Search results for: adverse drug events

Authors: Azar Baghtaghi

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Financial risk management is critically important as it enables companies to maintain stability and profitability amidst market fluctuations and unexpected events. It involves the precise identification of risks that could impact investments, assets, and potential revenues. By implementing effective risk management strategies, companies can insure themselves against adverse market changes and prevent potential losses. In today's era, where markets are highly complex and influenced by various factors such as macroeconomic policies, exchange rate fluctuations, and natural disasters, the need for meticulous planning to cope with these uncertainties is more pronounced. Ultimately, financial risk management means being prepared for the future and the ability to sustain business in changing environments. A company capable of managing its risks not only achieves sustainable profitability but also gains the confidence of shareholders, investors, and business partners, enhancing its competitive position in the market. In this article, the types of financial risk and risk management strategies for improving financial performance were investigated. By identifying the risks stated in this article and their evaluation techniques, it is possible to improve the organization's financial performance.

Keywords: strategy, risk, risk management, financial performance

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Authors: Murtada Ahmed Oshi, Jin-Wook Yoo

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Layer-by-layer (LBL) coating has gained popularity for drug delivery of therapeutic drugs. Herein we described a novel approach for enhancing the therapeutic efficiency of the locally administered dexamethasone (Dex) for inflammatory bowel disease (IBD). We utilized a LBL-coating technique on Dex microcrystals (DexMCs) with multiple layers of polyelectrolytes composed of poly (allylamine hydrochloride) (PAH), poly (sodium 4-styrene sulfonate) (PSS) and Eudragit® S100 (ES). The successful deposition of the layers onto DexMCs surfaces were confirmed through zeta potential measurement and confocal laser scanning microscopy. The surface morphology was investigated through scanning electron microscopy. The drug encapsulation efficiency was 95% with a mean particle size of 2 µm and negative surface charge (-40 mV). Moreover, in vitro drug release study showed a minimum release of the drug ( 15%) at an acidic condition during initial first 5 h, followed by sustained-release at an alkaline condition. For in vivo study, LBL-DxMCs were administered orally to ICR mice suffering from dextran sulfate sodium-induced colitis. LBL-DxMCs substantially enhanced anti-IBD activities as compared to DxMCs. Macroscopic, histological and biochemical (tumor necrosis factor-α, interleukin-6 and myeloperoxidase) examinations revealed marked improvements of colitis signs in the mice treated with LBL-DxMCs compared with those treated with DxMCs. Overall, LBL-DxMCs could be a suitable candidate for the treatment of IBD.

Keywords: dexamethasone, inflammatory bowel disease, LBL-coating, polyelectrolytes

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Authors: Vaishali Patil, Neeraj Masand

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In older people, Alzheimer’s disease (AD) is turning out to be a lethal disease. According to the amyloid hypothesis, aggregation of the amyloid β–protein (Aβ), particularly its 42-residue variant (Aβ42), plays direct role in the pathogenesis of AD. Aβ is generated through sequential cleavage of amyloid precursor protein (APP) by β–secretase (BACE) and γ–secretase (GS). Thus in the treatment of AD, γ-secretase modulators (GSMs) are potential disease-modifying as they selectively lower pathogenic Aβ42 levels by shifting the enzyme cleavage sites without inhibiting γ–secretase activity. This possibly avoids known adverse effects observed with complete inhibition of the enzyme complex. Virtual screening, via drug-like ADMET filter, QSAR and molecular docking analyses, has been utilized to identify novel γ–secretase modulators with sulphonamide nucleus. Based on QSAR analyses and docking score, some novel analogs have been synthesized. The results obtained by in silico studies have been validated by performing in vivo analysis. In the first step, behavioral assessment has been carried out using Scopolamine induced amnesia methodology. Later the same series has been evaluated for neuroprotective potential against the oxidative stress induced by Scopolamine. Biochemical estimation was performed to evaluate the changes in biochemical markers of Alzheimer’s disease such as lipid peroxidation (LPO), Glutathione reductase (GSH), and Catalase. The Scopolamine induced amnesia model has shown increased Acetylcholinesterase (AChE) levels and the inhibitory effect of test compounds in the brain AChE levels have been evaluated. In all the studies Donapezil (Dose: 50µg/kg) has been used as reference drug. The reduced AChE activity is shown by compounds 3f, 3c, and 3e. In the later stage, the most potent compounds have been evaluated for Aβ42 inhibitory profile. It can be hypothesized that this series of alkyl-aryl sulphonamides exhibit anti-AD activity by inhibition of Acetylcholinesterase (AChE) enzyme as well as inhibition of plaque formation on prolong dosage along with neuroprotection from oxidative stress.

Keywords: gamma-secretase inhibitors, Alzzheimer's disease, sulphonamides, QSAR

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Authors: Ankur Mundhra, Shubhadeep Chakraborty, Y. R. Singh, Vishal Das

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Seismic data scaling affects the dynamic range of a data and with present day lower costs of storage and higher reliability of Hard Disk data, scaling is not suggested. However, in dealing with data of different vintages, which perhaps were processed in 16 bits or even 8 bits and are need to be processed with 32 bit available data, scaling is performed. Also, scaling amplifies low amplitude events in deeper region which disappear due to high amplitude shallow events that saturate amplitude scale. We have focused on significance of scaling data to aid interpretation. This study elucidates a proper seismic loading procedure in workstations without using default preset parameters as available in most software suites. Differences and distribution of amplitude values at different depth for seismic data are probed in this exercise. Proper loading parameters are identified and associated steps are explained that needs to be taken care of while loading data. Finally, the exercise interprets the un-certainties which might arise when correlating scaled and unscaled versions of seismic data with synthetics. As, seismic well tie correlates the seismic reflection events with well markers, for our study it is used to identify regions which are enhanced and/or affected by scaling parameter(s).

Keywords: clipping, compression, resolution, seismic scaling

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Authors: Meltem Haktaniyan, Eda Cagli, Irem Erel Goktepe

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Polymers that change their properties in response to different stimuli (e.g. light, temperature, pH, ionic strength or magnetic field) are called ‘smart’ or ‘stimuli-responsive polymers’. These polymers have been widely used in biomedical applications such as sensors, gene delivery, drug delivery or tissue engineering. Temperature-responsive polymers have been studied extensively for controlled drug delivery applications. As regard of pseudo-peptides, poly (2-alky-2-oxazoline)s are considered as good candidates for delivery systems due to their stealth behavior and nontoxicity. In order to build responsive multilayer films for controlled drug release applications from surface, Layer by layer technique (LBL) is a powerful technique with an advantage of nanometer scale control over spatial architecture and morphology. Multilayers can be constructed on surface where non-covalent interactions including electrostatic interactions, hydrogen bonding, and charge-transfer or hydrophobic-hydrophobic interactions. In the present study, hydrogen bounded multilayer films of poly (2-alky-2-oxazoline) s with tannic acid were prepared in order to use as a platform to release Doxorubicin (DOX) from surface with pH and thermal triggers. For this purpose, poly (2-isopropyl-2-oxazoline) (PIPOX) and poly (2-ethyl-2-oxazoline) (PETOX) were synthesized via cationic ring opening polymerization (CROP) with hydroxyl end groups. Two polymeric multilayer systems ((PETOX)/(DOX)-(TA) complexes and (PIPOX)/(DOX)-(TA) complexes) were designed to investigate of controlled release of Doxorubicin (DOX) from surface with pH and thermal triggers. The drug release profiles from the multilayer thin films with alterations of pH and temperature will been examined with UV-Vis Spectroscopy and Fluorescence Spectroscopy.

Keywords: temperature responsive polymers, h-bonded multilayer films, drug release, polyoxazoline

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Authors: Taieb Kherafa Noureddine

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The paper presents a new approach regarding the management in sports that is based on the principles of reengineering. Applying that modern and pure management system, called reengineering, in sports activity, we hope to get better and better results, in order to increase both the health state and the performances of trained athletes. The paper also presents the similarities between BPR (Business Process Reengineering) and sports managements, as well as the proposed solution for a proper implementation of such model of management. The five components of the basic BPR model are presented, together with their features for sports management.

Keywords: business process reengineering, great sports events, sports management, training activities

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Authors: Sulalit Bandyopadhyay, Muhammad Awais Ashfaq Alvi, Anuvansh Sharma, Wilhelm R. Glomm

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Release of drugs from nanogels and nanogel-based systems can occur under the influence of external stimuli like temperature, pH, magnetic fields and so on. pNIPAm-AAc nanogels respond to the combined action of both temperature and pH, the former being mostly determined by hydrophilic-to-hydrophobic transitions above the volume phase transition temperature (VPTT), while the latter is controlled by the degree of protonation of the carboxylic acid groups. These nanogels based systems are promising candidates in the field of drug delivery. Combining nanogels with magneto-plasmonic nanoparticles (NPs) introduce imaging and targeting modalities along with stimuli-response in one hybrid system, thereby incorporating multifunctionality. Fe@Au core-shell NPs possess optical signature in the visible spectrum owing to localized surface plasmon resonance (LSPR) of the Au shell, and superparamagnetic properties stemming from the Fe core. Although there exist several synthesis methods to control the size and physico-chemical properties of pNIPAm-AAc nanogels, yet, there is no comprehensive study that highlights the dependence of incorporation of one or more layers of NPs to these nanogels. In addition, effective determination of volume phase transition temperature (VPTT) of the nanogels is a challenge which complicates their uses in biological applications. Here, we have modified the swelling-collapse properties of pNIPAm-AAc nanogels, by combining with Fe@Au NPs using different solution based methods. The hydrophilic-hydrophobic transition of the nanogels above the VPTT has been confirmed to be reversible. Further, an analytical method has been developed to deduce the average VPTT which is found to be 37.3°C for the nanogels and 39.3°C for nanogel coated Fe@Au NPs. An opposite swelling –collapse behaviour is observed for the latter where the Fe@Au NPs act as bridge molecules pulling together the gelling units. Thereafter, Cyt C, a model protein drug and L-Dopa, a drug used in the clinical treatment of Parkinson’s disease were loaded separately into the nanogels and nanogel coated Fe@Au NPs, using a modified breathing-in mechanism. This gave high loading and encapsulation efficiencies (L Dopa: ~9% and 70µg/mg of nanogels, Cyt C: ~30% and 10µg/mg of nanogels respectively for both the drugs. The release kinetics of L-Dopa, monitored using UV-vis spectrophotometry was observed to be rather slow (over several hours) with highest release happening under a combination of high temperature (above VPTT) and acidic conditions. However, the release of L-Dopa from nanogel coated Fe@Au NPs was the fastest, accounting for release of almost 87% of the initially loaded drug in ~30 hours. The chemical structure of the drug, drug incorporation method, location of the drug and presence of Fe@Au NPs largely alter the drug release mechanism and the kinetics of these nanogels and Fe@Au NPs coated with nanogels.

Keywords: controlled release, nanogels, volume phase transition temperature, l-dopa

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Authors: Jose Ramon Sanabria Navarro, Yahilina Silveira Perez

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The Pan American Games are one of the best regional sports integration events for the Americas, thousands of athletes from different countries are integrated based on obtaining satisfactory sports results and bringing the glory of the national identity of the sport to their country. There are countries that despite the small number of inhabitants have obtained very satisfactory results such as Cuba. Objective: To analyze the impact of Cuba's sports results in the Pan American Games. The methodology was based on the postulates of the materialist dialectic since the investigated reality was studied from historicity, systematicity and in its systemic character. The population and sample consisted of 41 countries of the American continent, and the 15 events carried out to date were analyzed. The impact of Cuba is very relevant because it is the country that has the second place by country in terms of number of medals, is among the first in terms of medals per inhabitants and in general sense of all the indicators treated assumes the fourth place integral. What is the current status of Cuba's sports results in Pan American Games? Having as a general objective, analyze the impact of Cuba's sports results in the Pan American Games. The hypotheses that will lead this research have the following methodological and interaction order: H1: Cuba's performance in Pan American Sports Games positively impacts the amount of medals obtained. H2: The amount of medals from Cuba in Pan American Sports Games positively impacts the general podium for countries of these regional events. H3: The amount of medals obtained by Cuba in Pan American Sports Games positively impacts the number of inhabitants. H4: The amount of medals obtained by Cuba positively impacts the overall result of the countries. H5: Cuba's performance in the Panamerican Sports Games positively impacts the overall results of these regional events. In general, it is possible to demonstrate the impact of Cuba's sports performance in Pan American Games and the organizational sports structure that has allowed the country to obtain them is evidenced.

Keywords: Cuba, history of sport, sports games, regional events, sport

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Authors: Kasun U. G. Palihakkara

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Although vaccine coverage in Sri Lanka is close to 100%, with the widely spreading vaccine rejection trend reaching South Asian regions, it is essential to catch on whether Sri Lankans are being misinformed from the common misconceptions regarding vaccines. As the rates of target diseases decrease, parents become less accepting of even minor common adverse events. It is essential to preserve the integrity of immunization programs and protect public health by finding out the prevalence of anti-immunization trends. The primary objective of this study was to assess the immunization practices and prevalence of trends related to anti-immunization among urban community in Sri Lanka. A descriptive cross-sectional quantitative study on 323 participants using convenient sampling with 213 self-administered questionnaires. Additionally, 110 online questionnaires were distributed. 31% of the study population does not maintain immunization records for their children. While majority seek information regarding immunization from reliable sources such as the family physician or specialist pediatricians, 30% also refer to unreliable sources such as online communities for their opinion. 31% of study population had not vaccinated for Japanese encephalitis. 73% of the study population had encountered with side effects of vaccination such as fever & 47% believed that such side effects are rare. 52% of the population had hostile attitude regarding the administration of several doses multiple vaccines within a child’s first year. Diseases like polio had been successfully eradicated from Sri Lanka with the help of vigorous vaccination programs. However, majority of the study population believe that there’s no need to keep vaccinating the children for those eradicated diseases and exposing the child for adverse effects of such vaccines. Majority of the population were aware of the existing misconceptions regarding immunization. The most popular misconceptions about vaccines popular among the study population were the MMR (Measles, Mumps, and Rubella) vaccine being a possible cause leading to autism and bowel disease and children getting infected with the disease even after they get vaccinated, may be due to the inactivated vaccine. Disturbingly 22% of the study population believed that vaccines are useless in preventing diseases nowadays. These data obtained from the urban study population reveals that even though statistically Sri Lankan immunization coverage is 100%, there is a possibility of anti-vaccination trend arising in Sri Lanka due to the prevalence of various misconceptions and rumors related to it. Therefore these data recommend the need for thorough awareness among the mothers.

Keywords: anti-vaccination, immunization, infectious diseases, pediatric health

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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For chemotherapy, a drug delivery system should be able to specifically target cancer cells and deliver the therapeutic dose without affecting normal cells. Folate receptors (FR) can be considered key targets since they are commonly over-expressed in cancer cells and they are the molecular marker used in this study. Here, cyclodextrin (CD) has being studied as a vehicle for delivering the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within the CD cavity. In this study, β-CD has been modified using folic acid so as to specifically target the FR molecular marker. Thus, the system studied here for drug delivery consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 9.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 10.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 8.5 for A549 and 132.6 µM ± 12.1 and 288.1 µM ± 16.3 for BEAS-2B. These results demonstrate that MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug.

Keywords: cyclodextrins, cancer treatment, drug delivery, folate receptors, reduced folate carriers

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Authors: Sophio Kobauri, Tengiz Kantaria, Temur Kantaria, David Tugushi, Nina Kulikova, Ramaz Katsarava

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Polymeric disperse systems such as nanoparticles (NPs) are of high interest for numerous applications in contemporary medicine and nanobiotechnology to a considerable potential for treatment of many human diseases. The important technological advantages of NPs usage as drug carriers (nanocontainers) are their high stability, high carrier capacity, feasibility of encapsulation of both hydrophilic or hydrophobic substances, as well as a high variety of possible administration routes, including oral application and inhalation. NPs can also be designed to allow controlled (sustained) drug release from the matrix. These properties of NPs enable improvement of drug bioavailability and might allow drug dosage decrease. The targeted and controlled administration of drugs using NPs might also help to overcome drug resistance, which is one of the major obstacles in the control of epidemics. Various degradable and non-degradable polymers of both natural and synthetic origin have been used for NPs construction. One of the most promising for the design of NPs are amino acid-based biodegradable polymers (AABBPs) which can clear from the body after the fulfillment of their function. The AABBPs are composed of naturally occurring and non-toxic building blocks such as α-amino acids, fatty diols and dicarboxylic acids. The particles designed from these polymers are expected to have an improved bioavailability along with a high biocompatibility. The present work deals with a systematic study of the preparation of NPs by cost-effective polymer deposition/solvent displacement method using AABBPs. The influence of the nature and concentration of surfactants, concentration of organic phase (polymer solution), and the ratio organic phase/inorganic(water) phase, as well as of some other factors on the size of the fabricated NPs have been studied. It was established that depending on the used conditions the NPs size could be tuned within 40-330 nm. At the next step of this research was carried out an evaluation of biocompability and bioavailability of the synthesized NPs using a stable human cell culture line – A549. It was established that the obtained NPs are not only biocompatible but they stimulate the cell growth.

Keywords: amino acids, biodegradable polymers, bioavailability, nanoparticles

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Authors: Jong Yeop Kim, Sung Young Park, Dae Hee Kim, Han Bum Joe, Ji Young Yoo, Jong Bum Choi, Sook Young Lee

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Emergence agitation (EA) is commonly reported adverse events after sevoflurane anesthesia in pediatric patients. The efficacy of prophylactic remifentanil, one of mu opioid agonist, in preventing EA is controversial. This meta-analysis assessed the effectiveness of remifentanil to decrease the incidence of EA from sevoflurane anesthesia in children. We searched for randomized controlled trials comparing sevoflurane alone anesthesia with sevoflurane and remifentanil anesthesia to prevent EA in the Cochrane Library, Embase, Pubmed, and KoreaMed, and included 6 studies with 361 patients. The number of patients of reporting EA was summarized using risk ratio (RR) with 95% confidence interval (CI), with point estimates and 95CIs derived from a random effects Mantel-Haenszel method. Overall incidence of EA was about 41%. Compared with sevoflurane alone anesthesia, intravenous infusion of remifentanil with sevoflurane significantly reduced the incidence of EA (RR 0.53, 95% CI 0.39-0.73, P < 0.0001), (heterogeneity, I2 = 0, P = 0.42). This meta-analysis suggested that continuous infusion of remifentanil could be effective in decreasing the EA of about 47% after sevoflurane anesthesia. However, considering limitations of the included studies, more randomized controlled studies are required to verify our results.

Keywords: emergence agitation, meta-analysis, remifentanil, pediatrics

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Authors: Bo Liu, Qingshan Kong, Weiqing Huang

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With the rapid development of modern communication, diagnosing the fiber-optic quality and faults in real-time is widely focused. In this paper, a Labview-based system is proposed for fiber-optic faults detection. The wavelet threshold denoising method combined with Empirical Mode Decomposition (EMD) is applied to denoise the optical time domain reflectometer (OTDR) signal. Then the method based on Gabor representation is used to detect events. Experimental measurements show that signal to noise ratio (SNR) of the OTDR signal is improved by 1.34dB on average, compared with using the wavelet threshold denosing method. The proposed system has a high score in event detection capability and accuracy. The maximum detectable fiber length of the proposed Labview-based system can be 65km.

Keywords: empirical mode decomposition, events detection, Gabor transform, optical time domain reflectometer, wavelet threshold denoising

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Authors: Rizwan Alam, Ikhtiar Khan, Aqib Iqbal

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Plants are naturally exposed to a wide variety of environmental stresses. The stresses may be biotic or/and abiotic. These environmental stresses have adverse effects on photosynthesis, water relation and nutrients uptake of plants. Fertilization of plants with exogenous minerals can enhance the drought tolerance in plants. In this experiment, canola (Brassica napus) was treated with solutions of calcium nitrate in different concentrations before the imposition of drought stress for 10 days. It was observed that drought stress decreased the tissue-K, Ca and K/Ca ratio of canola seedlings. The tissue-carbon and nitrogen contents were also depressed by the drought stress. Application of calcium nitrate, however, could alleviate the adverse effects of drought stress by showing a positive effect on all the aforementioned parameters.

Keywords: Brassica napus, calcium, carbon, potassium

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Authors: Christi Jackson, Chuka Onaga

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Introduction: We report a case of delayed diagnosis of extra-pulmonary INH-mono-resistant Tuberculosis (TB) in a South African patient with drug-resistant HIV. Case Presentation: A 36-year old male was initiated on 1st line (NNRTI-based) anti-retroviral therapy (ART) in September 2009 and switched to 2nd line (PI-based) ART in 2011, according to local guidelines. He was following up at the outpatient wellness unit of a public hospital, where he was diagnosed with Protease Inhibitor resistant HIV in March 2016. He had an HIV viral load (HIVVL) of 737000 copies/mL, CD4-count of 10 cells/µL and presented with complaints of productive cough, weight loss, chronic diarrhoea and a septic buttock wound. Several investigations were done on sputum, stool and pus samples but all were negative for TB. The patient was treated with antibiotics and the cough and the buttock wound improved. He was subsequently started on a 3rd-line ART regimen of Darunavir, Ritonavir, Etravirine, Raltegravir, Tenofovir and Emtricitabine in May 2016. He continued losing weight, became too weak to stand unsupported and started complaining of abdominal pain. Further investigations were done in September 2016, including a urine specimen for Line Probe Assay (LPA), which showed M. tuberculosis sensitive to Rifampicin but resistant to INH. A lymph node biopsy also showed histological confirmation of TB. Management and outcome: He was started on Rifabutin, Pyrazinamide and Ethambutol in September 2016, and Etravirine was discontinued. After 6 months on ART and 2 months on TB treatment, his HIVVL had dropped to 286 copies/mL, CD4 improved to 179 cells/µL and he showed clinical improvement. Pharmacy supply of his individualised drugs was unreliable and presented some challenges to continuity of treatment. He successfully completed his treatment in June 2017 while still maintaining virological suppression. Discussion: Several laboratory-related factors delayed the diagnosis of TB, including the unavailability of urine-lipoarabinomannan (LAM) and urine-GeneXpert (GXP) tests at this facility. Once the diagnosis was made, it presented a treatment dilemma due to the expected drug-drug interactions between his 3rd-line ART regimen and his INH-resistant TB regimen, and specialist input was required. Conclusion: TB is more difficult to diagnose in patients with severe immunosuppression, therefore additional tests like urine-LAM and urine-GXP can be helpful in expediting the diagnosis in these cases. Patients with non-standard drug regimens should always be discussed with a specialist in order to avoid potentially harmful drug-drug interactions.

Keywords: drug-resistance, HIV, line probe assay, tuberculosis

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Authors: Malay K. Das, Bhanu P. Sahu

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Furosemide is a weakly acidic diuretic indicated for treatment of edema and hypertension. It has very poor solubility but high permeability through stomach and upper gastrointestinal tract (GIT). Due to its limited solubility it has poor and variable oral bioavailability of 10-90%. The aim of this study was to enhance the oral bioavailability of furosemide by preparation of nanosuspensions. The nanosuspensions were prepared by nanoprecipitation with sonication using DMSO (dimethyl sulfoxide) as a solvent and water as an antisolvent (NA). The prepared nanosuspensions were sterically stabilized with polyvinyl acetate (PVA).These were characterized for particle size, ζ potential, polydispersity index, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) pattern and release behavior. The effect of nanoprecipitation on oral bioavailability of furosemide nanosuspension was studied by in vitro dissolution and in vivo absorption study in rats and compared to pure drug. The stable nanosuspension was obtained with average size range of the precipitated nanoparticles between 150-300 nm and was found to be homogenous showing a narrow polydispersity index of 0.3±0.1. DSC and XRD studies indicated that the crystalline furosemide drug was converted to amorphous form upon precipitation into nanoparticles. The release profiles of nanosuspension formulation showed up to 81.2% release in 4 h. The in vivo studies on rats revealed a significant increase in the oral absorption of furosemide in the nanosuspension compared to pure drug. The AUC0→24 and Cmax values of nanosuspension were approximately 1.38 and 1.68-fold greater than that of pure drug, respectively. Furosemide nanosuspension showed 20.06±0.02 % decrease in systolic blood pressure compared to 13.37±0.02 % in plain furosemide suspension, respectively. The improved oral bioavailability and pharmacodynamics effect of furosemide may be due to the improved dissolution of furosemide in simulated gastric fluid which results in enhanced oral systemic absorption of furosemide from stomach region where it has better permeability.

Keywords: furosemide, nanosuspension, bioavailability enhancement, nanoprecipitation, oral drug delivery

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Authors: Ada Yurman

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Social reactions to deviant groups with political goals follow two central patterns; one that associates personal characteristics with deviant behavior, and the other that claims that society is to be blamed for deviant behavior. The establishment usually tends towards the former notion and thus disclaims any responsibility for the distress of the underprivileged, while it is usually those who oppose government policies who believe that the fault lies with society. The purpose of the present research was to examine social reactions to the Wadi Salib riots that occurred in Haifa in 1959. These riots represented the first ethnic protest within Israeli society with its ideology of the ingathering of the exiles. The central question was whether this ideology contributed to the development of a different reaction when compared to reactions to similar events abroad. This question was examined by means of analyzing articles in the Israeli press of that period. The Israeli press representing the views of the establishment was at pains to point out that the rioters were criminals, their object being to obstruct the development of society. Opposition party leaders claimed that the rioters lived in poor circumstances, which constituted a direct result of government policies. An analysis of press reports on the Wadi Salib riots indicates a correspondence between the reaction to these events and similar events abroad. Nevertheless, the reaction to the Wadi Salib riots did not only express a conflict between different political camps, but also different symbolic universes. Each group exploited the events at Wadi Salib to prove that their ideology was the legitimate one.

Keywords: riots, media, political deviance, symbolic universe

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Authors: Maninderjeet K. Grewal, Sakshi Bhatnor, Renu Chadha

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The composition of pharmaceutical entities and the molecular interactions can be altered to optimize drug properties such as solubility and bioavailability by the crystal engineering technique. The present work has emphasized on the preparation, characterization, and biopharmaceutical evaluation of co-crystal of BCS Class II anti-osteoarthritis drug, Oxaprozin (OXA) with aspartic acid (ASPA) as co-former. The co-crystals were prepared through the mechanochemical solvent drop grinding method. Characterization of the prepared co-crystal (OXA-ASPA) was done by using analytical tools such as differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD). DSC thermogram of OXA-ASPA cocrystal showed a single sharp melting endotherm at 235 ºC, which was between the melting peaks of the drug and the counter molecules suggesting the formation of a new phase which is a co-crystal that was further confirmed by using other analytical techniques. FT-IR analysis of OXA-ASPA cocrystal showed a shift in a hydroxyl, carbonyl, and amine peaks as compared to pure drugs indicating all these functional groups are participating in cocrystal formation. The appearance of new peaks in the PXRD pattern of cocrystals in comparison to individual components showed that a new crystalline entity has been formed. The Crystal structure of cocrystal was determined using material studio software (Biovia) from PXRD. The equilibrium solubility study of OXA-ASPA showed improvement in solubility as compared to pure drug. Therefore, it was envisioned to prepare the co-crystal of oxaprozin with a suitable conformer to modulate its physiochemical properties and consequently, the biopharmaceutical parameters.

Keywords: cocrystals, coformer, oxaprozin, solubility

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Authors: Nasrin Hosseinzad, Ramin Ghasemi Shayan

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Chemotherapy is the most common procedure in the treatment of advanced cancers but is justsoberlyoperativeand toxic. Nevertheless, the efficiency of chemotherapy is restrictedowing to multiple drug resistance(MDR). Lately, plentiful preclinical experiments have revealedthatPaclitaxel-Curcumin could be an ultimateapproach to converse MDR and synergistically increase their efficiency. The connotationsamongst B-cell-lymphoma2(BCL-2) and multi-drug-resistance-associated-P-glycoprotein(MDR1) consequence of patients forecast the efficiency of paclitaxel-built chemoradiotherapy. There are evidences of the efficacy of paclitaxel in the treatment of surface-transmission of bladder-cell-carcinoma by manipulating bio-adhesive microspheres accomplishedthroughout measured release of drug at urine epithelium. In Genetically-Modified method, muco-adhesive oily constructionoftricaprylin, Tween 80, and paclitaxel group showed slighter toxicity than control in therapeutic dose. Postoperative chemotherapy-Paclitaxel might be more advantageous for survival than adjuvant chemo-radio-therapy, and coulddiminish postoperative complications in cervical cancer patients underwent a radical hysterectomy.HA-Se-PTX(Hyaluronic acid, Selenium, Paclitaxel) nanoparticles could observablyconstrain the proliferation, transmission, and invasion of metastatic cells and apoptosis. Furthermore, they exhibitedvast in vivo anti-tumor effect. Additionally, HA-Se-PTX displayedminor toxicity on mice-chef-organs. Briefly, HA-Se-PTX mightprogress into a respectednano-scale agentinrespiratory cancers. To sum up, Paclitaxel is considered a profitable anti-cancer drug in the treatment and anti-progress symptoms in malignant cancers.

Keywords: cancer, paclitaxel, chemotherapy, tumor

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Authors: Eda Cagli, Irem Erel Goktepe

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Externally triggered and effective release of therapeutics from polymer nanoplatforms is one of the key issues in cancer treatment. In this study, we aim to prepare polymer multilayer films which are stable at physiological conditions (little or no drug release) but release drug molecules at acidic pH and via application of AC magnetic field. First, novel stimuli responsive diblock copolymers composed of pH- and temperature-responsive blocks were synthesized. Then, block copolymer micelles with pH-responsive core and temperature responsive coronae will be obtained via pH-induced self-assembly of these block copolymers in aqueous environment. A model anticancer drug, e.g. Doxorubicin will be loaded in the micellar cores. Second, superparamagnetic nanoparticles will be synthesized. Magnetic nanoparticles and drug loaded block copolymer micelles will be used as building blocks to construct the multilayers. To mimic the acidic nature of the tumor tissues, Doxorubicin release from the micellar cores will be induced at acidic conditions. Moreover, Doxorubicin release from the multilayers will be facilitated via magnetothermal trigger. Application of AC magnetic field will induce the heating of magnetic nanoparticles resulting in an increase in the temperature of the polymer platform. This increase in temperature is expected to trigger conformational changes on the temperature-responsive micelle coronae and facilitate the release of Doxorubicin from the surface. Such polymer platform may find use in biomedical applications.

Keywords: layer-by-layer films, magnetothermal trigger, smart polymers, stimuli responsive

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Authors: Jinee Gogoi, Som K. Sharma, Kalyan Bhuyan

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The atmospheric layers are coupled to each other with the different dynamical, electrical, radiative and chemical processes. A large scale thermodynamical phenomenon in winter polar regions which affects the middle atmosphere vigorously is Sudden Stratospheric Warming (SSW). Two major SSW events were occurred during 1998-1999; one in December 1998 which is associated with vortex displacement and another in February- March 1999 associated with vortex splitting. Lidar study of these two major events from Mt. Abu (24.36⁰N, 72.45⁰E, ~1670 m amsl) has shown that though SSWs are mostly observed over high and mid latitudes, their effects can also be seen over India. We have studied ionospheric variations (primarily fₒF₂, h’F and hpF₂) over Ahmedabad (23.1⁰N, 72.58⁰E) during these events. Ionospheric disturbances have been found after four-five days of peak temperature. An increase (decrease) in critical frequency (fₒF₂) during morning (afternoon) has been noticed which may be in response to the updrift (down drift). Effects are stronger during displacement event (1998) than during the splitting event (1999). We have also studied some recent events occurred during 2006 (January), 2009 (January) and 2013 (January) using temperature data from Sounding of Atmosphere using Broadband Emission Radiometry (SABER) satellite. Though some modeling work supports the hypothesis that planetary waves are responsible for atmosphere-ionosphere coupling, there is still more significant works to do to understand how exactly the coupling can take place.

Keywords: sudden stratospheric warming (SSW), polar vortex, ionosphere, critical frequency

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Authors: Kok Meng Ng, Sulung Veronica

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Electronic Dance Music (EDM), a musical event that so sought-after amongst the youth, is getting prevailed around the world. The emergence of this à la mode event has magnetized lots of attentions from the media as well as the public due to its high probabilities in creating social problems and menacing social harmony of one destination, for instance, two death cases occurred during the EDM events in Malaysia caused a feeling of consternation of the society. The arguments over the impacts of such events towards the society are endless. This paper focuses on the study of the impacts of EDM towards social harmony in Klang Valley area, Malaysia by scrutinizing the contradiction of statements from several experts and the local communities. This study sampled 15-20 people that represent different social background with face-to-face and online interview through snowball sampling method. This study helps to understand the social context as a whole based on the impacts of EDM events that take place in Malaysia. It also provides valuable information to EDMs’ organizer as well as local authorities for a proper event management to minimize EDM impacts towards society as part of the sustainable growth of the event industry.

Keywords: electronic dance music, social harmony, impacts, Klang Valley

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Authors: Md. Rashed Aalm, Md. Nuruzzaman Khan, Yothin Sawangdee

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Background: Around 47% of the total pregnancies are unintended in Bangladesh, which lead to several adverse consequences, including maternal and child mortality. Use of menstrual regulation (MR) can help women to reduce unintended pregnancy related adverse consequences. We explored the prevalence and determinants of MR services among ever-married women in Bangladesh. Methods: Total of 14,346 ever-married women data were analysed from the 2017 Bangladesh Demographic and Health Survey. Our study variable was use or non-use of MR services. Individual, household, and community level factors were the explanatory factors. Multilevel mixed-effect Poisson regression model was used to determine the factors associated with MR services in Bangladesh. Results: Nearly 7% of the total women in Bangladesh use MR services. Use of MR services was found higher among women who were aged 20-30 ages (IRR 1.60, 95% CI: 1.17–2.17), who were overweight (IRR 1.43, 95% CI: 1.13–1.81), had at least 1 child (IRR 2.97, 95% CI: 2.34– 3.77) or > 2 children (IRR 3.22, 95% CI: 2.45–4.20), and the birth preceding birth interval was(2 – 4) years (IRR 1.56, 95% CI: 1.13–2.15). Around 1.39 times (95% CI: 1.11–1.73) higher likelihood of MR was found among women whose husbands were engage with business. At the community level, MR service was found lower among the women who resided in the community with higherilliteracy (IRR 0.67, 95% CI: 0.42–0.96) and the Mymensingh division (IRR 0.39, 95% CI: 0.31–0.91). Conclusion: Use of MR service is comparatively low, which indicate a significant proportion of unintended pregnancy continued toward life-birth. This could be responsible for higher adverse maternal and child health outcomes in Bangladesh. Initiatives should be taken to ensure MR services is available when women need this service.

Keywords: menstrual regulation, pattern, risk, maternal health, Bangladesh

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Authors: Rebecca A. Deek

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There is evidence that erratic and extreme weather is becoming a common occurrence, and even predictions that this will become even more frequent and more severe. It also appears that the severity of earthquakes is intensifying. Some observers believe that human conduct has given reasons for such change; others attribute this to environmental and geological cycles. However, as some physicists, environmental scientists, politicians, and others continue to debate the connection between weather events, seismic activities, and climate change, other scientists, engineers, and urban planners are exploring how can our habitat become more responsive and resilient to such phenomena. There are a number of recent instances of nature’s destructive events that provide basis for the development of defensive measures.

Keywords: biomimicry, natural disasters, protection of human lives, resilient infrastructures

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Authors: Shawn G. Gallaher, Lilli E. Hirth

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As permafrost thaws with the continued warming of the Alaskan North Slope, a progressively thicker active thaw layer is evidently releasing previously sequestered nutrients, metals, and particulate matter exposed to fluvial transport. In this study, we estimate material fluxes on the North Slope of Alaska during the 2019-2022 melt seasons. The watershed of the Alaskan North Slope can be categorized into three regions: mountains, tundra, and coastal plain. Precipitation and discharge data were collected from repeat visits to 14 sample sites for biogeochemical surface water samples, 7 point discharge measurements, 3 project deployed meteorology stations, and 2 U. S. Geological Survey (USGS) continuous discharge observation sites. The timing, intensity, and spatial distribution of precipitation determine the material flux composition in the Sagavanirktok and surrounding bodies of water, with geogenic constituents (e.g., dissolved inorganic carbon (DIC)) expected from mountain flushed events and biogenic constituents (e.g., dissolved organic compound (DOC)) expected from transitional tundra precipitation events. Project goals include connecting late summer precipitation events to peak discharge to determine the responses of the watershed to localized atmospheric forcing. Field study measurements showed widespread precipitation in August 2019, generating an increase in total suspended solids, dissolved organic carbon, and iron fluxes from the tundra, shifting the main-stem mountain river biogeochemistry toward tundra source characteristics typically only observed during the spring floods. Intuitively, a large-scale precipitation event (as defined by this study as exceeding 12.5 mm of precipitation on a single observation day) would dilute a body of water; however, in this study, concentrations increased with higher discharge responses on several occasions. These large-scale precipitation events continue to produce peak constituent fluxes as the thaw layer increases in depth and late summer precipitation increases, evidenced by 6 large-scale events in July 2022 alone. This increase in late summer events is in sharp contrast to the 3 or fewer large events in July in each of the last 10 years. Changes in precipitation intensity, timing, and location have introduced late summer peak constituent flux events previously confined to the spring freshet.

Keywords: Alaska North Slope, arctic rivers, material flux, precipitation

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Authors: Leslie Raphael de M. Ferraz, Salvana Priscylla M. Costa, Tarcyla de A. Gomes, Giovanna Christinne R. M. Schver, Cristóvão R. da Silva, Magaly Andreza M. de Lyra, Danilo Augusto F. Fontes, Larissa A. Rolim, Amanda Carla Q. M. Vieira, Miracy M. de Albuquerque, Pedro J. Rolim-Neto

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Efavirenz (EFV) is a drug used as first-line treatment of AIDS. However, it has poor aqueous solubility and wettability, presenting problems in the gastrointestinal tract absorption and bioavailability. One of the most promising strategies to improve the solubility is the use of solid dispersions (SD). Therefore, this study aimed to characterize SD EFZ with the polymers: PVP-K30, PVPVA 64 and SOLUPLUS in order to find an optimal formulation to compose a future pharmaceutical product for AIDS therapy. Initially, Physical Mixtures (PM) and SD with the polymers were obtained containing 10, 20, 50 and 80% of drug (w/w) by the solvent method. The best formulation obtained between the SD was selected by in vitro dissolution test. Finally, the drug-carrier system chosen, in all ratios obtained, were analyzed by the following techniques: Differential Scanning Calorimetry (DSC), polarization microscopy, Scanning Electron Microscopy (SEM) and spectrophotometry of absorption in the region of infrared (IR). From the dissolution profiles of EFV, PM and SD, the values of area Under The Curve (AUC) were calculated. The data showed that the AUC of all PM is greater than the isolated EFV, this result is derived from the hydrophilic properties of the polymers thus favoring a decrease in surface tension between the drug and the dissolution medium. In adittion, this ensures an increasing of wettability of the drug. In parallel, it was found that SD whom had higher AUC values, were those who have the greatest amount of polymer (with only 10% drug). As the amount of drug increases, it was noticed that these results either decrease or are statistically similar. The AUC values of the SD using the three different polymers, followed this decreasing order: SD PVPVA 64-EFV 10% > SD PVP-K30-EFV 10% > SD Soluplus®-EFV 10%. The DSC curves of SD’s did not show the characteristic endothermic event of drug melt process, suggesting that the EFV was converted to its amorphous state. The analysis of polarized light microscopy showed significant birefringence of the PM’s, but this was not observed in films of SD’s, thus suggesting the conversion of the drug from the crystalline to the amorphous state. In electron micrographs of all PM, independently of the percentage of the drug, the crystal structure of EFV was clearly detectable. Moreover, electron micrographs of the SD with the two polymers in different ratios investigated, we observed the presence of particles with irregular size and morphology, also occurring an extensive change in the appearance of the polymer, not being possible to differentiate the two components. IR spectra of PM corresponds to the overlapping of polymer and EFV bands indicating thereby that there is no interaction between them, unlike the spectra of all SD that showed complete disappearance of the band related to the axial deformation of the NH group of EFV. Therefore, this study was able to obtain a suitable formulation to overcome the solubility limitations of the EFV, since SD PVPVA 64-EFZ 10% was chosen as the best system in delay crystallization of the prototype, reaching higher levels of super saturation.

Keywords: characterization, dissolution, Efavirenz, solid dispersions

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Authors: Ikram Elsiddig, Yacouba Djamila, Amna Hamad

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Abstract—The worldwide increasing of using herbs in form of medicine with or without prescription medications potentiates the interactions between herbal products and conventional medicines; due to more research for herb-drug interactions are needed. for a long time hyperglycemia had been treated with several medicinal plants. A. sativum, belonging to the Liliaceae family is well known for its medicinal uses in African traditional medicine, it used for treating of many human diseases mainly diabetes, high cholesterol and high blood pressure. The purpose of this study is to determine the interaction effect between A. sativum bulb extracts and metformin drug used in diabetes treatment. The in vitro and in vivo evaluation were conducted by glucose reuptake using isolated rats hemidiaphgrams tissue and by estimate glucose tolerance in glucose-loaded wistar albino rats. The results showed that, petroleum ether, chloroform and ethyl acetate extracts were found to have activity of glucose uptake in isolated rats hemidiaphgrams of 24.11 mg/g, 19.07 mg/g and 15.66 mg/g compared to metformin drug of 17 mg/g. These activity were reducded to 17.8 mg/g, 13.59 mg/g and 14.46 mg/g after combination with metformin, metformin itself reduced to 13.59 mg/g, 14.46 mg/g and 12.71 mg/g in comination with chloroform and ethyl acetate. These decrease in activity could be due to herbal–drug interaction between the extracts of A. sativum bulb and metformin drug. The interaction between A. sativum extract and metformin was also shown by in vivo study on the induced hyperglycemic rats. The glucose level after administered of 200 mg/kg was found to be increase with 47.2 % and 17.7% at first and second hour compared to the increase of blood glucose in the control group of 82.6% and76.7%.. At fourth hour the glucose level was became less than normal with 3.4% compared to control which continue to increase with 68.2%. Dose of 400 mg/kg at first hour showed increase in blood glucose of 31.5 %, at second and fourth hours the glucose level was became less than normal with decrease of 3.2 % and 30.4%. After combination the activity was found to be less than that of extract at both high and low dose, whereas, at first and second hour, the glucose level was found to be increase with 50.4% and 21.2%, at fourth hour the glucose level was became less than normal with 14%. Therefore A. sativum could be a potential source for anti-diabetic when it used alone, and it is significant important to use the garlic extract alone instead of combined with Metformin drug in diabetes- treatment.

Keywords: Antagonistic, Garlic, Metformin, Synergistic

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Authors: Mohsen Yaghmoor, Sima Radmanesh, Ameneh Gholami

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Cities are the principal ground for manifestation of an information society. To create an entrepreneurial city, it is required that just and equal access to opportunities are provided for all segments of the city and technologies are intelligently employed. Furthermore, it is necessary for us to be electronically ready in all political, economic, social, cultural, and technological aspects. Also e-city creates enormous potentials and opportunities for development of the entrepreneurial city. After improvement of e-readiness for establishment of entrepreneurial e-city, potentials, and capitals of the city become productive and more suitable opportunities are offered to citizens, state sectors, and private sectors in order to become entrepreneurs. To create and develop an entrepreneurial city, we need to have readiness to detection and creation of entrepreneurial opportunities and finally exploitation of these opportunities which, in turn, lead to use of entrepreneurial events and their quality in the city. In this model, the quality of entrepreneurial events, the productivity of activities, the necessity of reducing the digital gap, positive and active attendance in information society and compatibility and aligning with the global society are emphasized. In an entrepreneurial city, citizens are not help seekers, private sector is not passive, and the government is entrepreneurial.

Keywords: e-city, e-readiness, entrepreneurial city, entrepreneurial events, technological entrepreneurship

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Authors: Sabry A. El Azazy

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Tourism plays an essential role in supporting the National Economy. Egypt was ranked as one of the most attractive touristic destinations worldwide. Tourism as a service sector affects political events and unstable conditions. Within the revolution of January 25th, 2011, tourism became below standards, and the archeological heritage sites were subject to threat. Because of the political tension and social instability, Egypt's tourism sector has drastically dropped. Currently, Egypt is working on overcoming the crisis caused by political unrest. However, it is expected to take a long time to get back to where it was, especially in terms of regaining the confidence of travelers in the country's ability to guarantee and maintain security and stability. Recently, many great projects have been done, such as; New Administrative Cairo Capital, New Suez Canal logistic project, New City of Al Alamin, New Grand Egyptian Museum, as well as other great projects that reflect positively on the tourism industry and archaeological heritage development in Egypt.

Keywords: archaeology, archaeological heritage, attractions, national economy, political events, touristic destinations, tourism industry

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Authors: Raj Mukta Sundaram

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The location of Ayodhya is distinctly described along river Sarayu in the epic Ramayan. On the contrary, even elaborate descriptions of Lanka and its environs are still proving elusive to human ingenuity to find a direct correlation on the ground. His-torically, there were hardly any attempts to locate Lanka, but some speculations have been made very recently, of which Sri Lanka has gained widespread public ac-ceptance for obvious reasons, such as Sri and Lanka. This belief is almost secured by the impression of Ram Setu on the satellite images, which has led the government to initiate a scientific mission to determine its age. In fact, other viewpoints believe Lanka to be somewhere far-flung along the equator, and another has long proclaimed it to be in central regions of India, but both are diminished by contemporary belief. This study emanates from the fact that Sri Lanka has no correlation to epic, and more importantly, satellite images are deceptive. So the objectives are twofold - firstly, to interpret the text from a holistic approach by analyzing the ecosystem, settlements, geological as-pects, and most importantly, the timeline of key events. Secondly, it explains the pit-falls in the rationale behind contemporary belief. At the outset, it categorically rejects the notion of Ram Setu, which, in geological terms, is merely a part of the continental shelf developed millions of years ago. It also refutes the misconception created by the word “Sri,” which is, in fact, an official name adopted by the country in the seventies with no correlation whatsoever with the events of Ramayana. Likewise, the study ar-gues for the establishment of a prosperous kingdom on a remote island with adverse climatic conditions for any civilization at that time. Eventually, the study demonstrates that travel time for the distances covered by Lord Rama does not corroborate with the description in the epic. It all leads to one conclusion that Lanka cannot be in Sri Lanka. Rather, it needs to be somewhere in the central-eastern parts of India. That region jus-tifies the environs and timelines for the journeys undertaken by Lord Rama, besides the fact that the tribes of the region show strong allegiance to Ravana. The study strongly recommends looking into the central-east region of India for the golden abode of a demon king and rejuvenating tourism of a scenic and culturally rich region hitherto marred by disturbances.

Keywords: spatial analysis, Ramayan, heritage, tourism

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