fibrillation (NVAF) who need coronary stenting is challenging. The objective of the study was to determine whether left atrial appendage occlusion (LAAO) could be a feasible option and benefit these patients. To this end, we studied the impact of LAAO plus antiplatelet drugs vs oral anticoagulants (OAC) (including direct OAC) plus antiplatelet drugs in these patients’ long-term outcomes. Methods: The results of 207 consecutive patients with NVAF who underwent coronary stenting were analyzed. A total of 146 patients were treated with OAC (75 with acenocoumarol, 71 with direct OAC) while 61 underwent LAAO. The median follow-up was 35 months. Patients also received antiplatelet therapy as prescribed by their cardiologist. The study received the proper ethical oversight. Results: Age (mean 75.7 years), and the past medical history of stroke were similar in both groups. However, the LAAO group had more unfavorable characteristics (history of coronary artery disease [CHA2DS2-VASc], and significant bleeding [BARC ≥ 2] and HAS-BLED). The occurrence of major adverse events (death, stroke/transient ischemic events, major bleeding) and major cardiovascular events (cardiac death, stroke/transient ischemic attack, and myocardial infarction) were significantly higher in the OAC group compared to the LAAO group: 19.75% vs 9.06% (HR, 2.18; P = .008) and 6.37% vs 1.91% (HR, 3.34; P = .037), respectively. Conclusions: In patients with NVAF undergoing coronary stenting, LAAO plus antiplatelet therapy produced better long-term outcomes compared to treatment with OAC plus antiplatelet therapy despite the unfavorable baseline characteristics of the LAAO group.

Keywords: stents, atrial fibrillation, anticoagulants, left atrial appendage occlusion

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Authors: Xiuzhan Guo, Arthur Berrill, Ajinkya Kulkarni, Kostya Belezko, Min Luo

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Ontology operations, e.g., aligning and merging, were studied and implemented extensively in different settings, such as categorical operations, relation algebras, and typed graph grammars, with different concerns. However, aligning and merging operations in the settings share some generic properties, e.g., idempotence, commutativity, associativity, and representativity, labeled by (I), (C), (A), and (R), respectively, which are defined on an ontology merging system (D~M), where D is a non-empty set of the ontologies concerned, ~ is a binary relation on D modeling ontology aligning and M is a partial binary operation on D modeling ontology merging. Given an ontology repository, a finite set O ⊆ D, its merging closure Ô is the smallest set of ontologies, which contains the repository and is closed with respect to merging. If (I), (C), (A), and (R) are satisfied, then both D and Ô are partially ordered naturally by merging, Ô is finite and can be computed, compared, and sorted efficiently, including sorting, selecting, and querying some specific elements, e.g., maximal ontologies and minimal ontologies. We also show that the ontology merging system, given by ontology V -alignment pairs and pushouts, satisfies the properties: (I), (C), (A), and (R) so that the merging system is partially ordered and the merging closure of a given repository with respect to pushouts can be computed efficiently.

Keywords: ontology aligning, ontology merging, merging system, poset, merging closure, ontology V-alignment pair, ontology homomorphism, ontology V-alignment pair homomorphism, pushout

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Authors: Janneth González, George Barreto, Ludis Morales, Angélica Sabogal

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Sea anemone neurotoxins are peptides that interact with Na+ and K+ channels, resulting in specific alterations on their functions. Some of these neurotoxins (1ROO, 1BGK, 2K9E, 1BEI) are important for the treatment of nearly eighty autoimmune disorders due to their specificity for Kv1.3 channel. The aim of this study was to identify the common residues among these neurotoxins by computational methods, and establish whether there is a pattern useful for the future generation of a treatment for autoimmune diseases. Our results showed eight new key common residues between the studied neurotoxins interacting with a histidine ring and the selectivity filter of the receptor, thus showing a possible pattern of interaction. This knowledge may serve as an input for the design of more promising drugs for autoimmune treatments.

Keywords: neurotoxins, potassium channel, Kv1.3, computational methods, autoimmune diseases

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Authors: Abonyi, Emmanuel Ebuka, Amina Jafaru O.

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Background: Illicit substance use among students is a phenomenon that has been widely studied, but it remains of interest due to its high prevalence and potential consequences. It is a major mental health concern among university students which may result in behavioral and academic problems, psychiatric disorders, and infectious diseases. Thus, this study was done to ascertain the prevalence and factors associated with the use of illicit drugs among these groups of people. Methods: A cross-sectional and descriptive survey was conducted among undergraduate students of the University of Lagos for the duration of three(3) months (August to October 2021). A total number of 938 undergraduate students were selected from seventeen faculties in the university. Pretested questionnaires were administered, completed, and returned. The data were analyzed using descriptive statistics and multivariate regression analysis. Results: From the data collected, it was observed that out of 938 undergraduate students of the University of Lagos that completed and returned the questionnaires, 56.3% were female and 43.7% were male. No gender differences were observed in the prevalence of use of any of the illicit substances. The result showed that the majority of the students that participated in the research were females(56.6%); it was observed that there were a total of 541 2nd-year students(57.7%) and 397 final-year students(42.3). Students between the age brackets of 20- 24 years had the highest frequency of 648(69.1%) of illicit drug use and students in none health-related disciplines. The result also showed that the majority of the students reported that they use Marijuana (31.7%), while lifetime use of LSD (6.3%), Heroin(4.8%), Cocaine (4.7%), and Ecstasy(4.5), Ketamine (3.4%). Besides, the use of alcohol was below average(44.1%). Additionally, Marijuana was among the ones that were mostly taken by students having a higher percentage and most of these respondents had experienced relationship problems with their family and intentions (50.9%). From the responses obtained, major reasons students indulge in illicit drug use were; curiosity to experiment, relief of stress after rigorous academic activities, social media influence, and peer pressure. Most Undergraduate students are in their most hyperactive stage in life, which makes them vulnerable to always want to explore practically every adventure. Hence, individual factors and social media influence are identified as major contributors to the prevalence of illicit drug use among undergraduate students at the University of Lagos, Nigeria. Conclusion: Control programs are most needed among the students. They should be comprehensive and focused on students' psycho-education about substances and their related negative consequences, plus the promotion of students' life skills, and integration into the family – and peer-based preventive interventions.

Keywords: illicit drugs, addiction, undergraduate students, prevalence, substances

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Authors: Rostyslav Horbay, Nick Korolis, Vahid Anvari, Rostyslav Stoika

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Introduction: Giant cancer cells (GCC) are common in all types of cancer, especially after poor therapy. Some specific features of such cells include ~10-fold enlargement, drug resistance, and the ability to propagate similar daughter cells. We used murine NK/Ly lymphoma, an aggressive and fast growing lymphoma model that has already shown drastic changes in GCC comparing to parental cells (chromatin condensation, nuclear fragmentation, tighter OXPHOS/cellular respiration coupling, multidrug resistance). Materials and methods: In this study, we compared morpho-functional changes of GCC that predominantly show either a cytostatic or a cytotoxic effect after treatment with drugs. We studied the effect of a combined cytostatic/cytotoxic drug treatment to determine the correlation of drug efficiency and GCC formation. Doses of G1/S-specific drug paclitaxel/PTX (G2/M-specific, 50 mg/mouse), vinblastine/VBL (50 mg/mouse), and DNA-targeting agents doxorubicin/DOX (125 ng/mouse) and cisplatin/CP (225 ng/mouse) on C57 black mice. Several tests were chosen to estimate morphological and physiological state (propidium iodide, Rhodamine-123, DAPI, JC-1, Janus Green, Giemsa staining and other), which included cell integrity, nuclear fragmentation and chromatin condensation, mitochondrial activity, and others. A single and double factor ANOVA analysis were performed to determine correlation between the criteria of applied drugs and cytomorphological changes. Results: In all cases of treatment, several morphological changes were observed (intracellular vacuolization, membrane blebbing, and interconnected mitochondrial network). A lower gain in ascites (49.97% comparing to control group) and longest lifespan (22+9 days) after tumor injection was obtained with single VBL and single DOX injections. Such ascites contained the highest number of GCC (83.7%+9.2%), lowest cell count number (72.7+31.0 mln/ml), and a strong correlation coefficient between increased mitochondrial activity and percentage of giant NK/Ly cells. A high number of viable GCC (82.1+9.2%) was observed compared to the parental forms (15.4+11.9%) indicating that GCC are more drug resistant than the parental cells. All this indicates that the giant cell formation and its ability to obtain drug resistance is an expanding field in cancer research.

Keywords: ANOVA, cisplatin, doxorubicin, drug resistance, giant cancer cells, NK/Ly lymphoma, paclitaxel, vinblastine

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Authors: Wendy I. E. Wesseling

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The unemployment rate has been on the rise since the outbreak of the global financial crisis in 2008. Especially labor market entrants suffer from economic downfall. Despite the abundance of programs and agencies that help to reintegrate unemployed youth, considerable less research attention has been paid to 'fit' between these programs and its participants that ensure a durable labor market transition. According to Self-Determination Theory, need satisfaction is associated with better (mental) adjustment. As such, three hypothesis were formulated: when workers’ needs for competence (H1), relatedness (H2), and autonomy (H3) are satisfied in the workplace, they are more likely to remain employed at the same employer. To test these assumptions, a sample of approximately 800 young people enrolled in a youth unemployment policy participated in a longitudinal study. The unemployment policy was aimed at the development of generic and vocational competences, and had a maximum duration of six months. Need satisfaction during the program was measured, as well as their employment outcomes up to 12 months after completion of the policy. All hypotheses were (partly) supported. Some limitations should be noted. First, since our sample consisted primarily of highly educated white graduates, it remains to be tested whether our results generalize to other groups of unemployed youth. Moreover, we are unable to conclude whether the results are due to the intervention, participants (selection effect), or both, because of the lack of a control group.

Keywords: need satisfaction, person-job fit, self-determination theory, youth unemployment policy

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Authors: J. C. Riaño-Rojas, J. D. Alzate-Cardona, E. Restrepo-Parra

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In this work, a study of generic magnetic nanoparticles varying the metric space is presented. As the metric space is changed, the nanoparticle form and the inner product are also varied, since the energetic scale is not conserved. This study is carried out using Monte Carlo simulations combined with the Wolff embedding and Metropolis algorithms. The Metropolis algorithm is used at high temperature regions to reach the equilibrium quickly. The Wolff embedding algorithm is used at low and critical temperature regions in order to reduce the critical slowing down phenomenon. The ions number is kept constant for the different forms and the critical temperatures using finite size scaling are found. We observed that critical temperatures don't exhibit significant changes when the metric space was varied. Additionally, the effective dimension according the metric space was determined. A study of static behavior for reaching the static critical exponents was developed. The objective of this work is to observe the behavior of the thermodynamic quantities as energy, magnetization, specific heat, susceptibility and Binder's cumulants at the critical region, in order to demonstrate if the magnetic nanoparticles describe their magnetic interactions in the Euclidean space or if there is any correspondence in other metric spaces.

Keywords: nanoparticles, metric, Monte Carlo, critical behaviour

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Authors: Tareg Belali, Mosleh Abomughaid, Muhanad Alhujaily

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HNF4a is one of the steroid hormone receptor family of transcription factors with roles in the development of the liver and the regulation of several critical metabolic pathways, such as glycolysis, drug metabolism, and apolipoproteins and blood coagulation. The transcriptional potency of HNF4a is well known due to its involvement in diabetes and other metabolic diseases. However, recently HNF4a has been discovered to be closely associated with several haematological disorders, mainly because of genetic mutations, drugs, and hepatic disorders. We review HNF4a structure and function and its role in haematological disorders. We discuss possible good therapies that are based on targeting HNF4a.

Keywords: hepatocyte nuclear factor 4 alpha, HNF4a nuclear receptor, steroid hormone receptor family of transcription factors, hematological disorders

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Authors: Muhammad Saqlain, Poom Kumam

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Language being an abstract system and creative act, is quite complicated as its meaning varies depending on the context. The context is determined by the empirical knowledge of a person, which is derived from observation and experience. About further subdivided attributes, the decision-making challenges may entail quantitative and qualitative factors. However, because there is no norm for putting a numerical value on language, existing approaches cannot carry out the operations of linguistic knowledge. The assigning of mathematical values (fuzzy, intuitionistic, and neutrosophic) to any decision-making problem; without considering any rule of linguistic knowledge is ambiguous and inaccurate. Thus, this paper aims to provide a generic model for these issues. This paper provides the linguistic set structure of the fuzzy hypersoft set (FLHSS) to solve decision-making issues. We have proposed the definition some basic operations like AND, NOT, OR, AND, compliment, negation, etc., along with Topology and examples, and properties. Secondly, the operational laws for the fuzzy linguistic hypersoft set have been proposed to deal with the decision-making issues. Implementing proposed aggregate operators and operational laws can be used to convert linguistic quantifiers into numerical values. This will increase the accuracy and precision of the fuzzy hypersoft set structure to deal with decision-making issues.

Keywords: linguistic quantifiers, aggregate operators, multi-criteria decision making (mcdm)., fuzzy topology

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Authors: Aedah Abd Rahman

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Software organisations may implement single or multiple frameworks in order to remain competitive. There are wide selection of generic Software Process Improvement (SPI) frameworks, best practices and standards implemented with different focuses and goals. Issues and difficulties emerge in the SPI practices from the context of software development and IT Service Management (ITSM). This research looks into the integration of multiple frameworks from the perspective of software development and ITSM. The research question of this study is how to define steps of methodology to solve the multi model software process improvement problem. The objective of this study is to define the research approach and methodologies to produce a more integrated and efficient Multi Model Process Improvement (MMPI) solution. A multi-step methodology is used which contains the case study, framework mapping and Delphi study. The research outcome has proven the usefulness and appropriateness of the proposed framework in SPI and quality practice in Malaysian software industries. This mixed method research approach is used to tackle problems from every angle in the context of software development and services. This methodology is used to facilitate the implementation and management of multi model environment of SPI frameworks in multiple domains.

Keywords: Delphi study, methodology, multi model software process improvement, service management

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Authors: Mathew Tran, Deepa Patel, Breann Prophete, Irandokht Khaki Najafabadi

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Status epilepticus is a neurological disorder requiring emergent control with medical therapy. Based on guideline recommendations for adults with status epilepticus, the first-line treatment is to start a benzodiazepine, as they are quick at seizure control. The second step is to initiate a non-benzodiazepine anti-epileptic drug to prevent refractory seizures. Studies show that the anti-epileptic drugs are approximately equivalent in status epilepticus control once a benzodiazepine has been given. This review provides a brief overview of the management of status epilepticus based on evidence from the literature and evidence-based guidelines.

Keywords: neurological disorder, seizure, status epilepticus, benzo diazepines, antiepileptic agents

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Authors: Zorica Tomičić, Ružica Tomičić, Peter Raspor

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Growing resistance of pathogenic yeast Candida glabrata to many classes of antifungal drugs has stimulated efforts to discover new agents to combat a rising number of invasive C. glabrata infections, which deserves a great deal of concern due to the high mortality rate in immunocompromised populations. One promising strategy is the use of probiotic microorganisms, which, when administered in adequate amounts, confers a health benefit. A selected number of probiotic organisms, Saccharomyces boulardii among them, have been tested as potential biotherapeutic agents. The aim of this study was to investigate the effect of the probiotic yeast S. boulardii on the adhesion of clinical isolates of C. glabrata at different temperatures, pH values, and in the presence of three clinically important antifungal drugs, such as fluconazole, itraconazole and amphotericin B. The method used to assess adhesion was crystal violet staining. The selection of antimycotics concentrations used in the adhesion assay was based on minimum inhibitory concentrations (MICs) obtained by the preliminarily performed microdilution modification of the Reference method for broth dilution antifungal susceptibility testing of yeast (Clinical and Laboratory Standards Institute (CLSI), standard M27-A2). the results showed that despite the nonadhesiveness of S. boulardii cells, probiotic yeast significantly suppressed the adhesion of C. glabrata strains. Besides, at specific strain ratios, a slight stimulatory effect was observed in some C. glabrata strains, which highlights the importance of strain specificity and opens up further research interests. When environmental conditions are considered, temperature and pH significantly influenced co-culture adhesion of C. glabrata and S. boulardii. The adhesion of C. glabrata strains was relatively equally reduced over all tested temperature range (28°C, 37°C, 39°C and 42°C) in the presence of S. boulardii cells, while the adhesion of a few C. glabrata strains were significantly stimulated at 28°C and suppressed at 42°C. Further, the adhesion was highly dependent on pH, with the highest adherence at pH 4 and lowest at pH 8.5. It was observed that S. boulardii did not manage to suppress the adhesion of C. glabrata strains at high pH. Antimycotics on the other hand showed a greater impact, since S. boulardii failed to affect co-culture adhesion at higher antimycotics concentrations. As expected, exposure to various concentrations of amphotericin B significantly reduced the adherence ability of C.glabrata strains both in a single culture and co-culture with S. boulardii. Therefore, it can be speculated that S. boulardii could substitute the effect of antimycotics in a range concentrations and with specific type of strains. This would certainly change the view on the treatment of yeast infections in the future.

Keywords: adhesion, antimycotics, candida glabrata, saccharomyces boulardii

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Authors: Shin Yoneda, Mikiya Kato, Kosuke Murate, Kodo Kawase

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In recent years, there have been numerous attempts to smuggle narcotic drugs and chemicals by concealing them in international mail. Combatting this requires a non-destructive technique that can identify such illicit substances in mail. Terahertz (THz) waves can pass through a wide variety of materials, and many chemicals show specific frequency-dependent absorption, known as a spectral fingerprint, in the THz range. Therefore, it is reasonable to investigate non-destructive mail inspection techniques that use THz waves. For this reason, in this work, we tried to identify reagents under high attenuation shielding materials using injection-seeded THz-wave parametric generator (is-TPG). Our THz spectroscopic imaging system using is-TPG consisted of two non-linear crystals for emission and detection of THz waves. A micro-chip Nd:YAG laser and a continuous wave tunable external cavity diode laser were used as the pump and seed source, respectively. The pump beam and seed beam were injected to the LiNbO₃ crystal satisfying the noncollinear phase matching condition in order to generate high power THz-wave. The emitted THz wave was irradiated to the sample which was raster scanned by the x-z stage while changing the frequencies, and we obtained multispectral images. Then the transmitted THz wave was focused onto another crystal for detection and up-converted to the near infrared detection beam based on nonlinear optical parametric effects, wherein the detection beam intensity was measured using an infrared pyroelectric detector. It was difficult to identify reagents in a cardboard box because of high noise levels. In this work, we introduce improvements for noise reduction and image clarification, and the intensity of the near infrared detection beam was converted correctly to the intensity of the THz wave. A Gaussian spatial filter is also introduced for a clearer THz image. Through these improvements, we succeeded in identification of reagents hidden in a 42-mm thick cardboard box filled with several obstacles, which attenuate 56 dB at 1.3 THz, by improving analysis methods. Using this system, THz spectroscopic imaging was possible for saccharides and may also be applied to cases where illicit drugs are hidden in the box, and multiple reagents are mixed together. Moreover, THz spectroscopic imaging can be achieved through even thicker obstacles by introducing an NIR detector with higher sensitivity.

Keywords: nondestructive inspection, principal component analysis, terahertz parametric source, THz spectroscopic imaging

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Authors: Rachel Matar, Maxime Merheb

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Chemical drugs have been used for many centuries as the only way to cure diseases until the novel gene therapy has been created in 1960. Gene therapy is based on the insertion, correction, or inactivation of genes to treat people with genetic illness (1). Gene therapy has made wonders in Parkison’s, Alzheimer and multiple sclerosis. In addition to great promises in the healing of deadly diseases like many types of cancer and autoimmune diseases (2). This method implies the use of recombinant DNA technology with the help of different viral and non-viral vectors (3). It is nowadays used in somatic cells as well as embryos and gametes. Beside all the benefits of gene therapy, this technique is deemed by some opponents as an ethically unacceptable treatment as it implies playing with the genes of living organisms.

Keywords: gene therapy, genetic disease, cancer, multiple sclerosis

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Authors: Fatima Doganc, Hakan Goker

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Benzimidazole moiety is an important pharmacophore and privileged structure for the medicinal chemists, since it exhibits various important biological activities. Some clinically used drugs have benzimidazole moiety, such as omeprazole, astemizole, albendazole and domperidone. 2-(4-tert-Butylphenyl)benzimidazole, is a PGC-1α transcriptional regulator shown to have beneficial effects in diabetic mice. We planned to modify the structure of this compound for developing new antidiabetic drug candidates. Hence, a series of guanidino or amidino, benzo/pyrido/pyrimidino-imidazole derivatives were freshly prepared. Mass, 1H-NMR, 13C-NMR, 2D-NMR spectroscopy techniques were used for the new derivatives to clarify their structures and their purity was controlled through the elemental analysis. Antidiabetic activity studies of the synthesized compounds are under the investigation.

Keywords: antidiabetic agents, benzimidazole, imidazopyridine, imidazopyrimidine

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Authors: Dawid Jakimiuk, Krzysztof Mitura, Leszek Szpakowski, Sławomir Pilip, Daniel Celiński

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The Emergency Medical Teams (EMS) of the Ambulance Service in Siedlce serve the population living in the Mazowieckie Voivodeship (the area of eastern Poland with approximately 550,000 inhabitants). They provide health services at the pre-hospital stage to all life-threatening patients. The analysis covered the interventions of emergency medical teams in cases of suicide attempts that occurred in the years 2015-2018. The study was retrospective. The data was obtained on the basis of digital medical records of completed call-outs. When defining the disease entity, the International Statistical Classification of Diseases and Health Problems ICD-10 prepared by WHO was used. The relationship between selected disease entities and the area of EMT intervention, the patient's sex and age, and the time of occurrence of the event were investigated. Non-urban area was defined as the area inhabited by a population below 10,000 residents. Statistical analysis was performed using Pearson's Chi ^ 2 test and presenting the percentage of cases in the study group. Of all the suicide attempts, drug abuse cases were the most frequent, including: X60 (Intentional self-poisoning by and exposure to nonopioid analgesics, antipyretics and antirheumatics); X61 (Intentional self-poisoning by and exposure to antiepileptic, sedative-hypnotic, antiparkinsonian and psychotropic drugs, not elsewhere classified); X62 (Intentional self-poisoning by and exposure to narcotics and psycholeptics [hallucinogens], not elsewhere classified); X63 (Intentional self-poisoning by and exposure to other drugs acting on the autonomic nervous system); X64 (Intentional self-poisoning by and exposure to other and unspecified drugs, medicaments and biological substance) oraz X70 (Intentional self-harm by hanging, strangulation and suffocation). In total, they accounted for 69.4% of all interventions to suicide attempts in the studied period. Statistical analysis shows significant differences (χ2 = 39.30239, p <0.0001, n = 561) between the area of EMT intervention and the type of suicide attempt. In non-urban areas, a higher percentage of X70 diagnoses was recorded (55.67%), while in urban areas, X60-X64 (72.53%). In non-urban areas, a higher proportion of patients attempting suicide was observed compared to patients living in urban areas. For X70 and X60 - X64 in total, the incidence rates in non-urban areas were 80.8% and 56%, respectively. Significant differences were found (χ2 = 119.3304, p <0.0001, n = 561) depending on the method of attempting suicide in relation to the patient's sex. The percentage of women diagnosed with X60-X64 versus X70 was 87.50%, which was the largest number of patients (n = 154) as compared to men. In the case of X70 in relation to X60-X64, the percentage of men was 62.08%, which was the largest number of patients (n = 239) as compared to women (n = 22). In the case of X70, the percentage of men compared to women was as high as 92%. Significant differences were observed (χ2 = 14.94848, p <0.01058) between the hour of EMT intervention and the type of suicide attempt. The highest percentage of X70 occurred between 04:01 - 08:00 (64.44%), while X60-X64 between 00:01 - 04:00 (70.45%). The largest number of cases of all tested suicide attempts was recorded between 16:01 - 20:00 for X70 (n = 62), X60 - X64 (n = 82), respectively. The highest percentage of patients undertaking all suicide attempts studied at work was observed in the age range of 18-30 (31.5%), while the lowest was in the age group over 60 years of age. (11%). There was no significant correlation between the day of the week or individual months of the year and the type of suicide attempt - respectively (χ2 = 6.281729, p <0.39238, n = 561) and (χ2 = 3.348913, p <0.9857, n = 561). There were also no significant differences in the incidence of suicide attempts for each year in the study period (χ2 = 3.348913, p <0.9857 n = 561). The obtained results suggest the necessity to undertake preventive measures in order to minimize the number of suicide attempts. Such activities should be directed especially at young patients living in non-urban areas.

Keywords: emergency med, emergency medical team, attempted suicide, pre-hospital

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Authors: Mina Boroujerdi, Javad Tavakoli

Abstract:

Hydrogels are extensively studied as matrices for the controlled release of drugs. To evaluate the mobility of embedded molecules, these drug delivery systems are usually characterized by release studies. In this contribution, an electronic device for swelling pressure measurement during drug release from hydrogel network was developed. Also, poly acrylic acid micro particles were prepared for prolonged and sustained controlled acetaminophen release. Effect of swelling pressure on drug release from micro particles studied under different environment pH in order to predict release profile in gastro-intestine medium. Swelling ratio and swelling pressure were measured in different pH.

Keywords: swelling pressure, drug delivery, hydrogel, polyelectrolyte

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Authors: Gredson Keif Souza, Nehemias Curvelo Pereira

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Kernel oil from Macaúba is an important source of essential fatty acids. Thus, a new knowledge of the oil of this species could be used in new applications, such as pharmaceutical drugs based in the manufacture of cosmetics, and in various industrial processes. The aim of this study was to characterize the kernel oil of macaúba (Acrocomia Totai) at different times of their maturation. The physico-chemical characteristics were determined in accordance with the official analytical methods of oils and fats. It was determined the content of water and lipids in kernel, saponification value, acid value, water content in the oil, viscosity, density, composition in fatty acids by gas chromatography and molar mass. The results submitted to Tukey test for significant value to 5%. Found for the unripe fruits values superior to unsaturated fatty acids.

Keywords: extraction, characterization, kernel oil, acrocomia totai

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Authors: Nikola Tomasevic, Marko Batic, Sanja Vranes

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Emerging Semantic Web technologies can be seen as the next step in evolution of the intelligent facility management systems. Particularly, this considers increased usage of open source and/or standardized concepts for data classification and semantic interpretation. To deliver such facility management systems, providing the comprehensive integration and interoperability platform in from of the facility data model is a prerequisite. In this paper, one of the possible modelling approaches to provide such integrative facility data model which was based on the ontology modelling concept was presented. Complete ontology development process, starting from the input data acquisition, ontology concepts definition and finally ontology concepts population, was described. At the beginning, the core facility ontology was developed representing the generic facility infrastructure comprised of the common facility concepts relevant from the facility management perspective. To develop the data model of a specific facility infrastructure, first extension and then population of the core facility ontology was performed. For the development of the full-blown facility data models, Malpensa and Fiumicino airports in Italy, two major European air-traffic hubs, were chosen as a test-bed platform. Furthermore, the way how these ontology models supported the integration and interoperability of the overall airport energy management system was analyzed as well.

Keywords: airport ontology, energy management, facility data model, ontology modeling

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Authors: Sihem Benaouda

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English is gaining an international identity as it affects every academic and professional field in the world. Without increasing their cultural understanding, it would obviously be difficult to completely educate learners for communication in a globalised environment. The concept of culture is intricate and needs to be elucidated, especially in an English language teaching (ELT) context. The study focuses on the investigation of the cultural studies integrated into the different types of English for specific purposes (ESP) materials, as opposed to English for general purposes (EGP) textbooks. A qualitative methodology based on a triangulation of techniques was conducted through materials analysis of five textbooks in both advanced EGP and three types of ESP. In addition to a semi-structured interview conducted with Algerian ESP practitioners, data analysis results revealed that culture in ESP textbooks is not overtly isolated into chapters and that cultural studies are predominantly present in business and economics materials, namely English for hotel and catering staff, tourism, and flight attendants. However, implicit cultural instruction is signalled in the social sciences and is negligible in science and technology sources. In terms of content, cultural studies in EGP are more related to generic topics, whereas, in some ESP materials, the topics are rather oriented to the specific field they belong to. Furthermore, the respondents’ answers showed an unawareness of the importance of culture in ESP teaching, besides some disregard for culture teaching per se in ESP contexts.

Keywords: ESP, EGP, cultural studies, textbooks, teaching, materials

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Authors: Safa Moussoud

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Contrary to modern misconceptions, women in the Muslim Middle Ages enjoyed a generous degree of liberty both in the public and private sphere. Poetry was a significant component of public life throughout the Muslim Civilization as its vitality and multi-generic nature acted as a way for medieval Muslims to communicate with each other. As such, a continuity of poetic literary heritage was preserved through multiple centuries and dynasties. This paper will argue that Muslim women were active participants in medieval Muslim society’s social and public sphere and therefore, can be seen as vital contributors to the intellectual and literary creation of the Muslim Civilization. This paper will examine poetry written by Safiyya al-Baghddadiya and Salma bint al-Qaratisi from the Abbasid period, as well as Wallada bint al-Mustakfi from the Andalusian period and focus particularly at the poetesses’ modes of self-expression regarding beauty and sexuality to argue that Medieval Muslim women enjoyed creative and literary liberty thus allowing them to proclaim their subjectivity publicly through poetry. By emphasizing women’s involvement in the social aspects of Medieval Muslim societies, this paper will ultimately urge for a more thorough investigation of Muslim women’s role and function in the making of the Muslim Civilization.

Keywords: Arabo-Islamic society, medieval Muslims, Muslim poetesses, self-expression

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Authors: Abdulsallam A. Bakdash, Aiyshah M. Alshehri, Hind M. Alenzi

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Benzatropine (benztropine) is used to treat symptoms of Parkinson's disease or involuntary movements due to the side effects of certain psychiatric drugs. We report in this study, results of a procedure for the determination of benzatropine in hair using LLE, once with methanol and second with phosphate buffer (pH 6.0), followed by filtration and then re-extraction with dichloromethane. A GC/MS method was developed and validated for this determination using selected ion monitoring (SIM) detection without derivatization. Linearity established over the concentration range 0.1-20.0 ng/mg hair, and the correlation coefficients were greater than 0.99. Recoveries were 52.2% and 21.1% using methanol and phosphate buffer extraction, respectively. Detection limits of benzatropine in hair were between 0.65 and 3.0 ng/mg hair, while the accuracy were 10.4% and 18.5% (RSD), respectively. We also applied this method to the analysis of soaked hair samples and demonstrated that the LLE using methanol meets the requirement for the analysis of benzatropine in hair.

Keywords: hair analysis, benzatropine, liquid-liquid extraction, GC/MS

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Authors: Thirumila Muthukamaru

Abstract:

The objective of a Health Risk Assessment (HRA) is to achieve a quality evaluation of risk assessments in a timely manner where adequate controls can be in place to protect workers health, especially during turnarounds where the exposure to health hazards is expected to rise during the performance of the many activities that take place, exposing workers to health risk. HRA development requires a competent team comprising experienced subject matter experts in the field, such as Industrial hygienists, Occupational Health Doctors, Turnaround Coordinators, Operation / Maintenance personnel, etc. The conventional way of conducting HRA is not only tedious and time-consuming but also less appreciated when it is not interpreted correctly, which may contribute to inadequate operationalization of it. Simplification can be the essence of timely intervention in managing health risks. This paper is intended as a sharing of the approach taken to simplify the methodology of developing the HRA report and operationalizing it. The approach includes developing a Generic HRA for turnaround activities to be used as a reference document and the empowerment of identified personnel through upskilling sessions to take up the role of facilitating HRA sessions. This empowerment is one of the key approaches towards the successful translation of the HRA into specific turnaround Job Hazard Analysis (JHA) that embed it in the Permit to Work (PTW) process. The approach used here increases awareness and compliance on HRA for turnaround activities through better interpretation and operationalization of the HRA report, adding value to the risk assessment for turnaround activities.

Keywords: industrial hygiene, health risk assessment, HRA, risk assessment

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Authors: Muhammad Bilal, Amelia Jane Llyod, Habsah Mohamad, Jia Hui Wong, Abdul Aziz Mohamed Yusoff, Jafri Malin Abdullah, Jingli Zhang

Abstract:

Epilepsy is one of the major brain afflictions occurs with uncontrolled excitation of cortex; disturbed 50 million of world’s population. About 25 percent of patients subjected to adverse effects from antiepileptic drugs (AEDs) such as depression, nausea, tremors, gastrointestinal symptoms, osteoporosis, dizziness, weight change, drowsiness, fatigue are commonly observed indications; therefore, new drugs are required to cure epilepsy. GABA is principle inhibitory neurotransmitter, control excitation of the brain. Mutation or dysfunction of GABA receptor is one of the primary causes of epilepsy, which is confirmed from many acquired models of epilepsy like traumatic brain injury, kindling, and status epilepticus models of epilepsy. GABA receptor has 3 distinct types such as GABA (A), GABA (B), GABA(C).GABA (A) receptor has 20 different subunits, α1β2γ2 subunits composition of GABA (A) receptor is the most used combination of subunits for screening of compounds against epilepsy. We expressed α1β2γ2s subunits of GABA (A) Receptor in Xenopus leavis oocytes and examined the enhancement potential of 4-Hydroxybenzoic acid compound on GABA (A) receptor via two-electrode voltage clamp current recording technique. Bamboo shoots are the young, tender offspring of bamboo, which are usually harvested after a cultivating period of 2 weeks. Proteins, acids, fat, starch, carbohydrate, fatty acid, vitamin, dietary fiber, and minerals are the major constituent found systematically in bamboo shoots. These shoots reported to have anticancer, antiviral, antibacterial activity, also possess antioxidant properties due to the presence of phenolic compounds. Student t-test analysis suggested that 4- hydroxybenzoic acid positively allosteric GABA (A) receptor, increased normalized current amplitude to 1.0304±0.0464(p value 0.032) compared with vehicle. 4-Hydrobenzoic acid, a compound from Dendrocalamus Asper bamboo shoot gives new insights for future studies on bamboo shoots with motivation for extraction of more compounds to investigate their effects on human and rodents against epilepsy, insomnia, and anxiety.

Keywords: α1β2γ2S, antiepileptic, bamboo shoots, epilepsy GABA (A) receptor, two-microelectrode voltage clamp, xenopus laevis oocytes

Procedia PDF Downloads 403