Search results for: drug research

Authors: S. Buloyan, V. Mamikonyan, H. Hakobyan, H. Harutyunyan, H. Gasparyan

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The liver is the strongest regenerating organ of the organism, and even with 2/3 surgically removed, it can regenerate completely. Hence, liver cirrhosis may only develop when the regenerating system is off. We present the results of a comparative study of structural and functional characteristics of rat liver tissue under the conditions of toxic liver cirrhosis development, induced by carbon tetrachloride, and its prevention/treatment by natural compounds with antioxidant and immune stimulating action. Studies were made on Wister rats, weighing 120~140 g. Grape seeds extracts, separately and in combination with well known anticirrhotic drug ursodeoxycholic acid (ursodiol) have demonstrated effectiveness in prevention of liver cirrhosis development and its treatment.

Keywords: carbon tetrachloride, GSE, liver cirrhosis, prevention, treatment

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Authors: Ewelina Musielak, Agnieszka Feliczak-Guzik, Izabela Nowak

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Based on the latest data, it is expected that the substances of therapeutic interest used will be as natural as possible. Therefore, active substances with the highest possible efficacy and low toxicity are sought. Among natural substances with therapeutic effects, those of plant origin stand out. Curcumin isolated from the Curcuma longa plant has proven to be particularly important from a medical point of view. Due to its ability to regulate many important transcription factors, cytokines, and protein kinases, curcumin has found use as an anti-inflammatory, antioxidant, antiproliferative, antiangiogenic, and anticancer agent. The unfavorable properties of curcumin, such as low solubility, poor bioavailability, and rapid degradation under neutral or alkaline pH conditions, limit its clinical application. These problems can be solved by combining curcumin with suitable carriers such as hierarchical zeolites. This is a new class of materials that exhibit several advantages. Hierarchical zeolites used as drug carriers enable delayed release of the active ingredient and promote drug transport to the desired tissues and organs. In addition, hierarchical zeolites play an important role in regulating micronutrient levels in the body and have been used successfully in cancer diagnosis and therapy. To apply curcumin to hierarchical zeolites synthesized from commercial FAU zeolite, solutions containing curcumin, carrier and acetone were prepared. The prepared mixtures were then stirred on a magnetic stirrer for 24 h at room temperature. The curcumin-filled hierarchical zeolites were drained into a glass funnel, where they were washed three times with acetone and distilled water, after which the obtained material was air-dried until completely dry. In addition, the effect of piperine addition to zeolite carrier containing a sufficient amount of curcumin was studied. The resulting products were weighed and the percentage of pure curcumin in the hierarchical zeolite was calculated. All the synthesized materials were characterized by several techniques: elemental analysis, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy, Fourier transform infrared (FT-IR), N2 adsorption, and X-ray diffraction (XRD) and thermogravimetric analysis (TGA). The aim of the presented study was to improve the biological activity of curcumin by applying it to hierarchical zeolites based on FAU zeolite. The results showed that the loading efficiency of curcumin into hierarchical zeolites based on commercial FAU-type zeolite is enhanced by modifying the zeolite carrier itself. The hierarchical zeolites proved to be very good and efficient carriers of plant-derived active ingredients such as curcumin.

Keywords: carriers of active substances, curcumin, hierarchical zeolites, incorporation

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Authors: Agnieszka E. Laudy, Karolina Stępien, Sergiusz Lulinski, Krzysztof Durka, Stefan Tyski

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1,3-dihydro-1-hydroxy-2,1-benzoxaborole and its derivatives are a particularly interesting group of synthetic agents and were successfully employed in supramolecular chemistry medicine. The first important compounds, 5-fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole and 5-chloro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole were identified as potent antifungal agents. In contrast, (S)-3-(aminomethyl)-7-(3-hydroxypropoxy)-1-hydroxy-1,3-dihydro-2,1-benzoxaborole hydrochloride is in the second phase of clinical trials as a drug for the treatment of Gram-negative bacterial infections of the Enterobacteriaceae family and Pseudomonas aeruginosa. Equally important and difficult task is to search for compounds active against Gram-negative bacilli, which have multi-drug-resistance efflux pumps actively removing many of the antibiotics from bacterial cells. We have examined whether halogen-substituted benzoxaborole-based derivatives and their analogues possess antibacterial activity and are substrates for multi-drug-resistance efflux pumps. The antibacterial activity of 1,3-dihydro-3-hydroxy-1,1-dimethyl-1,2,3-benzosiloxaborole and 10 halogen-substituted its derivatives, as well as 1,2-phenylenediboronic acid and 3 synthesised fluoro-substituted its analogs, were evaluated. The activity against the reference strains of Gram-positive (n=5) and Gram-negative bacteria (n=10) was screened by the disc-diffusion test (0.4 mg of tested compounds was applied onto paper disc). The minimal inhibitory concentration values and the minimal bactericidal concentration values were estimated according to The Clinical and Laboratory Standards Institute and The European Committee on Antimicrobial Susceptibility Testing recommendations. During the minimal inhibitory concentration values determination with or without phenylalanine-arginine beta-naphthylamide (50 mg/L) efflux pump inhibitor, the concentrations of tested compounds ranged 0.39-400 mg/L in the broth medium supplemented with 1 mM magnesium sulfate. Generally, the studied benzosiloxaboroles and benzoxadiboroles showed a higher activity against Gram-positive cocci than against Gram-negative rods. Moreover, benzosiloxaboroles have the higher activity than benzoxadiboroles compounds. In this study, we demonstrated that substitution (mono-, di- or tetra-) of 1,3-dihydro-3-hydroxy-1,1-dimethyl-1,2,3-benzosiloxaborole with halogen groups resulted in an increase in antimicrobial activity as compared to the parent substance. Interestingly, the 6,7-dichloro-substituted parent substance was found to be the most potent against Gram-positive cocci: Staphylococcus sp. (minimal inhibitory concentration 6.25 mg/L) and Enterococcus sp. (minimal inhibitory concentration 25 mg/L). On the other hand, mono- and dichloro-substituted compounds were the most actively removed by efflux pumps present in Gram-negative bacteria mainly from Enterobacteriaceae family. In the presence of efflux pump inhibitor the minimal inhibitory concentration values of chloro-substituted benzosiloxaboroles decreased from 400 mg/L to 3.12 mg/L. Of note, the highest increase in bacterial susceptibility to tested compounds in the presence of phenylalanine-arginine beta-naphthylamide was observed for 6-chloro-, 6,7-dichloro- and 6,7-difluoro-substituted benzosiloxaboroles. In the case of Escherichia coli, Enterobacter cloacae and P. aeruginosa strains at least a 32-fold decrease in the minimal inhibitory concentration values of these agents were observed. These data demonstrate structure-activity relationships of the tested derivatives and highlight the need for further search for benzoxaboroles and related compounds with significant antimicrobial properties. Moreover, the influence of phenylalanine-arginine beta-naphthylamide on the susceptibility of Gram-negative rods to studied benzosiloxaboroles indicate that some tested agents are substrates for efflux pumps in Gram-negative rods.

Keywords: antibacterial activity, benzosiloxaboroles, efflux pumps, phenylalanine-arginine beta-naphthylamide

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Authors: Ingrid Van Der Heijden, Naeemah Abrahams, Jane Harries

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Background: Women with disabilities are largely missing from global research on violence prevention, yet research shows that women with disabilities are a particularly marginalised group who experience heightened levels and unique forms of violence than men with disabilities, and women without disabilities. They face heightened stigma, discrimination, and violence due to their gender and their disability. Including women with disabilities in violence, research helps inform policy and prevention interventions that are relevant and inclusive. To ensure their inclusion in violence research, we need ethical guidelines that are sensitive to their heightened risk and vulnerability, that recognize the diversity in the disabled population, but that also promote disabled people’s agency in defining their own violence prevention needs and agendas. Objective: To highlight pertinent ethical issues around women with disabilities’ inclusion and participation in violence research. Methodology: Considering the lack of formalized guidelines for research of people with disabilities, we draw from the literature on international ethics guidelines for researching violence against women, and the Emancipatory Disability Research paradigm, as well as drawing from our own experiences from the field in applying the guidelines when doing research with disabled women. Findings: Following the guiding ethical principles of respect, benefit, justice, and do no harm, we argue that reasonable accommodation, capacity, and equal participation need to be considered in conceptualizing and conducting ethical violence research with women with disabilities. We conclude that disability research in the area of violence is highly politicized and must be carefully scrutinized to ensure justice and the contribution of women with disabilities to their own welfare. Implications: We suggest that these issues are practically applied in the field and tested and critiqued to enhance best practice for undertaking ethical research with this particular group. It is important that not only researchers and ethics committees, but also disabled women and disabled organizations, are involved in enhancing and formalizing ethical research guidelines for marginalized populations.

Keywords: capacity, emancipatory disability research paradigm equal participation, reasonable accommodation, research ethics, violence against women with disabilities

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Authors: R. C. Ferreira, H. H. C. De Lima, A. A. Cândido, O. M. Couto Junior, P. A. Arroyo, K. Q De Carvalho, G. F. Gauze, M. A. S. D. Barros

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Removal of the widespread used drug paracetamol from water was investigated using activated carbon originated from dende coconut mesocarp and babassu coconut mesocarp. Kinetic and equilibrium data were obtained at different values of pH. Babassu activated carbon showed higher efficiency due to its acidity and higher microporosity. Pseudo-second order model was better adjusted to the kinetic results. Equilibrium data may be represented by Langmuir equation. Lower solution pH provided better removal efficiency as the carbonil groups may be attracted by the positively charged carbon surface.

Keywords: adsorption, activated carbon, babassu, dende

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Authors: Lisdey Espinoza Pedraza

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Organised crime in Mexico evolves faster that our capacity to understand and explain it. Organised gangs have become successful entrepreneurs in many ways ad they have somehow mimicked the working ways of the authorities and in many cases, they have successfully infiltrated the governmental spheres. This business model is only possible under a clear scheme of rampant impunity. Impunity, however, is not exclusive to the PRI. Nor the PRI, PAN, or PRD can claim the monopoly of corruption, but what is worse is that none can claim full honesty in their acts either. The current security crisis in Mexico shows a crisis in the Mexican political party system. Corruption today is not only a problem of dishonesty and the correct use of public resources. It is the principal threat to Mexican democracy, governance, and national security.

Keywords: security, war on drugs, drug trafficking, Mexico, Latin America, United States

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Authors: Ning Kang, Marius Doornenbal

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Funding is a very important – if not crucial – resource for research projects. Usually, funding organizations will publish a description of the funded research to describe the scope of the funding award. Logically, we would expect research outcomes to align with this funding award. For that reason, we might be able to predict future research topics based on present funding award data. That said, it remains to be shown if and how future research topics can be predicted by using the funding information. In this paper, we extract funding project information and their generated paper abstracts from the Gateway to Research database as a group, and use the papers from the same domains and publication years in the Scopus database as a baseline comparison group. We annotate both the project awards and the papers resulting from the funded projects with linguistic features (noun phrases), and then calculate tf-idf and cosine similarity between these two set of features. We show that the cosine similarity between the project-generated papers group is bigger than the project-baseline group, and also that these two groups of similarities are significantly different. Based on this result, we conclude that the funding information actually correlates with the content of future research output for the funded project on the topical level. How funding really changes the course of science or of scientific careers remains an elusive question.

Keywords: natural language processing, noun phrase, tf-idf, cosine similarity

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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: Kanika Gupta, Ashok Kumar

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Biofilms are dense, highly hydrated cell clusters that are irreversibly attached to a substratum, to an interface or to each other, and are embedded in a self-produced gelatinous matrix composed of extracellular polymeric substances. Research in biofilm field has become very significant, as biofilm has shown high mechanical resilience and resistance to antibiotic treatment and constituted as a significant problem in both healthcare and other industry related to microorganisms. The massive information both stated and hidden in the biofilm literature are growing exponentially therefore it is not possible for researchers and practitioners to automatically extract and relate information from different written resources. So, the current work proposes and discusses the use of text mining techniques for the extraction of information from biofilm literature corpora containing 34306 documents. It is very difficult and expensive to obtain annotated material for biomedical literature as the literature is unstructured i.e. free-text. Therefore, we considered unsupervised approach, where no annotated training is necessary and using this approach we developed a system that will classify the text on the basis of growth and development, drug effects, radiation effects, classification and physiology of biofilms. For this, a two-step structure was used where the first step is to extract keywords from the biofilm literature using a metathesaurus and standard natural language processing tools like Rapid Miner_v5.3 and the second step is to discover relations between the genes extracted from the whole set of biofilm literature using pubmed.mineR_v1.0.11. We used unsupervised approach, which is the machine learning task of inferring a function to describe hidden structure from 'unlabeled' data, in the above-extracted datasets to develop classifiers using WinPython-64 bit_v3.5.4.0Qt5 and R studio_v0.99.467 packages which will automatically classify the text by using the mentioned sets. The developed classifiers were tested on a large data set of biofilm literature which showed that the unsupervised approach proposed is promising as well as suited for a semi-automatic labeling of the extracted relations. The entire information was stored in the relational database which was hosted locally on the server. The generated biofilm vocabulary and genes relations will be significant for researchers dealing with biofilm research, making their search easy and efficient as the keywords and genes could be directly mapped with the documents used for database development.

Keywords: biofilms literature, classifiers development, text mining, unsupervised learning approach, unstructured data, relational database

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Authors: Thusitha B. Abeysekara, M. A. Nihal Chandrathilake

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The aim of this research is to examine the legal mechanism of resolving maritime disputes by arbitration, and it would be a reference point on the analysis of USA approaches. In doing so, the research aims to analyse the relevant legal principles in the context of current maritime arbitration practices in selected jurisdictions. The research also aims to analyse the advantages and applicability of arbitration in maritime dispute settlements over the litigation and further approaches the role of specialist maritime arbitration institutes in the USA and the position of international merchant organizations in maritime arbitration. Further, research values the legislative aspects of maritime arbitration. The study would evaluate the contemporary issues in maritime arbitration practices in the USA and further analyses the statistical information on maritime arbitration. Finally, the research made remarks to often parallel consequence in USA legal systems in maritime arbitration and despite the fundamental divergences of the applicable principles and practices of maritime arbitration. The research finally suggests the doctrine should reshape with equitable remedies and international maritime arbitration practices with its institutional impact rather than using as statutory rules related maritime arbitration.

Keywords: arbitration, international shipping, maritime dispute, New York convention

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Authors: Tawqeer Ali Syed, Prakash Chandra

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This study aims to evaluate the antileishmanial activity of Nigella sativa black seed extract. This well-known plant extract was taken from the botanical garden of Kashmir. Materials and Methods: The methanolic extracts of these plants were screened for their antileishmanial activity against Leishmania major using 3‑(4.5‑dimethylthiazol‑2yl)‑2.5‑diphenyltetrazolium bromide assay or MTT assay. Results: The methanolic extract of Nigella sativa showed potential antileishmanial activity at an inhibition% value of 80.29% ± 0.65%. IC 50 was calculated after 48 hours to be 964.3 µg/ml. Conclusion: Considering these results, these medicinal plants from Kashmir could serve as potential drug sources for antileishmanial compounds.

Keywords: MTT assay, antileishmanial, cell viability, Nigella sativa

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Authors: Ahmad Abdi, M. Golzadeh Gangeraj, Alireza Barari, S. Shirali, S. Amini

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Aims: Diabetes is one of the common metabolic diseases in the world that has the dire adverse effects such as nephropathy, retinopathy and cardiovascular problems. Pharmaceutical and non-pharmaceutical strategies for control and treatment of diabetes are provided. Exercise and nutrition as non-drug strategies for the prevention and control of diabetes are considered. Exercises may increase oxidative stress and myocardium injury, thus it is necessary to take nutrition strategies to help diabetic athletes. Methods: This study was a semi-experimental research. Therefore, 24 men with type 2 diabetes were selected and randomly divided in four groups (1. control, 2. saffron extract, 3. aerobic exercises, 4. compound aerobic exercises and saffron extract). Saffron extract with 100 mg/day was used. Aerobic exercises, three days a week, for eight weeks, with 55-70% of maximum heart rate were performed. At the end, levels of Heart-type fatty acid-binding protein (HFABP) and Troponin T were measured. Data were analyzed by Paired t, One-way ANOVA and Tukey tests. Results: The serum Troponin T increased significantly in saffron extract, aerobic exercises and compound saffron extract -aerobic exercises in type 2 diabetic men(P=0.024, P =0.013, P=0.005 respectively). Saffron extract consumption (100 mg/day) and aerobic exercises did not significantly influence the serum HFABP (P =0.365, P =0.188 respectively). But serum HFABP decreased significantly in compound saffron extract -aerobic exercises group (P =0.003). Conclusions: Raised cardiac Troponin T and HFABP concentration accepted as the standard biochemical markers for the diagnosis of cardiac injury. Saffron intake may beneficially protect the myocardium from injuries. Compound saffron extract -aerobic exercises can decrease levels of Troponin T and HFABP in men with type 2 diabetes.

Keywords: Saffron, aerobic exercises, type 2 diabetes, HFABP, troponin T

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Authors: Linda Kauškale, Ineta Geipele

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Due to the rapidly changing external environment, portfolio management strategies became closely interconnected with real estate industry development and macroeconomic development tendencies. The aim of the research is to analyze sustainable real estate market development influencing factors, with particular focus on its economic and management aspects that influences real estate investment decisions as well. Scientific literature and article analysis, data analysis, expert evaluation, and other quantitative and qualitative research methods were used in the research. Developed real estate market sustainability model and index analysis approach can be applied by investors and real estate companies in real estate asset management and can help in risk minimization activities in international entrepreneurship. Future research directions have been identified in the research as well.

Keywords: indexes, investment decisions, real estate market, sustainability

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Authors: Arpita Mitra

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The research explores the concept of ‘guilt’ as understood in relation to children and young individuals associated with terrorist groups who are exiting these groups and returning to civilian lives (‘young returnees’). The study explores young returnees’ guilt – in its psychological, legal, and sociological manifestations and how it contributes to experiences of reintegration and justice administration. Streamlining it further, the research question on assessing guilt engages with young adults – between 18 and 30 years – who were part of a terrorist organization during their formative years and have returned to civilian life. Overall, the findings of the said research are intended to contribute first-hand operational research to criminological literature as well as transitional justice mechanisms with regard to narratives on truth, justice, reparations and institutional reform/guarantees of non-recurrence. Particularly for this paper, the focus of the paper shall be on one aspect of this research, that is, on the added value of conducting operational research and the methodological challenges encountered during this process with regard to informed consent, data protection, mental health and security considerations for the respondents and researcher.

Keywords: terrorism, reintegration, young returnees, criminology

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Authors: D. ChobfroushKhoei, S. K. Heidari , Sh. Dariadel

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Carbon nanotubes were used in medical sciences especially in drug delivery system and cancer therapy. In this study, we functionalized carboxylated single-wall carbon nanotubes (SWNT-COOH) with 2-en 4-hydroxy cyclo 1-octanon. Synthesized sample was characterized by FT-IR, Raman spectroscopy, SEM, TGA and cellular investigations. The results showed well formation of SWNT-Ester. Cell viability assay results and microscopic observations demonstrated that cancerous cells were killed in the sample. The synthesized sample can be used as a toxic material for cancer therapy.

Keywords: MWNT-COOH, functionalization, phenylisocyanate, phenylisothiocyanate, 1, 4-phenylendiamine, toxicity investigation

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Authors: Armen Yezekyan

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The main purpose of this research is to comprehensively explore and identify the problems of attestation of the public servants and to propose solutions for these issues through deeply analyzing laws and the legal theoretical literature. For the detailed analysis of the above-mentioned problems we will use some research methods, the implementation of which has a goal to ensure the objectivity and clarity of scientific research and its results.

Keywords: attestation, attestation commission, competition commission, public servant, public service, testing

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Authors: Kirsten B. Hillman

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There is a growing body of qualitative research in adult mental health and music therapy contexts which highlights user perspectives; however, only a very small sub-section of this literature pertains to people with lived experiences of psychological trauma. This paper will provide a meta-synthesis of this existing body of research, with the intention to present a cohesive overview of salient themes in this research and a platform for the under-represented voices of those with lived experience. This synthesis will be contextualised within a broader discussion of ‘Voice’ in trauma and music therapy research, considering its layered meanings: including literal expressive vocalising and musical expression, voicing after experiences of silencing, and the possibilities of experiencing self-determination and agency in therapy after trauma.

Keywords: lived experience, music therapy, trauma, user perspectives

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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: Maya Jaber

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In today's ever-changing world, organizational leaders will need to transform their organizations to meet the demands they face from employees, consumers, local and federal governments, and the global market. Change agents and leaders will need a new paradigm of thinking for creative problem solving and innovation in a time of uncertainty. A new framework that is developed from Design Science Research foundations with holistic design thinking methodologies (HTDM) and action research approaches has been developed through Dr. Jaber’s research. It combines these philosophies into a three-step process that can be utilized in practice for any sustainability, change, or project management applications. This framework was developed to assist in the pedagogy for the implementation of her holistic strategy formalized framework Integral Design Thinking (IDT). Her work focuses on real world application for the streamlining and adoption of initiatives into organizational culture transformation. This paper will discuss the foundations of this philosophy and the methods for utilization in practice developed in Dr. Jaber's research.

Keywords: design science research, action research, critical thinking, design thinking, organizational transformation, sustainability management, organizational culture change

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Authors: Virendra Nath, Vipin Kumar

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Background: TypeII Diabetes mellitus is a foremost health problem worldwide, predisposing to increased mortality and morbidity. Undesirable effects of the current medications have prompted the researcher to develop more potential drug(s) against the disease. The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptors family and take part in a vital role in the regulation of metabolic equilibrium. They can induce or repress genes associated with adipogenesis, lipid, and glucose metabolism. Aims: Investigation of PPARα/γ agonistic hits were screened by hierarchical virtual screening followed by molecular dynamics simulation and knowledge-based structure-activity relation (SAR) analysis using approved PPAR α/γ dual agonist. Methods: The PPARα/γ agonistic activity of compounds was searched by using Maestro through structure-based virtual screening and molecular dynamics (MD) simulation application. Virtual screening of nuclear-receptor ligands was done, and the binding modes with protein-ligand interactions of newer entity(s) were investigated. Further, binding energy prediction, Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit along with the structural comparative analysis of approved PPARα/γ agonists with screened hit was done for knowledge-based SAR. Results and Discussion: The silicone chip-based approach recognized the most capable nine hits and had better predictive binding energy as compared to the reference drug compound (Tesaglitazar). In this study, the key amino acid residues of binding pockets of both targets PPARα/γ were acknowledged as essential and were found to be associated in the key interactions with the most potential dual hit (ChemDiv-3269-0443). Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit and found root mean square deviation (RMSD) stabile around 2Å and 2.1Å, respectively. Frequency distribution data also revealed that the key residues of both proteins showed maximum contacts with a potent hit during the MD simulation of 20 nanoseconds (ns). The knowledge-based SAR studies of PPARα/γ agonists were studied using 2D structures of approved drugs like aleglitazar, tesaglitazar, etc. for successful designing and synthesis of compounds PPARγ agonistic candidates with anti-hyperlipidimic potential.

Keywords: computational, diabetes, PPAR, simulation

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Authors: Jamal Shokrzadehmadiyeh, Kambiz Kamkari, Shohreh Shokrzadeh

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According to the research topic, the purpose of the current paper is to research personality characteristics in adolescents under the care of the Tehran Juvenile Detention Centre, and a survey research method has been used. In this regard, through systematic random sampling, 120 people from the research population were selected as a sample, who were referred to Tehran Juvenile Detention Centre after the decision was reached by the court. Data collection was carried out by separate examination using NEO-PI-III personality inventory, and statistical analysis was done using a one-sample t-test. Finally, the results of the research revealed that the level of neuroticism is higher than the average level, the level of conscientiousness is lower than the average level, and the level of extraversion, agreeableness, and openness are at the average level.

Keywords: personality characteristics, adolescents, Juvenile Detention Center, Tehran city

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Authors: Nithipattara Balsiri

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The purposes of this research was to develop instructional model by using research-based learning enhancing critical thinking, cognitive skills, and culture and local wisdom knowledge of undergraduate students. The sample consisted of 307 undergraduate students. Critical thinking and cognitive skills test were employed for data collection. Second-order confirmatory factor analysis, t-test, and one-way analysis of variance were employed for data analysis using SPSS and LISREL programs. The major research results were as follows; 1) the instructional model by using research-based learning enhancing critical thinking, cognitive skills, and culture and local wisdom knowledge should be consists of 6 sequential steps, namely (1) the setting research problem (2) the setting research hypothesis (3) the data collection (4) the data analysis (5) the research result conclusion (6) the application for problem solving, and 2) after the treatment undergraduate students possessed a higher scores in critical thinking and cognitive skills than before treatment at the 0.05 level of significance.

Keywords: critical thinking, cognitive skills, culture and local wisdom knowledge

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Authors: Samuel Quashie

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PhDs in Construction Management often designs their methods based on those established in social sciences using theoretical models, to collect, gather and analysis data to answer research questions. Work aim is to apply qualitative and quantitative as a data analysis method, and as part of the theoretical framework - descriptive theory. To improve the ability to replicate the contribution to knowledge the research. Using practical triangulation approach, which covers, interviews and observations, literature review and (archival) document studies, project-based case studies, questionnaires surveys and review of integrated systems used in, construction and construction related industries. The clarification of organisational context and management delivery that influences organizational performance and quality of product and measures are achieved. Results illustrate improved reliability in this research approach when interpreting real world phenomena; cumulative results of research can be applied with confidence under similar environments. Assisted validity of the PhD research outcomes and strengthens the confidence to apply cumulative results of research under similar conditions in the Built Environment research systems, which have been criticised for the lack of reliability in approaches when interpreting real world phenomena.

Keywords: case studies, descriptive theory, theoretical framework, qualitative and quantitative research

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Authors: Sehrish Ather

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Introduction: To improve organizational achievements through the production of new knowledge, health policy and system research is the basic requirement. An aging population is always the source of the increased burden of chronic diseases, disabilities, mental illnesses, and other co-morbidities; therefore the provision of quality health care services to every group of the population should be achieved by making strong policy and system research for the betterment of health care system. Unfortunately, the whole world is lacking policies and system research for providing health care to their elderly population. Materials and Methods: A literature review of published studies on aging diseases was done, ranging from the year 2011-2018. Geriatric, population, health policy, system, and research were the key terms used for the search. Databases searched were Google Scholar, PubMed, Science Direct, Ovid, and Research Gate. Grey literature was searched from various websites, including IHME, Library of the University of Lahore, World Health Organization (Ageing and Life Course), and Personal communication with Neuro-physicians. After careful reviewing published and un-published information, it was decided to carry on with commentary. Results and discussion: Most of the published studies have highlighted the need to advocate the funders of health policy and stakeholders of healthcare system research, and it was detected as a major issue, research on policy and healthcare system to provide health care to 'geriatric population' was found as highly neglected area. Conclusion: It is concluded that physicians are more involved with the policy and system research regarding any type of diseases, but scientists and researchers of basic and social science are less likely to be involved in methods used for health policy and system research due to lack of funding and resources. Therefore ageing diseases should be considered as a priority, and comprehensive policy and system research should be initiated for diseases of the geriatric population.

Keywords: geriatric population, health care system, health policy, system research

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Authors: Maja Sajdak

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The aim of this paper is to present the concept of an agile enterprise model and to initiate discussion on the research assumptions of the model presented. The implementation of the research project "The agility of enterprises in the process of adapting to the environment and its changes" began in August 2014 and is planned to last three years. The article has the form of a work-in-progress paper which aims to verify and initiate a debate over the proposed research model. In the literature there are very few publications relating to research into agility; it can be concluded that the most controversial issue in this regard is the method of measuring agility. In previous studies the operationalization of agility was often fragmentary, focusing only on selected areas of agility, for example manufacturing, or analysing only selected sectors. As a result the measures created to date can only be treated as contributory to the development of precise measurement tools. This research project aims to fill a cognitive gap in the literature with regard to the conceptualization and operationalization of an agile company. Thus, the original contribution of the author of this project is the construction of a theoretical model that integrates manufacturing agility (consisting mainly in adaptation to the environment) and strategic agility (based on proactive measures). The author of this research project is primarily interested in the attributes of an agile enterprise which indicate that the company is able to rapidly adapt to changing circumstances and behave pro-actively.

Keywords: agile company, acuity, entrepreneurship, flexibility, research model, strategic leadership

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Authors: Akanksha Bhatnagar, Sandhya Kortegare, Felice Elefant

Abstract:

Context: Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by progressive cognitive decline and memory loss. The cause of AD is not fully understood, but it is thought to be caused by a combination of genetic, environmental, and lifestyle factors. One of the hallmarks of AD is the loss of neurons in the hippocampus, a brain region that is important for memory and learning. This loss of neurons is thought to be caused by a decrease in histone acetylation, which is a process that regulates gene expression. Research Aim: The research aim of the study was to develop mall molecule compounds that can enhance the activity of Tip60, a histone acetyltransferase that is important for memory and learning. Methodology/Analysis: The researchers used in silico structural modeling and a pharmacophore-based virtual screening approach to design and synthesize small molecule compounds strongly predicted to target and enhance Tip60’s HAT activity. The compounds were then tested in vitro and in vivo to assess their ability to enhance Tip60 activity and rescue cognitive deficits in AD models. Findings: The researchers found that several of the compounds were able to enhance Tip60 activity and rescue cognitive deficits in AD models. The compounds were also developed to cross the blood-brain barrier, which is an important factor for the development of potential AD therapeutics. Theoretical Importance: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Data Collection: The study collected data from a variety of sources, including in vitro assays and animal models. The in vitro assays assessed the ability of compounds to enhance Tip60 activity using histone acetyltransferase (HAT) enzyme assays and chromatin immunoprecipitation assays. Animal models were used to assess the ability of the compounds to rescue cognitive deficits in AD models using a variety of behavioral tests, including locomotor ability, sensory learning, and recognition tasks. The human clinical trials will be used to assess the safety and efficacy of the compounds in humans. Questions: The question addressed by this study was whether Tip60 HAT activators could be developed as therapeutic agents for AD. Conclusions: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Further research is needed to confirm the safety and efficacy of these compounds in humans.

Keywords: Alzheimer's disease, cognition, neuroepigenetics, drug discovery

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Authors: Sajeli A. Begum, Ameer Basha, Kirti Hira, Rukaiyya Khan

Abstract:

Cyclic dipeptides are simple diketopiperazine derivatives being investigated by several scientists for their biological effects which include anticancer, antimicrobial, haematological, anticonvulsant, immunomodulatory effect, etc. They are potentially active microbial metabolites having been synthesized too, for developing into drug candidates. Cultures of Pseudomonas species have earlier been reported to produce cyclic dipeptides, helping in quorum sensing signals and bacterial–host colonization phenomena during infections, causing cell anti-proliferation and immunosuppression. Fluorescing Pseudomonas species have been identified to secrete lipid derivatives, peptides, pyrroles, phenazines, indoles, aminoacids, pterines, pseudomonic acids and some antibiotics. In the present work, results of investigation on the cyclic dipeptide metabolites secreted by the culture broth of Pseudomonas species as potent pro-inflammatory cytokine inhibitors are discussed. The bacterial strain was isolated from the rhizospheric soil of groundnut crop and identified as Pseudomonas aeruginosa by 16S rDNA sequence (GenBank Accession No. KT625586). Culture broth of this strain was prepared by inoculating into King’s B broth and incubating at 30 ºC for 7 days. The ethyl acetate extract of culture broth was prepared and lyophilized to get a dry residue (EEPA). Lipopolysaccharide (LPS)-induced ELISA assay proved the inhibition of tumor necrosis factor-alpha (TNF-α) secretion in culture supernatant of RAW 264.7 cells by EEPA (IC50 38.8 μg/mL). The effect of oral administration of EEPA on plasma TNF-α level in rats was tested by ELISA kit. The LPS mediated plasma TNF-α level was reduced to 45% with 125 mg/kg dose of EEPA. Isolation of the chemical constituents of EEPA through column chromatography yielded ten cyclic dipeptides, which were characterized using nuclear magnetic resonance and mass spectroscopic techniques. These cyclic dipeptides are biosynthesized in microorganisms by multifunctional assembly of non-ribosomal peptide synthases and cyclic dipeptide synthase. Cyclo (Gly-L-Pro) was found to be more potentially (IC50 value 4.5 μg/mL) inhibiting TNF-α production followed by cyclo (trans-4-hydroxy-L-Pro-L-Phe) (IC50 value 14.2 μg/mL) and the effect was equal to that of standard immunosuppressant drug, prednisolone. Further, the effect was analyzed by determining mRNA expression of TNF-α in LPS-stimulated RAW 264.7 macrophages using quantitative real-time reverse transcription polymerase chain reaction. EEPA and isolated cyclic dipeptides demonstrated diminution of TNF-α mRNA expression levels in a dose-dependent manner under the tested conditions. Also, they were found to control the expression of other pro-inflammatory cytokines like IL-1β and IL-6, when tested through their mRNA expression levels in LPS-stimulated RAW 264.7 macrophages under LPS-stimulated conditions. In addition, significant inhibition effect was found on Nitric oxide production. Further all the compounds exhibited weak toxicity to LPS-induced RAW 264.7 cells. Thus the outcome of the study disclosed the effectiveness of EEPA and the isolated cyclic dipeptides in down-regulating key cytokines involved in pathophysiology of autoimmune diseases.In another study led by the investigators, microbial cyclic dipeptides were found to exhibit excellent antimicrobial effect against Fusarium moniliforme which is an important causative agent of Sorghum grain mold disease. Thus, cyclic dipeptides are emerging small molecular drug candidates for various autoimmune diseases.

Keywords: cyclic dipeptides, cytokines, Fusarium moniliforme, Pseudomonas, TNF-alpha

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Authors: Miroslava Rysová, Zdena Syrová, Tomáš Zajíc, Petr Exnar

Abstract:

Currently, attention of tissue engineers has been attracted to novel nanofibrous materials having advanced properties and ability to mimic extracellular matrix (ECM) by structure which makes them interesting candidates for application in regenerative medicine as scaffolding and/or drug delivering material. Throughout the last decade, more than 200 synthetic and natural polymers have been successfully electrospun leading to the formation of nanofibres with a wide range of chemical, mechanical and degradation properties. In this family, inorganic nanofibres represent very specific group offering an opportunity to manufacture inert to body, well degradable and in properties tunable material. Aim of this work, was to reveal unique properties of silica (SiO2, CAS 7631-86-9) nanofibres and their potential in field of regenerative medicine. Silica nanofibres were prepared by sol-gel method from tetraethyl orthosilicate (TEOS, CAS 78-10-4) as a precursor and subsequently manufactured by needleless electrospinning on NanospiderTM device. Silica nanofibres thermally stabilized under 200°C were confirmed to be fully biodegradable and soluble in several simulated body fluids. In vitro cytotoxicity tests of eluate (ES ISO 10993-5:1999) and in direct contact (ES ISO 10993-5:2009) showed no toxicity - e.g. cell viabilities reached values exceeding 80%. Those results were obtained equally from two different cell lines (Vero, 3T3). Non-toxicity of silaca nanofibres´ eluate was additionally confirmed in real time by testing on xCelligence (ACEA Biosciences, Inc.) device. Both cell types also showed good adhesion to material. To conclude, all mentioned results lead to resumption that silica nanofibres have a potential as material for regenerative medicine which opens door to further research.

Keywords: cytotoxicity, electrospinning, nanofibres, silica, tissue engineering

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Authors: A. Felimban, A. Prieto, U. Knaack, T. Klein

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This study aims to present an overview of recent research in building energy-retrofitting strategy applications and analyzing them within the context of hot arid climate regions which is in this case study represented by the Kingdom of Saudi Arabia. The main goal of this research is to do an analytical study of recent research approaches to show where the primary gap in knowledge exists and outline which possible strategies are available that can be applied in future research. Also, the paper focuses on energy retrofitting strategies at a building envelop level. The study is limited to specific measures within the hot arid climate region. Scientific articles were carefully chosen as they met the expression criteria, such as retrofitting, energy-retrofitting, hot-arid, energy efficiency, residential buildings, which helped narrow the research scope. Then the papers were explored through descriptive analysis and justified results within the Saudi context in order to draw an overview of future opportunities from the field of study for the last two decades. The conclusions of the analysis of the recent research confirmed that the field of study had a research shortage on investigating actual applications and testing of newly introduced energy efficiency applications, lack of energy cost feasibility studies and there was also a lack of public awareness. In terms of research methods, it was found that simulation software was a major instrument used in energy retrofitting application research. The main knowledge gaps that were identified included the need for certain research regarding actual application testing; energy retrofitting strategies application feasibility; the lack of research on the importance of how strategies apply first followed by the user acceptance of developed scenarios.

Keywords: energy efficiency, energy retrofitting, hot arid, Saudi Arabia

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Authors: Taissir Fekih Romdhane

Abstract:

This paper proposes a mobile web application named Pharmacy-Station that sells medicines and permits user to search for medications based on their symptoms, making it is easy to locate a specific drug online without the need to visit a pharmacy where it may be out of stock. This application is developed using the jQuery Mobile framework, which uses many web technologies and languages such as HTML5, PHP, JavaScript and CSS3. To test the proposed application, we used data from popular pharmacies in Saudi Arabia that included important information such as location, contact, and medicines in stock, etc. This document describes the different steps followed to create the Pharmacy-Station application along with screenshots. Finally, based on the results, the paper concludes with recommendations and further works planned to improve the Pharmacy-Station mobile application.

Keywords: pharmacy, mobile application, jquery mobile framework, search, medicine

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