Search results for: oral kinase inhibitors

Authors: Behnaz Mahdavi, Hamidreza Khodaei, Alireza Banitaba

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Conjugated Linoleic Acid is a group of long-chain unsaturated fatty acids with more than one double bond and a mixture of 28 isomers of Linoleic acid (C 18:2) and it is counted as one of the essential acids. The main purpose of this study was to investigate the effect of CLA on some reproductive hormones in rams. In this study, six rams 3 to 4 years old with an average weight of 90 kg were selected. Rams were randomly divided into 3 groups and were treated by CLA treatment for 30 days. The first group (as a control group) did not receive CLA, The second group received 0.5 gr and the third group received 1 gram of CLA. The blood testing was done on rams every 15 days using a 20 ml syringe. Data analysis was performed by SAS software. Also mean comparison was done using Duncan's test method (p<0.05). Obtained results showed that the serum concentration of testosterone hormone was decreased numerically as well as the concentration of FSH hormone however the concentration of LH was increased. Also, the CLA had a significant effect on Leptin concentration. CLA in oral form can reduce the concentration of testosterone in rams.

Keywords: CLA, ram, testosterone, conjugated linoleic acid

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Authors: Jungkyun Im

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Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective for relieving pain and reducing inflammation. They are nonselective inhibitors of two isoforms of COX, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and thereby inhibiting the production of hormone-like lipid compounds such as, prostaglandins and thromboxanes which cause inflammation, pain, fever, platelet aggregation, etc. In addition, recently there are many research articles reporting the neuroprotective effect of NSAIDs in neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). However, the clinical use of NSAIDs in these diseases is limited by low brain distribution. Therefore, in order to assist the in-depth investigation on the pharmaceutical mechanism of flurbiprofen in neuroprotection and to make flurbiprofen a more potent drug to prevent or alleviate neurodegenerative diseases, delivery of flurbiprofen to brain should be effective and sufficient amount of flurbiprofen must penetrate the BBB thus gaining access into the patient’s brain. We have recently developed several types of guanidine-rich molecular carriers with high molecular weights and good water solubility that readily cross the blood-brain barrier (BBB) and display efficient distributions in the mouse brain. The G8 (having eight guanidine groups) molecular carrier based on D-sorbitol was found to be very effective in delivering anticancer drugs to a mouse brain. In the present study, employing the same molecular carrier, we prepared the flurbiprofen conjugate and studied its BBB permeation by mouse tissue distribution study. Flurbiprofen was attached to a molecular carrier with a fluorescein probe and multiple terminal guanidiniums. The conjugate was found to internalize into live cells and readily cross the BBB to enter the mouse brain. Our novel synthetic flurbiprofen conjugate will hopefully delivery NSAIDs into brain, and is therefore applicable to the neurodegenerative diseases treatment or prevention.

Keywords: flurbiprofen, drug delivery, molecular carrier, organic synthesis

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Authors: Janaka B. Lewis

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“Narratives of Slavery and the Culture of Play” examines how play is discussed in early African American literature by both men and women to illustrate ways that they negotiated the hierarchy and oppression of enslavement. Reading narratives categorized as “slave narratives,” including those written by Frederick Douglass, Harriet Jacobs, and Olaudah Equiano, through the lens of play theory offers an illuminated analysis of the significance of play culture in these texts. It then reads late nineteenth-century play culture (or absence thereof) portrayed in literature as a lens for more contemporary African American oral and literary culture. These discussions of social constructions through literature bridge analyses of African American-authored texts and create a larger conversation about print media as a tool of activism and resistance. This essay also contributes to a larger body of analysis of nineteenth-century African American culture through literature.

Keywords: childhood, slavery, consciousness of play, 19th century African American culture

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Authors: Olga A. Gnatyuk

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The article is devoted to the phenomenon of interference that occurs in the case of the Russian-Spanish language contact. The questions of the definition of the term and levels, as well as prerequisites of interference occurrence, are considered. Interference, which is an essential part of bilingualism, may become apparent at different linguistic levels. Interference is especially evident in oral speech. The article reviews some examples of grammatical interference in Russian-Spanish bilingualism of Russian immigrants living in Spain. According to the results of the research, some cases of mother-tongue interference in Russian-Speaking Spanish language learners’ speech were revealed. Special attention is paid to such key spheres of grammatical interference as articles, personal pronouns, gender, and number of nouns. In the research, the drop of a link-verb, as well as its usage in some incorrect form, are observed in Russian immigrants’ speech. Conclusions are drawn that in the Spanish language, interference errors appear because of a consequence of both the absence in the Russian language of certain phenomena and categories of the Spanish language and the discrepancy of the linguistic systems of the two languages.

Keywords: bilingualism, interference, grammatical interference, Russian language, Spanish language

Procedia PDF Downloads 152

Authors: Hoda M. Eid, Abir Nachar, Farah Thong, Gary Sweeney, Pierre S. Haddad

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Caffeic acid methyl ester (CAME) and caffeic ethyl esters (CAEE) were previously reported to potently stimulate glucose uptake in cultured C2C12 skeletal muscle cells via insulin-independent mechanisms involving the activation of adenosine monophosphate-activated protein kinase (AMPK). In the present study, we investigated the effect of the two compounds on the translocation of glucose transporter GLUT4 in L6 skeletal muscle cells. The cells were treated with the optimum non-toxic concentration (50 µM) of either CAME or CAEE for 18 h. Levels of GLUT4myc at the cell surface were measured by O-phenylenediamine dihydrochloride (OPD) assay. The effects of CAME and CAEE on GLUT1 and GLUT4 protein content were also measured by western immunoblot. Our results show that CAME and CAEE significantly increased glucose uptake, GLUT4 translocation and GLUT4 protein content. Furthermore, the effect of the two CA esters on two insulin-sensitive cell lines: H4IIE rat hepatoma and 3T3-L1 adipocytes were investigated. CAME and CAEE reduced the enzymatic activity of the key hepatic gluconeogenic enzyme glucose-6-phosphatase in a concentration-dependent manner. In addition, they exerted a concentration-dependent antiadipogenic effect on 3T3-L1 cells. Mitotic clonal expansion (MCE), a prerequisite for adipocytes differentiation was also concentration-dependently inhibited. The two compounds abrogated lipid droplet accumulation, blocked MCE and maintained cells in fibroblast-like state when applied at the maximum non-toxic concentration (100 µM). In addition, the expression of the early key adipogenic transcription factors CCAAT enhancer-binding protein beta (C/EBP-β) and the master regulator of adipogenesis peroxisome-proliferator-activated receptor gamma (PPAR-γ) were inhibited. We, therefore, conclude that CAME and CAEE exert pleiotropic benefits in several insulin-sensitive cell lines through insulin-independent mechanisms involving AMPK, hence they may treat obesity, diabetes and other metabolic diseases.

Keywords: type 2 diabetes mellitus, insulin resistance, GLUT4, Akt, AMPK.

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Authors: Uchenna Bella Onu

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Traditional art is one of Nigerian cultural heritage. It is an excellent instrument for documentation and identification. Antiquities are priceless and irreplaceable. They are basically preserved for future generations. Sadly, preserving these highly prized cultural heritage is becoming a serious challenge. This paper examines the extent modernization has affected the preservation of traditional art in Nigeria. Particularly hit is the antiquities and traditional murals of eastern part of Nigeria. Participatory visual methods were used for this study. Efforts were made to reach the few surviving and aged mural artists. Oral information was collected from them as well as first hand drawings and some photographs of their works. Findings indicate that modernization has seriously affected the preservation of Nigerian artistic heritage. Further findings show that traditional mural artists are gradually dwindling and dangerously going into extinct. Antiquities are indiscriminately destroyed due to sheer ignorance and the blind quest to fit into the so called modern world.  

Keywords: antiquities, artistic heritage, cultural preservation, drawings, modernization, murals

Procedia PDF Downloads 160

Authors: Somchai Buaroong

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This research aims to investigating strong points and challenges in application of an online learning management system to an English course. Data were collected from observation, learners’ oral and written reports, and the teacher’s journals. A questionnaire was utilized as a tool to collect data. Statistics utilized in this research included frequency, percentage, mean, standard deviation, and multiple regression analysis. The findings show that the system was an additional channel to enhance English language learning through written class assignments that were digitally accessible by any group members, and through communication between the teacher and learners and among learners themselves. Thus, the learning management system could be a promising tool for foreign language teachers. Also revealed in the study were difficulties in its use. The article ends with discussions of findings of the system for foreign language classes in association to pedagogy are also included and in the level of signification.

Keywords: english course, foreign language system, online learning management system, teacher’s journals

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Authors: Dalila Bouamra, Chekib Arslane Baki, Abdelhamid Bouchebour, Fatiha Koussa, Amel Benamara, Seoussen Kada

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The activity of methanolic extract from Anacyclus pyrethrum was evaluated using λ-carrageenan 1% induced paw edema in Wistar Albinos rats. The oral administration of 200 mg/kg, 400 mg/kg and 600 mg/kg, body weight of methanolic extract, one hour before induction of inflammation, exerted a significant inhibition effect of 47%, 57% and 62% respectively after 4h λ-carrageenan treatment and highly significant inhibition effect of 57%, 66% and 75% respectively after 8h λ-carrageenan treatment, compared to non treated group (100%) and that treated with aspirin, a standard anti-inflammatory drug. On the other hand, the effect of the plant extract on stomach was macroscopically and microscopically studied. The plant extract has an impact on the loss ratio of granulocytes that have invaded the stomach after a period of inflammation at a dose of 600 mg/kg body weight.

Keywords: inflammation, Anacyclus pyrethrum, gastritis, Wistar Albinos rats

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Authors: Martina Maria Keitsch

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Critical Design (CD) confronts traditional design practice. Instead of reproducing and reinforcing contemporary perceptions of products and services, CD seeks to challenge them with the goal to stimulate debates and visions on societal innovation. CD methods comprise, among other narratives and design of critical objects. The oral presentation is based on a study that discusses concepts, methods, and applications of CD links CD to traditional design, and identifies CD benefits and challenges for design research and practice. The objective of the study is to introduce CD as an alternative for design researchers and practitioners supplementing commercially oriented design approaches. The study utilizes a literature review on CD concepts and methods based on current publications and online documents and illustrates CD practice with help of selected case studies. Findings of the study indicate that CD contribute, among others, to create new societal roles for designers, foster innovative relationships between designers and users, and encourage creativity through imaginative aesthetics.

Keywords: critical design, postmodern design theories, narratives, rhizome

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Authors: Amel Chenafa, Sihem Boulenouar, Linda Aoued, Imane Sediri, Ismahan Djebbar, Mohamed Adil Selka

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Introduction: The specialties intended for adults are often inadequate marketed for pediatric use, such as for a galenic form or in the dosage. For an industrial, development of a pediatric drug is confronted to various problems. So, the hospital pharmacies have to respond to adaptation needs of pharmaceutical forms for pediatric use. The objective of our work is to develop an oral form of prednisone for pediatric use since no adapted form to children is commercialized. Materials and Methods: Therefore an extemporaneous syrup of prednisone was prepared at the concentration of 0,5mg/ml from 5mg tablets and stored in amber glass bottles. Organoleptic and microbiological stability was studied in two temperatures: 5°C and 25°C, and evaluated at D0, D15, and D30. Results: No organoleptic changes have been detected on the syrup conserved at 25 and 5°C. The results show that there is no presence of bacteria, yeasts, and molds in the syrups stored at both temperatures during the analysis period. Conclusion: Sheltered from light, the developed syrup of prednisone remained stable at room temperature and/or refrigerator for 30 days.

Keywords: extemporaneous syrup, pediatric drug, prednisone, stability

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Authors: Md. Mizanur Rahman, Anquan Liu, Anna Frostegård, Johan Frostegård

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The role of the human immune system is essential in cardiovascular diseases and atherosclerosis. Activated cells in atherosclerosis produce abundant amounts of cytokines, but the exact mechanisms involved in the effects of these inflammatory cytokines are not clear in atherosclerosis. In a large clinical cohort, we have previously determined that antibodies against phosphorylcholine (anti-PC) are negatively and independently associated with both development of atherosclerosis and also a low risk of cardiovascular disease. Further, we reported that rheumatoid arthritis patients who were non-responders to TNF-inhibitors, where those with low anti-PC levels. Upon anti-TNF treatment, anti-PC levels increased. We, therefore, hypothesised that proinflammatory cytokines such as TNF could play a role in anti-PC regulation. Peripheral blood mononuclear cells (PBMC) were cultured with or without TNF and anti-TNF. The cell supernatants were collected after six days for ELISA measurements. In separate experiments, cells were cultured for 24 hours in both polystyrene plates and ELISPOT plates under a similar condition for ELISA and ELISPOT assays respectively. Total RNA was extracted after 6 hours of cell culture to perform RT-qPCR. Cell viability was confirmed by trypan blue staining and MTT assays. ELISA measurements detected less than 40% of anti-PC in TNF-treated cells, in comparison to control cells, whereas anti-PC production was recovered by anti-TNF treatment. ELISPOT assays showed that TNF suppresses anti-PC production by inhibiting anti-PC producing B-cells. In addition, RT-qPCR and ELISA showed that TNF also has effects also on B-cell activation as BAFF expression was inhibited by TNF treatment. Atherosclerosis is a major cause of cardiovascular diseases, but anti-PC is a protection marker for atherosclerosis development. Our findings show that TNF is a negative regulator of anti-PC production. Immune modulation and rising of anti-PC could be of major significance for the patients.

Keywords: anti-PC, Anti-TNF, atherosclerosis, cardiovascular diseases, phosphorylecholine

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Authors: Georgiana Ciobotaru

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The vocabulary that foreign students assimilate once they start studying the Romanian language must allow them to develop the linguistic competence of oral and written expression, but also the intercultural one, necessary for their integration into the new socio-cultural environment. Therefore, the familiarization courses with Romanian as a foreign language aim at fundamental language acquisitions in order to obtain the expected level of Romanian language. They also relate differently to the new culture and the new language they come in contact with, having a distinct way of expressing themselves. Foreign students want to continue their university and postgraduate studies at specialized faculties in the country; therefore, they need both a general language for their integration into society and for interaction with others, Romanians or students from countries other than their own, but also from a specialized language that facilitates didactic communication and professional development. The complexity of the vocabulary must thus cover the daily communication needs, but also the subsequent evolution of each one. This paper aims to illustrate the most important semantic fields that students must assimilate in order to crystallize a linguistic identity in the new context of their personal and professional development and to help them cope with the culture shock.

Keywords: integration, intercultural, language, linguistic, vocabulary

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Authors: Zahra Mirsanjari, Mohammad Reza Baradaran, Mehdi Rastegari Ghiri

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Research in the field of education has widely documented that teachers’ sense of efficacy has strong impacts on various aspects of teaching and learning. The present study is an attempt to examine Iranian EFL teachers’ degree of self-efficacy for teaching English. The data required for the study was gathered from Iranian EFL teachers teaching English as a foreign language in different schools and language institutes in Iran. Data were collected using Teacher’s Sense of Efficacy Scale (TSES). Results identified four dimensions of teachers’ English teaching-specific sense of efficacy: instructional strategies, classroom management, student engagement, and oral English language use. It was also found that teachers rated their self-efficacy in teaching English at a moderate level in the dimensions of instructional strategies, classroom management, and student engagement. Results have implications for language teachers and practitioners.

Keywords: Self-efficacy, teaching, EFL, teachers

Procedia PDF Downloads 519

Authors: Ryan Goh, Nicholas Beech

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Introduction: Le Fort I Osteotomies, although are common procedures in Oral and Maxillofacial Surgery, carry a degree of risk of unfavourable propagation of the down-fracture of the maxilla. This may be the first reported case in the literature for meningoencephalitis to occur following a Le Fort I Osteotomy. Case: A 32-year-old female was brought into the Emergency Department four days after a Le Fort I Osteotomy, with a Glasgow Coma Scale (GCS) of 8 (E3V1M4). A Computed Tomography (CT) Head showed a skull base fracture at the right sphenoid sinus. Lumbar puncture was completed, and Klebsiella oxytoca was found in the Cerebrospinal Fluid (CSF). She was treated with Meropenem, and rapidly improved thereafter. CSF rhinorrhoea was identified when she was extubated, which was successfully managed via a continuous lumbar drain. She was discharged on day 14 without any neurological deficits. Conclusion: The most likely aspect of the Le Fort I Osteotomy to obtain a skull base fracture is during the pterygomaxillary disjunction. Care should always be taken to avoid significant risks of skull base fractures, CSF rhinorrhoea, meningitis and encephalitis.

Keywords: meningitis, orthognathic surgery, post-operative complication, skull base, rhinorrhea

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Authors: Kinnsley Travis, Camerron M. Crowder

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Mapk8ip3 (Mitogen-Activated Protein Kinase 8 Interacting Protein 3) is a gene that codes for the JIP3 protein, which is a part of the JIP scaffolding protein family. This protein is involved in axonal vesicle transport, elongation and regeneration. Variants in the Mapk8ip3 gene are associated with a rare-genetic condition that results in a neurodevelopmental disorder that can cause a range of phenotypes including global developmental delay and intellectual disability. Currently, there are 18 known individuals diagnosed to have sequenced confirmed Mapk8ip3 genetic disorders. This project focuses on examining the impact of a subset of missense patient variants on the Jip3 protein function by overexpressing the mRNA of these variants in a zebrafish knockout model for Jip3. Plasmids containing cDNA with individual missense variants were reverse transcribed, purified, and injected into single-cell zebrafish embryos (Wild Type, Jip3 -/+, and Jip3 -/-). At 6-days post mRNA microinjection, morphological, behavioral, and microscopic phenotypes were examined in zebrafish larvae. Morphologically, we compared the size and shape of the zebrafish during their development over a 5-day period. Total locomotive activity was assessed using the Microtracker assay and patterns of movement over time were examined using the DanioVision assay. Lastly, we used confocal microscopy to examine sensory axons for swelling and shortened length, which are phenotypes observed in the loss-of-function knockout Jip3 zebrafish model. Using these assays during embryonic development, we determined the impact of various missense variants on Jip3 protein function, compared to knockout and wild-type zebrafish embryo models. Variants in the gene Mapk8ip3 cause rare-neurodevelopmental disorders due to an essential role in axonal vesicle transport, elongation and regeneration. A subset of missense variants was examined by overexpressing the mRNA of these variants in a Jip3 knock-out zebrafish. Morphological, behavioral, and microscopic phenotypes were examined in zebrafish larvae. Using these assays, the spectrum of disorders can be phenotypically determined and the impact of variant location can be compared to knockout and wild-type zebrafish embryo models.

Keywords: rare disease, neurodevelopmental disorders, mrna overexpression, zebrafish research

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Authors: Mohamed H. Khalifa, Fikry I. El-Shahawi, Nabil A. Mansour

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The cotton leafworm, Spodoptera littoralis (Boisduval) is a major insect pest of vegetables and cotton crops in Egypt, and exhibits different levels of tolerance to certain insecticides. Chlorantraniliprole has been registered recently in Egypt for control this insect. The susceptibilities of three S. littoralis populations collected from El Behaira governorate, north Egypt to chlorantraniliprole were determined by leaf-dipping technique on 4^th instar larvae. Obvious variation of toxicity was observed among the laboratory susceptible, and three field populations with LC₅₀ values ranged between 1.53 µg/ml and 6.22 µg/ml. However, all the three field populations were less susceptible to chlorantraniliprole than a laboratory susceptible population. The most tolerant populations were sampled from El Delengat (ED) Province where S. littoralis had been frequently challenged by insecticides. Certain enzyme activity assays were carried out to be correlated with the mechanism of the observed field population tolerance. All field populations showed significantly enhanced activities of detoxification enzymes compared with the susceptible strain. The regression analysis between chlorantraniliprole toxicities and enzyme activities revealed that the highest correlation is between α-esterase or β-esterase (α-β-EST) activity and collected field strains susceptibility, otherwise this correlation is not significant (P > 0.05). Synergism assays showed the ED and susceptible strains could be synergized by known detoxification inhibitors such as piperonyl butoxide (PBO), triphenyl phosphate (TPP) and diethyl-maleate (DEM) at different levels (1.01-8.76-fold and 1.09-2.94 fold, respectively), TPP showed the maximum synergism in both strains. The results show that there is a correlation between the enzyme activity and tolerance, and carboxylic-esterase (Car-EST) is likely the main detoxification mechanism responsible for tolerance of S. littoralis to chlorantraniliprole.

Keywords: chlorantraniliprole, detoxification enzymes, Egypt, Spodoptera littoralis

Procedia PDF Downloads 267

Authors: Zahra Mirsanjari

Abstract:

Research in the field of education has widely documented that teachers’ sense of efficacy has strong impacts on various aspects of teaching and learning. The present study is an attempt to examine Iranian EFL teachers’ degree of self-efficacy for teaching English. The data required for the study was gathered from Iranian EFL teachers teaching English as a foreign language in different schools and language institutes in Iran. Data were collected using Teacher’s Sense of Efficacy Scale (TSES). Results identified four dimensions of teachers’ English teaching-specific sense of efficacy: instructional strategies, classroom Management, Student Engagement, and Oral English Language Use.It was also found that teachers rated their self-efficacy in teaching English at a moderate level in the dimensions of instructional strategies, classroom management, and student engagement. Results have implications for language teachers and practitioners.

Keywords: self-efficacy, English Language teaching, EFL teachers, language teachers and practitioners.

Procedia PDF Downloads 445

Authors: Muhammad Jumat Dasuki

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The curbing of excesses of women in politics is a topic that has been extensively studied in the field of Islamic law. This issue is complex and involves various cultural and religious factors, making it a highly debated topic. This paper examines the role of Islamic law in regulating the behavior of women in politics. In many Islamic societies, women face restrictions and limitations when it comes to their participation in the political sphere. This paper investigates the reasons behind these restrictions and analyzes how Islamic law can be used to curb any excesses that may arise from women's involvement in politics. By examining various case studies and analyzing the principles of Islamic law, this paper sheds light on the issue of women's participation in politics and provides potential solutions for balancing their rights and duties according to Islamic law. The methodology includes primary sources through in-depth oral interviews and secondary sources like textbooks and journals, aiming for a holistic understanding of the ethical dimensions of support initiatives within the context of Islamic Law to establish the fairness of Islam Law in its approach to women in politics. The paper concludes with suggestions and recommendations.

Keywords: excess, Islamic law, principles, women

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Authors: Zahra Yaghoubi

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One of the initial occurrences that, according to observations of those who have temporarily experienced death, arises is encountering beings or individuals possessing supernatural powers. For some, these beings are described as beautiful and radiant, while for others, they are portrayed as dark and terrifying. In some experiences, they are mentioned as young and beautiful individuals. Islamic religious sources refer to these beings as angels or celestial beings assigned by God to take and collect human souls. This research, conducted through library methods, examines and justifies the initial stage of observations from an Islamic perspective based on first and second-hand religious sources. It relies on evidence, observations, and oral narratives of near-death experiencers, as well as interviews published in television programs. The goal is to investigate Islamic sources and validate the presence of angels in near-death experiences. The use of visual interview reports direct reliance on the narrative rather than the written text by someone other than the experiencer, is among the main criteria for enhancing transparency and authenticity in conveying the individual's experiences.

Keywords: angel, angels of death, Islamic sources, near-death experiences, death, soul

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Authors: Gurfateh Singh, Mu Khan, Razia Khanam, Govind Mohan

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Objective: The present study has been designed to investigate the beneficial role of Fenofibrate & Clofibrate in attenuated the cardioprotective effect of ischemic preconditioning (IPC) in hyperlipidemic rat hearts. Materials & Methods: Experimental hyperlipidemia was produced by feeding high fat diet to rats for a period of 28 days. Isolated langendorff’s perfused normal and hyperlipidemic rat hearts were subjected to global ischemia for 30 min followed by reperfusion for 120 min. The myocardial infarct size was assessed macroscopically using triphenyltetrazolium chloride staining. Coronary effluent was analyzed for lactate dehydrogenase (LDH) and creatine kinase-MB release to assess the extent of cardiac injury. Moreover, the oxidative stress in heart was assessed by measuring thiobarbituric acid reactive substance, superoxide anion generation and reduced form of glutathione. Results: The ischemia-reperfusion (I/R) has been noted to induce oxidative stress by increasing TBARS, superoxide anion generation and decreasing reduced form of glutathione in normal and hyperlipidemic rat hearts. Moreover, I/R produced myocardial injury, which was assessed in terms of increase in myocardial infarct size, LDH and CK-MB release in coronary effluent and decrease in coronary flow rate in normal and hyperlipidemic rat hearts. In addition, the hyperlipidemic rat hearts showed enhanced I/R-induced myocardial injury with high degree of oxidative stress as compared with normal rat hearts subjected to I/R. Four episodes of IPC (5 min each) afforded cardioprotection against I/R-induced myocardial injury in normal rat hearts as assessed in terms of improvement in coronary flow rate and reduction in myocardial infarct size, LDH, CK-MB and oxidative stress. On the other hand, IPC mediated myocardial protection against I/R-injury was abolished in hyperlipidemic rat hearts. However, Treatment with Fenofibrate (100 mg/kg/day, i.p.), Clofibrate (300mg/kg/day, i.p.) as a agonists of PPAR-α have not affected the cardioprotective effect of IPC in normal rat hearts, but its treatment markedly restored the cardioprotective potentials of IPC in hyperlipidemic rat hearts. Conclusion: It is noted that the high degree of oxidative stress produced in hyperlipidemic rat heart during reperfusion and consequent down regulation of PPAR-α may be responsible to abolish the cardioprotective potentials of IPC.

Keywords: Hyperlipidemia, ischemia-reperfusion injury, ischemic preconditioning, PPAR-α

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Authors: Makda Aamir, Sood Aayushi, Syed Omar, Nihan Khuld, Iskander Peter, Ijaz Naeem, Sharma Nishant

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Introduction:Glycogen Storage Disease Type-1 (GSD-1) is a rare phenomenon primarily affecting the liver and kidney. Excessive accumulation of glycogen and fat in liver, kidney, and intestinal mucosa is noted in patients with deficiency of Glucose-6-phosphatase deficiency. Patients with GSD-1 have a wide spectrum of symptoms, including hepatomegaly, hypoglycemia, lactic acidemia, hyperlipidemia, hyperuricemia, and growth retardation. Age of onset, rate of disease progression and its severity is variable in this disease.Case:An 18-year-old male with GSD-1a, Von Gierke’s disease, hyperuricemia, and hypertension presented to the hospital with nausea and vomiting. The patient followed an hourly cornstarch regimen during the day and overnight through infusion via a PEG tube. The complaints started at work, where he was unable to tolerate oral cornstarch. He washemodynamically stable on arrival. ABG showed pH 7.372, PaCO2 30.3, and PaO2 92.2. WBC 16.80, K+ 5.8, HCO3 13, BUN 28, Cr 2.2, Glucose 60, AST 115, ALT 128, Cholesterol 352, Triglycerides >1000, Uric Acid 10.6, Lactic Acid 11.8 which trended down to 8.0. CT abdomen showed hepatomegaly and fatty infiltration with the PEG tube in place.He was admitted to the ICU and started on D5NS for hypoglycemia and lactic acidosis. Per request by the patient’s pediatrician, he was transitioned to IV D10/0.45NS at 110mL/Hr to maintain blood glucose above 75 mg/L. Frequent accuchecks were done till he could tolerate his dietary regimen with cornstarch. Lactic acid downtrend to 2.9, and accuchecks ranged between 100-110. Cr improved to 1.3, and his home medications (Allopurinol and Lisinopril) were resumed. He was discharged in stable condition with plans for further genetic therapy work up.Discussion:Mainstay therapy for Von Gierke’s Disease is the prevention of metabolic derangements for which dietary and lifestyle changes are recommended. A low fructose and sucrose diet is recommended by limiting the intake of galactose and lactose to one serving per day. Hypoglycemia treatment in such patients is two-fold, utilizing both quick and stable release sources. Cornstarch has been one such therapy since the 1980s; its slow digestion provides a steady release of glucose over a longer period of time as compared with other sources of carbohydrates. Dosing guidelines vary from age to age and person to person, but it is highly recommended to check BG levels frequently to maintain a BG > 70 mg/dL. Associated high levels of triglycerides and cholesterol can be treated with statins, fibrates, etc. Conclusion:The management of hypoglycemia in GSD 1 disease presents various obstacles which could prove to be fatal. Due to the deficiency of G6P, treatment with a specialized hypoglycemic regimen is warranted. A D10 ½ NS infusion can be used to maintain blood sugar levels as well as correct metabolic or lactate imbalances. Infusion should be gradually weaned off after the patient can tolerate oral feeds as this can help prevent the risk of hypoglycemia and other derangements. Further research is needed in regards to these patients for more sustainable regimens.

Keywords: von gierke, glycogen storage disease, hypoglycemia, genetic disease

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Authors: So Hyun Ahn, Geu Rim Seo, Byungsoo Shin, Kwang-Won Yu, Hyung Joo Suh, Sung Hee Han

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We investigated the effects of GOS, lactulose and DuOligo in loperamide-induced constipation rat model. Dual-Oligo saccharide (DuOligo) was composed with galacto-oligosaccharide (GOS) and lactulose. GOS is an important dietary prebiotics that affects intestinal microbiota and barrier functions to have beneficial effect and lactulose is used as a laxative to treat constipation. To study the DuOligo, after adaptation period of four weeks of Spraque-Dawley rats, loperamide (5 mg/kg, twice per day) was injected to induce constipation for 1 week. DuOligo increased the fecal pellet amount, fecal weight, and water content of feces in rats with loperamide-induced constipation. DuOligo groups tended to produce more total fatty acid than that of observed for the control group. Gastrointestinal transit ratio and length and area of intestinal mucosa increased after treatment with DuOligo in loperamide-induced rats. These results showed that oral administration of DuOligo significantly modulated intestinal peristalsis.

Keywords: constipation, DuOligo, GOS, lactulose

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Authors: Menan M. Elsayed, Hussein A. Heshmat

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The aim of the study is to determine the effect of 100 mg/d Pregnenolone on biological variables after plyometric training for volleyball players. Methods: 15 male volleyball players participated in this study. Serum levels of testosterone, creatine phosphokinase (CPK), lactate, and glucose were measured before and post-exercise. Results: Testosterone was not altered, while creatine phosphokinase (CPK), lactate, and glucose levels significantly decreased. It is recommended to use Pregnenolone administration to decreased muscle damage and delayed fatigue for volleyball players after plyometric training. In conclusion, this study demonstrated that oral Pregnenolone administration of 100 mg/d might decrease muscle damage and delayed fatigue which may affect positively the volleyball players after a plyometric training bout.

Keywords: biological variables, plyometric exercise program, pregnenolone, volleyball player

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Authors: Alireza Pesarakloo, Masoumeh Najibzadeh

Abstract:

We studied the development and morphology of different larval stages of Pelophylax bedriagae at two rearing temperatures (20 and 24°C). Eggs collected from a breeding site in south-western Iran. Diagnostic morphological characters are provided for Gosner (1960) larval stages 1-46. The larvae hatched about seven days after egg deposition. Principal diagnostic feature including the formation of the funnel-shaped oral disc became discernible about ten days after hatch at Gosner stage 21 and degenerated at Gosner stage 42. Larvae developed faster at higher temperatures. The largest body length of larval P. bedriagae measured about 54mm in 70 days after egg deposition. Based on our results, the longest metamorphosis time was observed on temperature (20°C) whilst the shortest metamorphosis time occurred on temperature (24°C). Compared with the majority of other Palearctic Anurans, it appears that embryonic and larval development is usually slow rapid in P. bedriagae.

Keywords: development, larval stages, Pelophylax bedriagae, temperatures

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Authors: Fatimah Abd Elghani, Raymonde Szargel, Vered Shani, Hazem Safory, Haya Hamza, Mor Savyon, Ruth Rott, Rina Bandopadhyay, Simone Engelender

Abstract:

Background: PINK1 is a mitochondrial kinase mutated in some familial cases of Parkinson’s disease. Down regulation of PINK1 results in abnormal mitochondrial morphology and altered membrane potential. Although PINK1 has a predicted mitochondrial import sequence, it’s cellular, and submitochondrial localization remains unclear, in part because it is rapidly degraded. In this work, we investigated the mechanisms involved in PINK1 degradation and how this may affect PINK1 stability and function, with implications for mitochondrial function in PD. In addition, pharmacological inhibition of proteasome activity was shown to lead to PINK1 accumulation, indicating that PINK1 degradation depends on the ubiquitin-proteasome system (UPS). Methods: Using co-immunoprecipitation assays, we identified E3 ubiquitin ligase SIAH1 as a PINK1-interacting protein in HEK293 cells as well as on rat brain tissues. In addition, we determined the effect of SIAH 1, SIAH2 and Parkin on PINK1 steady-state levels by Western blot analysis, and checked their possibility to ubiquitinate and mediate PINK1 degradation through the proteasome carried out in vivo ubiquitination experiments. Results: We have obtained results showing that SIAH-1 interacts with and ubiquitinates PINK1. The ubiquitination promoted by SIAH-1 leads to the proteasomal degradation of PINK1. We confirmed these findings by knocking down SIAH-1 and observing important accumulation of PINK1 in cells. Besides, we found that SIAH-1 decreases PINK1 steady-state levels but not the E3 ligase Parkin. We also investigated the interaction of SIAH-1 with PINK1 disease mutants and its ability to promote their ubiquitination and degradation. Although, no clear difference in the ability of SIAH-1 to promote the degradation of PINK1 disease mutants was observed. It is possible that dysfunction of proteasomal activity in the disease may lead to the accumulation and aggregation of ubiquitinated PINK1 in patients with PINK1 mutations, with possible implications to the pathogenesis of PD. Conclusions: Here, we demonstrated that SIAH-1 ubiquitinates and promotes the degradation of PINK1. In addition, SIAH-1 represents now a target that may help the improvement of mitophagy in PD. Further investigations needed to understand how mitophagy is regulated by PINK1-SIAH-1 axis to provide targets for future therapeutics.

Keywords: PD, Parkinson's disease, PINK1, PTEN-induced kinase1, SIAH, seven in absentia homolog, SN, substantia nigra

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Authors: Geliashvili T. M., Tyulyandina A. S., Valiev A. K., Kononets P. V., Kharatishvili T. K., Salkov A. G., Pronin A. I., Gadzhieva E. H., Parnas A. V., Ilyakov V. S.

Abstract:

Aim/Introduction: Metastasis (Mts) to the sternum, while extremely rare in differentiated thyroid cancer (DTC) (1), requires a personalized, multidisciplinary treatment approach. In aggressively growing Mts to the sternum, which rapidly become unresectable, a comprehensive therapeutic and diagnostic approach is particularly important. Materials and methods: We present a clinical case of solitary Mts to the sternum as first manifestation of a papillary thyroid microcarcinoma in a 55-year-old man. Results: 18F-FDG PET/CT after thyroidectomy confirmed the solitary Mts to the sternum with extremely high FDG uptake (SUVmax=71,1), which predicted its radioiodine-refractory (RIR). Due to close attachment to the mediastinum and rapid growth, Mts was considered unresectable. During the next three months, the patient received targeted therapy with the tyrosine kinase inhibitor (TKI) Lenvatinib 24 mg per day. 1st course of radioiodine therapy (RIT) 6 GBq was also performed, the results of which confirmed the RIR of the tumor process. As a result of systemic therapy (targeted therapy combined with RIT and suppressive hormone therapy with L-thyroxine), there was a significant biochemical response (decrease of serum thyroglobulin level from 50,000 ng/ml to 550 ng/ml) and a partial response with decrease of tumor size (from 80x69x123 mm to 65x50x112 mm) and decrease of FDG accumulation (SUVmax from 71.1 to 63). All of this made possible to perform surgical treatment of Mts - sternal extirpation with its replacement by an individual titanium implant. At the control examination, the stimulated thyroglobulin level was only 134 ng/ml, and PET/CT revealed postoperative areas of 18F-FDG metabolism in the removed sternal Mts. Also, 18F-FDG PET/CT in the early (metabolic) stage revealed two new bone Mts (in the area of L3 SUVmax=17,32 and right iliac bone SUVmax=13,73), which, as well as the removed sternal Mts, appeared to be RIRs at the 2nd course of RIT 6 GBq. Subsequently, on 02.2022, external beam radiation therapy (EBRT) was performed on the newly identified oligometastatic bone foci. At present, the patient is under dynamic monitoring and in the process of suppressive hormone therapy with L-thyroxine. Conclusion: Thus, only due to the early prescription of targeted TKI therapy was it possible to perform surgical resection of Mts to the sternum, thereby improve the patient's quality of life and preserve the possibility of radical treatment in case of oligometastatic disease progression.

Keywords: differentiated thyroid cancer, metastasis to the sternum, radioiodine therapy, radioiodine-refractory cancer, targeted therapy, lenvatinib

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Authors: Harun Bozna

Abstract:

MOOC (massive open online course) is a groundbreaking education platform and a current buzzword in higher education. Although MOOCs offer many appreciated learning experiences to learners from various universities and institutions, they have considerably higher dropout rates than traditional education. Only about 10% of the learners who enroll in MOOCs actually complete the course. In this case, perceptions of participants and a comprehensive analysis of MOOCs have become an essential part of the research in this area. This study aims to explore the MOOCs in detail for better understanding its content, purpose and primarily drop out issues. The researcher conducted an online questionnaire to get perceptions of graduate students on their learning experiences in MOOCs and arranged a semi- structured oral interview with some participants. The participants are Turkish graduate level students doing their MA and Ph.D. in various programs. The findings show that participants are more likely to drop out courses due to lack of time and lack of pressure.

Keywords: distance education, MOOCs, drop out, perception of graduate students

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Authors: Saimir Heta, Ilma Robo, Nevila Alliu, Tea Meta

Abstract:

Background: Plasma levels of inflammatory markers are the expression of the infectious wastes of existing periodontitis, as well as of existing inflammation everywhere in the body. Materials and Methods: The study consists of the clinical part of the measurement of inflammatory markers of 23 patients diagnosed with chronic periodontitis and the recording of parental periodontal parameters of patient periodontal status: hemorrhage index and probe values, before and 7-10 days after non-surgical periodontal treatment. Results: The level of fibrinogen drops according to the categorization of disease progression, active and passive, with the biggest % (18%-30%) at the fluctuation 10-20 mg/d. Fluctuations in fibrinogen level according to the age of patients in the range 0-10 mg/dL under 40 years and over 40 years was 13%-26%, in the range 10-20 mg/dL was 26%-22%, in the 20-40 mg/dL was 9%-4%. Conclusions: Non-surgical periodontal treatment significantly reduces the level of non-inflammatory markers in the blood. Oral health significantly reduces the potential source for periodontal bacteria, with the potential of promoting thromboembolism, through interaction between thrombocytes.

Keywords: chronic periodontitis, atherosclerosis, risk factor, inflammatory markers

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Authors: Yann Jean Tan, Hui Meng Er, Choy Sin Lee, Shew Fung Wong, Wen Huei Lim

Abstract:

Griseofulvin is a long standing fungistatic agent against dermatophytosis. Nevertheless, it has several drawbacks such as poor and highly variable bio availability, long duration of treatment, systemic side effects and drug interactions. Targeted treatment for the superficial skin infection, dermatophytosis via topical route could be beneficial. Nevertheless, griseofulvin is only available in the form of oral preparation. Hence, it generates interest in developing a topical formulation for griseofulvin, by using lipid nano particle as the vehicle. Lipid nanoparticle is a submicron colloidal carrier with a core that is solid in nature (lipid). It has combined advantages of various traditional carriers and is a promising vehicle for topical delivery. The griseofulvin loaded lipid nano particles produced using high pressure homogenization method were characterized and investigated for its skin targeting effect in vitro. It has a mean particle size of 179.8±4.9 nm with polydispersity index of 0.306±0.011. Besides, it showed higher skin permeation and better skin targeting effect compared to the griseofulvin suspension.

Keywords: lipid nanoparticles, griseofulvin, topical, dermatophytosis

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Authors: Zahra Dehghani, Hoda Dehghani, Elham Zarenezhad

Abstract:

1,2,3-Triazole derivatives are important compounds in medicinal chemistry owing to their wide applications in drug discovery. They can readily associate with biologically targets through the hydrogen bonding and dipole interactions. The 1,2,3-triazole core is a key structural motif in many bioactive compounds, exhibiting a broad spectrum of biological activities, such as antiviral, anticancer, anti-HIV, antibiotic, antibacterial, and antimicrobial. Additionally, they have found significant industrial applications as dyes, agrochemicals, corrosion inhibitors, photo stabilizers, and photographic materials. we disclose the synthesis and characterization of 1-azido-3-(aryl-2-yloxy)propan-2-ol drivatives. The chemistry works well with various ß-azido alcohols involving aryloxy, alkoxy and alkyl residues, and also tolerates a wide spectrum of electron-donating and electron-withdrawing functional groups in both alkyne and azide molecules. Most of ß-azidoalcohols used in these experiments were pre-synthesized by the regioselective ring opening reaction of corresponded epoxides with sodium azide, whereas the majority of terminal alkynes were prepared via SN2-type reaction of propargyl bromide and corresponded nucleophiles. To evaluate the bioactivity of title compounds, the in vitro antifungal activity of all compound was investigated against several pathogenic fungi including Candida albicans, Candida krusei, Aspergillus niger, and Trichophyton rubrum , clotrimazole and fluconazole was used as standard antifungal drugs, also To understand the antibacterial activity of synthesized compounds, they were in vitro screened against E. coli and S. aureus as Gram-negative and Gram-positive bacteria, respectively. The in vitro tests have shown the promising antifungal but marginal antibacterial activity against tested fungi and bacteria.

Keywords: biological activities, antibacterial, antifungal, 1, 2, 3-Triazole

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